Hyperinsulinemia and Insulin Resistance: New Metabolic Markers for Cancer ?

Image may be NSFW.
Clik here to view.I've talked a lot about insulin as it relates to disease but recently it is being discussed as a marker for cancer [1].  Though elevated blood insulin and insulin resistance (calculated HOMA) are emerging as new correlated factors for cancer and tumour progression, modern conventional medicine still has little solutions for either 'identifying' or 'treating' hyperinsulinemia other than two classes of drugs (PPAR agonists and biguanides/metformin). BTW be aware Crestor (rosuvastatin) and other statins can cause diabetes, higher blood glucoses (BG) and insulin resistance. Photo credit: modified [2].



Hyperinsulinemia? Insulin resistance (IR)?

How to recognize signs of hyperinsulinemia and IR?

Hyperinsulinemia and insulin resistance are associated with the initiation and growth of:

--central abdominal adiposity

--intraorgan adiposity (fatty liver, fatty pancreas, fatty gallbladder, fatty heart, fatty coronary/renal/peripheral arteries, fatty ovaries (e.g. PCOS and ensuing infertility), fatty muscles/sarcopenia)

--fatty liver (on ultrasound or reliable predictor: elevated liver test, ALT)

--skin tags

--warts

--acanthosis nigricans (darkening in armpits, behind knees, neck)

--melasma (skin darkening from insulin resistance induced by hormone imbalance by birth control, pregnancy, menopause, hormone replacement therapy)

--benign tumours

--malignant cancers, leukemias and lymphomas

--fatty brain degeneration, Alzheimer's ('Type 3 Diabetes Mellitus')




Pervasive Refined, Pesticide-Coated Monsanto-Grains, the S.A.D. and Other Nonsense

For many decades, like heart disease and stroke, cancer had high rates of association with diabetes and obesity. But recently the stats changed. I can agree with higher rates of insulin-related problems being secondary to macronutrient overnutrition of carbohydrates derived from refined sources (wheat, cereals, sugar, white monospecies potatoes, etc) however with the advent of pesticide technology since the Vietnam War and introduction of GMO crops in the 1990s, I believe that our burden of toxicants and insidious intestinal perturbation from GMO Bt crops are having subtle but immense influences on the growing rates of excessive insulin resistance and hyperinsulinemia.

Prior Animal Pharm: Pesticides Cause Insulin Resistance and Obesity


This is concerning...Before embolic diseases were #1 and #3 for mortality in the U.S.A. (heart disease, strokes, respectively) however, a few years ago, mortality from cancer eclipsed heart disease death as the #1 killer for the first time. Are Americans smoking more (no)? Is the GMO Bt corn/wheat(gluten) based Food Pyramid more engrained than ever in dietary, medical and public school education (yes YES and yes...)?

What are Americans doing differently compared to 5-10 yrs ago? Are they getting more influenza, swine flu, whooping cough, HPV and other mercury-laden or aluminum-laden vaccines (metals can contribute to insulin resistance and hypothyroidism)...? Is our diet and lifestyles more devoid of nutrients, saturated fat, and vitamins (choline, n-3 pufa, methyl donors like animal sourced-folates, magnesium, zinc, selenium, and animal sourced-retinol, etc)?

Why has the cancer rate suddenly jumped? What other factors are behind the story? Is it toxin related, lifestyle related, stress related, epigenetic related?  I believe all have a factor... and like hypertension, heart disease, obesity, metabolic syndrome, migraines, and autism, I think it's 50 shades of f-cked up... [ref Twilight fan fiction]

*2.6-fold increase prostate CA at highest insulin quartiles (J Natl Cancer Inst. 2009 Sep 16;101(18):1272-9. Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer.)

* 2.2-fold increase breast CA at highest waist-to-hip ratio (Cancer Causes Control. 2000 Sep;11(8):721-30. Markers of insulin resistance and sex steroid hormone activity in relation to breast cancer risk: a prospective analysis of abdominal adiposity, sebum production, and hirsutism (Italy).)

* Higher quartiles of insulin were predictive in non-diabetic breast CA women of 'poorer outcomes, consistent with the existence of a prognostic effect of insulin across broad categories of body weight.' Goodwin et al. J Clin Oncol 2001;20:42-51.




Aging, Cancer, IR -- AMPK Downregulated and NFkB/Inflammation Ramped Up

Tumor cells can initiate and grow with neolithic, post-agriculture, high/refined carbohydrate, grain-dominant diets as a result of constant and incessant switching to glucose-burning cell metabolism instead of energy efficient fat-burning fluxes. Environmental and food toxicants, stress, lack of exercise, 'iSolation' (excess electronics, less face-to-face contact), deficiency of micronutrients and vitamins (including choline and methyl donors from liver, organ meats and egg yolks) and broken sun-dark circadian rhythms merely add to these heavy metabolic disturbances.








Image may be NSFW.
Clik here to view.Insulin and AMPK

Most cancers may take 10-20 years to initiate, progress and amass to recognizable sizes in the prostate, breast, colon, brain, abdominal or other areas [4]. What triggers oncogenes and mutations to occur? To promote diversity of our genes and accelerated evolution to climactic changes in ecological microniches, it is natural for our genes to accumulate DNA mutations and changes. Just as developing abdominal fat and a 'summer mode' of adiposity is protective short term, humans and other lifeforms are built for these changes. Plasticity of DNA expression gives us the benefit of longevity and reverting to forms more adaptable to diverse conditions, environments and shifting situations. Photo credit: modified [5].

Insulin is an ancient growth hormone and mitogenic; its function is to grow tissue. It's essential for life. Type 1 Diabetes individuals have none and, without insulin, may go into diabetic comas within 24-36 hours. Often Type 1 Diabetes patients have a sarcopenic, low muscle phenotype because adequate and correctly timed insulin spikes with meals are necessary for appropriate muscle growth and maintenance. All animals require low basal amounts of insulin for metabolism and energy however the consequences of high, constant and postprandial (aftermeal) insulin levels are activation of mTOR to grow tissues, inflammation, increased ROS and the inability of the mitochondria to phosphorylate ATP for metabolic energy.

Image may be NSFW.
Clik here to view.AMPK is among many networked pathways known to regulate whole organism and single cell energetics [2, 4-8]. AMPK is found in all eukaryotes and is considered a highly conserved, master metabolic switch by some to coordinate growth, metabolism, food intake, body weight, autophagy, mitophagy, mitochondrial biogenesis and inflammation. AMPK fluxes on and off depending on fasting v. feeding states and energetic demands.  In mammals, AMPK is turned on under situations of perceived low cellular energy, e.g. low ATP which occur whilst exercise demands increase, periodic starvation and long-term starvation. Feeding, hyperglycemia (high BG), insulin spikes and other situations temporarily shut off AMPK. This makes sense, no? The body is accumulating energy, storing for the future, and replenishing depleted reserves. Under normal situations, the pattern is intermittent.  Unfortunately, AMPK can be shut off chronically instead of following a pattern of periodic flux. This is associated and observed in conditions such as clinical hyperinsulinemia, obesity, metabolic syndrome, aging and cancer [5-8]. Metformin  is an indirect stimulator of AMPK.  It is a diabetes drug, that can improve BG control, insulin resistance and shown to reduce both diabetic microvascular complications and cardiac events (macrovascular). Photo credit [7].



Metformin Appears to Desist Cancer Growth

Apparently in triple-negative breast cancer (TNBC; negative for estrogen, progesterone, and the type II tyrosine kinase (RTK) HER-2 receptor), effects of metformin are showing promise in vitro and human prospective studies are underway.  In a 2012 retrospective chart review, metformin combined with adjuvant chemotherapy in triple negative breast cancer was associated with reduced incidence of distant metastatic disease (p=0.06), however no significant differences in survival rates were observed [10].

Other observational studies show significant 25-62% relative risk reduction of colorectal, liver, pancreatic, breast, endometrial/uterine, and other cancers in metformin users versus non-users in Type 2 Diabetes trials. By the way, research shows that diabetes treatments with insulin and/or sulfonylureas (mechanism: increase endogenous insulin secretion) are associated with 500% and 250% SIGNIFICANTLY MORE CANCER, respectively, over other therapies or metformin in a comprehensive, non-industry funded U of T M.D. Anderson retrospective study that shook up the the Big Pharma world [11]. Really?

Yes. Again, many many many shades of f-cked up...

Hold your breath. More exciting research is coming... since there are no 'textbook' neoplasm solutions (besides hack, irradiate, chemo).  Treatment and therapeutics are lacking IMHO just as prevention and treatment for clinical hypertension, obesity, metabolic syndrome, heart disease and other insulin-related consequences are woefully inadequate [12,13].





Metformin: Drug That Lowers Insulin and Insulin Resistance (But Prevents Exercise-induced Muscle Growth and VO2 Max Benefits)

The effectiveness of metformin goes without fanfare. It is the #1 firstline medication for diabetes and the only diabetic drug that has been shown to lower cardiac mortality.  Other diabetic medications like PPAR-gamma agonists (Actos, Avandia) display marginal reductions in mortality but this is negated or even trumped by the associated increased prevalence of drug-associated sudden death, heart disease, heart failure, peripheral edema and heart failure mortality in the published clinical trials [Why? PPAR-gamma increases insulin sensitivity in the brown and subcutaneous white fat, exactly WHERE WE DO NOT WANT IT i.e. epicardial adipose depots ('fatty heart')].

Image may be NSFW.
Clik here to view.Until recently the mechanism of action of metformin was unknown. Recent studies suggest that metformin affects LKB1 which activates and increases AMPK activity. We have discussed earlier AMPK as it's role is important in conserving proliferation and growth per demand and for the purpose of energy production. Simply put, AMPK increases fat uptake into peripheral cells, fat burning, and mitochondrial biogenesis in muscles upon energetic demands (e.g. when ATP goes down at the cellular level). When I used to counsel patients on metformin, I added sometimes that metformin is like 'exercise in a pill' -- it results in lower glucoses, lower insulin resistance, reduction in adiposity, lowering of inflammation, and weight loss.  Unlike starvation and exercise, however, metformin generally does not induce eventual hunger (in fact it can induce nausea and anorexia). Metformin apparently has no hypothalamus AMPK effects,  and this is perhaps why hunger does not ensue despite weight loss associated with metformin.  Other notable effects of metformin are -- GI upset, nausea, diarrhea, unpredicted 'explosive' diarrhea (as several patients have complained to me), abdominal cramping, intestinal dysbiosis leading to clinical vitamin B12 deficiency and related cognitive deficits over time. Photo credit: [9].

New research from Braun and his brainiac research group showed that metformin actually does mimic exercise yet when combined with exercise, metformin (2000 mg/day) appears to negate the complete, skeletal muscle benefits of exercise in prediabetic individuals [14,15]. Braun and his lab have done fantastic work on elucidating how our bodies utilize varied macronutrient substrates, handle energy deficits/surpluses and teasing out how metformin fits into the metabolic picture IMHO.  Unlike exercise or periodic starvation which typically leads to muscle gains and growth (e.g. protein synthesis) upon refeeding, when the synthetic drug, metformin, is added to an exercise program, the lean mass growth and increases of expected VO2 max benefits are BLUNTED. The exercise program was 12 weeks, 3 times weekly, of 60-75 cycling (45 min, 70% of pretraining max) and progressive resistance training including chest press, leg press, and latissimus pull-downs. Protein synthesis appeared blocked -- the FFM (fat-free mass, proxy for lean body mass) decreased significantly in the span of the 12-week experiment in both drug groups: metformin alone (M-alone, lost 1.7 kg) and metformin+exercise (EM, lost 0.5 kg), whereas the pure exercise group significantly gained 2.0 kg of lean, fat-free mass.

AMPK activation which may be devoid of natural on-off fluxes appears to be ultimately associated with sacrifice of protein and muscle construction post-exercise stimulus. When AMPK is turned-on, the function is to increase net energy (ATP). The metabolic pathways are shunted toward producing energy for IMMEDIATE demands and shunted toward eliminating short-term energy-sucking processes, like pancreatic insulin secretion, liver gluconeogenesis, and growing nice musculature, physiques and hot bodies. Makes sense, no? Yes, it does improve the metrics of conventional diabetes medicine (BG, HgbA1c), but at what cost? Is 'metabolic flexibility' over-compensated and lost without natural AMPK rhythms [16]?  Exercise obviously improves the balance between dysfunctional carbohydrate oxidation and lipid oxidation, yet synthetically knocking out carbohydrate oxidation via constant AMPK appears to induce sarcopenia and hinder the full insulin-sensitizing, anti-inflammatory benefits of exercise. Actually it is no surprise that exercise trumps metformin drug use in cases where insulin resistance may be reversible, as it seems.

Other negatives of metformin are that higher blood lactate may result (build up from anaerobic or hypoxic glucose/carb metabolism). One risk with metformin use is lactic acidosis from toxic accumulation of lactate which can be ~~50% fatal. The danger for this adverse effect is higher in kidney- and liver-compromised states such as dehydration, binge/chronic alcohol use, kidney disease, liver disease, heart failure, elderly, and co-adminstration with kidney-toxic drugs -- therefore use is contraindicated.



Controlling Insulin and Insulin Resistance With Paleo-Ancestral Eating: Frasetto et al

In PCOS women, metformin has some success at improving fertility. What about diet and exercise? At Crossfit and RobbWolf.com, numerous stories of *cough cough* unintended pregnancies in (previously) infertile couples abound! Exercise +paleo/ancestral eating reverse infertility more effectively than pharmaceuticals and current reproductive technology IMHO as it appears from stories in paleo-land.

Frasetto et al (EJCN 2009) 68% Decrease Insulin and 72% Improvement on Insulin Resistance on Hunter-Gatherer 7-Day Paleolithic Diet

In the 10-day experiment, Frasetto et al demonstrated that basal insulin in overweight men and women age 18 to 50 could be lowered by 68% from 69 mol/L to 21 pmol/L on a grain-free, legume-free, dairy-free (~220 grams carbs/day, Low Glycemic Index) diet that simulated our evolutionary roots. Additionally, HOMA, a measure of insulin resistance, dramatically decreased from 3.2 to 1.0 by 72%. Elevated blood pressure and weight naturally decreased. The study aimed for neutral weight (no change) and required higher caloric intake to offset the weight loss in the Paleo group.

This experiment was indeed short. Most of us in the evo/ancestral/paleo/primal community hear of similar success stories of health reversal on this type of timeline all the time.

Why? Because perhaps the evolutionary-based diet is aligned with older DNA and optimal expression of insulin sensitivity?



Ketones Appear to Desist Cancer Growth

Ketones are generated by either consuming MCT oil/coconut oil or a low or no carbohydrate diet. Ketones are the metabolic currency of the (a)  fasting or starving energetic state and (b) when physical training is fat burning (25-70% max heart rate) and extended.

The brain runs naturally well on ketones (granted the adrenals are healthy; ketone generation requires cortisol and adrenaline). We are built to intermittently fast and run on ketones when required (postnatal, extended chronic aerobic exercise, intermittent or chronic starvation).

Several studies show the surprisingly positive benefits of MCT oil, ketotic diets or infusion of ketones for treating cancer [17,18,19]. Why? Ketones are the opposite of IR-promoting, refined, high-carb, grain-intensive diets.

In our evolutionary fitness and paleo communities, it is popular to practice periodic starvation of 18-36 hours several times during a month (granted healthy adrenals and good deep rest/sleep). The practice elicits many health promoting effects as it increases ketone bodies to utilize as fuel for the brain and muscles, synthesized from visceral and subcutaneous fat stores.

[**  FYI... I rarely do intermittent fasting (IF) now since my adrenal glands are borderline-frail. As an individual experiment to combat body fat increases (15 lbs) due to the Mirena IUD (18 months of synthetic progestin toxicity), I did try frequent IF but found it further deteriorated adrenal function. So I'd caution anyone with  un-compensated, frail or marginal adrenal function to consider the value of avoidance of IF and consider the merit of varied, low glycemic index carbs in adrenal exhaustion protocols (100 - 150 grams daily --nonallergenic starches and whole foods) like Dr. Lam's adrenal optimization protocol. **]




Ketones and Metformin are Epigenetic HDAC-Inhibitors

Bioactive components of our food have epigenetic influence on potentical cancer profiles and insulin/IR signatures. We live now in the post-genomic DNA world. DNA may be the text and chromatin, the words, of our chapters, but epigenetic modifications are the punctuation, paragraphs and grammar that give words life and context. Researchers Shaw and Mihaylova at the Salk Institute in San Diego studied the effects of metformin and AMPK and elucidated one of the core mechanisms of metformin and AMPK's action for reversing chronic insulin resistance defects [8]. AMPK activation stimulates downstream inhibition of an enzyme, histone deacetylase (HDAC), that blocks 'punctuation', or in other words, normal chromatin DNA 'editing.'  HDAC inhibition leads to activation of intracellular antioxidant pathways and resumption of normal DNA chromatin form and function.

It turns out that ketones and metformin have similar epigenetic molecular mechanisms; both are HDAC inhibitors [8,20]. This is believed to be how they may elicit some of their powerful effects in insulin resistant conditions. Many spices, herbs, vegetables, animal products, fermented dairy products (phenylbutyrate), royal jelly (phenylbutyrate) and polyphenol-rich foods contain bioactive components that behave by editing and providing clarity/context to our DNA blueprint via inhibition of HDAC [21]. Photo credit [21].






How About An Evolutionary Medicine Based Approach to Cancer Treatment and Prevention?

Radiation, chemotherapy and treatment of cancer take a toll on pediatric, adult and elderly patients. Some of the long term effects including cardiotoxicity, nerve ending and brain damage and even increased risk for other cancers. Many cancer treatments fail with 5- and 10-year survival rates of 25-50% or less. The monetary costs of cancer treatment can add up and may eventually bankrupt Medicare and current health insurances provided by large and small businesses. Can we afford to continue and ignore the misalignment between government sanctioned dietary advice (whole unprocessed lectins, Rockefeller-wheat-gluten-galore, GMO-corn-soy-everything, low fat, high refined carbs, n-6 pufa overload) and the chronic and acute diseases including cancer? How best for modern conventional medicine to mutate, re-align, evolve and provide healthcare from the perspective of evolution?

I have no answers but would be interested in your thoughts...





Evolutionary Bloggers:

Robb Wolf: Sept 2007 post and his interview with Dr. Seyfried 'Cancer and ketosis' [18]

Dr. Eades: Metabolism and Ketones






References:

1. Obesity related hyperinsulinaemia and hyperglycaemia and cancer development.
Becker S, Dossus L, Kaaks R.
Arch Physiol Biochem. 2009 May;115(2):86-96.

2. AMPK and the biochemistry of exercise: implications for human health and disease.
Richter EA, Ruderman NB.
Biochem J. 2009 Mar 1;418(2):261-75.

3.  Mechanisms linking obesity to insulin resistance and type 2 diabetes.
Kahn SE, Hull RL, Utzschneider KM.
Nature. 2006 Dec 14;444(7121):840-6.

4.  Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer.
Yadav VR, Prasad S, Sung B, Kannappan R, Aggarwal BB.
Toxins (Basel). 2010 Oct;2(10):2428-66.

5.  AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network.
Salminen A, Kaarniranta K.
Ageing Res Rev. 2012 Apr;11(2):230-41.

6 . An energetic tale of AMPK-independent effects of metformin.
Miller RA, Birnbaum MJ.
J Clin Invest. 2010 Jul 1;120(7):2267-70.

7. AMPK: a metabolic gauge regulating whole-body energy homeostasis.
Lage R, Diéguez C, Vidal-Puig A, López M.
Trends Mol Med. 2008 Dec;14(12):539-49.

8.  The AMPK signalling pathway coordinates cell growth, autophagy and metabolism.
Mihaylova MM, Shaw RJ.
Nat Cell Biol. 2011 Sep 2;13(9):1016-23.

9 . Understanding the benefit of metformin use in cancer treatment.
Dowling RJ, Goodwin PJ, Stambolic V.
BMC Med. 2011 Apr 6;9:33.

10. Effect of metformin on survival outcomes in diabetic patients with triple receptor-negative breast cancer.
Bayraktar S, Hernadez-Aya LF, Lei X, Meric-Bernstam F, Litton JK, Hsu L, Hortobagyi GN, Gonzalez-Angulo AM.
Cancer. 2012 Mar 1;118(5):1202-11.

11. Antidiabetic therapies affect risk of pancreatic cancer.
Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL.
Gastroenterology. 2009 Aug;137(2):482-8.

12. Dietary energy availability affects primary and metastatic breast cancer and metformin efficacy.
Phoenix KN, Vumbaca F, Fox MM, Evans R, Claffey KP. Breast Cancer Res Treat. 2009 Nov 22.

13. Expanding the arsenal: metformin for the treatment of triple-negative breast cancer?
Jiralerspong S, Gonzalez-Angulo AM, Hung MC.Cell Cycle. 2009 Sep 1;8(17):2681.

14. Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes.
Malin SK, Gerber R, Chipkin SR, Braun B.
Diabetes Care. 2012 Jan;35(1):131-6.

15. Combining short-term metformin treatment and one bout of exercise does not increase insulin action in insulin-resistant individuals.
Sharoff CG, Hagobian TA, Malin SK, Chipkin SR, Yu H, Hirshman MF, Goodyear LJ, Braun B.
Am J Physiol Endocrinol Metab. 2010 Apr;298(4):E815-23.

16.  Metabolic flexibility in the development of insulin resistance and type 2 diabetes: effects of lifestyle.  [Free PDF -- click]
Corpeleijn E, Saris WH, Blaak EE.
Obes Rev. 2009 Mar;10(2):178-93.

17. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports.
Nebeling LC, Miraldi F, Shurin SB, Lerner E.
J Am Coll Nutr. 1995 Apr;14(2):202-8.

18. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet.
Seyfried BT, Kiebish M, Marsh J, Mukherjee P.
J Cancer Res Ther. 2009 Sep;5 Suppl 1:S7-15. Review.

19. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides.
Otto C, Kaemmerer U, Illert B, Muehling B, Pfetzer N, Wittig R, Voelker HU, Thiede A, Coy JF.
BMC Cancer. 2008 Apr 30;8:122.

20. From natural products to small molecule ketone histone deacetylase inhibitors: development of new class specific agents.
Jones P, Steinkühler C.
Curr Pharm Des. 2008;14(6):545-61.

21. Epigenetic impact of dietary polyphenols in cancer chemoprevention: lifelong remodeling of our epigenomes.
Vanden Berghe W.
Pharmacol Res. 2012 Jun;65(6):565-76.






[Re-tweaked old Nephropal(eo) post]

Food, Sunlight and Nuclear Receptors

I've discussed RXR/RAR (carotenoids/ vitamin A receptor), VDR (vitamin D receptor) and PPAR-α (saturated fat/omega-3 receptor). These are a constellation of receptors found in the nucleus of all cells which control growth, maturation, reproduction, proliferation, apoptosis (cell suicide), autophagy (cell re-cycling) and inflammation.  Bioactive components of our food and hormone vitamin D from sunlight exposure (or organ meat consumption) bind and control nuclear receptors.

See prior posts:
PPAR -- Dagger in the Heart of CAD and all Chronic Conditions
Benefits of Grassfed Butter





Phytanic Acid Generates Carnitine

A recent study looked at the level of phytanic acid (PA), a
Image may be NSFW.
Clik here to view.fatty acid found in red meat, dairy fat, and seafood which has activity on receptors known to control and regulate cancer, inflammation, triglycerides/cholesterol and even energy status in skeletal muscles. It may have several mechanisms for health regulation. One mechanism found is that phytanic acid is an agonist for several nuclear receptors including RXR and PPAR-α. I would not be surprised if it has affinity and binds other receptors as well.

We don't synthesize phytanic acid on our own; we can only source from food (animal based). Phytanic acid and its metabolite pristanic acid contribute to the activation of carnitine in peroxisomes which are later transported to mitochondria for fatty acid oxidation (burning and synthesis of energy, ATP). A lack of carnitine has been shown to lower mitochondrial processes and is significant factor in disease. Like phytanic acid, carnitine can mainly be sourced only from MEAT and seafood, not vegetables. We produce it but not very well. Many factors affect carnitine levels (kidney function, ACTH/cortisol, thyroid and diet. French authors write 'L-carnitine ensures regeneration of coenzyme A and is thus involved in energy metabolism. L-carnitine also ensures elimination of xenobiotic substances. Carnitine deficiencies are common.'  Photo credit: [1].

Do butter and bison do a body good?

YESSSSSS.




Chlorophyll Is Biotransformed into Phytanic Acid by Fish and Mammals

Apparently the chlorophyll content of the meat, seafood or dairy is what determines the amount of this important fatty acid, phytanic acid. 'PA (3,7,11,15-tetramethylhexadecanoic acid) is a branched-chain fatty acid generated by the oxidation of the phytol side chain of chlorophyll in mammals. Because humans cannot release phytol from chlorophyll, PA in the human body comes from dairy products and ruminant fats in the diet' [2]. Shore-based food such as fish, salmon, molluscs, snails and krill have significant levels too since these consume smaller fish which consume chlorophyll from algae and green phytoplankton. Phytanic acid is also found in menhaden oils. There is a vague association with prostate cancer and levels of phytanic acid however the below authors discuss "the available data do not support a general causal link between circulating phytanic acid and prostate cancer risk." Phytanic acid is metabolized in peroxisomes -- little fatty storage droplets where enzymes breakdown and metabolize fatty acids. Many of the metabolic breakdown products then go to the mitochondria to provide energy, intermediaries for the respiratory and energy producing complexes, and/or to absorb and quench ROS (reactive oxygen species, aka POLLUTION generated from energy production). If mitochondria are working awry, I suspect phytanic acid accumulation occurs because it is not being appropriately metabolized which could be genomic or post-genomic (Refsum syndrome).



Evolutionary Medicine: Mitochondrial Dysfunction

Many of our chronic diseases are a result of mitochondrial dysfunction -- our tiny nuclear power plants are on the 'blink'...often preferring glycolytic combustion over superior fatty-acid burning.  Mitochondria provide awesome power but can wreak untold destruction as well.

--compromised controls, directions and regulation for proper nuclear plant functioning (AMPK, cAMP)
--lacking power grid efficiency (leptin, insulin, cortisol, SIRT1, adiponectin, secretin, fertuin-A)
--malfunctioning or missing power plant cogs and parts (minerals, carnitine, AcCoA/pantothenic acid, omega-3)
--deficiency of buffering, recycling and containment of nuclear waste (coenzyme Q10/ ubiquinol)
--lacking managers and communicators (cell membrane stability and communication: omega-3 vitamins A B D E K2 thyroid cortisol estrogen progesterone DHEA pregnenolone testosterone saturated fat etc)
--excessive disruptions (high carb diets, endocrine disruptors, PCBs, heavy metals)





From Bacteria 4.5+ bya To Mitochondria

Other strategies to keep mitochondria free of breakdowns -- lifestyles and diet aligned with our evolutionary past from 4.5+ Billion Years Ago:

--lowish carbish (~150 grams or less net effective carbs I like...varying on goals, gut, adrenals, etc)
--saturated fat (~20% or more -- dietary or butt-sourced)
--low fructose
--low omega-6
--high omega-3
--high phytanic acid *wink*
--organic shore-based and grassfed/pasture-based fat and protein
--organic mineral rich plants, berries, nuts, meat/fish/fowl
--intermittent feast v. fast (seasonality)
--optimal hormesis status
--low pollution (air, water, mind)
--enjoyment of culture, music, arts, spiritual enlightenment
--engaging in community and social networks
--movement: rapid intense and languid continuous (yeah S*X counts)


Prior animal pharm:
You are only as strong as your weakest mitochondria...





Health and Food Connection

When I consume ghee (clarified butter), egg yolks, veggies, adequate starches and adequate grassfed beef, pork and lamb, I notice more and easy weight maintenance and improved muscle composition. Mental and physical performance are pretty excellent too. How do you break down food and its effects on mitochondria? Researchers are trying and it's a good thing....

Phytanic acid--an overlooked bioactive fatty acid in dairy fat?

Hellgren LI. Ann N Y Acad Sci. 2010 Mar;1190(1):42-9.

Abstract
Phytanic acid is a multibranched fatty acid with reported retinoid X receptor (RXR) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist activity, which have been suggested to have preventive effects on metabolic dysfunctions. Serum level in man is strongly correlated to the intake of red meat and dairy products and the concentration in these products is strongly correlated to the chlorophyll content in the feed of the cattle. Available data suggest that phytanic acid is a natural agonist for RXR at physiological concentrations, while it is more likely that it is the metabolite pristanic acid, rather than phytanic acid itself, that acts as PPAR-alpha agonist. Animal studies show increased expression of genes involved in fatty acid oxidation, after intake of phytol, the metabolic precursor of phytanic acid, but it is at present not possible to deduce whether phytanic acid is useful in the prevention of ectopic lipid deposition. Phytanic acid is an efficient inducer of the expression of uncoupler protein 1 (UCP1). UCP1 is expressed in human skeletal muscles, were it might be important for the total energy balance. Therefore, phytanic acid may be able to stimulate energy dissipation in skeletal muscles. Phytanic acid levels in serum are associated with an increased risk of developing prostate cancer, but the available data do not support a general causal link between circulating phytanic acid and prostate cancer risk. However, certain individuals, with specific single-nucleotide polymorphisms in the gene for the enzyme alpha-methylacyl-CoA racemase, might be susceptible to raised phytanic acid levels. PMID: 20388135

Phytanic Acid (Cheese, Butter) Human RCT

How does phytanic acid perform as a drug? In a tiny Denmark RCT, this was tested.  The control group however also received phytanic acid therefore the results were substantially diluted out IMHO. Methods: In a double-blind, randomized, 4 wk, parallel intervention study 14 healthy young subjects were given 45 g milk fat/d from test butter and cheese with 0.24 wt% phytanic acid or a control diet with 0.13 wt% phytanic acid. The outcomes were positive and associate with metrics that indicate improved mitochondrial functioning (better insulin sensitivity, more fat oxidation, decreased glycolysis).   The lipoprotein changes were impressive but unfortunately the study was too small for meaningful stats. HDL-cholesterol increased by 10% in only one month.  No drug achieves this... or without killing patients or raising BG and diabetes (particularly Crestor).  Is it all phytanic acid?  I dunno...  The researchers enriched the test dairy products by feeding the cows more green material. Subsequently the omega-3 to omega-6 profile in test butter and cheese also improved. They discussed, 'The test butter with the highest content of phytanic acid, also had the highest content of α-linolenic acid [omega-3] and a lower n-6:n-3 ratio of about 1.8. This is in agreement with the higher proportion of clover and grass in the green feeding regime.'   Notwithstanding the beneficial numbers, butter and cheese have other proven bioactive food components which improve heart health, inflammation, insulin resistance and cancer risks, principally, cholesterol, vitamin A/retinol, saturated fatty acids including butyrate, omega-3, taurine (if raw), stigmasterol (if raw; Wulzen factor), folate (5-MTHF) and vitamin K2 (menaquinones).

Results:
(a) HDL increase 10% 
(b) Insulin reduction 15%
(c) TG reduction 22% 




References

1.Verhoeven NM et al. Phytanic acid and pristanic acid are oxidized by sequential peroxisomal and mitochondrial reactions in cultured fibroblasts. The Journal of Lipid Research, Vol. 39, 66-74, January 1998. [Free PDF here]

2. Cell proliferation inhibition and alterations in retinol esterification induced by phytanic acid and docosahexaenoic acid.
Tang XH, Suh MJ, Li R, Gudas LJ.
J Lipid Res. 2007 Jan;48(1):165-76.

3. Novel branched-chain fatty acids in certain fish oils.
Ratnayake WM, Olsson B, Ackman RG.
Lipids. 1989 Jul;24(7):630-7.

4. Oxidative stress and mitochondrial dysfunction in Fibromyalgia. MINIREVIEW.
Cordero MD, Miguel MD, Carmona-López I, Bonal P, Campa F, Moreno-Fernández AM.
Neuro Endocrinol Lett. 2010 Apr 29;31(2):169-173.

5. Oxidative stress: emerging mitochondrial and cellular themes and variations in neuronal injury.
Higgins GC, Beart PM, Shin YS, Chen MJ, Cheung NS, Nagley P.
J Alzheimers Dis. 2010;20 Suppl 2:453-73.

6. Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease.
Cordero MD, De Miguel M, Moreno Fernández AM, Carmona López IM, Garrido Maraver J, Cotán D, Gómez Izquierdo L, Bonal P, Campa F, Bullon P, Navas P, Sánchez Alcázar JA.
Arthritis Res Ther. 2010;12(1):R17. Free PMC ArticleFree text

7. Connecting the Dots: Molecular and Epigenetic Mechanisms in Type 2 Diabetes.
Goh KP, Sum CF.
Curr Diabetes Rev. 2010 Jun 9.

8. Fetal programming of atherosclerosis: possible role of the mitochondria.
Leduc L, Levy E, Bouity-Voubou M, Delvin E.
Eur J Obstet Gynecol Reprod Biol. 2010 Apr;149(2):127-30.

9. Spinal cord repair in MS: does mitochondrial metabolism play a role?
Ciccarelli O, Altmann DR, McLean MA, Wheeler-Kingshott CA, Wimpey K, Miller DH, Thompson AJ.
Neurology. 2010 Mar 2;74(9):721-7.

10. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential.
Desbois AP, Smith VJ.
Appl Microbiol Biotechnol. 2010 Feb;85(6):1629-42.

11. Eating, exercise, and "thrifty" genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases.
Chakravarthy MV, Booth FW.
J Appl Physiol. 2004 Jan;96(1):3-10. [Free PDF here]

12. Glycolysis: a bioenergetic or a survival pathway?
Bolaños JP, Almeida A, Moncada S.
Trends Biochem Sci. 2010 Mar;35(3):145-9.

13. Type 2 diabetes, cardiovascular disease, and the evolutionary paradox of the polycystic ovary syndrome: a fertility first hypothesis.
Corbett SJ, McMichael AJ, Prentice AM.
Am J Hum Biol. 2009 Sep-Oct;21(5):587-98.

14. Liver fattening during feast and famine: an evolutionary paradox.
van Ginneken VJ.
Med Hypotheses. 2008;70(5):924-8.

15. Biochem pages http://themedicalbiochemistrypage.org/fatty-acid-oxidation.html

16. Carnitine: an overview of its role in preventive medicine.
Kendler BS.
Prev Med. 1986 Jul;15(4):373-90. Review.

17. [L-carnitine: metabolism, functions and value in pathology]
Jacob C, Belleville F.
Pathol Biol (Paris). 1992 Nov;40(9):910-9. Review. French.

18. The metabolism of phytanic acid and pristanic acid in man: a review.
Verhoeven NM, Wanders RJ, Poll-The BT, Saudubray JM, Jakobs C.
J Inherit Metab Dis. 1998 Oct;21(7):697-728. Review.

19. Phytanic acid--an overlooked bioactive fatty acid in dairy fat?
Hellgren LI.
Ann N Y Acad Sci. 2010 Mar;1190:42-9.

20. Effect of dairy fat on plasma phytanic acid in healthy volunteers - a randomized controlled study.  [Free PDF here.]
Werner LB, Hellgren LI, Raff M, Jensen SK, Petersen RA, Drachmann T, Tholstrup T.
Lipids Health Dis. 2011 Jun 10;10:95.

21. Bioactive food components, inflammatory targets, and cancer prevention.
Kim YS, Young MR, Bobe G, Colburn NH, Milner JA.
Cancer Prev Res (Phila). 2009 Mar;2(3):200-8.

Adipose is Alive

In ancestral times, adipose stores may have determined longevity and survival past harsh cold winters. My ancestors moved from northern China 8-10+ generations ago to the mountainous areas of Taiwan (according to my dad several hundred years ago). I suppose those who didn't live past the impoverished seasons where food resources were scarce would not have made it, nor would their genes. I can thank them for my persistent fat stores *haa*. Adipose tissue is an endocrine gland which is know to secrete hormones such as leptin and adiponectin to control hunger, body energy balance and energy expenditure. These hormones are involved directly with mitochondrial biogenesis as well, in other words the production and destruction of the mini powerhouses found in all cells (except perhaps glycolytic-dependent cancer cells, which I think are all of them).

Whole body energy balance are determined by many factors, including most importantly:
1) demand
2) diet
3) d*ng hormones (or lack of)



All Organs Sync For Survival

Our brain coordinates many of the hormones that either mobilize or store adipose, e.g. fat. The brain includes the hypothalamus, pituitary, pineal, forebrain, hindbrain, midbrain and our senses for perception (ears, eyes, nose, taste, temperature, barometric pressure, etc). For example, insulin is triggered cephalically (via the brain): by tasting sweetness whether artificial or real, by smelling food, seeing food or even imagining food. Hearing? Hearing the neighborhood ice cream truck as a kid?




Humans Killed for Fat

Fat may have been the biggest boon for man during evolution (see prior animal pharm: humans as marine-based carnivores). Fat contained omega-3s concentrated up the food chain from green chlorophyll sources (grass, algae, etc) and into the muscle fat, organ meats, brains and fat stores of animals and seafood. The encephalization of ancient man is believed to be highly associated with the intake of dietary omega-3s. Perhaps the current de-encephalization over the last 100 yrs is related to the relative deficiency of dietary omega-3s? Or growing overabundance of omega-6s? THANK YOU VERY MUCH corn-fed cows and Keys.




Fat Yields the Most Energy in Human/Mammalian Energy Systems

Hormones for MOBILIZING fat stores far out number the hormones that ACCUMULATE fat. See diagram, modified from Gary Taubes GCBC from a 1965 table of hormonal regulation. Forgive me I use the term 'hormone' loosely because food is hormonal. Fatty acids bind PPAR receptors. We have ~ 3-4 routes to produce energy (some cells utilize glutamine, but I don't know which... neurons only?). Burning fatty acids yields the highest net energy unit (ATP). Why I've wondered? So many hormones promote the escape of fatty acids from temporary storage -- intramuscular, liver, visceral fat, brown fat and subcutaneous fat. Why do we readily release fatty acid energy? Sex, power, survival/suicide? Heat for 37C?

Taubes quoted Hans Krebs who received the Nobel in Medicine in 1953 'All three major constituents of food supply carbon atoms.. for combustion." GNG= gluconeogenesis (glucose/glycogen from any source -- protein, fat, carbs); ATP lesson (click HERE and UCD Lecture and med biochem):



Low Yield but Mandatory Without Oxygen
--anaerobic glycolytic (glucose/GNG) [Yield: 2 ATP]


High Yield in the Presence of Oxygen
--aerobic glycolytic (glucose/GNG) [Yield: 38 ATP] 
--aerobic beta-oxidation of fatty acids like palmitate [Yield: 129 ATP]
--aerobic beta-oxidation of fatty acids like stearate [Yield: 146 ATP]
--aerobic beta-oxidation of fatty acids like ketones [Yield: 51 ATP]
--aerobic oxidation of alcohol [Yield: 16 ATP]


Carbon lengths:
Glucose: 6-carbon carb
Palmitate: 16-carbon saturated fatty acid
Stearate: 18-carbon saturated fatty acid
Ketones (b-oh-butyrate, Ac-Acetate): 4 carbon fatty acid
Alcohol: 2-carbon 'the fourth food group' *haa* tequila is paleo, no?

Prior animal pharm: Palmitate Utilized Between Meals




Mitochondrial Medicine

Where does all this high energy production occur? Of course. Your mitochondria (the lower-net-energy anaerobic pathway is independent of mitochondria, occurs in the cytoplasma).

So. Don't scr*w up your mitochondria. That's like jacking your ride. Blowing out your carburetor.

...FLUNKING your human SMOG TEST.

Mitochondrial medicine is a new field but old premises still apply. The paleo evolutionary paradigm for which your mitochondria and DNA were perfected and honed over 2.5M years of natural and sexual selection are what we believe optimize health and maximize vitality.

Fuel and Fluxxx...

Why do we store fat? Why do we eat?  A scientist who wrote about reproduction, fuel, photoperiods and fecundity wrote the below abstract...[1]

Image may be NSFW.
Clik here to view."While there is a relatively direct connection between
circulating levels of metabolic fuels and the GnRH [gonadotropin releasing hormone] pulse generator [in SCN behind the retina], this might not be the only energy-related pathway influencing the secretion of this neuropeptide. The overall control of energy balance is an immensely complex process and a number of pathways involved in it might secondarily influence the activity of GnRH neurons. Peripheral signals influencing energy balance and thus possibly GnRH secretion could come from the liver, pancreas, stomach, duodenum or adipose tissue, and these signals could be sent to the brain via the vagus nerves or by hormones such as leptin, insulin, insulin-like growth factor 1 or ghrelin. These hormones could act directly on the neural circuits controlling the GnRH neurons or they could act by modulating the availability of metabolic fuel. Likewise, the neuropeptides regulating GnRH secretion in the forebrain could also include galanin, orexin, the urocortins and endogenous opioids. Recent interest has focused on kisspeptin, the product of the KISS1 gene. The presence of kisspeptin is necessary for normal reproductive development and it can override the reproductively detrimental effect of mild food restriction."

Obviously how we expend fuel is highly complex and humans are ruled by a big, big, big, hungry, hot brains... Grow or growl? Feast or fast? F-ck or forage? Repair or repast?





HEAT: Cellular Bioenergetics Creates Wildly Explosive, Exothermic Reaction Generating Water

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CALORIES IN  ≠  CALORIES OUT

...we are not neat bomb-calorimeters, but open, conserved, networked metabolic and energy systems...
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Photos credit: [2].













The Evolution of Body Heat?

Image may be NSFW.
Clik here to view.When oxidized, the great majority of our food and stored energy goes to the production of HEAT.      What governs this? It is multifactorial but adrenaline, thyroid, cortisol and mitochondria quality are just a few [2]. Active tissues contain more mitochondria. Heat makes us mammals and birds. We have hot bodies, precisely 37C for the great majority.

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In the 'Hot Brain:  Survival, Temperature, and the Human Body' the authors theorized that temperature gave us advantages over eukaryotic infections (yeast, fungal origins -- we are eukaryotic) which plagued bird/reptile species which were not armed with high 37C temperatures or fever-inducing capabilities [3].  It is a very interesting theory. Control of thermoregulation (heat loss v. heat gain) is believed to have evolved in the brain of therapsids. Our sinuses are larger. Mammalian brains have a Circle of Willis where 4 arteries (internal carotids and vertebral arteries) provide a complete internal brain circulation with collaterals, such that despite blockage of one or more of the 4 major arteries circulation in the brain and to the body remains intact.  Unfortunately only 25-33% of us have a 'perfect' classic circle of Willis; others have degrees of narrowing or asymetry in certain areas or another. Photos courtesy: Hot Brain, pp. 44, 142.

Recently a microbiologist, Casadevall, from Albert Einstein had the same theory that the rise of mammals can be attributed to 'endothermy and homeothermy [which] are thought to contribute to mammalian resistance to mycosis by creating a thermal exclusionary zone that inhibits most fungal species. The remarkable resistance of mammals to mycotic diseases is probably a combination of a vertebrate immune system, with both innate and adaptive arms, and elevated body temperatures... The currently favored hypothesis for the demise of dinosaurs and end of the age of reptiles is a bolide impact approximately 65 million year ago with the possibility that other events, such as increased volcanism, contributed to disrupting the cretaceous ecosystem. That ecological calamity was accompanied by massive deforestation, an event followed by a fungal bloom, as the earth became a massive compost. Although one cannot know which spores were present at the time, the likelihood that pathogenic fungi existed at the K-T boundary is enhanced by the finding that the potential for pathogenicity probably arose independently several times in evolution...'[3]

'Although we do not know the timeline for the recovery of the planet climate, it is estimated that photosynthesis was shut down for 6 months and climate cooling persisted for at least 9 years, and the occurrence of a fungal bloom sufficient to have left fossil evidence implies that surviving animals were exposed to massive numbers of fungal spores. The darkened skies and cooler temperatures that accompanied the K-T cataclysm would have shielded the sun and reduced the ability of ectothermic creatures such as reptiles to induce fevers by insolation, a necessary activity for protection against fungal diseases. Hence, it is reasonable to posit that ectothermic creatures unable to induce behavioral fevers and in weakened states from environmental stress would have been at a severe disadvantage relative to small mammals with their innate thermal exclusionary zones for fungal growth. Further complicating the situation for reptiles is that eggs can be vulnerable to fungal attack, whereas mammalian progeny would be protected in placentae.'[3]

I think it has merit. We generate a lot of HEAT and it comprises a cr*pload of our total energy losses (as many in NY know without electricity due to Storm Sandy and no heat to fight night time drops to freezing temperatures). As Casadevall reported  'the mammalian lifestyle is energetically costly.'






Mitochondria: Water (H2O) = 286 kJ of P-O-W-E-R

Many obesity researchers appear to forget these multiple evolutionary and hormetic factors in their Big Pharma funded, tenure-track equations. One did not (though partly Joslin funded which is Big Pharma).
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In a Nature article, Tseng et al discuss mechanisms to find a drug target to increase cellular bioenergetics and energy expenditure as an anti-obesity strategy [2]. (But... Drug targets are always silly, no?) They discuss PPAR-delta, AMPK and several other pathways with potential promise.  A succinct explanation of how mitochondria produce energy on demand by harnessing the energy from the formation of water in the cellular bioenergetics of mitochondrial metabolism of fuel is provided. They define bioenergetics as the 'Studies the flow of chemical bond energy within organisms. In a living cell, the principal reactions of fuel metabolism take place in the mitochondria, where food energy is released,oxygen is consumed, and water and carbon dioxide are produced.'

All life on earth utilizes the energy formed from water formation to power pathways and metabolism. Remember the Calvin Cycle/Photosynthesis where carbs (glucose) are formed from air (CO2), and energy of the sun? In the mitochondria, the opposite reaction occurs. Energy from the exothermic reaction of water forming from air (O2) and the enzymatic burning of fuel (oxidizable food, glucogen, glucose, fat) result in HEAT and ATP. When one mole of H2O is created from one H2 (hydrogen) and half O2 (oxygen), 286 kJ of power are released (in other words, 68 kcal, which is about one small potato).... FROM FORMATION OF ONLY ONE MOLE OF WATER.

"When the body sinks into death, the essence of man is revealed. 
Man is a knot, a web, a mesh into which relationships are tied. 
Only those relationships matter."




Sex: The Birds and The Bees

Sometimes one has to talk about the euphemistic 'birds and the bee's to young adults in one's hormonally peaked household... but really upon contemplation of evolutionary sexual biology, do we want to talk about the mating systems of the b-i-r-d-s and the b-e-e-s (adjunct to plant s*x), unless one is into hardcore advocation of polyamorous systems of mating?

Dunbar et al has produced a fascinating comparison of 4 mammalian groups and birds, comparing the average residual brain volume (corrected for body size and phylogeny) in pair-bonding members and non-pair-bonding members (polygamous, polygynous, etc). Interestingly among primate species (like us) there is no significant difference between average residual brain volumes and respective mating systems. It appears quite vanilla and equally diversified. However for carnivores, the larger the brain volume residual, the higher the percentage of carnivores in pair-bonding mating systems. For non-pair bonding carnivores, the average brain residual was even slightly negative.



Bird-Brains and Bat-Brains

For bats, this differential is way more pronounced.  Smaller-brained bats breed in groups and rear offspring in commune-like settings (e.g. two dads and two moms per two kids).  I've previously discussed bat s*xxxx (NSFW).  What I find the most fascinating about bats is that these omnivorous mammals are so varied and diverse in the way they look and appear and like humans the more complex the social network, the smarter and the more pair-bonded they are.

Birds (yellow circle) display an even greater relationship between small-residual brain volumes and non-pair bonded mating systems. The biological truth is that most birds mate quite non-selectively every season, and, for many species, several times a season if conditions prevail.

What about bees?  Yes they generously help flowers have flower-sex, to inseminate across space and long distances....spreading and mingling pollen from stamen to stamen. Yet bees mate too but only between the chaste newly hatched queen and a squadron of male drones, bred only to inseminate her. Upon escaping the egg casing, a new virgin queen is reared then goes upon a nuptial flight to be mated with a dozen male drones (or even 100). The sperm is saved and the queen lays fertilized eggs for the next few years for the life of the hive and its entire future population. Diagram PDF (click).





Oxytocin

An earlier post discussed a seminal PNAS article which reviewed how ancestral divergence among proteins contributed to the rapid evolution of the primate and hominid brain. Oxytocin is one such protein, a nona-neuropeptide (9 amino acids) which is secreted in nearly every organ system in humans. Tremendous interspecies variation in receptor density and secretion patterns exist. It is quite dangerous to extrapolate animal data to human data. Humans are not voles. Or bees or birds (yellow circle).
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Our human hominid oxytocin is different. It goes up with so many of our human deep emotional interactions,  cements the memories we have for positive connections and enables trusted communication in relationships. It helps us to mind-read. To tell the thoughts of our loved ones and others. It helps us to read visual and non-visual environmental cues. It produces perhaps both the hunter's trance and lover's glance....




Carnivores and Iron Deficiency Anemia (Driving Evolutionary Force)

Been reading a lot of Shlain lately, his brilliant and magnificent STP ('Sex Time Power').  He proposes that humans had vast evolutionary changes in our relationships when there was perhaps a bottleneck of female hominids some 150,000 years ago.  Something changed 150,000 years ago and perhaps it was the way that females and males related and hooked up with one another...

Going back to the birds and bees, many things may have changed the last 150,000 years. His theory was that if suddenly there were scarce and only a few female hominids but a relative overpopulation of male hominids (Hss, Hs. neanderthalenesis, H. heidelbergenesis, H. ergaster, H. erectus, etc), something drove a dramatic change in archaic human interconnectedness and relationships. He postulated that maternal mortality was high. Many females may have been suffering and dying from a coalescence of evolutionary events --  bipedalism, narrow hips, early ontogeny and neonatal prematurity, troubled tortuous births and a doubling of neonatal brains (during the first year of life). The demand for iron during maternal gestation, birth and lactation for the maternal hominid was never higher. And still is (except for those genetically adapted with hemachromatosis).

And how could she hunt with babies clinging or fecund bellies? Or leaving predator-triggering, blood-tainted tracks during the period of menstrual blood??

Shlain hypothesizes a lot and I think he is actually right on about the majority.....  from the evolutionary point of view, iron is not only a critical brain nutrient for neurons but it is also crucial for all mitochondrial (e.g. cytochrome structures) and oxygen-related metabolic and circulatory processes. Have you ever drowned? Been anemic? Suffocated? Had CO (carbon monoxide) poisoning?  Seen a subpar-IQ kid with an iron-deficient mom?  Because iron deficiency anemia still plagues humans to this day, I think his point has huge merit and requires consideration.

Iron.

Need it for life or will die... slowly or dumbly or both.



Origins of Human Pair-Bonding?

I can see from Shlain's point of view (a surgeon's) the importance of iron for blood, metabolism, brain growth and maturation, and IQ. Perhaps with other factors, human relationships required the binding transcendant force of a tight pair-bond that only carnivorous pairing could achieve?  When food resources were scarce and fecund females too fatigued to procure, defend, hunt or fight?

In China, a small sexual revolution is occurring.  Because of the last few decades of China's 'one-child birth policy', many families are faced with a crisis and burgeoning population of male offspring and insufficient brides.  Brides are not only scarce, some marry outside of the Chinese race.  As a result many Chinese local females are in a position to bargain for the best candidates.  The resources brought to the table by the male and their familes are I think higher than normal -- house, job, wealth, health, right province, etc.  Looks, romance, hearts-n-flowers?  I don't actually know but if you watch Chinese dating shows (I don't) apparently the check off list also includes talents like killer singing, wooing, and more vocal display.

Is this any different than Paleo or Pleistocene times?

Perhaps no.

The scavenger/hunter/gatherer/fisherperson of the past 10,000 - 2 million years learned to bring home the bacon (iron)... and provide shelter, warmth, extended family help, and other resources to trade.



Meat/Seafood = Outsourced Nutrition

Nutritional science is fascinating to me.  So many nutrients must be consumed by carnivores and omnivores because they are not produced or synthesized endogenously in any significant amount -- Vitamin B12, Taurine, Vitamin K2 (menaquinones), Retinol/Vitamin A, Vitamin C, etc.   Some require our gut microbiome participation to conjugate or produce these nutrients, but again, outsourcing of these nutrients to the hominid diet was far more nutritionally economical over the millenia as our guts shrunk from transforming from primate frugivores to carnivores and later omnivores.  During gestation, a brain is built from scratch.  In the first year of life, the brain DOUBLES in size. The vehicle which carries our DNA forward, the baby, needs nutrients.

Other nutrients and micronutrients that are 100% or profoundly outsourced:
--iron
--methylated B-vitamins, 5-MTHF, formyltetrahydrofolates, choline (all from yolks, meat/seafood, organ meats)
--long-chain omega-3 fatty acids (IQ-increasing)
--other minerals: zinc selenium iodine

Meat and seafood contains all of the above, particularly iron which is the most bioavailable and easily assimiliated form of iron in existence. Regarding folates, be careful of supplementation with folic acid, one of the synthesized vitamins that is not find in food in great abundance (less than 10%). Animal- and plant-sourced food has a broad spectrum of folates and reduced derivatives: folinic acid, 5-MTHF (5-methyltetrahydrofolate; Dr.Tim Gerstmar's post), and formyltetrahydrofolates (meat meat meat).

Synthetic folic acid supplementation and industrial food fortification are associated with higher incidences of many cancers.  More shades of uber f-cked upness....

All the above nutrients affect a newborn's brain growth and subsequent intelligence.

All the above nutrients are not found in great quantities in vegetable sources, if at all.




The Carnivore-Fisherman Genetic Codes: SNPs

As an ancient SNP, Apo E4 confers longevity to those who follow the native diet of their ancestors.  Perhaps humans were hunter-gatherer-fishermen for so long, that outsourced all fat-soluble nutrients and cholesterol to the diet rather than producing on our own.  This makes sense as these are all downregulated in both absorption from the intestines and for endogenous production.  The global gradient for the E4 allele is increasing northward in Euroasia. The distribution for agrarian-adapted allele, apo E2, is the opposite and radiates in higher frequencies toward the fertile crescent where the birth of grain-dependence occurred. Several other adaptations are I believe protective reactions to phytates and grains/lectins (which chelate and reduce iron bioavailability or cause intestinal permeability, respectively) and less animal-sourced foods to secure nutrients for the fetal and postnatal brain growth and maturation -- altered metabolism of folates (MTHFR) and hemachromatosis (HFE),  higher fluffier LDL and HDL and less chronic diseases in long-lived Ashkenazi-Jewish (I405V CETP) and increased and larger fluffier LDL and HDL in intelligent Ashkenazi-Jewish with exceptional longevity (I405V CETP).





Tripling of Brain Size: Australopithecus to Now (0.45 L to present 1.4 L cranial volume)

For most of our existence, I think we have been predators. However, we are unique, different from lions, tigers, hyenas and bears. We are the only line of successful carnivores that descended from primates.   The introduction of meat to the diet may have occured about ~2 million years ago. The cooking of meat and other foods may have occurred gradually since that time.  Each become more consistent and regular over time.  Shlain asserted that humans experienced an increase in the neocortex and tripling of the hominid brain over that period of time. He believed it was related to a combination of forces -- choosy and picky, bipedal, big brained females and a dire iron deficiency syndrome.  Language flourished. Like gorgeous song birds attracting mates, dancing bees or croaking bullfrogs, suddenly men and women were able to communicate their attraction outside of  pheromonal scents. Tasting kisses and tender touch blossomed. Love songs and lyrics exploded. Symphonies swayed heart and minds.  Operatic drama captured dreams and imagination.

Sexual dimorphism retreated to the neocortex (brain, the big phat brain). All overt signs of estrus disappeared.  Humans are the ONLY animal species on the planet that does not enter into estrus -- we are sexually receptive ALL THE TIME. (sorta, except during PMS 'pack my suitcase' for the guys) Males can beready to go at any hour, any minute, any second given appropriate cues (visual, verbal, scent, sex-text, etc). Testicular size moderated. Scents, hair, and apocrine glands downgraded. Harems extinguished. Hominid males lost the flaming red cues that signaled female hominid ovulation (without an app). Hooking up became subtle (or tribal orgies, e.g. clubbing). Human males and females were and are both pair bonded and polygamous (83%, Murdock, 1967).

Language became the main sexual dimorphism.  Shlain points to the evidence that iron started it.  Then as brain size and its subsequent accoutrements (language, art, culture) thrived, so did our thinking and metaphysical cognition.

I think on our march of evolution as beings, we have zigged and zagged -- starting as frugivores then emerging as carnivores and then reverting slightly back to herbivores (some ethnicities more than others). Our brains perhaps have followed the same analogous path. We started as primate groups, then had small tribal coalitions similar to social carnivores, then we have perhaps reverted back to large complex primate social networks. We no longer groom each other for hours and hours on end chewing the cud picking off fleas and varmin, but we gab and gossip.  We share stories and tell tales. We admonish our children and train them with truths.  We holler and heed our mentors' words. We solve problems and support in tears and laughter over coffee or sweating out.

The brain and our language serve dimorphic purposes as well maintenance of tight social/family connections and possibly hierarchy.




Foresight

Shlain posits that at a vital point in history, humans determined the relationship between death and its finality. Our thoughts transcended the present dimension and envisioned the future. Funeral ceremonies, burial rituals and grave artifacts may have developed around 50,000 years ago at the same time in human history when art, culture and language erupted ('Great Leap').  Securing consistent brain nutrient and micronutrients I believe heralded these adjustments.  Society brought on more regular trade. Trade of goods enabled complex social networks and enhanced stability.




Play/Foreplay

Only carnivores and certain omnivores engage in play... Why? Why do little boys play guns and war? Why take 10 years of piano or violin lessons?  Why compete in speech and debate, chess or tennis matches? Why enjoy the sparring with kickboxing gals in class or watching MMA fights?

Why?

'It takes 10 years to grow a tree, but 100 years to grow a human being' (ancient Chinese proverb; thanks W).

(Is it all foreplay? . . . m a y b e)



Transcendance: Brain-F-cking (Merging)

Rapid changes have occurred in our communication in just the last short years. Technology has provided tools that never existed. How is our neocortex is adapting? Do you interact differently? Are we more deeply connected? How potent is virtual oxytocin? Is merging of our cognitive beings transforming our brains?  [Personally I've been in deep DEEP awe of my iPhone 4G since I graduated from the archaic one (no camera, no nothing) in January.  Recently I dropped the beloved (phone) which required the LCD to be repaired. Realized in the few days it was broken how we are affected, dependent, and emotionally reliant on technology and being so-called plugged in.]

Shlain believed that a new human species is evolving. Similar insights have been put forth by other luminary thinkers like Gerald Hüther PhD and Bruce Lipton PhD.  Love, harmony, compassion, oxytocin, empathy, and our complex interconnectedness are leading adaptations and understanding that may be creating evolved beings that transcend the physical, hierarchical, material and other barriers.  'Increasing numbers of us live up to the potential that was encoded into each of our chromosomes at the moment of our conception. There can be little doubt that all these drastic alterations in our environment are collectively functioning as transformative agents fueling the human species' metamorphosis....' (Shlain STP, 2003)

[NSFW] As you are reading my thoughts and we connect, am I finger f-cking your brain?

The NCEP/ATP III Cholesterol Guidelines Bogus: 'Cholesterol Limits Lose Their Lustre'

Conventional medicine at this time uses Big Pharma-funded assessment and treatment guidelines which promote the use of statins as first line in order to 'treat' the LDL (goal less than 70, 100, or 130 mg/dl) to targets based on risk stratification, e.g. age, prior family history coronary events, low HDL, smoking and presence of hypertension.

What are the true root causes of these 'risk factors' in light of evolution (if you believe in evo)? Is LDL really 'bad'?

Indeed.

Hormonal havoc and energy balance dysregulation caused by neolithic excess of refined n-6 vegetable oils, high fructose GMO-corn syrup, intestinal permeability, refined carbohydrates, sugar, mercury/arsenic/lead/cadmium, gut dysbiosis, failures of vitamin/mineral absorption by the action of phytates and lectins, and endocrine-disrupting consequences of pesticides and other environmental persistent-organic toxins are more likely factors.

And they have nothing to do with LDL. Half of heart attacks occur in individuals where the LDL is already less than 70 mg/dl.

The old cholesterol guidelines NCEP/ATP-III  that were first put out over a decade ago are now being revamped.  Nature has a new article on the future NCEP/ATP-IV.

'Since 2002, when ATP III called on doctors to push LDL levels below set targets, the concept of low cholesterol has become synonymous with heart health. Patients brag about their cholesterol scores, physicians joke about adding statins to drinking water, and some hospitals reward doctors when patients hit cholesterol targets.'

Amount of LDL-C and LDL-P Determined by ApoE

We each individually and uniquely have widely varied lipoprotein patterns (LDL, TG, HDL) determined by our genetics, the microniche our ancestors evolved and survived in, and our apolipoprotein E. Apo E is mainly found in HDL and LDL particles but also free form in the circulation as well. It aids lipoprotein particles in docking up to cell membranes to unload contents into a destination cell or the liver.

Apo E determines the LDL-quantity. Three alleles for apoE exist and we each have 2 copies from a mix from our parents - E2, E3 or E4. ApoE to me is like a special key to unlock troubled doors. Those with E4 alleles have lipoproteins with the least apoE (perhaps true H-G, more cholesterol hung out longer in circulation).  Geographically the incidence of E4 rises toward a northern distribution in Europe, away from the equator.  Those with E2, more apoE (perhaps more agarian adapted).  Energy flux patterns and metabolism are mildly different: E4, more carbohydrate sensitive; E2, less.  

Many 'cardiac' rat models use apoE-deficient mice because these animals inevitably develop horrific plaque and atherosclerotic disease and blocked arteries, on high carb rat chow.

The lower the apo E alleles, the lower the total cholesterol [ref 2]. The researchers (above) demonstrate the LDL and HDL trend in parallel with total cholesterol and the higher the E.  Conversely, triglycerides grow higher, the lower the apo E.

It seems finally that the medical community be viewing the true science and questioning the BS.  If LDL is genetically determined by the apoE type and is a false coronary risk factor, then what is the true cause of coronary events, MIs, angina and plaque destabilization? 

Naturally if one is apoE 4/4 (rare), then one is likely to have the highest LDL amongst friends and aquaintances. Is it harmful? Depends. ApoE 4/4 are more likely to be HIGHLY insulin resistant, inflamed and carbohydrate sensitive. In the modern industrial environment where whole food, ancestrally-inclined meals are endangered species... perhaps.  

Are apoE 4/4 the true survivors of Earth? They are less likely to suffer from infections or starvation which were the major reasons for mortality outside of predation prior to neolithic times. Add to that vascular protection from Lp(a) from vitamin C-deficiency hemolysis and one has a winning combination for longevity given the right circumstances when inflammation is well regulated and gene-protein expression optimal. 

The higher the LDL, the higher the Lp(a), the better survival?



Size of LDL Determined by Diet and Lifestyles: Microecological Niche

Environment dictates the LDL-particle-size. Exercise, high saturated fat, cholesterol-intake, low carb, low fructose, low omega-6/omega-3 ratio and antioxidants/flavonoids are factors that high influence and create more large, buoyant, resistant-to-oxidation LDL-particle-sizes, despite apoE status.



LDL Less Than 70 mg/dL is Dangerous

So why are cardiac 'experts' prescribing a one-size-fits-all LDL goal of less than 70 mg/dl and statins for all individuals with heart disease, diabetes, aneurysms, chronic kidney disease, and other atherosclerotic equivalents?

Does this take into account apoE status and genetically-predetermined LDL amounts?

An LDL less than 70 mg/dl is not magic.  At TYP, very rarely did I observe CAC Agatson coronary artery calcification reversal.  Members were on potent statins or suppressed their LDL to (unnatural) goals of 60 mg/dl. 

Seth Roberts did achieve reversal, by consuming cholesterol (butter). No pharmaceuticals.

I have noticed countless, sad times where statins do nothing to regress or stop the progression plaque. In fact, they are associated with progression in 12 out 14 published coronary calcification studies.

Many studies show that statins are also highly associated with cancer, increased incidence of congestive heart failure (CHF), accidents, violent death, depression/suicide, and all-cause mortality.

Low cholesterol and low LDL, independently, additionally are significantly correlated to cancer, increased incidence of chronic heart failure and all-cause mortality.

Let's probe this... because statins lost their allure years ago for me.




Image may be NSFW.
Clik here to view.Overview of Transporters

Every vital vitamin, hormone and steroid exists both 'free' and available in the blood circulatory system and bound to degrees to a transporter-protein. Some vitamins, hormones and steroids interact directly with receptors on cell membranes and other cases the transporter-protein interacts with receptors on cell membranes to translocate the vitamin, hormone or steroid into the cell. From the gut to the liver, food gets processed into free fatty acids, triglycerides (3 fatty acids attached to one sugar backbone) and bundled into particles with antioxidants for circulation and storage in peripheral tissues like the muscles, adipose, gonads, and adrenals.



Cholesterol

Every cell membrane is composed of cholesterol -- this is the asphalt and infracture of our communication highways. Another way to appreciate these conductors of electronic charge is to recognize that cholesterol in our cellular membranes is analogous to the DSL or Comcast cables of our high-speed computers, our brain and nervous systems.

How do 'dropped signals' feel? Perhaps your cholesterol is impaired?

Roles of cholesterol:
a) formation of cellular walls
b) formation of aldosterone (important for blood pressure regulation)
c) formation of the sex hormones
d) formation of Vitamin D
e) formation of bile to eliminate and recycle wasted and precious fat-soluble molecules
f)  formation of corticosteroids which are involved with glucose regulation and suppressing inflammation
g) formation of steroidal derivatives including the vital and potent antioxidant Ubiquinol/ CoenzymeQ10
h) antioxidant with scavenger functions for harmful microbial endotoxins

Without cholesterol, humans cannot survive, brain and organ function deteriorate, and eventually cancer and other inflammatory conditions are triggered. Without sufficient cholesterol, cortisol, testosterone, progesterone, estrogens and other potent steroidal hormones cannot be made.



Statins Lower Testosterone

As one would expect, statin pharmaceuticals which block the rate-limiting enzyme for cholesterol production in the liver and all extrahepatic sites (e.g. BRAIN, ADRENALS, TESTICLES, etc), HMG-CoA reductase, are highly associated in reduction of total testosterone and subsequent low testosterone signs and symptoms [ref 3-9].

Low testosterone is also considered a risk factor for heart disease due to the inflammatory state that occurs including obesity, metabolic syndrome, hyperinsulinemia, poor immunity and diabetes[ref 7]. I question the prudence in the strategy behind initiating a statin and potentially lowering testosterone further, thereby inducing yet another cardiac risk factor.  Would you like to be a eunuch?

Diabetic eunuch?  Chuckle with Peter at Hyperlipid: 
Sta'ins, CoQ, diabetes and Dr Andreas Eenfeldt's link



Ancient Transporters

Our lymphatics and blood vessels form the highways that transport nutrition, oxygen and necessary constituents for organ maintenance and rebuilding. They also remove wastes, CO2 and recycled cellular parts and spent steroid hormones for elimination via the gut or 'recycling' via enterohepatic recirculation.

How are antioxidants, pro-vitamins, vitamins, pro-hormones and hormones from our food and endocrine glands/tissues carried to the peripheral sites? Ancient tranports have evolved (if you believe in evolution) in all living systems for the role of carrying these items to the appropriate target tissues.

Vitamin A (retinol): free and bound to RBP (retinol-binding protein)
Vitamin D (cholecalciferol): free and bound to VDBP (vitamin D binding protein, aka Gc globulin)
Estrogen (E1 E2 E3): free and bound to SHBG (sex-hormone binding globulin) and EBP (estrogen-binding protein)
Testosterone, DHT: free and bound to SHBG and ABP (androgen-binding protein)
Progesterone: free and bound to SHBG and PBP (progesterone-binding protein)
DHEA: free and bound in HDL particles
Cortisol: free and bound to CBP (cortisol binding protein)

Ubiquinol/CoQ10:  bound in HDL and LDL
Menaquinones (MK4 to 9; vitamin K2):  bound in HDL and LDL
Retinoids (vitamin A):  bound in HDL and LDL
Carotenoids (vitamin A): bound in HDL and LDL
Tocopherols, tocotrienols (vitamin E): bound in HDL and LDL
Minerals - iodine zinc selenium copper: Free form and bound in HDL and LDL
Cholesterol: Free form and bound as Esters in HDL and LDL

Image may be NSFW.
Clik here to view.
See prior animal pharm: LDL, HDL Transporters



Purpose of LDL and HDL Transporters: Evo Perspective

Lipid transport and delivery systems existed in the earliest animals including insects. Our lipoprotein systems are not that dissimilar [ref 1]. Fat-soluble nutrients like cholesterol, carotenoids, vitamin E and coenzyme Q10 would form a two-layered oil-vinegar like concoction in our blood circulatory system if it were not for specialized transporters for fat-like substances.

HDLs are much more compact and smaller in size than LDL. They fit between the gap and communication junctions in the endothelium (lining of blood vessels). Whereas, LDL particles are larger and barely fit between normal gap junctions of endothelium. If the LDL particles however are 'small' their purpose is different. They are more oxidizable and denser. This tighter conformation allows movement into damaged endothelium and traumatized and inflammed tissues to provide ammunitions for macrophages to do their work and relinquish the waste and end products for disposal. I don't read French (see below if you do).

Once HDL and LDL are done, they can re-enter the blood stream, return to the liver for future processing.


Image may be NSFW.
Clik here to view.




Image may be NSFW.
Clik here to view.Ubiquinol Protects Against Failure of the Heart and All Organs

Ubiquinol is lowered by statins since ubiquinol and its derivatives are cholesterol structures [ref 19]. Unfortunately ubiquinol is necessary in all cells and mitochondria where it serves a role as mandatory antioxidant and a recycling nazi [16-18]. Low ubiquinol in the blood is associated with faster progression of heart failure [ref 17].

Statins lower the LDL contents of ubiquinol and all fat-soluble nutrients, vitamin E and carotenoids. Does this have consequences?

Prior animal pharm: Role of Ubiquinol



Higher the Cholesterol, Higher the CHF Survivorship
Image may be NSFW.
Clik here to view.

Our understanding of survival and the evolution of insulin resistance provides the foundation to understand the causes of all diseases of modern civilizations including CHF. The studies bear this out in which the higher glucose and higher insulin resistance, the higher the association to mortality in CHF [ref 12-16]. Interestingly several studies demonstrate the lower the cholesterol, the higher the CHF mortality. Some clinicians raised the potential risks of statins in light of these adverse outcomes in individuals with CHF [ref 31].

In patients with progressive CHF, their LDL are all small packages which can barely hold vital antioxidants like ubiquinol. Add a statin which deplete the crucial functioning ubiquinol for pumping heart muscles, spelling catastrophe.




Low Cholesterol Associated With Increased Cancer Incidence: 17-Year Basel Study Image may be NSFW.
Clik here to view.

The prospective 17-year Basel study showed a 2-7 fold increase in cancer mortality in males at various cancer sites with low serum cholesterol. This study confirms what some of the other cancer epidemiology studies have already shown. Researchers tested blood from 2974 participants stored from 1971-1973. Co-founders such as vitamin blood levels were adjusted for in the analysis.

Quality will always trump quantity of LDL.


Prior animal pharm: Cardio Controversies -- Tale of 2 LDLs




Carcinogenicity of Statins: The Lower the Final LDL, the Higher Cancer Rate

Image may be NSFW.
Clik here to view.
Finally the statin and lipid-lowering drug trials themselves have demonstrated that the lower the cholesterol, the higher mortality from cancer in a meta-analysis in JACC, 2007 by Alsheikh-Ali et al [ref 27]. Plotting final LDL with cancer, the graph depicts a firm association between the lower the LDL and increased cancer incidences.





References:

1. Circulatory lipid transport: lipoprotein assembly and function from an evolutionary perspective.
Van der Horst DJ, Roosendaal SD, Rodenburg KW.
Mol Cell Biochem. 2009 Jun;326(1-2):105-19.

2. Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis.
Dallongeville J, Lussier-Cacan S, Davignon J.
J Lipid Res. 1992 Apr;33(4):447-54.

3. The Effect of Statin Therapy on Testosterone Levels in Subjects Consulting for Erectile Dysfunction.
Corona G, Boddi V, Balercia G, Rastrelli G, De Vita G, Sforza A, Forti G, Mannucci E, Maggi M.
J Sex Med. 2010 Feb 5. [Epub ahead of print]

4. A multi-center, open label, crossover designed prospective study evaluating the effects of lipid lowering treatment on steroid synthesis in patients with Type 2 diabetes (MODEST Study).
Kanat M, Serin E, Tunckale A, Yildiz O, Sahin S, Bolayirli M, Arinc H, Dirican A, Karagoz Y, Altuntas Y, Celebi H, Oguz A.
J Endocrinol Invest. 2009 Nov;32(10):852-6. Epub 2009 Sep 11.

5. Statin therapy is associated with lower total but not bioavailable or free testosterone in men with type 2 diabetes.
Stanworth RD, Kapoor D, Channer KS, Jones TH.
Diabetes Care. 2009 Apr;32(4):541-6. Epub 2008 Dec 29.PMID: 19114614 [PubMed - indexed for MEDLINE]Free PMC ArticleFree text

6. Do statins affect androgen levels in men? Results from the Boston area community health survey.
Hall SA, Page ST, Travison TG, Montgomery RB, Link CL, McKinlay JB.
Cancer Epidemiol Biomarkers Prev. 2007 Aug;16(8):1587-94.PMID: 17684132 [PubMed - indexed for MEDLINE]Free Article

7. Evaluation of the male reproductive organs after treatment with continuous sustained delivery of statin for fracture healing.
Adah F, Benghuzzi H, Tucci M, Russell G, Tsao A, Olivier J, England B.
Biomed Sci Instrum. 2005;41:54-61.

8. Effects of high-dose simvastatin on adrenal and gonadal steroidogenesis in men with hypercholesterolemia.
Dobs AS, Schrott H, Davidson MH, Bays H, Stein EA, Kush D, Wu M, Mitchel Y, Illingworth RD.
Metabolism. 2000 Sep;49(9):1234-8.

9. Testosterone deficiency: a risk factor for cardiovascular disease?
Jones TH.
Trends Endocrinol Metab. 2010 Apr 6.

10. The dark side of testosterone deficiency: III. Cardiovascular disease.
Traish AM, Saad F, Feeley RJ, Guay A.
J Androl. 2009 Sep-Oct;30(5):477-94. Epub 2009 Apr 2. Review.

11. Better memory functioning associated with higher total and low-density lipoprotein cholesterol levels in very elderly subjects without the apolipoprotein e4 allele.
West R, Beeri MS, Schmeidler J, Hannigan CM, Angelo G, Grossman HT, Rosendorff C, Silverman JM.
Am J Geriatr Psychiatry. 2008 Sep;16(9):781-5.

12. [Cholesterol and glucose levels belong to independent predictors of death and hospitalizations in patients with chronic systolic heart failure]
Smetanina IN, Deev AD, Gratsianskiĭ NA.
Kardiologiia. 2007;47(8):12-6. Russian.

13. The relationship between cholesterol and survival in patients with chronic heart failure.
Rauchhaus M, Clark AL, Doehner W, Davos C, Bolger A, Sharma R, Coats AJ, Anker SD.
J Am Coll Cardiol. 2003 Dec 3;42(11):1933-40.

14. Impaired insulin sensitivity as an independent risk factor for mortality in patients with stable chronic heart failure.
Doehner W, Rauchhaus M, Ponikowski P, Godsland IF, von Haehling S, Okonko DO, Leyva F, Proudler AJ, Coats AJ, Anker SD.
J Am Coll Cardiol. 2005 Sep 20;46(6):1019-26.

15. The relationship between cholesterol and survival in patients with chronic heart failure.
Rauchhaus M, Clark AL, Doehner W, Davos C, Bolger A, Sharma R, Coats AJ, Anker SD.
J Am Coll Cardiol. 2003 Dec 3;42(11):1933-40.

16. Coenzyme Q10: an independent predictor of mortality in chronic heart failure.
Molyneux SL, Florkowski CM, George PM, Pilbrow AP, Frampton CM, Lever M, Richards AM.
J Am Coll Cardiol. 2008 Oct 28;52(18):1435-41.

17. Coenzyme Q10 and statins: biochemical and clinical implications.
Littarru GP, Langsjoen P.
Mitochondrion. 2007 Jun;7 Suppl:S168-74. Epub 2007 Mar 27. Review.

18. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments.
Littarru GP, Tiano L.
Mol Biotechnol. 2007 Sep;37(1):31-7. Review.

19. The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzyme Q10. A review of animal and human publications.
Langsjoen PH, Langsjoen AM.
Biofactors. 2003;18(1-4):101-11. Review.

20. Effects of diet and simvastatin on serum lipids, insulin, and antioxidants in hypercholesterolemic men: a randomized controlled trial.
Jula A, Marniemi J, Huupponen R, Virtanen A, Rastas M, Rönnemaa T.
JAMA. 2002 Feb 6;287(5):598-605.

21. Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol.
Stocker R, Bowry VW, Frei B.
Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1646-50.

22. Serum lipid and antioxidant responses in hypercholesterolemic men and women receiving plant sterol esters vary by apolipoprotein E genotype.
Sanchez-Muniz FJ, Maki KC, Schaefer EJ, Ordovas JM.
J Nutr. 2009 Jan;139(1):13-9. Epub 2008 Dec 3.

23. [A new property of known proteins: specific binding of thyroid hormones by human plasma apolipoproteins] [apoE]
Sviridov OV.
Biokhimiia. 1994 May;59(5):625-38. Review. Russian.

24. High-density lipoproteins can act as carriers of glycophosphoinositol lipid-anchored CD59 [protectin] in human plasma.
Väkevä A, Jauhiainen M, Ehnholm C, Lehto T, Meri S.
Immunology. 1994 May;82(1):28-33.

25. LDL isolated from plasma-loaded red wine procyanidins resist lipid oxidation and tocopherol depletion.
Lourenço CF, Gago B, Barbosa RM, de Freitas V, Laranjinha J.
J Agric Food Chem. 2008 May 28;56(10):3798-804. Epub 2008 May 3.

26. Comparative antioxidant activity of tocotrienols and other natural lipid-soluble antioxidants in a homogeneous system, and in rat and human lipoproteins.
Suarna C, Hood RL, Dean RT, Stocker R.
Biochim Biophys Acta. 1993 Feb 24;1166(2-3):163-70.

27. Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer: insights from large randomized statin trials.

28. Carcinogenicity of lipid-lowering drugs.
Newman TB, Hulley SB.
JAMA. 1996 Jan 3;275(1):55-60. Review.

29. Use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors is associated with risk of lymphoid malignancies.
Iwata H, Matsuo K, Hara S, Takeuchi K, Aoyama T, Murashige N, Kanda Y, Mori S, Suzuki R, Tachibana S, Yamane M, Odawara M, Mutou Y, Kami M.
Cancer Sci. 2006 Feb;97(2):133-8.

30. Coenzyme Q10: clinical benefits with biochemical correlates suggesting a scientific breakthrough in the management of chronic heart failure.
Mortensen SA, Vadhanavikit S, Muratsu K, Folkers K.
Int J Tissue React. 1990;12(3):155-62. Review.

31. Statins in the treatment of chronic heart failure: biological and clinical considerations.
van der Harst P, Voors AA, van Gilst WH, Böhm M, van Veldhuisen DJ.
Cardiovasc Res. 2006 Aug 1;71(3):443-54. Epub 2006 Apr 27. Review.

32. Schurgers LJ, Vermeer C.
Differential lipoprotein transport pathways of K-vitamins in healthy subjects. 
Biochim Biophys Acta 2002;1570:27–32. [PubMed] 

I have a talk in Shanghai coming up FYI...You are invited!


Topic: Balancing Hormones To Improve Mood, Energy, Body Fat and Breast Cancer Prevention



Functional/integrative medicine resources:

http://drhyman.com/blog/2010/04/28/ultrawellness-lesson-5-detoxification/ http://drhyman.com/blog/2010/05/21/breast-cancer-how-to-reduce-your-risk-now-2/

http://www.imjournal.com/resources/web_pdfs/popular/1008_evans.pdf

I think this is cool (...naught really).

This is a (user-friendly) compilation of the data collected in individual and large studies by the Environmental Working Group's Human Toxome Project. You can click on the right side on the study or an individual to review the toxic metals, pesticides, solvents, PCBs, POPs, and other chemicals found and at what level (low, mod, high).



The data below is from the EWG/Commonweal Study #1.



In each of these 9 adult participants over 150 chemicals, pesticides, solvents and heavy toxic metals were found. Fifty chemicals and metals that have been shown to cause dysfunction of the immune system were detected.  I talked about these factors above at AHS2011 'Rainforest of Your Gut' because not only do they disrupt our immunity but also intestinal barriers and permeability.  Researchers estimate that the intestinal system contains 70-80% of the immune cells.  Once chronic intestinal permeability occurs, all hell breaks loose.  Signs can be acute or terribly subtle....Bloating, dyspepsia, heartburn, hormonal disruptions (men become fem/moobies and grrrrls masculinize), inflammation, insulin resistance, suboptimal adrenals/thyroid, low HDL/high LDL, heart disease, endothelial hardening, penises softening, mental vulnerabilities, autoimmunity, autism spectrum, skin disorders, sinus disorders, candida overgrowth, allergies, oxidative DNA damage, and 50 Shades of F-Cked (cancer).

How do all these multiple industrial neolethal toxic factors influence our health?  From a systems biology perspective, do multiple factors amplify the depth of damage as each organ system one-by-one fails to accomplish what it is designed to do?

People eat whole foods, filtered water, organic, sustainable, ancestral, paleo, et cetera, but is it enough?  What if an individual has a low exposure but genetic variants for particular detox/antioxidant pathways which keeps an industrial toxin or metal hanging around? ApoE4, COMT, MTHFR, MT, and GST are just a few. Granted most of us have decent flux and adaptive mechanisms to survive most assaults but what are the thresholds for coping for multiple exogenous assaults combined with unique endogenous frailities?

On the other hand, what if a person just gets an accumulated butt-load of low exposure from frequent or daily soaked, arsenic- or lead-laced brown rice or heart-healthy omega-3 mercury/flame retardant- and selenium rich wild seafood?  Sorry -- I don't buy that urban mythology.

When I used to go for miles and miles jogging in the neighborhood, on weekdays I watched unprotected city workers spraying pesticides and herbicides on grass edges and around the municipal parks. Where does all the herbicide water run-off go? Where do contaminated water sources originating from Big Agro GMO Monsanto crop fields end up?  How is it tracked? Why not?

67% of the 9 individuals had 'high levels' of mercury detected and 22% 'low levels'.  Mercury used to be in our mouths; my kids and I are amalgam-free for one year now. We rarely eat wild fish with our histories and above is why.

Fukushima radiation is another now (here and here).

Before a first breath of air, 10 babies via cord blood lab analysis (EWG study #4) were found to have 287 heavy metals, pesticides and chemicals. All 10 had mercury (60% moderate levels, 40% low). 100% had dioxin. 100% had PCBs. 100% had organochlorine pesticides.





Recently pesticides from Bt GMO crops were found in 80% of fetuses and 93% of adults (healthy pregnant) randomly tested in one Canadian study (Aris and Leblanc, Reproductive Toxicology, 2011). This herbicide is used as a topical spray as well genetically spliced into the DNA of GMO crops with promoters for high-copy amplification and expression of of a bacterial toxin bacillus thuringiensis (Bt). Bt toxin is also known as Cry1Ab protein.  It is a gut specific delta-endotoxin which exerts toxicity through increasing larvae/insect intestinal permeability causing the death of crop pests like leaf- and needle-feeding caterpillars (lepidopteran insects --butterflies, moths), beetles (coleoptera--weevils, ladybugs, beetles), and the larvae (e.g. babies) of leaf-beetles. It has been designed to be toxic to mosquitoes (dipteran)now.  Fun, no?

Has lateral transfer of Bt DNA to our gut bacteria and microbial communities already occurred (or at least the unborn and adult Canadians in Aris and Leblanc's study)?  Are we transformed? Mutant gut-hybrids of GMO experiments gone awry?

Like advising pregnant moms to avoid fish and seafood to minimize exposure to bioaccumulation of mercury and other pollutants, the American Academy of Environment Medicine (AAEM) issued a GM Foods Position Paper on May 8, 2009 for everyone to avoid all GMO foods in their diets.  Why such adamant recommendations for exclusive GM-free diet prescriptions?



For physicians and healthcare practitioners, they encourage looking at the role of GM foods in health disorders and diseases in integrated medical evaluations.  Why are we fat?  Why does USA obesity trends track and follow herbicide use? Why are hypothalamus and brain reward centers so SO BROKEN?  How is the global use of herbicides and Bt gut-perforating pesticides related to our health woes and epidemic cancer and diabesity/heart disease/strokes?



In 1998 two scientists fed mice for two weeks potatoes (a) soaked for 30min in a dilute suspension of harvested Bt toxin (from bacterial spores grown in the lab; 1 g/L concentration), (b) transgenic Bt potatoes, and (c) control potatoes. Mild structural changes in the microvilli of the ileum of the transgenic GMO Bt potatoes were seen in.However in the Bt delta-endotoxin soaked potato-fed mice, the ileum changes were quite substantially greater in scale -- '...basal lamina along the base of the enterocytes was damaged at several foci. Several disrupted microvilli appeared in association with variable-shaped cytoplasmic fragments.' The authors further report 'in the group of mice fed on the delta -endotoxin-treated potatoes, the Paneth cells of the crypts of Lieberku¨hn were highly activated and contained a large number of secretory granules. These cells are believed to have an important role in the activation of phagocytes and controlling the bacterial flora of the gut (Ariza et al., 1996; Fawcett, 1997). They contain elevated levels of lysozyme in their large eosinophilic secretory granules, an enzyme capable of digesting bacterial cells walls, and antibacterial peptides called cryptdins (Junqueira et al., 1998). Ouellette (1997) revealed that Paneth cell secretory products seem to contribute both to innate immunity of the crypt lumen and to defining the apical environment of neighboring cells....The antimicrobial polypeptides of the Paneth cell secretory products kill a wide range of organisms, including bacteria, fungi, viruses and tumor cells (Aley et al., 1995).'  Lysozymes are 'cutters' -- they cleave and cut things, for instance, tumour/cancer cells and cell walls of pathogens that take a ride in our food.

Damage to the ileum and small intestines can lead to changes in microbial population and the disorder known as SIBO (small intestinal bowel overgrowth).  An expanding body of knowledge links SIBO with nearly every chronic systemic and skin disease seen in outpatient medicine (John Hopkins Turnbull, Mullin et al)

Bt toxin appears to induce self-digestion -- (increased Paneth cell and lysozymal activity) and damage from the inside out.  Lovely! And it is present in unborn children and adults.




References

Nutrient tasting and signaling mechanisms in the gut. II. The intestine as a sensory organ: neural, endocrine, and immune responses.
Furness JB, Kunze WA, Clerc N.
Am J Physiol. 1999 Nov;277(5 Pt 1):G922-8.

Adult Women’s Blood Mercury Concentrations Vary Regionally in the United States: Association with Patterns of Fish Consumption (NHANES 1999–2004)
Kathryn R. Mahaffey, Robert P. Clickner, Rebecca A. Jeffries
Environ Health Perspect. 2009 January; 117(1): 47–53.

Blood mercury reporting in NHANES: identifying Asian, Pacific Islander, Native American, and multiracial groups.
Hightower JM, O'Hare A, Hernandez GT.
Environ Health Perspect. 2006 Feb;114(2):173-5.

Pesticides in Shanghai and Globally

Pesticides May Cause USA Insulin Resistance and Obesity Trends

Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada. (FREE PDF)
Aris A, Leblanc S.
Reprod Toxicol. 2011 May;31(4):528-33.

Fine structural changes in the ileum of mice fed on delta-endotoxin-treated potatoes and transgenic potatoes [GMO Bt toxin] Free PDF
Fares NH, El-Sayed AK.
Nat Toxins. 1998;6(6):219-33.

Principles of Integrative Gastroenterology, Systemic Signs of Underlying Digestive Dysfunction and Disease, Turnbull, Mullin, et al.

Assessing Cumulative Health Risks from Exposure to Environmental Mixtures—Three Fundamental Questions
Ken Sexton, Dale Hattis
Environ Health Perspect. 2007 May; 115(5): 825–832.

Combined toxic exposures and human health: biomarkers of exposure and effect.
Silins I, Högberg J.
Int J Environ Res Public Health. 2011 Mar;8(3):629-47.

Sorry for the delay.... Old scathing editorial in QJM (hat tip: Peter D'Adamo), by D.D. Adams 'The great cholesterol myth; unfortunate consequences of Brown and Goldstein’s mistake.'



The Mistaken Implication of FHC and Elevated Blood Cholesterol

Abstract  Following their Nobel Prize-winning discovery of the defective gene causing familial hypercholesterolaemia, Brown and Goldstein misunderstood the mechanism involved in the pathogenesis of the associated arterial disease. They ascribed this to an effect of the high levels of cholesterol circulating in the blood. In reality, the accelerated arterial damage is likely to be a consequence of more brittle arterial cell walls, as biochemists know cholesterol to be a component of them which modulates their fluidity, conferring flexibility and hence resistance to damage from the ordinary hydrodynamic blood forces. In the absence of efficient receptors for LDL cholesterol, cells will be unable to use this component adequately for the manufacture of normally resilient arterial cell walls, resulting in accelerated arteriosclerosis. Eating cholesterol is harmless, shown by its failure to produce vascular accidents in laboratory animals, but its avoidance causes human malnutrition from lack of fat-soluble vitamins, especially vitamin D.

Unfortunate consequences of Brown and Goldstein’s mistake

Brown and Goldstein’s burst of fascinating information dazzled the medical profession, most of whom consequently accepted the false cholesterol hypothesis. This has led to unfortunate consequences that include:

• Waste of money on misdirected research.
• Waste of money on blood cholesterol tests.
• Waste of money on statins.
• Malnutrition from lack of fat-soluble vitamins (A,D,K,E) present in butter, full-cream milk and animal fat but lacking in margarine and skim milk (green-top bottles in New Zealand).
• Fear of eating eggs, contributing to unhealthy, starchy diets.
• Ricketts in middle-aged men from lack of vitamin D due to use of margarine and skim-milk.
• Distortion of the Dairy Industry, causing unnecessary marketing of skim milk.
• Distortion of the Meat Industry with unnecessary production of lean meat.

The author concludes 'The fact that of the thousands of people involved in achieving this spurious result did not include a single elementary mathematician with intellectual independence is in accord with the whole sorry story of the great cholesterol myth, starting with the false statistics used in analysing the Framingham data.10 The meta-analysis of Ray et al.,13 showing no prolongation of life by use of statins in randomized controlled trials involving 65 229 participants, is the final nail in the coffin of the great cholesterol myth.'



Insulin 101, Diabesity and Cancer Malignancies....

The lifetime risk of developing any invasive cancer is over 1:3 (males nearly 1:2) currently and by 2020, the WHO estimates, the stats will be 1:2 for both males and females.  The XX chromosomes no longer will protect us gals.

Why?

Does it have anything to do with 'Great Cholesterol Diet Myth' that the above authors have dispelled on unfounded, false scientific interpretations?  The refined whole-wheat-unhealthy-heart debacle may be nearing its end after this editorial, perhaps.

Is our diabesity and cancer epidemics related to the growth over the last few decades of 'low fat,' government-sanctioned, high refined carbs, grain-based propaganda and GMO (Bt-gut busting zonulin-opening lectins), pesticide laced grains and grain-fed commercial meat, poultry, dairy and eggs?  And the environmental havoc that plays out...?  Our original gut flora are nearly extinct much like most of the rainforest species.  Compound this with other endocrine- and gut-disrupting toxins like mercury and arsenic that  rain out from coal burners which still supply greater than 50% of USA energy.  BTW China is now #1 globally for coal utilization, eeking out over the USA in recent years. Go China for exceeding USA's giant industrial pollution footprints.




BRCA1/2 and Chopping Off B**bies

Breast cancer is complex, yet it is quite simple. Is it necessary to contemplate IMHO surgical removal and reconstruction of any beautiful body part that may fall to cancer? Where does one logically start? Where does one end because everything that undergoes DNA replication and editing may fall to cancer and mutations...?  Ms. Angelina Jolie, I lurrv u, please stop. Your message is IMHO short-sighted and not sustainable.




Pardon, Let's Look at A Couple of BRCA1/2 Facts: 

BRCA1/2 is a defect in DNA repair and fails to fix 8OHdG (oxidative DNA damage product, 8-hydroxy-2'deoxyguanosine)

BRCA1/2 raises risk in men of breast, prostate, pancreatic, gastric and hematologic cancers

BRCA1/2 raises risk in women of breast (73%), ovarian (41%), colon (2-fold), pancreas (3-fold), stomach (4-fold) and fallopian tube (120-fold) cancers

BRCA1/2 like all mutation genes is under epigenetically controlled regulation -- for example, silencing of the gene occurs with polyaromatic hydrocarbons (pollution), insulin, and hypomethylation (lack of methyl donors -- either depletion or dietary deficiency -- or COMT, MTHFR, etc variants). Best food sourced methyl donors are methylB12, choline and methylfolates (free range egg yolks, liver, meat, seafood -- sorry no plant sources you crazy vegans).  Insulin 101: Insulin is a growth hormone and one function is to induce stimulation of female ovaries to increase testosterone secretion.  Unfortunately, in both men and women, normal levels and excess testosterone may be converted into estrogens under insulin induction by P450-aromatase (aka, CYP19), in many tissues including fat tissues, breast cells, endothelial cells and prostate cells.... Certain gene variants accumulate significantly more estrogens than non-carriers (COMT, CYP19).

• Compared with noncarriers, women carrying at least one CYP19 8r allele had 20% higher estrone (P = 0.003), 18% higher estradiol (P = 0.02), and 21% higher free estradiol concentrations (P = 0.01). Women with the COMT Met/Met genotype had 28% higher 2-hydroxyestrone (P = 0.08) and 31% higher 16α-hydroxyestrone concentrations (P = 0.02), compared with Val/Val women. Cancer Epidemiol Biomarkers PrevJanuary 1, 2004 13; 94.

BRCA1/2 silencing may be epigenetically avoided by diet, resveratrol and other antioxidants

BRCA1/2 needs a genetic 'cofactor' like MTHFR, COMT, CYP19 (aromatase which converts testosterone to estrogens), CYP1B1 (pathway increases 16OHE1, estrogen carcinogen adduct) and CYP1A1 to be carcinogenic according to emerging evidence. These genetic polymorphisms are all related to raised toxic estrogen metabolites and creation of estrogen dominant states.





Functional Medicine and Tracking/Lowering 8OHdG

GDX/Metametrix Labs and other functional medicine lab testing centers offer a wonderful test that measures and helps practitioners to track oxidative DNA damage, the 8OHdG biomarker.  This goes up and down with oxidative damage. Many things have been shown to lower and raise 8OHdG.  Diet and supplements (melatonin, vitamin C, berry extracts, resveratrol, etc) have been shown to lower 8OHdG.  Please check out more HERE and HERE (p. 361 of 'Lab evals for integrative and functional medicine' 2nd ed, 2008).

In a hepatitis C trial in participants at risk for hepatic carcinoma and iron overload, a low-iron diet and phlebotomy lowered 8OHdG to near normal 8OHdG rates after 6 yrs. Additional observed benefits were improvements in liver function: lower ALT and liver function tests, improved scarring and hepatitis, no progression to carcinoma. Viral Hep C titers remained the same but cancer was avoided despite originally sky-high 8OHdG six years prior at trial onset.



Prior animal pharm:

Pesticides May Be Behind USA Diabesity, Disrupting Insulin and Tissue Insulin Resistance
50 Shades of F_cked Up (Cancer medical management in the USA)



Other Citations:

http://www.cancer.org/cancer/cancerbasics/lifetime-probability-of-developing-or-dying-from-cancer
http://whattofeedyourkids.blogspot.jp/2009/10/xenoestrogens-and-breast-cancer-why-we.html
http://www.scientificamerican.com/article.cfm?id=earth-talk-the-coal-truth
http://www.lef.org/magazine/mag2012/nov2012_Epigenetics_Breast_Cancer_01.htm
Aromatase up-regulation, insulin and raised intracellular oestrogens in men, induce adiposity, metabolic syndrome and prostate disease, via aberrant ER-α and GPER signalling.
MTHFR Polymorphisms, Dietary Folate Intake, and Breast Cancer Risk Results from the Shanghai Breast Cancer Study [hat tip: Todd Lepine MD]
Breast. 2008 Oct;17(5):441-50. Counseling for male BRCA mutation carriers: a review.
Methionine-Dependence Phenotype in the de novo Pathway in BRCA1 and BRCA2 Mutation Carriers with and without Breast Cancer. [need for methyl donors]
Epigenetic diet: impact on the epigenome and cancer.
Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells.
Epigenetic impact of dietary polyphenols in cancer chemoprevention: Lifelong remodeling of our epigenomes.

If you know me (and this blog) you know I love racks and b**bies (incl mine).

So it is exxxtremely disheartening when I hear of individuals choosing to go through the agony of cortisol-spiking surgeries to remove their respective rack and b**bies. Now that Jolie' preventive bilateral mastectomay has hit the big news, I see chopped off b**bies and ovaries everywhere. [Cue: Sixth Sense movie music]







Breasts and B**bies: Chock Full of Both Omega-3, MCT (medium chain triglycerides) and Taurine

Our breasts serve an evolutionary function as storage for all the goods things that need to be passed to the next generation, besides adipose storage and breastfeeding. Omega-3 fatty acids from seafood, grassfed game, herds, and free range poultry are selectively stored in breast, gluteal, abdominal and thigh fat. And the amount that gets stored in the breasts and other fatty tissues is governed in a dose-dependent fashion over time. The nutrients in the breast are important not only for lactation (year 1-2 for newborns) but also for gestation.  Our breasts become factories to feed the next generation all the things that nourish and grow the massive homo sapien brain and forward-gazing, stereoscopic, color vision, X-ray eyeballs, which doubles in physical size during the first 12 months of life. The contents of breast milk are super foods for newborns: MCTs (caprylic acid, lauric acid), omega-3 fatty acids (EPA + DHA), taurine, vitamin A, vitamin D, magnesium, zinc, iodine, colostrum, amino acids, galactose, IgM, immunoglobulins, protective enzymes, epidermal growth factor, etc. For certain nutrients, naturally, maternal supplementation also works when the mom cannot breastfeed (hormone imbalances, anatomical issues, neonatal twisted tongue, etc).

A baby is born with inherent 'leaky gut' (intestinal permeability) for the first few months in order for some of the larger protein molecules and mom's immunity to pass directly into their blood stream for immunoprotection. Since the baby has an underdeveloped and immature immune system, there is no point in vaccinations (full of toxic aluminum or mercury) on Day 1 of life (assinine).

Many factors in breastmilk subsequently raise of the IQ of newborns who breastfeed.  In one study, the breastmilk (not necessary connected with the close maternal-baby contact, milk in tube) was associated with a 8.3 point increase in IQ testing in preterm children at age 7.5-8 years of age compared with no breastmilk.

See prior animal pharm:  MCT Oil (coconut oil, breastmilk) kick the crapola out of olive oil



On Nursing

"Its unique recipe of fatty acids boosts brain growth and results in babies with higher I.Q.'s than their formula-slurping counterparts. Nursing babies suffer from fewer infections, hospitalizations and cases of sudden infant death syndrome. For the mother, too, breast-feeding and its delicate plumbing of hormones afford protection against breast and ovarian cancers and stress. Despite exhaustion, the in-laws and dirty laundry, every time we nurse our babies, the love hormone oxytocin courses out of our pituitaries like a warm bath. Human milk is like ice cream, Valium and Ecstasy all wrapped up in two pretty packages."  Source:  NYT Toxic Breast Milk?

Breastfeeding: Good way to detox pesticides, metals and PCBs (flame retardants)

Unfortunately our breasts store both the good and the bad... our fatty breast tissues are magnets and reservoirs for fat-soluble toxins and heavy metals from our produce (pesticides), commercial meat (growth hormones, pesticides), marine fish and seafood, pharmaceuticals (aluminum antacids, mercury/Al from vaccines, etc), dental (mercury and other metals from amalgam and titanium dental implants), Teflon cookware and coated clothing (PFOA), and environment (flame retardants, mercury/arsenic from coal burning plants which supply 40-50% of USA energy, aluminum from municipal water, blah blah blah).  The individuals who are least likely to have the biochemical mechanisms to chaperone and eliminate these modern industrial toxins, are the individuals most highly likely to develop inflammatory conditions including cancer, autoimmune diseases and Western chronic diseases.

Some of the identified genetic variants are MTHFR (Amy Myers MD), GSTM1 (Mark Hyman MD), COMT, ApoE4, CBS, GSTT, BRCA1/2, and several other emerging ones. A functional medicine doctor and dietician, Dr. Elizabeth Boham MD talks about how she developed breast cancer in her 30's despite 'doing all the right things' eating low fat, exercising regularly, etc HERE. She talks about how to identify and remove toxins in our food, lifestyles and environment.  A functional medicine and SNP case study: 'George'. To see more on SNPs and diverse associated human diseases, go into OMIN (online Mendelian inheritance in man), RegulomeDB.org/GWAS and PrometheASE.

Who has pesticides and PCBs in their toxome?  Apparently everyone -- adults and newborns before even their first breath of air according to CDC, NHANES and EWG studies. Even the President's Panel reported so in 2008.

In the '80s and '90s apparently Europe cracked down and starting banning dousing all home furnishings and clothing products with flame retardants (PCB and its cogener, polybrominated diphenyl ethers, PCBEs). Not the case in the USA.  In California for several decades, PCBs were required on pajamas, pillows, mattresses, couches, etc and thus many other states (and China) have followed suit.  PCBs end up in the ocean and rivers and marine life especially large predators bioaccumulate PCBs, mercury, dioxins, and pesticides. Cats and other indoor pets (and children) inadvertently consume dust and lick their fur, subsequently becoming exposed to PCBs.  All of our cats unfortunately developed endocrine disorders and I can never be certain that it was not secondary to the PCBs in their seafood/tunafish soft food that we 'treated' them with (combined with BPA-lining of the catfood cans).  They were all healthy and fine until 3-9 months after introducing them to seafood canned catfood....

In 'A retrospective study of PBDEs and PCBs in human milk from the Faroe Islands' the authors tested and tracked flame retardants in the milk from women who live on the Faroe Islands. They concluded 'Although remote from pollution sources, the Faroe Islands show high concentrations of POPs in human milk, particularly PCBs, but also PBDEs. The PBDEs show increasing concentrations over time.'

From Dr. Pizzorno in Is Toxin Exposure Relevant?

We know that considering the effect of one chemical at a time is no longer suficient. The Centers for Disease Control (CDC) published data on the levels of selected persistent organic pollutants (POPs) – a category of toxins which includes dioxins, phthalates, PDBEs, PCBs, etc. – and found that among a representative sample of the US population, some toxins were present in essentially every individual over the age of 12, including, for example, p,p’-DDE and hexachlorobenzene.5 An analysis of NHANES data found up to a 38-fold adjusted increase in risk for diabetes prevalence in those with the highest levels of 6 POPs,6 and increased risk has also been documented for cardiovascular disease,7 insulin resistance, impaired neurological development, learning and attention deicit disorders, endometriosis, and deficits in the hypothalamic-pituitary-thyroid axis8,9,10,11 (Figure 1 shows the increasing concentration of PBDEs (polybrominated diphenyl ethers) in breast milk).12 While very little data for humans is available, current evidence suggests that PDBEs are likely to be developmental neurotoxins, and are likely to have synergistic effects with similar chemicals.13

In addition to exogenous toxins such as POPs and heavy metals, a number of endogenous substances also require efficient functioning of detoxification enzymes to prevent a build-up of harmful metabolites. For example, endotoxins from bowel flora have been associated with depression, chronic fatigue, inflammatory bowel disease, and atherosclerosis, effects partly influenced both by bacterial species as well as intestinal permeability.14,15,16,17,18 Also, catechol estrogens and estrogen quinones are estrogen derivatives associated with oxidative damage and reproductive tissue cancers, which accumulate due to alterations in enzymatic activity.19,20 Other examples are the build-up of methylmalonic acid and homocysteine - both metabolic by-products known to have vascular, renal, and neurological toxicity, consequences of genetic susceptibility and poor B vitamin status.21,22,23,24

What Can We Do?

We must do much.  The statistics for lifetime sporadic cancer risk is currently 1:3 and will exponentially increase to 1:2 by 2020 according to WHO statistics.  I believe it.  Our toxome is excessive and unfortunately no diet (even paleo or ancestral diets) frees us from the pollution and the body burden accumulated over generations (our mothers, their grandmothers and, particularly, this current one).  We can thank the World Wars which ushered in technology (nitrogen fertilizers, Agent Orange).  It is rather wicked and ironic that the best green for liver support and thus elimination of pesticides, metals and PCBs is dandelion greens (e.g. a weed) introduced to the Americas by the British.

Good luck as we shall all need it.





See other animal pharm:
BRCA 1/2 Myths and Measuring Oxidative DNA Damage, 8-OHdG
USA Cancer Management: 50 Shades of F%$*# UP

Other resources:
Our Feel-Good War on Breast Cancer
Dr. Cate, BRCA Testing: Are the Medical Options Sensible
Mercury: How to Get This Lethal Poison Out of Your Body
How to Rid Your Body of Mercury and Other Heavy Metals: A Three-Step Plan To Recover Your Health
Kaayla Daniel and Galen Knight (WAPF) -- Oral Chelation and Mercury/metal-free Living (How to Avoid Toxic Metals and Clear Them From The Body)
Soy Recovery: The Toxic Metal Component
The Little Known Soy Gluten Connection
WAPF -- Environmental Toxins (comprehensive list of Wise Tradition articles)
Toxic Ignorance and Right-To-Know Biomonitoring

We moved and it's been hectic. This past summer, my kids were so fortunate to attend the most jiving cooking class at the Albany Community Center in Northern California, where their sweet teacher Ilah Jarvis is not only a Baumann College Nutrition graduate but also an integrated practitioner. They learned all the basics for soaking and cooking nuts, (GF) grains and legumes, dairy-free pesto, meats, salads, dressings, sides, and spent ONE WHOLE DAY on the benefits and techniques of fermenting vegetables (kim chee, sauerkraut, pickles).

Their second batch of hot pink kraut is in the crock (gift from our Fujian ayi) and bowl. You fill the moat at the top with water to provide a tight seal that allows anaerobic fermentation.  Formed gas can escape one-way across the seal.  I used the old 'kraut as a starter for our inaugural batch at the new abode in the burbs.  (Yes we are outta the grind and grime of the Shanghai Pudong city...) This recipe below is my daughters' favorite because it tastes like kim chee but sans spiciness.  I had no idea how easy, inexpensive and gratifying it is to eat your own 'kraut... In the States, I fell in love with Sonoma Brinery's RAW SAUERKRAUT this summer.  Was so pleased I could find it in fresh supply everywhere (WH, Andronico's, etc).  Though we love it but kraut is a bit of work -- need a minimum 3 hours to prepare 1-2 weeks worth (one person; for 2 kids = 2 hours + undisclosed hours clean up (MOM)).  However, it's so guuuuud...we eat it almost as fast as it's made...




Ingredients
1 Head Green Cabbage
2 Heads Purple Cabbage
6 Carrots
4-5 tbsp Sea Salt
2-4 tbsp Fresh Garlic
1 Lemon Squeezed

Combine and squeeze squeeze squeeze.  Minimizes the juicing out and 'organic explosions' later, as my kids told me.  If you add a starter, days on the counter is shortened to only 3 days, otherwise 5-7 days at room temp is needed to get a good ferment going.  Sander Katz's book Wild Fermentation is awesome for more ideas.










New science media on the microbiome and evolution...



(1) Convergent Evolution of Hyperswarming Leads to Impaired Biofilm Formation in Pathogenic Bacteria (hat tip: NB)
Image may be NSFW.
Clik here to view.
Cell Reports, Volume 4, Issue 4, 697-708, 15 August 2013

AuthorsDave van Ditmarsch, Kerry E. Boyle, Hassan Sakhtah, Jennifer E. Oyler, Carey D. Nadell, Éric Déziel, Lars E.P. Dietrich, Joao B. Xavier
HighlightsExperimental evolution of swarming in P. aeruginosa generates hyperswarmers
Parallel evolution in the flagellar regulator FleN is causal for hyperswarming
Point mutations in FleN produce multiflagellated hyperswimming bacteria
There is an evolutionary trade-off between motility and biofilm formation
SummaryMost bacteria in nature live in surface-associated communities rather than planktonic populations. Nonetheless, how surface-associated environments shape bacterial evolutionary adaptation remains poorly understood. Here, we show that subjecting Pseudomonas aeruginosa to repeated rounds of swarming, a collective form of surface migration, drives remarkable parallel evolution toward a hyperswarmer phenotype. In all independently evolved hyperswarmers, the reproducible hyperswarming phenotype is caused by parallel point mutations in a flagellar synthesis regulator, FleN, which locks the naturally monoflagellated bacteria in a multiflagellated state and confers a growth rate-independent advantage in swarming. Although hyperswarmers outcompete the ancestral strain in swarming competitions, they are strongly outcompeted in biofilm formation, which is an essential trait for P. aeruginosa in environmental and clinical settings. The finding that evolution in swarming colonies reliably produces evolution of poor biofilm formers supports the existence of an evolutionary trade-off between motility and biofilm formation.

(2) How hormones and microbes drive the gender bias in autoimmune diseases (hat tip: Angela)

Immunity, Yurkovetsky et al.: "Gender bias in autoimmunity is influenced by microbiota."Free PDF.

Sex hormones are known to play an important role in the gender bias of autoimmune diseases. But studies have shown that environmental influences and other non-hormonal factors also make a difference. For instance, animals that lack gut microbes because they were raised in a germ-free environment do not show a pronounced gender bias in type 1 diabetes, which is generally considered to be an autoimmune disorder. Until now, it has not been clear how hormones and microbes work together to influence the gender bias in type 1 diabetes and other autoimmune diseases.
In the new study, Chervonsky and his team found that microbial communities in male and female mice became different once the mice reached puberty, whereas microbes in females and castrated males were more similar to each other. These results suggest that sex hormones contribute to gender-specific changes in microbial communities. When the researchers raised mice in a germ-free environment and then exposed them to different types of bacteria, they discovered that only certain microbes specifically protected males against type 1 diabetes.
Taken together, the findings suggest that hormones and microbes cooperate with each other to protect males against autoimmune diseases. "Our study has helped to establish the general principles of how hormones and microbes interact with the immune system, which is the first significant step to get to the stage of developing new therapies."

I find this umbrella publication of multiple mouse experiments really fascinating and neat as it found robust and vigorous testosterone levels to be protective for male mice against the Type 1 Diabete (T1D)  mouse model (usually it is high estrogens -- E1 E2 4OHE1 16OHE1 etc).  I wish these researchers measured the estrogens in these mice because the picture seems incomplete...

Segmented filamentous bacteria (SFB) were the population found to be not only most protective but also associated with the highest testosterone levels in male mice.  It appeared to elevate mouse androgen concentrations to a threshold necessary for autoimmunity protection.  Can poor gut flora knock out your T?  Also interestingly, the commercial VSL #3 frequently used therapeutically for IBS, Crohn's and other GI disorders was found (again, remember, in mice) to be associated with lower T.  That was an odd finding as VSL #3 is high in Lactobacillus and other strains typically associated with balanced flora.




We know already that gut dysbiosis and anything excessively taxing raises cortisol which can sap and suck the steroids out testosterone (for males) and progesterones (for females), if chronic and enduring.  When this dysregulation occurs, inflammatory estrogens are favored over metabolism of anti-inflammatory estrogen moieties. Estrogen has a role as a stress signal across both plant and animal kingdoms. Some of our best antioxidants (EGCG, curcumin, genistein, resveratrol) are weak phytoestrogens synthesized by plants in response to stressors.  In every chronic disease -- prostate cancer, breast cancer, hypertension, heart disease (TACT), osteoporosis, PCOS, infertility, autoimmunity -- endogenous inflammatory hydroxyestrogens and/or xenoestrogens/metallo-estrogens are either elevated or outweigh the beneficial the estrogens (2-OHE1, etc).


Heretofore virtually undiscovered in humans (only insects and many mammals), earlier this year 2013, Yin et al in Hangzhou, China characterized one of the earliest human commensal SFB. Via 16S rRNA-specific PCR detection, the intestinal contents of 251 humans, 92 mice and 72 chickens were analyzed. The researchers state "The results showed SFB colonization to be age-dependent in humans, with the majority of individuals colonized within the first 2 years of life, but this colonization disappeared by the age of 3 years... In summary, our results showed that SFB display host specificity, and SFB colonization, which occurs early in human life, declines in an age-dependent manner." Formerly known as 'Candidatus Arthromitis' , like 80-90% or more of our intestinal microbiota, they are unculturable anaerobic bacteria.  SFB hail from the Firmicutes phylum (Order: Clostridia). Like many of the good gut flora they appear to play instructive roles in stimulating proper TH17 and Treg responses in for immune fitness. We need some Firmicutes -- not a ton as it is overdistributed in nearly every obesity microbiota analysis compared with Bacteroides (or it can be too low and eclipsed by Bacteroides) -- but an adequate and sufficient amount it seems and the right kind appear good. Might there be a spectrum of good v. bad Firmicutes like all things? Can 'kraut and other fermented veggies help add the good anaerobic micro critters?  I hope so.

One analysis using pyrosequencing techniques to quantify and identify the microbial composition of traditional Korean fermented kochujang which is a ubiquitious condiment made of of red pepper, glutinous rice, salt, soybean and the naturally occurring microanimalia (e.g. dirt organisms). Of the 223 species discovered, 93.1% were Firmicutes, including Bacillus subtilis, a strain known to digest gluten and casein (as also found in traditional sourdough and other fermented foods). YUM! Gochujang is the hot pepper paste for bibimbap.  Modern, post-industrial gochujang actually is tainted by high amounts of gluten/wheat as a filler, flavor, preservative and 'spice' unfortunately.  FYI, for the real stuff, find a Korean market and look in the refridgerated area.

Gochujang -- Staple at our House

When we first moved to Shanghai, we ate Bibimbap at least once or even twice every week.  It was our go-to comfort (Cali) food until our food sources diversified and expanded with the help of other expats and finding reliable organic/local/non-GMO purveyors.  Gochujang (which contains soil-based Firmicutes, B. subtilis, etc) is good for HEAT and tummies. The one on the right is a traditional product which I brought (eg smuggled) in from California (refridgerated area of the Korean shop in Albany, north of Berzerkeley). Both are Korean products but unfortunately the red one on the left is ubiquitious and popular in markets both in America and Shanghai, China. (BTW neither are gluten-free.) The first ingredient of the modern, processed version (red box) is guess?

Prior to 2008, apparently Korea didn't open its doors to GMO corn but that changed when the price of non-GMO corn went up to $400usd per ton (from $150); GMO corn was only $50usd per ton (source: ENN). Money talks and the grind of multinational corporations continues..?? Did this trump the price of cane sugar?!? GMO corn infiltrates internationally... Why does our food continue to become more and more perverted and unrecognizable (AND SUPRATASTY, ADDICTIVE, AND UNSUBTLE).









'Seed Malt' (?Arsenic, Heavy metals) in Modern Processed Gochujang

The tastiest ingredient is perhaps the most vile, seed malt. Even the traditionally prepared one contains malt syrup which is likely to come from gluten-containing barley malt.  I had to look up what seed malt is. In many Asian countries, the unami flavor is so desired and favored but hard to achieve from a food science perspective without time-consuming aging processes and fermentation.  Seed malt is the short cut.  Fast, cheap and full of nasties.  The starch that it is all germinated and cultured in is not specified but the food industry generally uses: corn, wheat, barley or the like.  Definition of seed malt (source: KFDA Korean Food Additives Code) There are crude seed maltand powdered seed malt. Crude seed malt is obtained from a culture where starter of Aspergillus kawachii, Aspergillus oryzae, Aspergillus usamii, Aspergillus shirousamii, Aspergillus awamori or Rhizopus genus are separately or mixedly inoculated so that spores are inserted into a pasteurized raw material containing starch. Powdered seed malt is obtained by collecting pure spawn spores by a special method. 

Lot of fungal species...(but Aspergillus at least contains xylanases which break down gluten)

To eliminate the fungal species and 'clarify' I believe production of 'seed malt' uses an absorber which contains heavy metals and/or arsenic. This is a problem in German beer. Kieselguhr (diatomaceous earth) is used in beer processing to filter and remove yeasts, hops and particles (source: sciencedaily.com). How heavy metals and arsenic otherwise can test positive in a starch malt, I don't know. Fungicide-contaminated rice sources? HFCS (high fructose corn syrup) due to mercury containing chlor-alkali processing (Dufault et al, EH 2009)? Right: list of arsenic food contaminants (source: Codex Committee 2011).




Science Behind Ancestrally/Traditionally Fermented Gochujang

Being in Asia has certainly given me an appreciation of the variety of fermented foods in countries outside of the USA. We have always been fans of Korean food which has one of the most easily accessible sources because typically in the USA, every good Korean restaurant ferments their own variety of fermented tofu, beans, radishes, green beans, cabbage and raw crab/seafood... (as each family does in traditional homes that adhere to the old way... and after making our own hot pink sauerkraut HOT D**MN THIS IS A PART TIME JOB)

Good news, it is all worth it.

Fermented foods are packed with cheap prebiotics and even cheaper soil based organisms that make the gue microbiota a friendlier and happier place, crowding out overgrowths of yeast, parasites, worms and other un-friendlies and promoting growth of healthier gut epithelium and immunity (70-80% of our immune system is in the gut).





Brand Spanking New Study...

• Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice

This clever study verifies many things that we know already.  Eating the poop/probiotics from healthy, lean people is perhaps not harmful for you...  It can make a mouse leaner, thinner and move from a fat phenotype to a leaner, less body fat profile.  Clostridia (Firmicutes) from Ln (lean) types invaded the guts' microbiota of Ob (obese) cagemates via copraphagia (eating of poo).

Recall, I like coprophagia... [cough cough] for B12-deficient vegans.  It's like a fecal transplant... (DIY fecal transplant: Silverman et al, 2010).






New Study: 'Kochujang [KCJ], fermented soybean-based red pepper paste, decreases visceral fat and improves blood lipid profiles in overweight adults' (Cha et al, 2013)  [PDF HERE]

"The KCJ is produced by fermenting powder red peppers
combined with powdered meju (fermented soybean
powder), salt, malt-digested rice syrup, and rice flour for
about six months. The fermentation process extends the
storage period while increasing bioavailability of bioactive
ingredients [4] such as free amino acids, peptides,
alcohols, organic acids, capsaicin and flavonoids [5,6].
KCJ has unique flavors of sweet and hot red pepper
combined with savory soybean protein hydrolyzate and
nucleic acids. In recent years, KCJ has gained its popularity
outside Korea for its taste and health benefits derived from
the several ingredients [7-16] that are produced by the
fermentation process [17-22]. The functional substances
either singularly or in combinations have exhibited antiobesogenic,
anti-oxidative, and anti-mutagenic properties
in several in vitro experiments and in various murine
models [7-16]. Anti-obesogenic and anti-atherogenic properties
of fermented soy products have been demonstrated
in obese adults [23], possibly through modulation of
hepatic acyl-CoA synthase, carnitine palmitoyltransferase I,
and acyl-CoA oxidase [24]."

My Summary

• The n=56 overweight subjects were given ~2 tablespoons of Kochujang daily (approx daily Korean consumption amount) as supplements in this RCT, and checked at 5 clinic weights during the 12-week long study duration.  Visceral fat was assessed by CT.
• WHR (~0.9), BMI (~26-27%), body fat % (~33-34%), BP (~117-119/75) and HgbA1c (~5.4%) all did not change however both groups lost subcutaneous fat (47.9 cm2 v. 53.2 cm2, study v. control, respectively).
• Visceral fat was dramatically dropped in the study group receiving the kochujang supplements (which were ++ in addition to regular daily amount) compared to placebo: -4.8 cm2 v. +0.4 cm2 (p=0.001).  ~~Ten-fold differences...
• Interesting placebo effect on subcutaneous fat loss...
• Perceptible changes in TG and apoB (which is super-tightly related to TG) were seen too (p=0.049). TG decreased.  It's hard to see HDL changes unless big weight, fat, dietary changes are seen, and that was the case.
• Thankfully, none of the researchers were funded by SunChang (the modern, processed Kochujang manufacturer).

Thoughts? 

 I don't agree with their conclusions entirely. Yes, 'capsaicin in red pepper, isoflavon aglycones, and peptides from fermented soy' all are good things, but the placebo group probably ate these as well in small amounts (because they lost subcu body fat).  In fact, researchers admit they really are clueless stating 'However, the mechanisms responsible for these observed effects are yet to be elucidated.'




Evolution, Interspecies Guts, Soil-Based Organisms and Achieving Leanness

Discounting eating disorders and celebrity/model fanatics, most normal people can achieve leanness by normal lifestyle habits, balanced diets, fixing nutritional deficiencies, avoiding being 'germ-free' and broad spectrum antibiotics/antifungals, avoiding nutritional pitfalls (excess n6 pufa, excess refined starches, mercury, arsenic, PCB/pesticides/BPA/plastics and other estrogen-mimics), detoxing environmental toxins, avoiding stupid excesses (alcohol binges, brownie binges, sleep deprivation, chronic endurance sports, etc) and balancing hormones. All the above also fix the gut microbiota according to emerging pubmed data.

This study exemplifies it... though the research authors fail to identify the role of the gut, immune system, and microanimalia found in fermented kochujang.

Kim chee: The biome structure of kochujang's counterpart kim chee has been more deeply profiled.  Kim chee has been massively PCR microarrayed, and it does indeed also contain as one would expect (from dirt) archaebacteria and good yeasts (like Saccharomyces).  I cannot find in this article if the species S. boulardii  -- one of my favorite yeasts -- is listed but fermenting rice bran with S. boulardii yields  bioactive candidate metabolites that reduce B lymphoma growth in vitro.   Kim chee in most studies is characterized by 3 main genera Lactobacillus, Leuconostoc and Weissella. Particular species that are speculated to be found in kim chee cultures are: Leuconostoc species-- Le. mesenteroides, Le. kimchii, Le. citreum, Le. gasicomitatum, and Le. gelidum, the Lactobacillus species -- Lb. brevis, Lb. curvatus, Lb. plantarum, and Lb. sakei, Lactococcus lactis, Pediococcus pentosaceus, Weissella confusa, Weissella kimchii, and Weissella koreensis.

Human GITs (gastrointestinal tracts) are part-carnivore and part-frugivore.  Our shrunken, medium-sized small intestines possess exceptional digestive capacities and hyper-efficient absorptive surfaces synonymous with carnivores, not herbivores (3-5X our height, not 10X as in herbivores).   We have enzymes to breakdown protein, fats and complex carbs to base, fundamental constituents (amino acid, fatty acids, glucose). The rest (soluble and insoluble fiber) is fermented in the hindgut by our friendlies into further end-products that we harvest and absorb (B12, butyrate, etc)...

Kochujang is special.

Maybe it is because it is fermented and digested by dirt-commensal microbial critters in carby, high protein/fat environment (rice + soybeans? ...which are fatty AND proteinous (complete proteins incidentally).  Why it sounds... SO ODDLY... OMNIVOROUS...

Our gut microbiota in the large intestines has the ability to manufacture enormous supplies of butyrate, a short chain fatty acid, that plays an imperative role in healthy guts for regulating and controlling inflammation.  Butyrate is mostly produced by Firmicutes species.  Butyratenot only enhances the integrity of the gut by inducing mucin synthesis but also is the main energy source for colonic epithelia. By lowering inflammation, I believe, butyrate and gut microbiota synergism/cross-talk with immune system lymphocytes and gut epithelia produced the lowering of the (minor) visceral fat compartment and improvements in metabolic flux in the test subjects with Kochujang supplements.

Previous animal pharm:
Burn Body Fat Loss with Saturated Fat (Butyrate and MCT Oil)







Kochujang Contains Mostly SBO, Soil Based Organisms (E.G. FROM DIRT)

Kochujang has been analyzed it contains more soil-based organisms (SBO) Bacillus versus kim chee's Lactobacillus genera.  The bacteria in Kochujang is predominantly Firmicutes (93.1%) species, simliar to the SFB (segmented filamentous bacteria) discussed in the last post.

"Through the analysis of 13524 bacterial pyrosequences, 223 bacterial species were identified, most of which converged on the phylum Firmicutes (average 93.1%). All of the kochujang samples were largely populated (90.9% of abundance) by 12 bacterial families, and Bacillaceae showed the highest abundance in all but one sample. Bacillus subtilis and B. licheniformis were the most dominant bacterial species and were broadly distributed among the kochujang samples. Each sample contained a high abundance of region-specific bacterial species, such as B. sonorensis, B. pumilus, Weissella salipiscis, and diverse unidentified Bacillus species. Phylotype- and phylogeny-based community comparison analysis showed that the microbial communities of the two commercial brands were different from those of the local brands. Moreover, each local brand kochujang sample had region-specific microbial community reflecting the manufacturing environment [e.g. probably not SunChang, Inc]." Source : Nam et al, J of Food Science, 2012.

Please Pass Your Good Cuddies/Firmicutes -- SBO Also Breakdown Gluten

The two most dominating species found in this study of Kochujang are soil based organisms -- B subtilis and B. licheniformis. In experiments, B subtilis and B. licheniformis, digest gluten; they're frequently found in sourdough ferments, naturally-occurring on rice straw, Japanese traditional natto, Chinese fermented black bean sauce, Nigerian fermented soy 'Daddawa', Thai fermented foods, Indian fermented soy Hawaijar, fermented shrimp heads, Korean fermented black soybean Chungkookjang, and raw dairy.

The undigested gluten peptide, that is most toxic to celiacs and induces immuno-triggering damage to the small intestine, is broken down by enzymes from either B. subtilis* or B. licheniformis*.  HLA DQ2/8 on APCs have extremely attractive binding affinity ('epitope') to undigested gluten (for example, 33-mer alpha-gliadin).  Consequently, APCs will present undigested gluten to CD4+ T-cells as invaders, thus setting off the cascade of TH1, Th17 and Treg hyperimmune responses.

Celiac is actually an autoimmune disease of the DQ2/8-gluten complex (IC, immune complex) in the small intestines and other affected organs.  At least 60 immunogenic gluten peptide sequences exist in wheat.



Conclusion

In gluten intolerant folks, TH17 is usually slightly or entirely j**cked up.  TH17 may lack training/regulation, and intestinal hyperpermeability is likely present.  Food antigen intolerances consequently pop up secondary to hyperpermeability.  The commensals in the gut microbiota shape immunity and prime and promote the proper differentiation of TH17 and other cell subsets.  Is this one of the primary differences between the obese and the lean?  The gluten intolerant and the gluten tolerant? The celiac HLA DQ2/8 and the non-celiac HLA DQ2/8?  What gut toxins prevent seeding of commensals? Bt GMO corn? Mercury and other DPP-IV inhibitors (microvilli DPP-IV digests gluten)?

SBO and their molecular components appear to play a great part in re-balancing the distribution between arms of the vast immune system: TH1 v. TH2 v. TH17 v. Treg.  When the gut barrier becomes tight and competent again, food intolerances reverse or disappear.  Undigested gluten won't pass through.  The gut epithelium is but one cell layer thick.

Permeability perhaps is the bane of advanced hominids. We diverged from primates with zonulin, the gate keeper of intestinal permeability.

Why?  For the the continuation of post-natal growth of the gigantic human brain?  For the extended longevity and flexibility of advanced hominids? I'm not certain but I suspect it has to do with ontogeny and how our premature babies require maternal immunoglobulins, IgM in breastmilk, for 18 months to 3 years old of age for the immunoprotection until their own immune systems mature, interact with the environment and develop.

For some individuals, soil-transmitted hookworms are solutions and the key... together, SBO/dirt, kochujang, coprophagia, and 'kraut may be fine, and problematic pathogenic (microbial/yeast) overgrowth and parasites can perish.





SBO Related Sources:

These are all shelf-stable because SBO are spore-forming and don't require refridgeration. In immunocompromised and susceptible individuals, probiotics can exacerbate the root problem. Introduction of lactobacillus organisms, bifida, SBO or other probiotics may increase gas and bloating if SIBO (small intestinal bowel overgrowth) is severe, just as introduction of fiber/inulin/FODMAPs can induce gas and bloating until gut initation and adaptation has gradually occurred.


Probiotic that includes B. licheniformis:  Body Biotic

Protiotics that include SBO:
Prescript Assist (B subtilis, etc)
FloraBalance, Bacillus Laterosporus BOD
Ultimate Acidophilus with Bacillus Coagulans
Thorne Bacillus Coagulans
Threelac (B subtilis, etc)
Primal Flora (B coagulans, etc)
Primal Defense (B subtilis etc)   [the wildly successful original formulation had both, ~ + B licheniformis]


Gluten-digesting Digestive Enzymes:
Devigest (B subtilis + enzymes from B licheniformis, etc)




Catch This:  Making Gluten-Free Korean Chili Paste Gochujang (CriticalMas blog)

Human Guts = Super-Organs
Image may be NSFW.
Clik here to view.
Human intestines are really part-carnivore, part-frugivore and part-microbe. As living entities, we are 'super organisms' or hybrids of microbes (over 100 trillion cells) + human (~10 trillion cells).  Did you do the arithmetic? (sorry -- I can't do math)

We are ~90% microbial cells. In fact all living organisms have gut flora microbes from termites, cockroaches to fish to frogs to birds to carnivores to omnivores.  Recall SFB (segmented filamentous bacteria; Firmicutes; Clostridia; Candidatus Savagella) the commensal (symbiotic) bacteria intimately residing in the ileum (small intestine) of insects, humans, chickens and rodents improving TH17 and immune system regulation and protecting against autoimmunity and T1DM.

The caecum and appendix (animals that have one -- see photo) may serve the job of storing and maintaining the microbiota that seed the gut (fore and hind). In a phylogenetic analysis of a variety of animals, evolutionary biologists have various theories that the appendix was retained for a functional purpose (Smith et al, 2010. Photo credit: PDF.)



The Human Appendix is Not Vestigial 

The appendix is not a vestigial organ. In modern healthcare, broad spectrum antibiotics are handed out carelessly and tonsils and appendices are removed without much thought -- acute symptoms or persistent infections precipate the surgery in otherwise healthy and young folks. However, a recent study shows that there is an un-ignorable and increased relative risk of unexpected sequelae (e.g. subsequent heart attack) in these people following surgery -- 44% and 33%, respectively.

Why? Tonsils and appendices are part of the hybrid microbiota-immune system and control of inflammation.  According to Smith et al, our ancient predecessors most likely had appendices for at least since 60 million years ago if not extensively longer, 80 mya.  Come on... 80 mya... that's a long time.

"The appendix has evolved independently at least twice
and has been extensively maintained, albeit not uniformly,
in at least three and perhaps four groups of
mammals; glires, primates, Diprotodont marsupials and
perhaps monotremes. The possibility that the appendix
occurred at the base of the primates suggests that the
appendix may have been preserved in that clade since
before the two primate suborders, Strepsirrhini and
Haplorrhini, diverged an estimated 60–63 million years
ago (Gingerich, 1986; Shoshani et al., 1996; Pouydebat
et al., 2008). Similarly, the conclusion that the appendix
evolved at the base of the glires indicates that the
appendix has been maintained since before the K–T
extinction, when rodents and lagomorphs diverged
approximately 80 million years ago (Bininda-Emonds
et al., 2007)."

Caecums, Carb/Fiber Digestion, VFAs

Caecams are organs at the juncture between small and large intestines. Mammals have one, gallinaceous birds (ground-feeding) two, and fish several.  Humans and primates have a small caecum and vermiform appendix (worm-like, blind pouch). Caecums appeared to have evolved as chambers for microbial fermentation. It has made multiple appearances in evolution. Sizes vary in the animal kingdom from none to some to fully functional appendices. In species without appendices, the great majority of microbial fermentation occurs in the stomach (ruminant herbivores).  Ruminants have evolved small caecum (no appendix) since most of the fermentation occurs in the foregut. Smith et al theorize "Thus, the evolution of small ceca in some species that are foregut fermenters seems likely to have involved loss of the digestive function of a cecum with an appendix, with maintenance of the immunologic function of the cecal appendix."

Certain herbivores do a HUGE amount fermentation in the caecum -- rabbits, pika, guinea pigs.  These vegan-animals also exclusively practice coprophagia to obtain nerve/brain nutrients (vitamin B12) from caecal protein and vitamin synthesis (e.g. poo consumption).  [Curiously, porcupines have big caecums but no  observed coprophagia behavior (though dogs and tortoises have been observed to eat porcupine poo).  Yet in one study 16% of energy requirements were produced in caecal fermentation (versus 4.7%, rat).  BTW resistant starch (RS -- corn) provides different volatile acids, caecum expansion and improved insulin and blood glucose profiles in rodent studies, compared to high GI wheat/gluten starch.]



Our caecum is microscopic (see below); herbivores, gargantuan.  The human caecum and appendix serve more of an immune function, reservoir for microbiota; the function for digestion is minor.  Both our caecums and large intestines can ferment carbs (fiber, resistant) then release the digested products into the blood circulation as volatile organic acids.  The small intestines should not... except under illness (SIBO, small intestinal bowel overgrowth).  We are not foregut fermenters.  These metabolites can be measured (propionate, acetate, butyrate, etc). GDX/Metametrix organic acids testing is available-- Nutri Eval, Organix, ION, ONE.  I favor the ONE -- requires only the first morning void urine (FMV) so non-invasive and you get the cancer/inflammatory marker 8OHdG, mineral/vitamin deficiencies are other functional metrics.

Fig. 1 The cecal appendix(a through l) or appendix-like structures (m through o) in a
variety of mammals. The cecum ⁄ appendix is oriented toward the top of each drawing,
the distal end of the small intestine toward the left and the proximal end of the largeintestine toward the bottom.
  (a) human, Homo sapiens;
  (b) Pongo pygmaeus, orangutan;
  (c) Lepilemur leucopus, sportive lemur;
  (d) Lasiorhinus latifrons, Southern hairy-nosed wombat;
  (e) Oryctolagus cuniculus, rabbit;
  (f) Phalanger gymnotis, ground cuscus;
  (g) Anomalurus derbianus, scaly-tailed flying squirrel;
  (h) Trichosurus vulpecula, common brushtail possum;
  (i) Bathyergus suillus, Cape dune mole-rat;
  (j) Atherurus africanus, brushtailed porcupine;
  (k) Castor canadensis, beaver;
  (l) Microtus pennsylvanicus, meadow vole, shown with a partially uncoiled large bowel//
  (m) Phascolarctos cinereus, koala;
  (n) Ornithorhynchus anatinus, platypus;
  (o) Tachyglossus aculeatus, echidna.

Volative organic acids include polyamines, short chain fatty acids (VFA) and others.  These can be quantified on the GDX/Metametrix GI function stool test and blood/urine organic acids testing.  This test is the best on earth. It assesses both large and small intestine function, and additionally accurately pinpoints pathogenic overgrowth, parasites, and worms which are frequent invaders despite 'clean' air, water and soil in modern continents. If pathogens exist in the small intestines, caecum and/or large intestines, putrification of undigested fats, proteins and carbs occurs.  Certain volative by-products are highly odiferous-- cadaverine, putrescene, spermidine, etc.

Treatment includes pathogen killing (charcoal, clay, herbals), healing the broken gut/brush border/GI peritalsis/acidity/pH, and replacing lost gut flora (commensal Firmicutes, Bacteroides, facultative anaerobes, SBO, good yeasts, etc).

The entire human gut has only ~17% of surfaces for fermentation compared with 50% for an animal like guinea pig. (TO ME, this is like the diff betw a select post-harvest wine versus mass produced Coors light.)

Bergman talks in-depth about VFAs. "Current estimates are that VFA contribute approximately 70% to the caloric requirements of ruminants, such as sheep and cattle, approximately 10% for humans, and approximately 20-30% for several other omnivorous or herbivorous animals. The amount of fiber in the diet undoubtedly affects the amount of VFA produced, and thus the contribution of VFA to the energy needs of the body could become considerably greater as the dietary fiber increases." I don't think we are gorillas (57.3% energy obtained from VFAs) though some humans may exist as such (functional..? debatable?).




Role of Appendix and Failed Fecal Transplants

Our comparatively tiny human appendix is nearly non-functional yet appears to serve a purpose for maintaining maternal, birth- and early life-derived microbiota and biofilms.  This is why -- I've heard -- that fecal transplants often fail 1-3 years post-transplant (anecdotal communication,  Metametrix/GDX Tony Hoffman).  Were these cases Paleo? Consuming fermented foods frequently? Root causes for dysbiosis/permeability identified and reversed?  Toxins, mercury, pathogens addressed??




Appendectomies, Gluten Sensitivity, Gallbladders, Nutrigenomics and TMI

Not all animals have an appendix...... including members of my family; two out of 4 siblings have had surgical removal of the appendix. We also have 3/4 (diagnosed) autoimmune disorders. And 2/4 have documented gliadin sensitivity (me, positive fecal anti-gliadin sIgA in 2011 on Metametrix GI fx stool testing). Is there a connection? You tell me.

I'm Paleo because I'm protecting my gallbladder, appendix and other precious ~~.  Not into chopped off organs, boobies, etc.

Integrative medicine, treatment and prevention for gallbladder disease HERE (Gaby 2009).

Recently my kids and I did 23andme genotype testing. Have you done it? It revealed many gluten-sensitivity related conditions we are susceptible to based on known SNP analysis (alkylosing spondylitis, primary biliary cirrhosis, T1DM, etc).  Not a shock. I'm grateful for discovering the Paleo and gluten free diet in 2007, then functional medicine and intestinal permeability/gut dysbiosis in 2010.  We have made appropriate changes and seen improvements -- some mild, some dramatic.

This is the year of personal nutrigenomics.  We are negative for MTHFR but have the GSTT1 (glutathione, detox, heavy metals), deletion and are heterozygous for COMT (methylation -- detox of toxins, metabolism of adrenaline, dopamine, estrogens, 4OHE1, cortisol, etc).

Gallbladder stones and removal are super super super common in primary biliary cirrhosis (one of many celiac/silent-celiac conditions -- just like fatty liver, fatty pancreas, fatty heart, blah blah blah). Why? Look how anatomically close they are together to the liver, portal vein, stomach and duodenum/small intestine. When intestinal permeability allows undigested gluten through (or gluten just opens zonulin), gluten causes immunogenic havoc, scarring and immune system activation.  Same with the appendix.  When gluten and resident microbes translocate from the caecum/small/large intestines to proximal and distal organs, they hit neighbors the hardest.  Appendectomies are mega-crazy-common (my dad's a surgeon; gluten paid for my college).


Often I hear stories that the spasms and pain remain despite surgery.  Despite diligently avoiding 'high fat diets', they suffer (eating wholehealthylectins).  It's not just the 'fat, forty, fertile female' (4F's) who are afflicted (as all hazed med students are taught).  Males are affected too. Children are now affected.

It's a silent epidemic across the world in sync with vegetarianism (vegetarian males: 3-fold; vegetarian +alcohol, 7-fold) and westernized, Big Agra crop-users (like Saudi Arabia).

Gluten? Dietary removal of gluten helps a ton as Gaby above reports (two studies in celiacs 1985 and 1999).  Gluten is heat/cooking resistant. The toxic gliadin peptides can resist GI enzymatic digestion when microvilli DPP-IV  is disabled (by mercury) and when brush border enzymes are missing (SIBO, gut dysbiosis, pathogens/parasites).  At least 60 gliadin protein sequences are immunotoxic, triggering immune system reactions for susceptible individuals.  These were in relatively low concentration in ancient wheat but 50-100 years ago, transgenic hydridization and GMO techniques have bred (pun, bread) the concentration of the toxic gliadins to an estimated 500-fold amplication.

Peter at Hyperlipid cogently discusses Gluten and Gallbladders (circa 2008); good stuff, good comments.





Safe Guarding Appendices?

Smith et al talks about how the caecum is a "‘safe-house’ for biofilms containing commensal bacteria." How does antibiotics affect this? Antibiotics in food, cattle/chicken feed, eggs and their products?  How do we revive extinct commensals and healthy biofilms....? Wish I knew definitively because there are few ways to test the contents of the caecum and appendix.

If I could repeat preconception, conception, birth, postnatal, and lactation periods with my kids, I would certainly do a million things differently from the gut and gut microbe perspectives.

Further Smith et al concludes on the relationship between the caecum (which contains a region of lymphoid tissue), gut microbiota and the immune system....

 'Although microbial biofilms in the proximal large
bowel are apparently a hallmark of immune support for
the microbial flora in a wide range of mammalian species,
the biofilm distribution in the gut of an outgroup for
mammals had not been evaluated previously. Thus, the
observation that biofilms are distributed in frogs in a
manner similar to mammals, with a preference for the
proximal large bowel (Fig. 4), strongly suggests an
ancient origin for a pro-microbial immune function in
the proximal large bowel. Specifically, this observation
suggests that the adaptations supporting biofilm growth
by commensal bacteria are more ancient than blind sacs
of the gut, such as the cecum, which are involved in
fermentation. In support of this idea, microbial biofilms
are not only strengthened by secretory Immunoglobulin
A (SIgA) produced by the adaptive immune system, but
can also be supported by mucin (Orndorff et al., 2004;
Bollinger et al., 2005), a major biomolecule produced by
the more ancient innate immune system. This finding
points toward increased immune support of the gut
microbes as one of the potential driving forces for the
evolution of blind sacs in the proximal large bowel.'

Our Gut Anatomy and Physiology:  Part Carnivore + Part Frugivore

The curious thing is that advanced hominids are not exclusive frugivores. Though it makes sense that we lost the capacity to synthesize Vitamin C and must find and outsource this to dietary Vitamin C, our digestive tract length, volume and capacity to produce low pH and secretions are akin to carnivores.  Additionally, our shrunken small intestines possess really exceptional digestive capacities and efficient absorptive surfaces synonymous with carnivores, not herbivores (3-5X our height, not 10X as in herbivores).



Nearly ALL digestive work and absorption are concentrated in the small intestines, which varies in length by individuality, 15 -30 feet. This is why illness in the small intestines (SIBO/gut dysbiosis) disrupts all health, including even distant, peripheral tissues (brain, breasts, fat/belly, bones, joints, vasculature, gonads-b**ners), not only proximal (liver, pancreas, gallbladder). Energy dense food provide long acting fuel (fats, complex carbs). Our small intestines, gallbladder bile acids for fats and carbs, pancreatic enzymes (lipases, proteases, carb-ases) compensated.   Our carnivorous small intestines are the super gift we acquired through evolution.

Our immune system is 70-80% based in the gut. Despite, our immunity being outsourced to microbes (caecal, appendix, intestines), only a fraction of our nutrition is (~10% from VFAs) because we obtain the energy from broken down, digested high-energy bonded food (e.g. fatty acids, complex carbs) in the small intestines.  Our sophisticated and elite human small intestines suck all this energy up taking what first-pass at the liver misses. Human nutrition is super nutrient dense and fat based (my diet is 30-40% fat) allowing us to forgo chewing and grazing but only every 3-5 hours.

The remaining marginal allotment of our nutrition is brewed by symbiotic bacteria and yeasts... It's arguable that butyrate is both a nutrient for the intestinal cells as well as an extension of the ancient immune system for the entire body. Our hindgut (large intestines) continues methodical fermentation and microbial metabolite harvesting (organic acids, volatile fatty acids, B12, butyrate, other bacterial Firmicutes/Bacteroides end-products).  It's absolutely not necessary to produce heaps and heaps of dung like our four-legged herbivore friends all day post-digestion without anal control.

Functional Lab Testing: GI Effects Stool Test (GI Fx)

There are several tests I think everyone should get if they are suffering from any chronic conditions, cancer, or inflammatory condition. One is the Metametrix/GDX GI Fx Stool test.  This is one of the most advanced tests that accurately, reliably and thoroughly evaluates the entire intestinal tract and the gut microbiota.

Using PCR sequencing on the 16S ribosome of microbial species and parasites, it accurately assesses both our microbiome (genetics) and those of any parasites.  The old 200-year technology of O&P x3 (ova and parasite) from 3 samplings of stool should be over; to achieve a positive identification, one must rely on the luck and fortune of the microbiologist viewing the smear on the slide to observe a parasite glide by or tiny ova like needles in a haystack.  I believe stool cultures are equally primitive technology and unreliable. Over 80-90% of stool microbes are obligate anaerobes and/or symbionts which are difficult or impossible to grow in culture or without their neighboring microbes necessary to sustain life.

***Read the Metametrix/GDX Interpretative Guide for the GI Fx Stool Test: HERE.




Example of a Super Super-Organism: B. Pottenger

My m=1 Microbiome: Data for Epimicrobiomics Thinkering

Brent Pottenger is not only hawwt, lean, muscular, sexxxy and smart... so is his poo.

Characteristics of excellent health and excellent poo:
(a) Pancreatic Enzyme Digestion:  Elastase 1, marker for pancreatic enzymes (greater than 300 = decent; greater than 500 or immeasurable = PALEO AWESOMENESS).  No deficiency of pancreatic enzymes, fat malabsorption, undigested plant fibers, undigested fats
(b) No microbial overgrowths detected
(c) No yeast overgrowths detected
(d) No parasites, worms, flukes, protozoa or pathogenic overgrowths
(e) No gut inflammation, anti-gliadin sIgA (current gluten reactions)
(f) No excessive or missing SCFA (products of microbial fermentation -- both good and bad flora)
(g) Excellent adiposity ratio of Firmicutes:Bacteroidetes (leanness) and correlates with Mr.Pottenger's BF (~~ 8-10% I estimate).




Digestion, Fermentation 101

Here's a primer on the gastrointestinal tract, digestion and fore/hindgut fermentation in humans.   I co-lectured with Tim Gerstmar ND at the inaugural Ancestral Health Symposium in 2011 at UCLA.

• "The Rainforest in Your Gut: A Brief Tour of the Biome, Why It's Messed Up, and How to Fix It" 
• Slides

Ironically, I was ill at AHS and suffering from chronic fatigue (CFS).  Leanness was difficult to achieve, brain fog massive, and immune tolerances extreme (gluten, dairy, fiber, FODMAPS). It had all started immediately after a titanium dental implant, lasting from 2010 until summer of 2012 when I had it removed.  Nothing worked (yes, I tried everything). Finally, last summer, all the titanium, mercury amalgams, and gold crowns were extracted, and almost within 10 minutes I lost 5 lbs of peripheral edema and gained clear headedness.  Gradually signs and symptoms of metal toxicity, adrenal dysregulation and gut dysbiosis mostly disappeared.  A few months ago, I started dreaming again. Off/on I've been lucky to have leanness but it wouldn't last long.  Gluten actually was no big issue for me after Paleo, but dairy/nut intolerances became very problematic causing ankle swelling, mild joint achiness, and bloating.

Follow up is based on the latest labs below and Dx: bacterial/amoeba overgrowth. Starting to feel already even better and digestion improved.  Here are snapshots of AFTER v. BEFORE treatment.



(a) Pancreatic Enzymes (SIBO)
In 2011, my gut was not digesting. Enzymes were not produced at either the brush border (microvilli/small intestine) or apparently secreted in adequate amounts by the pancreas. Why? Gut stress, immune dysregulation from both microbial overgrowth and metal toxicity/suppression. With undigested carbs, fermentation occurs producing volative SCFA (small chain fatty acids) where it's not supposed: the small intestine. Undigested fats are delivered to the large intestine causing sometimes greasy, floating stools. I never had this, but the GI Fx test was positive. Undigested proteins (vegetable, meat) ferment into volatile SCFA, polyamines and stinky compounds (sulfur groups are stinky, like rotten eggs). Together, these further damage the small intestinal mucosal surface and induces SIBO (small intestine bowel overgrowth). Good protective flora are lost and both good and pathogenic flora overgrow, in the wrong place. Undigested fats and plant fibers make it intact to the feces. After treatment (diet, exercise, lifestyle, supps), this imbalance all reversed.  See AFTER, 2013. No red zones.


(b) Microbial Overgrowth (SIBO, Caecum/Appendix, Large Colon)

Overgrowth of 'good' flora occurred: Clostridias, Fusobacteria, E.coli.  A spike in SCFA propionate increased correspondingly.  I lost good species -- carb-eating Bacteroides, Prevotella, and huge populations of Lactobacillus and Bifidobacter. In his NYT article on the gut microbiota, Michael Pollan talks about how he lost his brawny Prevotella spike and developed a 'creepy E.coli bloom' after only one round of oral antibiotics, HERE.  He appears to eat a metric ton of fermented foods, so no doubt he has regained his Prevotella by now.  I'm so grateful that my gut did!  In fact the little tube regained most of what was lost --Firmicutes, Bacteroides, Prevotella, Lactobacillus --- except some Bifido.  Prevotella is considered one of the best ecological microbiome metrics for neurotypical and healthy guts. In a recent study of autistic v. neurotypical children, it was found that the main 'core' genus missing was Prevotella by B Kang and James B Adams, PLoS, 2013.  In the enterotypes of neuroatypical autistic children, Prevotella was entirely absent.  The researchers also noted that a spectrum of both Bacteroides and Prevotella appeared optimal. Prevotella is also one of the top 3 genera observed to line our GI tract from mouth to anus. Its primary role in the large intestines is digestion of indigestible plant polysaccharides from cellulose, xylan, plants, legumes/lentils, and whole grains.   Children in Burkino Faso have the most stellar Prevotella spikes (53% of total B + F) on earth -- they eat little meat but obtain protein from both (1) consumption of termites and (2) I hypothesize microbiota-N2-fixation (amino acid byproducts from air + cellulose fermentation... ??carnitine, etc) from Prevotella and other Bacteroidetes originally from the termite gut microbiota.

For more info, read Dr. Leo Galland: Intestinal Permeability, aka Leaky Gut.  Once gut imbalance occurs, SIBO can take over and wreak havoc. Recall the gut epithelial layer tis one single cell layer thick. Undigested food and enteric bacteria, yeasts and parasites can quickly breach a damaged gut-barrier and proceed straight into blood circulation.  They can translocate to other organs and induce food allergies (soy, corn, nuts, eggs, citrus, dairy, wheat, oats, etc).  When the immune system tries to eradicate these perceived invaders with antibodies, then auto-immune diseases unfold. Muscles/joints, body fat and organs start to dysfunction when the immune-complexes (antigen+antibody) junk up joints, receptors, tissues and blood/lymph vessels.


(c) Yeast/Fungi Overgrowth (SIBO, Caecum/Appendix, Large Colon)
Normal is 'zero' yeast. Except for Mr. Pottenger's, I've never seen a report where yeast is less than 2. NEVER.  (I've never seen parasite-free/overgrowth-free result either.)  I run the GI Fx on nearly every client. Everyone shows fungal overgrowth and  it's indicative of dysbiosis.  Yeast is opportunistic and quite literally a bugger.  For over one year, I was on oral fluconazole 1-2x/month (I h**te pharmaceuticals especially liver-damaging ones). Nothing else controlled the yeast and in fact I had to dose escalate for only marginal control. When I returned to the U.S. my sister introduced me to Natren, and with immense gratitude, it worked in 24hrs (despite titanium/mercury).  Later, Natren, Prescript Assist, FloraMend and FloraBalance all helped to restore balance and minimize out-of-control fungi and allowed me to 100% discontinue Rx fluconazole.




(d) Parasites Are Not Paleo (generally speaking)

Overgrowth of pathogens, parasites and worms do not cause problems for everyone when the gut is anti-fragile, robust and resilient.  In fact, these stressors can even improve gut health and stability by stimulating the immune system.

However for the great majority of individuals sadly this isn't the case in my clinical experience. Perhaps, people's toxome is too excessive. When parasites or pathogenic overgrowth are found in the context of dysbiosis symptoms, IMHO it is best to treat.  Test, not guess... Or treat empirically like you would treat a dog/cat/pet. There are many sources of parasites in the USA and third world countries (like China).  They are overlooked, underdiagnosed, and ultra prevalent. The CDC reports more than 60 million men, women and children carry the Toxoplasmo gondii parasite. Salads, fresh fruit and vegetables, pet dogs, pet cats, tap water, cash $$, electronics, work computers, open bodies of water, licking doorknobs, camping, etc. are all common sources of parasites.  Read Dr. Leo Galland: Parasites.

Image may be NSFW.
Clik here to view.D*mn, can't get lean. Though I gradually appeared to regain health and hormones, I couldn't achieve leanness. Somewhere between 2010 and now, I picked up an amoeba growth (Endolimax nana, see above) and opportunistic bacteria Morganella morganii.  Both are relatively easy to treat with 2-3 rounds of combination botanicals which have anti-microbial/anti-parasitic/anti-candidal spectrums (berberine, wormwood/artemisinin, oregano oil, curcumin, black walnut, herbs/garlic/ginger/biopiperine, etc). Sometimes these overgrowths can be benign. I have no symptoms except inability to achieve desired leanness and mild (but annoying) residual food intolerances.  Being compromised by metal toxicity, CFS and adrenal exhaustion may also have been factors for the inability to 'crowd' out overgrowth. In countries, like South America, anti-parasitics are sold over-the-counter. Several excellent botanical formulations are at iherb, my favorite international farmacy: Para-Shield, Thorne Berberine-500, Curcumin +Biopiperine, Tricyline, Paradex, Scram, Vermi-Purge, Paracid Forte, etc. I've used Metagenics Parex before, but it appears no longer made in the US. Metagenics Candibactin-BR is also excellent but no longer at iherb.




(f) Gut Inflammation, Anti-Gliadin sIgA
Gut inflammation all normalized after treatment. I had been gluten-free for months prior to the initial GI Fx test but we had gone to France and Germany for Thanksgiving six months earlier and ate hordes-of-irresistible-gluten (e.g.buttery croissants). The positive anti-gliadin sIgA shows that the immune system was apparently still reacting. Depending on the person, antibodies may require 6-24 months or longer to clear.



(f) Volatile SCFA (products of microbial fermentation)
With gut dysbiosis, butyrate and SCFA were all disrupted and low.  Propionate spiked -- likely due to excessive fermentation in the small intestines by overgrowth of supposedly 'good' gut flora (Clostridias, Fuso and E coli).  After treatment, this trend flipped.  Butyrate and total SCFA were all up to upper-normal ranges. This indeed matches my overall health -- less food intolerances, better digestion, far less bloating/distention, improved sleep, resumption of REM/brain-dreaming, adrenal tolerance, good adrenal hormones, great gonadal hormones, regained ability to do endurance training.


(g) Adiposity Profile: Firmicutes to Bacteroidetes ratio
Too much of either Firmicutes or Bacteroidetes is not ideal. Both help in extracting energy from chemical bonds in food. SCFA are metabolites of Firmicutes and Bacteroidetes fermentation. Partly the way they work is that the SCFA end products bind to G-proteins (GPR41) to control inflammation, brain-gut-gonad axis (cortisol/heart rate/etc), immunity and fatness. Just as omega-3 EPA + DHA increase lean muscle, reduce body fat and improve insulin sensitivity and inflammation, SCFA appear to do the same. Approx 55/45 to 60/40 may appear ideal.




Urine Organic Acids and Oxidative Stress Evaluation:  2013

The urine organic acids (ONE=optimal nutrition eval) confirms that the gut dysbiosis was not severe.  No yeast dysbiosis was detected outside of normal range (very happy about the lack of brain fog/aldehydes/mycotoxins, too). In fact, vitamins, minerals, adrenal function, mitochondrial energy production and fat burning were all decent or exceptional.  It did point out that I'm a little low on detox nutrients -- vitamin A, all the B vitamins (COMT (+/-) hetero), tocopherols, glycine, glutamine, magnesium and zinc.

The O.N.E. shows toxins -- alpha-ketophenylacetic acid (from my #*$&@ iPhone cover, styrene, synthetic rubber, resins, polyesters (sports bras, workout outfits), plastics, Saran wrap) and a-hydroxyisobutyric acid (from MTBE, gasoline additive meant to help gas burn 'clean' now major contaminant in California drinking water despite banning in 2003). Apparently mod-high levels of both are being excreted in the urine (after having spent 2mon in Cali 'detoxing' LOL aha). These are endocrine disruptors and damage DNA.

My kids and I have the GSTT1 deletion (glutathione S-transferase T1), and do not detox many xenobiotics well. Studies are finding oxidative, DNA damaging, and hormonal effects with even low exposures of polyaromatic hydrocarbons, pollution, benzene, acrylonitrile (gloves, plastics), styrene, gasoline, mercury (thimerisol sensitization -- eye drops, vaccines), mercury (low birthweight babies), mercury (compromised urine detox-elimination), mercury in medical students (increased mercury body burden), and countless other chemicals/metals in GSTT1 null individuals.  This genotype is even linked to whacked gender ratios of their offspring when chemically exposed... Dr. Mark Hyman MD reports he has the GSTM1 deletion and its effects, here.




SIBO Treatment, Healing the Gut-Brain-HPAT-Gonad Axis, and Followup

How did this SIBO &!amp;#$@ mess get fixed? Functional medicine labs, diagnostics, and treatment provided all the tools that were needed to finally reclaim my prior health, leanness, and brain-gut-gonad axis.  I am thankful for the opportunities to interact with several practitioners, my brilliant sister 'M', functional medicine doctors, and WAPF leaders over the last few years -- some very briefly -- they gave me the insight that I needed.

The root cause and antecedent event was the titanium implant which appeared to trigger some immune compromised reaction. There are implant failures (not me -- purrrfect, excellent ossification) but not many test Ig-positive on traditional or functional testing (MELISA, Clifford) at this time. Clifford CCR testing showed reactions to all mercury amalgam and nickel, but nothing for gold or titanium. After it and all metal were removed, the typical integrative medicine strategies all worked -- probiotics, raw fermented vegetables, exercise (earlier too fatigued to do any workouts), naps, yoga, laughter/friends, spiritual support, digestive enzymes, omega-3, mag/zinc/minerals, adrenal adaptogens, adrenal protocols (carb+protein+fat, every 4 hrs, sea salt 1/4 tsp daily), pycnogenol, gut support (marshmallow, slippery elm), betonite clay, charcoal, ghee, organic lard, rainbow vegetables, pastured pork and egg yolks, frequent bone broths, etc.  For followup, I hope the next phase will yield further insights.



SHOW ME

Share and show me your GI Fx tests or integrative medicine lab testing results... I'd love to see it!

Microbial Influence

We co-evolved with the microbes in our gut to escape pathogens, parasites, predation and starvation (emo, nutritional, mental, etc), whilst hunting for palatable food, prey and partners.  (Isn't your partner palatable?) Simultaneously we enjoy all benefits that our co-existing gut microanimalia provide -- digestion of indigestible fibers/resistant starches, butyrate/short-chain-fatty-acids, neuroendocrine modulation, boosted immunity and tolerance, to name only a few.  They weigh 1-2 kg in our daily feces, contribute to massive biofilms (slime communities) in our guts and sinuses, and line every interface where human interiors meet exteriors.  The microbiota are not a small forgotten organ any longer.

It has been realized for decades that 70-80% of human immune cells are in the GI system; I believe however a large proportion (70-80%??) of our total immune system IS the gut microbiota. The # of genes collectively in a microbiome are 150 times larger than the genome of their host human. Besides digestion and metabolism, our microbiota perform far more than we perhaps currently understand in cross-talking with the immune system, its maturation and role in homeostasis and energy balance.




Emerging data like the study reviewed here showing the rodent T1DM disease model was averted by the presence of a soil based microbial strain known as SFB (segmented filamentous bacteria; genus Arthromitus) confirm and highlight the vital role played by commensal gut species in our immune system. I find it notable that the hearty and robust spore-forming ones that originate from dirt sources are producing some of the most interesting scientific findings since we co-evolved with ancient dirt for millenia.

Since the vast majority of microbial fermentation occurs in the caecum, appendix, and remainder of the large colon in humans, our small intestines are nearly sterile and absent of bacteria and fungi except at the end (ileum) where commensal species take residence.  Studies on TH17, one of the important arms of the immune system, show that no TH17 cells will appear in the small intestines until commensal microbes inhabit the area. Germ-free rodents will miss an entire arm of the immune system until colonization with introduction of a SFB-containing commensals.



Toxic and Germ-free Fetuses, Babies, Children and Adults

The collective status of our guts pretty much reflects the status of our current macroecological niche for humans I think... massively insolvent, blatantly bereft of vision, and irrevocably impoverished.  In China I read everyday of villages blighted with river and ground water poisoning by illegal corporate dumping of industrial waste.  Post-modern towns are plaqued with leagues of cadium or arsenic poisoned children. Even locally in our neighborhood Pudong, Shanghai, lead toxicity was detected in many children living near manufacturing plants called Johnson Controls International Battery Inc.  In the USA, coal burning which provides 30-50% of current energy demands has tainted the air/water/soil and caused mercury and arsenic accumulation in marshes and wetlands and the flora and fauna that reside there. Birds no long sing, woo, mate or care for their young appropriately.  Mercury-toxic birds are literally the canaries in our toxic macroecological niche.  What about human canaries, our children?  I think epidemic rises in toxin related diseases are accurate and reliable reflections because toxins disrupt the intestines and microbiotia:
--AUTISM (1:50 currently compared with 15 years ago 1:10,000)
--CELIAC DISEASE (6.4-fold increase in 20 yrs, Scotland)?
--OBESITY AND METABOLIC DISEASES

Our hyper-hygiene and dirt-avoidance culture extends to the over utilization of potent broad spectrum antibiotics piled into the feed of poultry, pigs, cattle dairy/egg production and in modern conventional healthcare.  In the a new study by Stanford researchers, the mechanism for why pathogenic gut strains invade after a single course of antiobiotics has been illuminated.  Pathogenic strains C. diff and S. typhi are shown to take advantage of the abundant sialic acid and fucose sugars that are left after antibiotic extermination of 'good' commensal gut flora.  The researchers also report in a model where C. diff and S. typhi were genetically altered to fail to utilize sialic acid, expansion by the pathogens was impaired.





Toxins Delete the Good Microflora, Stimulate the Bad Microflora

When I had toxicity from gluten, oral birth control, antibiotic overutilization, thimerosal vaccines (tetanus, annual flu, blah blah blah), titanium and mercury amalgams, I had no idea that each and every one of these factors promote pathogenic gut flora, vitamin B12 deficiency, and kill or inhibit beneficial 'good' gut flora.

 Did these toxic factors make me fat?  Absolutely.

It was not [CALORIES IN = CALORIES OUT].

Fermented Fiber Produces SCFA Which Activate Immunomodulating G-Protein Receptors (GPRs): In pubmed studies, each of the above toxic factors are highly linked to gut dysbiosis and obesity.  Stopping or eliminating each of the above eliminated subsequent inflammation and obesity for me (combined with Asian paleo + exercise).  Understanding the human superorganism anatomy and physiology gives pause to recognize the role the gut flora had in the ups/downs of my health over the decades.  Recall about ~10% of total energy expenditures are estimated to be supplied by hindgut fermentation that occurs in the caecum and colon (versus 20-30% for other omnivores).  Production of SCFA, small chain fatty acids (acetate, proprionate, butyrate), and other downstream metabolite byproducts (succinate) bind receptors known as FFA2/FFA3 and SUCNR1, respectively, that control and regulate inflammation (TNF, interleukins, NFkB) and immune function.  Metabolite sensing occurs through these G-protein receptors much like how omega-3 EPA+DHA bind 'omega-3 receptors' GPR120 and elicit their anti-inflammatory and immunomodulating actions.  FFA2 (GPR41) receptors are found in enteroendocrine cells, adipocytes, neutrophils, eosinophils and pancreatic islets; and FFA3 (GPR43), enteroendocrine cells, pancreatic islets and sympathetic ganglia.

I believe these effects on GPRs design a metabolic flux which tunes metabolism UP and DOWN based on the messages that our food, movement, minds, and microbiota co-create.  My new formula for comprehending energy balance might be...


     Calories In       = Calories Out (MICROBIOTA) + Calories Out (HUMAN) + [HEAT]*FLUXXX
(SUPERORGANISM)




Diabesity:  Recall pesticides are highly associated with Diabesity.... Coming to China actually forced our family to go as much as we can 100% organic and non-GMO (although all labels are dubious).  In the States, when my in-laws cooked for our family I didn't have control (eg they were too cheap to buy organic).  In the USA, the organic label is also dubious to me but for the most part it's way way way better than in China.


Recent research demonstrated that glyphosate (Round-Up Ready) allows growth of pathogens and kills the friendlies in studies of intestinal microecology in chickens.  EWP studies show babies and people's toxomes contain on average 200-300 known carcinogens, chemicals, heavy metals and pesticides. 100% of all participants (n=9) in the EWG #1 Commonweal Study had metabolites of organophosphate pesticides, and 55% -- organochlorine pesticides.   Do pesticides in our food and contaminating our water/soil disrupting our gut? I would say emphatically yes.  In China, Round Up Ready sweet corn is mega popular.  China imports that and millions of metric tons of GMO cotton, soy beans, corn, rapeseed and sugar beet.

For several years now, commercialized GM cotton, papaya, sweet pepper, tomato, poplar, and petunia have been grown without public awareness.  One journalist reports that 90% of China grown cotton is GMO cotton (2008).   The report also found 40 billion tons of soybeans were imported  in 2009.  GMO Soy likely goes into thousands of Chinese products here -- (rancid) cooking oil, animal/poultry/aquaculture feed, tofu, soy milk, soy sauce, etc. 40 BILLION TONS OF GMO. Asians love their soy OY OY OY... It's truly the land of sarcopenia and soy, no? Is this behind the epidemic of obesity and diabetes in China among children, adults and elderly alike?



Horizontal Gene Transfer. Does horizontal gene transfer (HGT) between DNA from consumed GMO corn and corn products to our gut microbiota occur? Another emphatic YES.  How do you reverse it if your microbiota is transformed? I wish I knew... Bacteria and fungi live in biofilms and exchange DNA within the matrix.  Like a meme gone viral.  Evidence for both DNA and lectin proteins from GMO Bt corn has been found in animals and humans that consume Bt corn. The DNA was found to survive and persist for a long time in the gut/rumen.


I talked about Bt corn previously here: 50 Shades of F*ckd and Cancer.  Every pesticide corporation has a GMO Bt corn brand.  Bt is a lectin (like gluten) and disrupts intestinal epithelium in susceptible victims which can lead to gut dysbiosis and/or death.  It was very effective pesticide in the beginning.

Rootworms and other pests have rapidly shown field resistance to nearly every brand -- Syngenta's Agrisure and Monsatan's YieldGuard.  Dupont/Dow's Herculex has not as much, therefore Monsatan has reported they are planning to incorporate Herculex to synthesize TWO TOXINS into their new SmartStax corn -- in an attempt to overcome inherent field resistance. GMO is brilliant, no?

Unfortunately significant Bt lectin protein has been detected in fetus, pregnant women and non-pregnant women in already one clinical trial. Can we look forward to double the toxins next?  Can we afford to because we are kinda 50 Shades of F*ckd already...



Boobies and Breastmilk Microbiota

Symbionts Are Everywhere:  Our microvilli produce siliac acid and fucose (9- and 6-carbon sugars) at the tips for commensal gut flora to feast and graze on. I call it 'pharming the gut'.  Again, like much of life on earth -- hominids, insects, fish, frogs, mammals -- we have evolved with gut symbionts, encouraging them to take residence and producing incentives for their maintenance.  We should strive to avoid screwing our symbionts...

The baby-mother relationship is another example of the ultimate symbiosis.
Babies receive everything from mom -- life, love, heat, immunity (IgM), food, and water.  It's one of the most symbiotic relationships on earth outside of pair-bonded couples and tight knit families and communities. The baby is born sterile with no immune system, relying on mother's immunoglobulins to handle environmental viral or microbial assaults.  If advanced hominids and other mammals outsourced 70-80% of its immune system to gut microbiota, what does the timeline for acquisition of gut flora look like in babies?



Initially breastmilk was considered sterile but like many things in science, this was inaccurate. Colostrum contains over 700 live organisms (European Society of Neurogastroenterology and Motility: Gut Microbiota Worldwatch). Are these important? Why? Lysates of strains such as Lactobacillus and Bifodobacter have been shown to tighten up the intestinal tight junctions. Several strains in probiotics have been shown to be associated reduced mortality in NICU settings and against often fatal necrotizing enteric colitis.

Although babies are born with leaky guts to accomodate mothers' large proteins direct access into blood and lymph circulation  (immunoglobulins, IgM), they appear to get a lot of help from natural commensals to switch and develop intestinal impermeability.


Where does mammary microflora originate from? Some researchers hypothesize there is a special conduit that transfers gut flora to the mammary glands, an 'entero-mammary pathway'.  Lymph circulation? It is unknown and not entirely elucidated.  Researchers looked at microbiota in breast milk (at 0 mon/colostrum, 1mon and 6 months), different areas of the mother's body and compared flora between elective C-section and vaginal/non-elective C-sections. Breastmilk from C-section moms resembles mouth/oral and skin flora; whereas, breastmilk from moms who went through vaginal birth or some modicum of vaginal delivery that ended in non-elective C-section (that was me) showed flora that matched the gut and feces. Birth does something to make proper milk.  "The fact that the milk microbiome of mothers who gave birth by nonelective cesarean section had a normal microbial composition that was comparable to that of breast milk from mothers who delivered vaginally suggests that physiologic (eg, hormonal) changes produced in the mother during the labor process may influence the composition of the bacterial community."
Another finding from this study was 'Milk from obese mothers tended to contain a different and less diverse bacterial community compared with milk from normal weight mothers.'

Are Toxins + Early Post-Natal Gluten Exposure J*cking Us?  Gluten peptides also traverse and are dispensed to the baby during lactation from a gluten-eating moms.  Does this contribute to the gargantuan rise in celiac and autism?  Babies are born sterile but breastmilk has over 700 organisms to colonize and modulate intestinal permeability. If babies are born under circumstances where mom doesn't provide the needed commensal gut bacteria (overweight/obese mom (me, again), elective C-section, antibiotics at birth), it could be plausible IMHO that peptides like gluten in mother's milk will cross directly into the baby's blood circulation without the 'blockage' or junction tightening effect from missing commensals.  Gluten on its own also opens zonulin, further impairing, I suspect, a baby's gut permeability.

We may need commensal gut critters not only for immunity but also for chelation and elimination of modern, industrial heavy metals.  Studies show several soil-based bacteria microbes chelate and bind toxic metals.






Citations

"During the co-evolution of man and microbes, the human intestinal tract is colonised by some thousand species of bacteria. Gut borne microbes outnumber the total of body tissue cells by a factor of ten. Recent metagenomics analysis of the human gut microbiota has revealed the presence of some 3.3 million genes, as compared to the mere 23 thousand genes present in the cells of the human body tissues."

--Rijkers et al, Gut Microbiota in health and disease: a personalised summary of 
the 3rth workshop




Seed, Weed and Feed the GUT

I've talked already about many ways to seed the gut (fermented foods, SBO probiotics, dirt, etc) to complement the existing microbiota and weed the gut -- removing toxins, mercury, pathogenic overgrowth, parasites and worms.  How should we properly water and feed the gut?

The primary foods are fiber, mucous and starch that resists small intestine digestion. If the gut is diseased, crowding out pathogens and removing parasites is also important. If the microbiota lacks diversity, then diversity needs to be cultivated and nurtured.  Studies show the obese, inflamed, autistic and heart diseased lack microbiota diversity of species and phyla.

Feeding and nourishing the microbiota isn't a special skill... our ancestors thrived and survived in special microecological as well as macroecological niches... and so did the gut microbes.  How did ancestrally derived foods benefit the microbes and what do they specifically provide for us?  Do we rely on them for immunity? For activation of important immune factors (glutathione, our #1 master antioxidant)?  For activation of plant-derived antioxidants like lignans, etc?  For removal of toxic and carcinogenic bile acids?  To balance the steroid hormone pool?

Yes to all.

I like ancestral diets. They must've worked I figured because we are here...

Being Asian I enjoy starches and after regaining insulin sensitivity (after being 50 lbs overfat), I burn starches adequately during glycolytic activity. With VLC/ketosis, I had cortisol dysregulation and to heal metabolism fully I had to eat carbs regularly. Being previously metabolically broken and still recovering from some toxicity (heavy metals, contraceptive endocrine disruption), however, I don't overdo the starches because I'll notice that I regain bodyfat mega fast.  Typically intake may be 1/4 of plate at most meals).

Our family eat certain starches regularly -- carrots, radishes, steamed pumpkin, bamboo shoots, fermented sauerkraut/carrots/radishes, tubers (yellow, purple, white, small potatoes, yams), flours (tapioca, sweet potato) and soaked grains/seeds (psyllium, millet, sorghum, black sesame, rice (purple, brown, white, glutinous)).   The variety depends on what is in season and carried by the organic farms -- Mahota, FIELDS, BioFarm/Cityshop, etc.  All the above contain both fiber and resistant starches (RS) which the microbiota feed on.  Ultimately, both types of microbial food benefit us on many levels.

In fact some studies show synergism when both fiber and RS are consumed together compared to fiber alone (beta-glucan) or RS alone for insulin and glucose reduction and regulation. Behall, et al:  synergism -- MEN and WOMEN. Below is the outcomes from the female study examing the impact on BG and insulin with intake of beta-glucan + RS. The levels of both were modulated low v. high and vice versa. Higher beta-glucan and higher RS produced the most marked improvements in metabolism. High amounts of either were satisfactory as well (see yellow/insulin,  orange/glucose lines and green circles).  Low amounts of either fiber or RS, not nearly as wonderful metabolic outcomes in this study.



Beta-glucan is a special soluble fiber (NSP)-- it's not made by mammals. It's found in yeast cell walls, whole grains, and mushrooms.  It's been shown to not only affect the microbiota but also improve immune function, wound healing, metabolic dysregulation, cancer/tumour sizes, and inflammation.  A recent study tracked the fate of beta-glucan in the gut and immune lymphoid tissues.  Researchers found "these large -1,3-glucans were taken up by gastrointestinal macrophages and shuttled to reticuloendothelial tissues and bone marrow. Within the marrow, the macrophages degraded the -1,3-glucan and secreted small soluble biologically active fragments that bound to CR3 of mature bone marrow granulocytes. Once recruited from the bone marrow by an inflammatory stimulus, these granulocytes with -1,3-glucan-primed CR3 could kill iC3b-coated tumor cells."

Resistant starch (RS) is found to be quite as plentiful as beta-glucan and plant fibers however cooking breaks it down to a form that we can digest (enzymatic, mastication, acidic).  The amount remaining in a food that escapes our digestive juices varies by many factors -- species, maturity of the plant, cooking/cooling methods, food acidity, to name just a few. RS is different from beta-glucan and fiber due to its tightly bound double helical glucose polymer structure.  Yes it is coiled up like DNA....  Solubilization in cooking water 'releases' the starches into a gelatin matrix which our spit amylases and pancreatic carb-ases can breakdown to glucose for absorption in the stomach and small intestine.  Any undigested amounts enter the caecum and colon.  The amount of SFCA produced upon caecal and colon fermentation varies as well depending on an individuals microbiota species, large intestine health status, etc.

The average intake of RS in China is 14.9 g/day from wheat, rice and starch products (mung bean, sweet potato noodles); compared with average USA 3-8 g/day intake it is about 2 to 5 fold increased. However, I don't think this holds true any longer for Chinese urban dwellers. When my parents grew up in a small rural village in Taiwan (with pigs and 'home organic' e.g. subsistence farms), they were poor and only ate potatoes, yams, mung beans, rice, and vegetables with very scarce meat/fish/pork belly or chicken or eggs. I believe their childhood intake fiber and RS intake were far more than currently, if not triple or quadruple.

Combined with veggies, most people's diets contain a mix of carbohydrates: rapid digesting (simple sugars, disaccharides), slow digesting (complex carbohydrates), nonstarch polysaccharides (FIBER = b-glucan, xylan, glycan, gums, pectin, mucin, cellulose, hemi-cellulose etc), and resistant starches (RS) to fuel both our human cells and the microbiota.  Our microbiota in the large intestines will eat and ferment fiber, RS, and the mucous produced in the protective layer of the gut.



For SIBO and intestinal permeability, it's actually healing to minimize fermentation if it is occurring pathogically in the small intestines... where it shouldn't be.  The surface of the small intestines is not designed to support extensive networks of microbial growth which requires thick mucous.  The integrity of the small intestines can easily be compromised and fail to serve its function (digestion and absorption) when inappropriate growth manages to perpetuate whether it's 'good' v 'pathogenic' bacteria, yeasts or mycobacteria or parasites/worms.

The ONE (optimal nutri eval) is one of the best tools to measure the microbial/fungal metabolic by-products in the urine by opportunistic and pathogenic species in the small intestines.  The GDX/Metametrix GI function stool test is unique to identify microbial overgrowth, dysbiosis, pancreatic digestive enzyme capacity, small intestinal fat/fiber/protein malabsorption, and parasites/worms as well as assess microbial sensitivity to herbal and pharmaceutical antimicrobials.

Diet absolutely shifts bacterial communities in the gut ecology -- simple sugars lowers the good, raises the bad. More fiber and RS both raise the good (in Bacteroidetes -- Prevotella, etc), lowers the bad (in Firmicutes -- virulent strains of clostridas, E. coli's, enterococci, streps).  This is borne out in pig, children and human studies.  Flint et al do a great review here which includes a raffinose study (fiber from legumes) that enriched and ↑ F. prausnitzii, Bifidobacterium spp.  Like many of the good gut flora, Bifidobacter tightens up the intestinal tight junctions as super tight as a nun's **ss, which is enteroproctive and immunoprotective again gastroenteritis, intestinal permeability and necrotizing enterocolitis in trials. Guess what?  Magnesium deficiency compromises Bifidobacter and intestinal permeability (or which came first?).  Bifido appears to enjoy magnesium. In rodent studies fed a mag-deficient diet, intestinal permeability and quantitative changes to cecal bifidobacteria were associated.

My kids and I have scr*wed up Bifido(not bad but could be far better -- 3.2; Brent Pottenger's Bifodobacter is over 20% more and rocks at 3.9)... and we have low mag...  Brent has also has had zero cavities and therefore zero mercury amalgams.  Perhaps my fam and I need to forage us  some raw unpasteurized human breastmilk because it is enriched with Bifido?

Below is a human study n=10 on the microbiota shifts comparing RS2 and RS4 intakes (55 grams/day x3wks, then 2 wk washout).  Even among resistant starches, there is selective species enrichment.


The authors state in the results:  "Ten human subjects consumed crackers for three weeks each containing either RS2, RS4, or native starch in a double-blind, crossover design. Multiplex sequencing of 16S rRNA tags revealed that both types of RS induced several significant compositional alterations in the fecal microbial populations, with differential effects on community structure. RS4 but not RS2 induced phylum-level changes, significantly increasing Actinobacteria and Bacteroidetes (+++)while decreasing Firmicutes(-). At the species level, the changes evoked by RS4 were increases in Bifidobacterium  adolescentis and Parabacteroides distasonis, while RS2 significantly raised the proportions of  Ruminococcus bromii and Eubacterium rectale when compared to RS4. The population shifts caused by RS4 were numerically substantial for several taxa, leading for example, to a ten-fold increase in bifidobacteria in three of the subjects, enriching them to 18–30% of the fecal microbial community. The responses to RS and their magnitudes varied between individuals, and they were reversible and tightly associated with the consumption of RS."


Similar enrichment in enterocytes occurred in a rat weanling study feeding either basal diet or RS 5% for 28 days. I like this study because it demonstrated increased glutathione (our #1 master antioxidant; I have a GSTT1 deletion so mine is mildly compromised) by over 2-fold and improved pancreatic elastase secretion (digestive enzymes) in the RS fed groups.  [***Personally I eshew all rat studies unless they're vegetarian studies because (1) rats don't have a gallbladder and (2) they're not as omnivorous as humans or pigs so the data is incomparable, particularly the (ludicrous) meat/colon ca/nitrosamine studies.]



Shifting Microbiota Communities: GI Fx Stool Test and Optimal Nutri Eval (ONE)

Brent Pottenger's case:  Recall his Prevotella, Bacteroidetes and Firmicutes are quite stunning and no biomarkers of dysbiosis.  He has likely very little mercury (no history of cavities). His diet: near carnivory, fermented full fat Greek + some veggies both raw/cook (per Pottenger's cats).  The microbiota sequencing reveals a beautiful display of healthy guts.  Previously he c/o acne and migraines which are signs of SIBO and intestinal permeability.

My case: The Prevotella, Bacteroidetes and Firmicutes (2013) are impressively improved and robust compared with the initial 2011 when I had CFS, fogginess, fraility (sarcopenia), rank mood, and on/off body fat.  The SIBO is gone except for residual dysbiotic biomarkers from a parasite and Morganella. [yes wtf I dunno where the origin was but my children also have pathogenic overgrowth or parasites but we all different. I suspect I got it from one the irresistable poopers, see below]

Would you like to do a GI fx stool test and see your microbiota and do a ONE to evaluate nutrient deficiencies, dysbiotic markers and 8OHdG (DNA damage)?  Let me know and show me!  (Cost $99 and $129, respectively, plus admin fee $50).  Let's conduct paleo gut experiments.



What had I done?
--for two years

• gluten free, casein free, exercise/yoga (some barefoot on soil/lawn)
• removed mercury, gold, titanium parts and oral chelation on/off
• sleep, adrenal/gut support, antioxidants incl pycnogenol, omega-3, minerals
• Prescript Assist, FloraMend
• whole food diet (rainbow tubers, veggies, organic meat, lard/ghee)
• fermented pao cai, Beijing radishes, carrots

--for two months prior to the GI fx stool test

• Seed: Raw unpasteruized sauerkraut at nearly every meal and drank the brine, SBO probiotics
• Weed: charcoal and bentonite clay; removed gut irritants (alcohol -- studies here and here)
• Feed: Kraut and fiber rich foods (basmati rice, vegetables, potatoes, etc)

Energy Flux and Metabolism in Superorganisms

I consider this formula for energy flux:

Calories In (SUPERORGANISM) = Calories Out (MICROBIOTA) + Calories Out (HUMAN) + HEAT*Fluxxx

Rapid and slow digesting starches (RDS, SDS) impact blood sugars and insulin sensitivity by raising BG. The effect on insulin sensitivity and how they burn fat in the mitochondria actually depends on the individual, their insulin sensitivity and the carb/glycemic load.  See Major Paleo De-Mything.

On the other hand, insoluble or soluble fiber and RS do not raise insulin or blood sugars. In fact fiber and RS have been shown in several trials to behave like protein and omega-3 fats by raising insulin sensivity.  Both fiber and RS naturally have glycemic indices of 'zero', 'bulk' up food, increasing fecal transmit time as well as fecal microbial biomass. Combined with digestible carbs, RS and fiber both tend to prevent spiking of glucoses, thus blunting the effects of high GI (glycemic index) foods and sweets. Both fiber and RS definitely lower inflammation but appear to do so via routes which are intimately tied to the microbiota.





The mouth and stomach digest ~10% of our carbs and the rest 90% is digested in the small intestines if all is functioning (pancreas, gallbladder, oral amylases, GI acidity, microvilli brush border enzymes, pepsin secretion, bile, peristalsis).  What escapes small intestinal degradation is later fermented by the microbiota in the large intestines (caecum, appendix, colon) to volatile organic acids, known as short chain fats -- acetate, proprionate and butyrate.  Although microbial byproducts provide some fuel to us  and the local enterocytes in the gut ecosystem (~10% of our total energy requirements compared with ~30% in other omnivores), actually much of the butyrate and other SCFA goes to provide energy to the microbiota . See above diagram 'Fermentation -- energy for bacterial growth'.  From my reading this amount varies. The SCFA collected at the colon depends on inflammation, IBD status, diabetic v. nondiabetic, etc.  I think it reflects SIBO and intestinal permeability factors which affect the microbiota.

SCFA play a role in the immune system and metabolic pathways by as binding fat-sensor receptors such as PPAR alpha, gamma, delta and GPR41/43.

How we chew the food and shear the particle sizes of resistant starch granules determines how much may be broken down in the small intestines. The first, top diagram above shows how digestive amylases 'etch' granules of resistant starches recovered in the intestines.  Food preparation also transforms the digestibility, crosslinks and polymerization of the starch matrix.  Longer heat, higher boiling/gelatinization, and maturity of the plant are all factors that predispose to higher digestibility and potential blood sugar impacts.   Cooling the starch and adding acidity (lemon, vinegar, fermentation) all lower small intestine digestibility by changing the coagulation of starches and protecting the starch granules from enzymatic degradation. Both refridgeration and autoclaving (high moist heat) polymerize the starch chains and raise RS.

So certain foods will have more RS as a result of food prep compared to the original food:
Fried rice or 'al dente' rice versus rice boiled in large volumes of water
Cold chinese rice ball snack rolled in lard/oil and seaweed versus warm steamed white rice
Sushi rice (room temp rice, sweetener +vinegar) versus warm steamed white rice
German cold potato salad with vinegar versus a boiled LARGE American monoculture GMO potato
Whole grain wheat pasta versus overboiled white pasta

Fermentation breaks down RS
Boiled poi (more) vv. Fermented poi (less)
Unfermented cooked rice v. Fermented Indian dosa rice or idli (less)

Autoclaving polymerizes amylose so raises RS
Processed (heating/reheating process) Uncle Ben's rice (but beware of the endocrine disrupting plastic it's encased in) v. freshly cooked long grain rice (less)




Evolution of RS

The amount of resistant starch appears to me to be related to the amount of protein in the tuber or grain/seed, on cursory review. I've tried to dig further but can't find anything.  The food sources which appear to have the most RS are the starch containing foods with intact cell walls and higher protein content legumes (9.5-11.1% dal, lentils, beans), whole grains (4.5-6%), or complete proteins (2% potato; 4.8-5.9% processed non-modified PS; steamed/cooled potato 31% and roasted/cooled potato 52.5%).  Perhaps amylose and other RS protect the peptides embedded in the starch matrix for tuber and grain/seed winter storage to buffer the Ice Age chill? Sprouting and germinating grains/seeds raise protein and nutritional content, but lowers RS.  Additionally, fermentation of starches is a trade-off -- fermentation lowers RS but raises protein/vitamin content.

Image may be NSFW. Clik here to view.

I GAVE HER PROBIOTICS SINCE THE FORMULA DIDN'T HAVE

Image may be NSFW. Clik here to view.

ADORABLE POOPER

Why We Are Sick and Fat: Calories In (SUPERORGANISM) = Calories Out (MICROBIOTA) + Calories Out (HUMAN) + HEAT*Fluxxx


Centenarians and the Microbiota

I'll go over this one below soon -- BIG THANK YOU TO TATER/TIM AND M.O. FOR THE PDF!!! What is it about healthy, long-lived centenarians? I dunno... Their immunity? Their guts? let's delve deepper and find out more...

Cultivable and pyrosequenced fecal microflora in centenarians and young subjects.

The above diagram is from the Marchesi piece (adapted from Biagi et al).

Biagi et al studied the microbiota of centarians (C), elderly (E) and young (Y).  Distinct differences were noted.  The microbiota of centenarians were distinctly unique and different from both the young and the elderly groups. Less Clostridium cluster XIVa, higher Bacilli and rearrangement of the Clostridium cluster IV composition were noted in the centenarians. Some things were expected in centenarians -- lower diversity, less of the good butyrate producers, less Bifido, and more pathogenic strains.

Quite unexpectedly, special characteristics of the gut ecosystems of the long-lived were discovered in this Biagi et al 2010 study which may define what an elite microbiota with a high G.I.Q. looks like.

(a) Enrichment of special butyrate producers Anaerotruncus colihominis et rel. (Clostridium cluster IV), and Eubacterium limosum et rel. (Clostridium cluster XV). Biagi et al concluded in a 2012 followup'The increase of E. limosum is high (approximately 15- fold), and could point to a group of bacteria characteristic of the long life.' E. limonus is a soil strain which lives in ruminants like sheep and cow. Its very good at converting METHANOL. In one in vitro colitis model experiment, E. limonus had positive outcomes.

(b) Increase in facultative anaerobes, such as bacteria belonging to the groups Bacillus. Does this include my favorite soil based organism Bacillus licheniformis or Bacillus subtilis?  Does B licheniformis and B subtilis produce supercharged bionic Gut I.Q....?!  What are foods that contain these?  ANSWER here.


Biagi et al also found the connection between "The decrease of both Clostridium cluster XIVa and F. prausnitzii group members was also correlated to frailty condition, hospitalisation, antibiotic treatment and non-steroidal anti-inflammatory therapy." Clostridium cluster XIVa is also referred to as the Clostridium coccoides/Eubacterium rectale group which are potent cross feeders of resistant starch and raw potato starch in clinical experiments.  E rectale are poor RS fermenters but they live symbiotically with keystone gut species that eat and ferment RS to secondary food (substrates) which E rectale consumes like a hog on fire. Hattip: Tater/Tim.




Smart Gut I.Q.

There are a couple of elements that I believe are fundamental in a stable, homeostatic gut ecosystem that will take one to advanced longevity:
--genetics (respect your ancestry... don't mess genetic expression with synthetic hormones, vitamins, endocrine-disrupting pollution, pesticides, GMO food/products, lifestyles, thoughts or people)
--super tight junctions and intestinal IMPERMEABILITY
--balanced flora
--special 'keystone leaders' like E. limosum, B subtilis, B licheniformis, and many others
--seed (return to the earth and intake healthy earth -- soil based organisms in fermented organic vegetables, fresh salads, and supplements if necessary (list here I like))
--weed (avoid mercury, toxins, food allergens/gluten and detox/chelate safely)
--feed with fiber (resistant starches, heirloom and native tubers, organic whole non-gluten grains, lentils, chana dal, legumes)
--exercise daily to move the gut (peristalsis), e.g. 10,000 steps or one hour mild to mod intensity. SIBO causes impaired gastric and intestinal peristalsis (and vice versa, sitting/atrophy can affect SIBO)
--misc (avoid unnecessary hospitalizations, CDAD (iatrogenic or antibiotic-induced C. difficile-associated diarrhoea), antibiotics, and other gut irritants like non-steroidal anti-inflammatories (NSAIDs) -- ibuprofen, motrin, aleve, excedrine, etc)

Guest Post: Tim/TATERTOT, the revolutionary, rebellious and slightly irreverent on the gut microbiota, fermentable substrates, butyrate colonocyte preference, and risk of colon cancer on a Paleo Diet lacking RESISTANT STARCH.




"Roly Poly
Eatin' corn and taters
He's hungry every minute of the day
Roly Poly
Gnawin' on a biscuit
As long as he can chew it it's okay

He can eat an apple pie
And never even bat an eye
He likes anything from soup to hay
Roly Poly
Daddy's little fatty
I bet he's gonna be a man someday"



In 1950 fat people didn't get the respect they do today...everybody knew it was simply a matter of eating too much pie. Fat kids were lazy and ate too much candy--a day hoeing the field would put an end that!

Flash forward 50 years, we've come to realize it's not Roly Poly's fault, sugar is the problem. And not just sugar--all carbohydrates make us fat. Every Paleo blogger will challenge you: Do you want to be a sugar-burner or a FAT BURNING BEAST???? The answer is obvious. We don't want to be Roly-Poly, we want to be Grok.

So, we give up sugar and most carbs, cutting out the easy ones first...grain, bread, potatoes, rice, beans, yams, and most sugary fruit. We lose weight, become FAT BURNING BEASTS and live our life swinging through the treetops in top physical form. Or so it would seem.

Sometimes our outward appearance doesn't match what's going on inside. We may lose weight and improve many health markers like blood pressure, cholesterol, and triglycerides, but what is happening in our guts?

More and more attention is being given to the trillions of microbes living in our large intestine. Advanced methods have been devised to identify the different species and families of microbes that make up our gut flora. A healthy gut flora is an amazing thing. The gut flora's main contribution is it's ability to ferment undigested carbohydrates and turn them into short chain fatty acids, such as butyrate, propionate, and acetate, which are used by cells which line the colon (colonocytes), the liver, and muscle tissue. This fermentation of undigested carbohydrates also results in the production of vitamin B and K as well as some important brain chemicals, like serotonin. There is hardly a single facet of our metabolism and biochemistry that isn't effected by our gut microbes.

Reports come out regularly that meat consumption is harmful to the health of humans.

In 2009, it was Meat Intake and Mortality which concluded, ""Red and processed meat intakes were associated with modest increases in total mortality, cancer mortality, and cardiovascular disease mortality."

In 2012, it was Red Meat Consumption and Mortality, which warned us, "we found that greater consumption of unprocessed and processed red meats is associated with higher mortality risk. Compared with red meat, other dietary components, such as fish, poultry, nuts, legumes, low-fat dairy products, and whole grains, were associated with lower risk."

And just recently in 2013, Intestinal Microbiota Metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis, "Our studies reveal a new pathway potentially linking dietary red meat ingestion with atherosclerosis pathogenesis."

So, it would seem settled that red meat is bad for us, leading to heart disease and early death. All of the major media outlets were all over these studies--proof that maybe we should all be vegans! Then these stories hit the paleosphere; every blog and forum joined forces to tear these studies apart...'may cause...''potentially leads to...''modest increases in...'. Maybe it's not settled. Even our own Dr BG joined forces with the low carb elite, saying in 2009:

"Low carb, high sat fat...Is it really that easy?
--raise HDLs
--lower dense small LDL
--shift to Pattern A from BBBBAD
--feel more energetic, vibrant, younger with maximum vitality"

Meat's not bad...carbs are bad.



But back to those funny critters residing in our guts, the ones that comprise 90% of our total cells. The ones that do so much for us...what do they want to eat? Carbs! And not just any carbs, in fact they don't like sugar and refined grains like white bread, it causes them to grow out-of-control in the most awkward places. No, they like the carbs that nature intended for them to get. Carbs from starchy tubers and fruits, tough plant cell walls, seeds, nuts, and even those found in honey. Non-starch polysaccharides, oligosaccharides, resistant starch, arabinogalactin, or whatever the form--we need it. Human Breast Milk contains over 100 different forms of Human Milk Oligosaccharides (David E Mills 'A Milk-Oriented Microbiota (MOM) in Infants—How Babies Find their MOMs'; photo credit from slide 11).  Babies who get none of these prebiotic substances fail to thrive. All formula for non breastfed babies will contain some form of prebiotic, usually a galacto-oligosachharide.

Lack of a suitable fermentable substrate is bad for babies, but why should an adult care? Especially an adult FAT BURNING BEAST? If you don't eat sugar (or many carbs) why should you care if you have microbes who ferment them?

A recent paper examined this question:
Colorectal Carcinogenesis: A Cellular Response to Sustained Risk Environment

Luckily, the words Red and Meat didn't appear in the title, otherwise it would have already been spread across the airwaves and summarily dismissed by the low carb warriors. This paper looks specifically at what happens at the gut level in people who willfully, or otherwise, disregard the feeding of their gut flora.

Guess what happens? We become SUGAR BURNING BEASTS! You read that right--the cells which line our intestines, the ones that prefer to burn indigestible carbohydrates, must now burn sugar. Roly Poly, daddy's little fatties! Bet they're gonna be a man some day.

"In normal healthy large intestine, butyrate is a preferred energy source. However, in the shortage of butyrate, attributed partly by "Western diet", glucose is substituted as the energy source for survival of these colonocytes. As they evolve to adapt to the new conditions, genetic manipulations are initiated with subsequent loss of function of critical genes and eventual loss of ability to undergo programmed cell death."

"Digestion of the major nutrients in the human small intestine is incomplete, especially that of complex carbohydrates. Humans possess only one intrinsic polysaccharidase, α-amylase, which can hydrolyse only one polysaccharide (starch). Dietary fibre consists principally of NSP which resists small intestinal enzymatic hydrolysis completely such that they pass into the large bowel quantitatively. There is also strong evidence that the ileal digestibility of starch is less than 100% and a fraction, depending on the nature of the food and an individual's characteristics, pass into the large bowel. This fraction is termed RS. The importance of NSP to colonic function is recognised. However, it is becoming apparent that RS may be as (or even more) important."

"Diets that are high in fermentable fibre, in particular RS, and low in fat and protein lead to an environment in the colon which is considered low risk for the development of CRC. Experimental studies in humans and animals have shown that this gives a colonic environment which is relatively high in SCFA and of low pH, leading to a low level of free ammonia and other basic cytotoxins. The mucosa itself is well perfused, giving high oxygenation, while the availability of SCFA spares glucose utilisation. There is strong evidence that O2 supply is critical for hepatic metabolism, especially glucose homoeostasis, and there is evidence also that the entero-pancreatic axis may be involved in CRC risk with high insulin and insulin-like growth factors being implicated. Animal and human studies suggest that fermentable carbohydrates improve blood glucose control so that it is possible that insulin may also be low in this scenario. Populations with a low risk of colonic cancer have been shown to have lower faecal pH than in higher risk groups"

'Hold on!', you say, 'We've been eating fiber for years! My Protein Bar alone has 15 grams of fiber!'

This is where we need to re-think our views on fiber. The term 'dietary fiber' is actually meaningless as far as our gut flora is concerned. What we need to be concerned with is prebiotic fiber. It doesn't take much for a manufacturer of health food to get a 'high in fiber' rating for it's processed crap-in-a-bag.

The following terms describe products that can help increase fiber intake:

• High fiber: 5 g or more per serving
• Good source of fiber: 2.5 g to 4.9 g per serving
• More or added fiber: At least 2.5 g more per serving than the reference food

According to this, 'high fiber' is only 5g in a serving. That's pitiful. A small green banana has 15-30g of resistant starch. A cup of cooked and cooled rice has 10g. It's very important we eat a variety of whole foods, as Dr BG says:

--feed with fiber (resistant starches, heirloom and native tubers, organic whole non-gluten grains, lentils, chana dal, legumes)

I'm glad she's come around, aren't you?

1. Fermented veggies made the ancient way with organic dirt-covered vegetables, ex. kraut, kvass, kim chee, kefir, etc. Read Sandor Katz.

2. Ancient heirloom potatoes, tubers, roots that are low glycemic index (or high if good insulin sensitivity) and ancient heirloom grains, legumes, lentils/dal that are low glycemic index (or high if good insulin sensitivity), prepared the ancient way (soaked, fermented, etc)

3. Soil-based probiotic 1-2 daily if not severely immune compromised (Bacillus licheniformis, Clostridium butyricum, etc)

4. Raw PS (potato starch) 1-3 Tbs + psyllium (if not allergic) 1-3 Tbs + high ORAC green powder (I like amazing grass, LOL) in 2 cups plenty of water

5. Exercise low-moderate intensity one hour daily continuously (10,000 steps) to move the gut/peristalsis and overcome broken myenteric musculo-neuro junctions

6. Avoid allergenic foods (corn, soy, gluten/wheat, dairy, nuts, egg whites, etc). Avoid GMO products and livestock/poultry fed GMO crops (corn, soy, etc).

7. Heal hormones and immunity -- take adrenal support, liver support, antioxidants etc (I use biocurcumin and berberine to combine with anti-microbials/anti-parasitics). This is particularly imperative for those with reactive hypoglycemia and BG crashes when they go longer than 3-4 hours between meals.

Optional
8. If the above fail, then you have more fastidious overgrowths and require 2-3 rounds of anti-parasitics/anti-microbials/anti-fungals.  See what worked for my family and I HERE.  If the above still does not fix SIBO, then consider mercury toxicity. Mercury saturates and kills microvilli in the small intestines and also disables enzymes including digestive enzymes.

(*hominids ate SGG small grass grains in the Paleo times fyi ~see Middle to Late Paleolithic: Neanderthals Consumed Grains and Legumes)

Guest Post: Tim (aka Tatertot)

The first step in Dr. BG's 7 step protocol is "Fermented veggies made the ancient way with organic dirt-covered vegetables, ex. kraut, kvass, kim chee, kefir, etc. Read Sandor Katz."

Fermented foods are a must for anyone serious about their gut health.  It is the first step you should get a grip on before proceeding with Dr. BG's 7-Steps Paleo* Gastro IQ SIBO Protocol. Eating a variety of fermented foods will ensure a healthy gut stays healthy and a troubled gut returns to it's healthy state.  Try to eat or drink something fermented at least once or twice a week, every day is even better!  

Fermented foods are a cornerstone of the paleo diet.  Despite the fact that fermenting food as a means of preservation was a neolithic invention, those living during paleolithic times ate loads of fermented foods...overripe fruit, rotting vegetation, decomposed meat, and the contents of animals stomachs to name a few.  Later, as man became more civilized, he learned to control this fermentation process as a means to ensure a steady supply of food during times of scarcity.  

Just about any food item can be fermented:  Beans, grains, vegetables, fruit, honey, dairy, fish, meat and tea.  Every culture has its favorites, from the very familiar European sauerkraut to the not-so-familiar Japanese Natto and Stinky Tofu.  The Inuit were very fond of fermented foods.  They would bury fish, fish heads, sea-mammal flippers, seal oil, and whole birds in grass-lined holes in the summer and dig them up during the winter and next spring.  Another method was to stuff a freshly killed caribou's stomach with sea-birds and seal oil and bury for several months.  

Fermentation in food processing is 'the conversion of carbohydrates to alcohols and carbon dioxide or organic acids using yeasts, bacteria, or a combination thereof, under anaerobic conditions.  Fermentation usually implies that the action of the microorganisms is desirable...The term "fermentation" is sometimes used to specifically refer to the chemical conversion of sugars into ethanol, a process used to produce...wine, beer, and cider.  Fermentation is also employed in the leavening of bread; in preservation techniques to produce lactic acid in sour foods such as sauerkraut, dry sausages, kimchi, and yogurt; and in pickling of foods with vinegar (acetic acid).' 


For purposes of gut health, we like to focus on fermentation processes involving lactic acid as these generally recognizable foods are easy and safe to make at home or can be readily purchased.  Lactic acid fermented foods include sauerkraut, kimchee, yogurt, kefir, and kombucha.  All of these foods, when properly prepared, will contain several strains of Lactobacillus, an important microbe for not only gut health but other bodily eco-systems as well.  

Image may be NSFW.
Clik here to view.An easy homemade sauerkraut can be made following the lead of Dr. BG and her children, with their famous Hot Pink 'Kraut!.  

Kefir, or fermented milk, is extremely healthy, tasty, and easy to make.  Richard Nikoley at Free the Animal has written extensively on the subject and in this blog, Richard tells you how to become and expert at making kefir.   Please read if you want to learn to make kefir...it's well worth it. 

Another great resource is the website of Sandor Katz.  Updated frequently with new recipes such as Raw Black-eyed Pea Miso Paste and Fermented Radish you will have no excuse not to try some of these amazing fermented foods, made in your own kitchen.  

In this article, Ann Marie Michaels aka CheeseSlave, gives you 8 Reasons to Eat Fermented Foods and great tips for getting started.

Traditional Russian Beet Kvass is easy and delicious.  We are told that "Beet kvass carries with it all the benefits of beets, marrying them with the benefits of fermented foods for a deeply cleansing tonic.  Rich in betacyanins – the pigments responsible for beets’ characteristic hue, beets possess strong antioxidant capacity with an ORAC value of 1,776 which may be why beets seem to help mitigate inflammatory states in the body which may contribute to cardiovascular disease, cancer and diabetes."  It is also probably one of the easiest fermented drinks to make.  All that is needed is a jar, water, and a beet.  Learn to love it!  



If you absolutely cannot prepare fermented foods at home due to space and time considerations, there are luckily numerous great products on the market that won't break the bank.  Kimchee, sauerkraut, yogurt, kefir, and kombucha are in almost every supermarket.  Look for fermented foods that have not been overly processed, pickled, or heated in ways that destroy the probiotic bacteria.  Also avoid overly sweetened products like sugary yogurt and kombucha.