Saturday, October 27, 2012

Cancer: 50 Shades of F-cked Up?

Galena Officinalis (French Lilac or Goat's Rue)
Ancient remedy for polyuria
(sign of diabetes mellitus, frequent urine and sugar in the urine)

Original source of chemical that
was tweaked and patented into diabetes drug known as
metformin, which is emerging as the newest cancer drug
Photo Credit: Agro Semena

Hyperinsulinemia and Insulin Resistance: New Metabolic Markers for Cancer ?

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


--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
Photo credit: Oberlin Thesis [3]

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.

Photo credit: [4]

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.

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')].

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, 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


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]


Puddleg said...

And carbohydrate restriction causes PPAR-alpha activation, as does calorie restriction. So who needs Actos...
Some phytochemicals (e.g. naringenin) are also PPAR-alpha agonists.

I feel blessed to be in a country (NZ) where GMOs must be labelled and no-one ever buys them.

Dr. B G said...


You are so lucky to be in NZ! And shoppers are smart. Hopefully California may follow suit (fingers crossed)...

Yes -- CR and CR are fantastic (granted no micronutrient deficiencies) I think. I love many phytochemicals.

PPARs are neat. They are ancient but one of the newest according to research by Joseph Thornton (see below links). PPAR nuclear receptors are promiscuous and bind all sorts of fatty acids but I think especially those fatty acids that are particularly important for mammals to bear babies, store fat, create brain software+hardware, and efficiently burn fat for heat and extended energy.

In fact, per Thornton's analysis of the phylogeny and evolution of NRs, fatty acids are the agonists for ALL nuclear receptors. This says a lot for the vital importance of fats in our diet and how the avoidance of fats is ultimately detrimental on many levels. The toxins that are most detrimental are the fat-soluble ones, as well. Fats, fatty organs and fermented fats are the most nutrient dense foods and contain the epigenetic signals (HDACi, methyl donors, etc) for keeping transcription of the DNA healthy and strong, even transcending between past and future generations...


Dr. B G said...

[fresh spankin new]

[old but fascinating nonetheless]

Anonymous said...


Luv it.

Dr. B G said...


js290 said...

I thought lactate was produced from anaerobic metabolism (glycolysis->pyruvate->lactic acid). If the lactic acid is stacking up, they may not have trained their metabolism to use lactic acid as a fuel (cori cycle).

Why We All Don't Get Cancer -- Sloan-Kettering

Dr. B G said...

js290-- UR THE BEST!! The sloan-kettering link is so provocative. 'We gave up the ability to eat as multicellular creatures...cells have to be told how much to eat everyday...10 hundred trillion cells will starve to death unless they communicate and work as a social organism to...parse out nutrients that we share as a host.' BRILLIANT!

Corrected the brain fart-- thanks! ;)

Actually metformin is deploringly safe compared with drugs that directly inhibit mitochondria or raise insulin (statins, insulin, sulfonyureas) that poison every American in the conventional medical system... I've heard of only one single case of death vaguely associated with metformin (in a hydrocodone/acetaminophin liver failure patient -- both Tylenol and liver failure are independently associated with lactic acidosis). On the other hand at every health institution I've been, there are several cases of statin related death or morbidity (multi-organ failure) despite rigorous institution liver monitoring. Lactate is never monitored because the only time high levels may cause problems is in hypoperfusion states (hypoxemia) but I think it may on the rise with the chronic inflammation that people seem to be experiencing related to carbs and IR -- diastolic heart dysfunction (even athletes), high-fructose corn syrup, grain-related anemia and thiamine deficiency, epidemic hypothyroidism, infection/PNA and other reasons for hospitalization, blah blah.

The Cori cycle finishes metabolism by metabolizing lactate to glucose (gluconeogenesis). Metformin blocks gluconeogenesis and lactate burning... in the liver (60%) and kidneys (30%) so dysfunction of these organs compounds hypoperfusion in the rare, rare cases of toxicity.

Dr. B G said...

(love love love Warburg and glucose shifting in cancer proliferation)

Sataran said...

Dr. BG, I've seen this being done by people suffering from cancer. And it's all with good intentions. But it's not gonna help those with gastrointestinal/colorectal cancer. The issue here is that a ketogenic diet will actually evaporate mucins and secretory IgA from your digestive tract. In fact, you see this right away if you restrict carbs: this is one of those glucose deficiency symptoms that PHD talks about. When I read about possible susceptibility to cancer for zero carbers due to mucin deficiency, I didn't quite know what to make of it. But PHD is right: it's not just cancer but infections and autoimmune diseases. Ketosis has an immediate leukopenic effect upon starting. Anyone who doesn't know this hasn't seen blood tests. Such people end up developing either immunodeficiency or autoimmune diseases down the road. Cancer, also, due to the association with H.Pylori.

In fact, I think the late Neil Grove who passed recently from a relapse of colorectal cancer may have died from that exact pheonomenon: the mucin defiency that culminated in cancer returning. He was supposedly in remission. Of course, for other types of cancers, you need to balance that with the benefits you're expecting. But it's very hard to justfiy ketosis unless you're dealing with neurological diseases like epilepsy.

Dr. B G said...


You know I have heard Paul Jaminent blog often about 'mucin deficiency' but I'm not clear what he means by that and the science behind it. Paul is good so I'm sure there are studies but I havent had the chance to review yet.

For FUT2 secretors, the microbiome utilizes secreted glycans like fucose and there is this dynamic interplay where the biome INDUCES fucosyslation and more fucose to be 'grown on the lawn' of our microvilli. Granted the biome exists.

i believe you are very correct to suspect that these glycans and induction does not incur in VLC diets. I have the same criticisms. Actually I have quite a few if you've read the post called Paleo De-Mything.

My precise probs with VLC and ketosis are not limited to the below:
--low mag
--heart irregularities and arrhyhmias that go with low mag
--adrenal depletion
--high cortisol
--belly fat and sarcopenia go with high compensated cortisol
--high adrenaline to maintain BG
--insomnia with low mag and high adrenaline
--low thyroid and high RT3 and metabolism of a ROCK
--digestive issues, extinction of butyrate producers UNLESS EATING SOIL or SBO probiotic