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]

Saturday, October 13, 2012

Anti-Stress, Growth, Healing, Well-being and Oxytocin -- Recent Research and Hypotheses

View from a walking 
path in Century Park
Shanghai, China

Hunter's Trance Link to Oxytocin?
'He [Edward O. Wilson, Harvard evolutionary biologist] called this state the “hunter’s trance”, connecting it to the anecdotal reports of many hunters and argued that the ability to enter such a trance is connected to humans’ enormous evolutionary success.  When they left the forest for a life on the savannah, hominids who entered the “hunter’s trance”  were able to learn the habits of carnivorous predators as well as the animals they hunted.  Those who didn’t have the ability were most likely to get eaten...

Enter oxytocin, a hormone best known for starting childbirth and inducing lactation.  It turns out that it does a lot more than that.  It is secreted at the base of the brain, in the hypothalamus, and the entire nervous system is sensitive to its effects.  Oxytocin production is stimulated by estrogen, but it is not a female-only hormone, because men produce it as well.

Oxytocin lowers the heart rate and blood pressure, quiets the brain’s fear centers, and suppresses the production of stress hormones.  Childbirth begins with a flood of oxytocin that contracts the uterus and stimulates milk production.  Nursing stimulates the production of more oxytocin, as does the sight or sound of the baby.  New mothers will even produce oxytocin at the mention of their baby’s name or upon seeing a photograph.  It’s oxytocin that puts new mothers in the brain-addled state that allows them to spend hours gazing at their babies, finding new and fascinating details in their faces and tiny bodies.  The equivalent of a “hunter’s trance” in the mother ensures survival for the otherwise helpless infant.'
Author /Blogger Nancy Casey

Chillout Music Love Chapter 2
Scenes of beautiful natural scenery, goddesses 
and other gorgeous creatures of Mexico

Biophilia, 'Lover of Life'

E.O. Wilson the Harvard evolutionary biologist has written and spoken about many topics in regards to our evolutionary past and misalignments with the modern age (de-forestation, insufficient exploration of our natural world, excessive wheat and grain fields replacing natural habitats, etc). One topic I like a lot is based on a term that he coined biophilia, 'lover of life' because this type philosophy sums up a lot of my current thoughts on modern pharmaceuticals and the problems with the entrenched disease-model which tries to match a  (drug, synthetic toxin) to every symptom on a growing list of symptoms modern men and women inevitably accrue with the reliance on perhaps what is an unnatural human diet and lifestyle (consistent stressors, refined grains, GMO crop products, neurotoxins, EDCs, environmental pollution).  For every little sniffle, cough or stomach ailment, a conventionally-trained practitioner will happily prescribe antibiotics without reserve.  With each new study on the gut, immunology and their connections to health, it verifies to me that antibiotics are indeed fulfilling their definition... anti-life or against-life. Antibiotics eradicate both the good and bad bacterial species, leaving the few, hardier pathogenic yeast and bacteria species to thrive in cleared out niches -- to putrify and overgrow in the small (SIBO) and large intestines.. Naturally they can  fester in the other orifices and compartments (e.g. sinus cavities, v*gina cavities, oral cavities, etc) and/or translocate to internal organs. Worse, the 'good' microbiota may never ever be restored or replaced according to some new data, despite even use either of probiotics and fecal transplants.  Pandemic food allergies, skin conditions, chronic illnesses, autism and autoimmune diseases continue to expand despite so-called advances in pharmaceutical medical care.  Probiotics, PRO-LIFE, are great and pro-biotic foods are even better (dirt-containing, traditionally prepared fermented vegetables, meat, seafood, fowl (kiviak), kopi luwak, beans, buckwheat, dairy, etc).

Root Transplant:  Ex-Pat Living in Shanghai, China

We've lived now in Shanghai for one year after moving from California and the transition was not smooth (for me; kids were only disgruntled for a few months).  Displacement was a humongous stressor and I went straight into adrenal dysfunction for 6 long weeks which I've written about earlier: ADRENALS ONE AND TWO.  When you tend to be 'rigid' I think it takes quite a bit longer to adapt and figure out the terrain... Do you how a gardener can improve success of transplanting a plant by dusting  powdered GA (gibberillic acid) on the roots prior to transferring?  Before coming here, I wish I had me some magic rooting dust...

Anyway after having the f-cking sh-t kicked out of my mojo, life turned around, this January when we came back. I actually tremendously missed our new space, friends and our adventures.  Subsequently, I became busy whilst tending to the new root system... resuming and enjoying a transformed life (China stuff... family activities, reading, expat friends, working out, cooking, yoga, tai chi, kickboxing, sprint tri's). 

Sorry for the absence on the blog! I did really miss it...

Oxytocin: You don't have any when you are depressed

In my little n=1 self experiment I can probably attribute a couple of super vital things that factored into re-establishing allostasis.  Last fall my children brought back a high maintenance kitten Angel.  She was about a few weeks old and had to be hand-fed every 2-3 hours. I believe she raised my oxytocin.   We had to give her up to a foster home eventually due to anaphylactic like allergy reactions that my daughter ('N') used to have (instant asthma, face and eye swelling). However, this past spring my children surprisingly appeared to have grown out of most of their cat dander allergies, a discovery made after fostering 'Sylvia/Seal', another kitten!  Melissa McEwen (Hunt Gather Love) told me a reassuring story once how she had overcome cat dander allergies after her gut was healed.  I believe we all enjoyed better gut health, gradually since the Paleo diet, and for 'N' it was possibly related to how 'N' lost the last of her molars which were riddled with mercury amalgam (we are all mercury-free now).  One of their classmates found a box of kittens that was left by their international school in March, and guess what? Yes. They brought them (all) home. And raised my OXYTOCIN  ;)  *haa ahaaha*  

They fostered two kittens initially from the remaining litter. After two nights of round the clock feeding, as well-intentioned as they were, they could NOT for their life wake up to syringe- and bottle-feed on schedule).  My oldest daughter found a home for one kitten after about one week and continued to provide excellent alloparenting of the second one, 'Sylvia/Seal'... See end for photoalbum...

Oxytocin is low in many chronically ill conditions according to studies (chronic pain, depression, autism, schizophrenia, surgically menopausal rodents with heart disease).  Certain factors (sometimes at certain developmental stages) inhibit oxytocin production: touch deprivation, chronic pain, alcoholism, female estrogen deficiency.  

Many factors can influence and positively affect oxytocin secretion... exercise (even in surgically menopausal rodents with heart disease; in humans any kind works but perhaps not until exhaustion), yoga, positive social contact, sex/climax, massage, having an attached pet gazing at you (see refs), you gazing at an attached pet, baby-at-your-boob, etc. 

What are the effects of oxytocin per recent evidence [cute, source:]?

11. Oxytocin promotes attachment
10. Oxytocin solidifies relationships
9.  Oxytocin eases stress
8.  Oxytocin crystallizes emotional memories
7. Oxytocin facilitates birth and breastmilk
6. Oxytocin boosts sexual arousal (may even revive dead  d*cks and v*ginas)
5. Oxytocin decreases drug abuse and cravings (alcohol, cocaine, narcotics, ecstasy, meth, cannabis, ??FOOD??!)
4. Oxytocin improves social skills
3. Oxytocin triggers protective instincts
2. Oxytocin induces sleep
1. Oxytocin fosters generosity

Animals Release Oxytocin from Everywhere

Oxytocin an ancient neuropeptide conserved across the animal kingdom. It is released and targets every important organ and site for the important processes: living, love, rest, digestion, immunity and reproduction. Emerging data that one of the target organs for oxytocin release and modulation is the gut and integrity of the intestinal lining which I think has great implications for resolving health issues and optimizing health. Any model for intestinal permeability uses a major stressor (physiological, pathological, pharmacological, psychological) on the experimental animal such as LPS (toxin from a microbial outer membrane), acid, large dose n-6 pufa, mercury, exercise stress, heat stress, physical isolation (particularly extended separation of babies from their mother). What occurs? Immediate and irrevocable micro and macroperforation (ulcers) of the gut.

Did you give and get your hugs today (including e-hugs)? Have you stroked your beloved feline or canine or children or neglected significant other? That's good...  According to prolific oxytocin researchers Peterssen and Uvnäs-Moberg, oxytocin is not only extensively interconnected to the cortisol, noradrenaline and several neurotransmitter systems to produce long-term effects but may be highly correlated to resilience to stress, growth, healing and well-being.


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Horm Behav. 2009 Mar;55(3):434-41

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Photoalbum: Our Oxytocin-Inducers, the Kittens We Fostered

 'Twix' (Day 3-7?)... Alloparented (by 'N') for one week 
before finding a permanent home

Twix's sister, 'Sylvia/Seal' (Day 5-7?)
Alloparented for nearly 7 weeks

Initially, bottlefed for a few weeks. Later we
weaned her onto softened 
paleo/ancestral food (Orijens),
raw egg yolks, pork belly,
and occasional chicken liver bits

Bottle fed every 3 hours, pooped-pee'd every 3 hours, 
loved, gazed at and stroked EVERY WAKING MINUTE ;)


Seal/Sylvia (4-5 wks old) on right... 
Another feline Xiao Bai (Little White, left) rescued by
my neighbor who found him in a box at Century Park
whilst walking her dog. We get to babysit catsit Xiao Bai
when she's out of town on business.

Tuesday, October 9, 2012

Random Thoughts on Migraine Headaches, Oxytocin, and Mind-Reading

Migraine Headache Syndrome

Definition: 'A migraine is a throbbing, unilateral headache that is 
often associated with nausea, vomiting, photophobia, or an aura
~i.e., a transient disturbance of vision or of various aspects
of neurological function. More than 10% of Americans
suffer from migraines, with the prevalence in women
being about 3 times that in men. The cause of migraine is
not well understood, although it is thought to be due in
part to vasoconstriction followed by reactive vasodilatation.'
Nutritional Medicine textbook, Ch 136, Dr. Alan Gaby MD

Disclosure -- I'm not afflicted by headaches often (unless my child flunks a math quiz) and, never, migraines, yet I've met a ton of people with migraines. Many of my friends experience migraines or used to (half of my favorite gal pals and guy friends). Certain phenotypic characteristics and 'gifts' are inescapable IMHO that I have observed in these individuals: extreme intuition, sometimes clairvoyance, approachability, and super-powered senses (smell, sound, sight, sensory stimuli, barometric pressure, mind-reading).  Additionally, migraineur patients, acquaintances and friends have told me that random people just enjoy blindly going up to them and spilling their entire life stories.  (No one does that to me) I think that is notable.  What do you think of your migraineur family or friends?  I'd like to hear other perspectives on this...

These pals who suffer headaches are special to me. They read my mind and I don't need to talk or articulate...wish I could marry them (...just kidding).  Some I speak to rarely like Patrik V. who runs, yet before he has said things and I'll think 'wtf exit my head.'  When some paleo friends first convened, he reported that he had once suffered incapacitating migraine headaches since age six (hiding under tables whilst his mother couldn't find him for hours) until he serendipitously discovered the headache-banishing benefits of the grain-free and dairy-free paleo diet. That's a common story in paleo-land.

Migraine headaches are a P-A-I-N and that is a distinct understatement if you talk to any patient who suffers from migraines which are described as debilitating to the point of impairing function leading to lost quality of life and days of work, family, and leisure time. 

Takano and Nedergaard (see above photo) describe a migraine headache as a sweeping change in electrical depolarization across the brain which is followed by an extended period of neural torpor or suppression. They call it cortical spreading depression (CSD), stating 'Written accounts of migraine are nearly as old as writing itself. Descriptions of headaches, dating to roughly 3000 BCE, have been found in the ruins of the ancient Sumerian civilization.' Perhaps like narrow jaws, occclusions, and tight dental arches (per Weston A. Price), mass migraines and brain pain initiated with the advent of agriculture and the ubiquitous introduction of refined grain carbohydrates into the prehistoric human hunter-gatherer diet?  Perhaps migraineurs have indeed a set of gifts that were naturally selected for despite the outstanding pain and discomfort? 

Evolutionary Advantage of Migraine Headaches?

Harvard neurology professor Loder wrote a Cephalalgia review and presentation 'Migraineur in the Interictus' suggesting evolutionary benefits of the development of the characteristics seen in migraineurs.  Highly responsive nervous systems that detect sensory stimuli at low inputs definitely would be traits worthy of evolutionary selection and retention in the progress of human civilization.  'Hearing the approach of enemies, being eaten by a saber-tooth tiger or detecting or avoiding spoiled or adulterated food' might have been compelling pressures that were affected by the communication of low or nearly negligible levels of sensory information in the environment, plants, people, animals and other living creatures. 

Ancient Treatment for Migraine Headaches: Hole(s) in the Head, Trepanation

In ancient times, it is hypothesized that headaches and migraines were treated with trepanation (boring a hole or holes into skull to release the pressure and pulsation). If I had severe head pain I'd seriously consider but, yeah, I need a hole in my head like a new Jimmy Choo fake purse!  Several lines of evidence relating to archaeological remains report that clinical outcomes and survival were astonishingly decent:  HERE.

Photo credit: Asylum Science

Our Brains are Still Evolving

I'd wildly speculate that the ancestors of individuals with migraines had unique abilities which allowed them to thrive in certain conditions requiring sensitivity to environmental changes and influence in group cooperation, gaining trust, tight social networks and perhaps weather/storm predictions.  In is not a coincidence that the individuals with migraines (if not completely unfunctional) are frequently leaders in their little (or big) so-called tribal units, in my shallow awareness.  NY Times science writer Nicholas Wade wrote in The Twists and the Turns of History, Our DNA, 'The political scientist Francis Fukuyama has distinguished between high-trust and low-trust societies, arguing that trust is a basis for prosperity. Since his 1995 book on the subject, researchers have found that oxytocin, a chemical active in the brain, increases the level of trust, at least in psychological experiments. Oxytocin levels are known to be under genetic control in other mammals like voles.' He has written quite a bit more extensively that our sapien brains grew in size for the machinery necessary to handle intricate, complicated and peaceful social complexity.

Super Perception, e.g. Mind Reading

Many new studies highlight the salient features of oxytocin for perception, feedback, empathetic accuracy and affiliation reward reinforcement. Two recent human controlled trials showed a demonstrated increased gaze focus and the ability to visually read and interpret facial emotional cues after oxytocin administration (some authors called it mind reading). From one of the researchers Lerknes explained "We found that oxytocin intensified test subjects' awareness of the emotions present in the photos. Faces expressing anger stood out as angrier and less happy, and correspondingly, faces expressing happiness were happier."  Graded results occurred -- "It turns out that those with the lowest aptitude for judging emotional expression properly -- that is, those with the poorest scores during the saltwater round -- were the ones who showed the greatest improvement using oxytocin."

Author Nancy Casey hypothesizes in a post 'Oxytocin Gaze' that human hunters emulated carnivorous predators in their meticulous gaze and visual assimilation of the terrain. She posits that the same gaze that is possibly related to oxytocin which maybe employed by mothers in surveying and tracking their newborn babies, meeting their needs, and ensuring their survival in the face of vast helplessness and under-maturity.

Modern Conventionally-Schooled Medical Treatment of Migraines:  Overwhelmingly Uneffective

One out of every six women experiences migraine headaches of some form in America. The population prevalence is 11.7% and comparatively higher than the insane diabetes epidemic in adult Americans (11.3%, 2011 data). Migraine headaches are no small statistic.  With a wide gender divide, women have triple (17.1%) the incidence as men (5.6%).  It's also no coincidence women have more oxytocin than men as well; for us it can regulate love, lust, labor, lactation, and maternal caregiving.  

Funny thing is that if migraineurs have mega mindfulness and their oxytocin is messed up by being either super fluctuating high/low or inappropriately inconsistent or unstable levels  (like blood glucoses in the reactive hypoglycemia model), then it may explain why oxytocin given as a I.V. drug it was 100% successful in halting immediately two cases of refractory migraines seen in an ER unit and in a prospective human study where oxytocin was provided (intranasally, ya know, like cocaine) by Yeomans and Jacobs, Stanford pain researchers, to refractory patients was associated with halting 50% of migraines and reducing 27% (total, 77% better) compared with 11% of placebo. 

My observations are that migraine prevalence and occurrence are unchanged despite great 'advances' in pharmacology (abortive triptans and preventive pharmaceuticals), diagnostic science and understanding of the physiology of this condition.  Like essential hypertension and the great majority of textbook medical conditions, the underlying pathophysiology are still elusive and undetermined, despite wonderful and fantastic fMRI and genetic sequencing techniques. A recent review confirms these considerations, the prevalence of migraines is still the same as 15 years; absolutely no improvements despite the triptan class of medications (which can abort a migraine in 20-60 min 50-70s%, versus placebo 17-40%), preventive therapy (modification of neurotransmitters and vasculature; BP drugs, antidepressants, anti-epileptic drugs), and the standard 'migraine trigger avoidance diet' of avoiding the 5 C's (cheese chocolate coffee coke citrus).  Pharmaceuticals and ridiculous wheat-based diets fail long-term.

What Does Work Long-Term for Migraines: Paleo/Oligo-Antigenic Diet (OAD)

Some of oxytocin's target organ sites include the brain, the gut and thymus. All are organs responsible for the enormous function of homeostasis, immunity and controlling inflammation. It is no wonder that the brain cannot function optimally in isolation from the gut, and no wonder at all that all things that promote healing of the gut can improve migraine headache prevention and amelioration.  

The medical literature from the last 30-80 years in fact identifies wheat (78% Grant, Lancet 1979), cow milk (37%), other cereals, cane sugar, yeast, corn, citrus, and eggs as top migraine-inducing factors.  Identification and elimination of food antigens is key to healing the gut. Sealing of the damage and microperforations by altering intestinal permeability is secondary and vital.  The paleo/ancestral diet and oligo-antigenic diets maybe best with focus on individual susceptibilities and immuno-endocrine optimization. Similar to the results obtained by Frasetto et al in their 10-day paleo experiment for reversal of pre-clinical hypertension in overweight patients, the researcher Grant (Lancet, 1979) in a seminal study looked 60 migraineurs with food antigen immunoreactivity. After only 5-days of an elimination diet (pseudo paleo) she reported 'When an average of ten common foods were avoided there was a dramatic fall in the number of headaches per month, 85% of patients becoming headache-free. The 25% of patients with hypertension became normotensive.'

Dealing with circulating antigen-antibody and immune complexes that are formed in the body when food antigens and microbial peptides (cell walls, DNA, cellular contents, junk) interact with immune system may help permanently to achieve and to maintain disease resolution, I believe. Two recently published human RCTs (Aplay et al and Mitchell et al) showed that by eliminating foods linked to high food-antigen related immune globulin IgG titers, an association for statistically significant reductions in migraine headaches occurred at 6 weeks and 4 weeks, respectively.  Heal...Seal...Deal...


Takahiro Takano, Maiken Nedergaard
J Clin Invest. 2009 January 5; 119(1): 16–19. 

What is the evolutionary advantage of migraine?  [Free PDF CLICK]
Loder E.
Cephalalgia. 2002 Oct;22(8):624-32. Review. [Elizabeth Loder MD]

Marcelo C. A. Rodrigues et al.
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Leknes S, Wessberg J, Ellingsen DM, Chelnokova O, Olausson H, Laeng B.
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Qiao Y, Winkle C, Frey W. Nasal Oxytocin for Head Pain. 13th World Congress on 
Pain, 2010.

Yeomans DC, Pascual CR, Jacobs A, Angst MS, Jacobs D, Winkle CC, Frey WH. 
Intranasal Oxytocin for Craniofacial Pain. Annual Meeting of the Society for 
Neuroscience, 2009.

An Integrative Model of Migraine Based on Intestinal Etiology
David McMillin, MA  [Oligo-Antigenic Diet abstracts]  [Benefits of binding immune complexes or OAD abstracts]

Food allergies and migraine.
Grant EC.
Lancet. 1979 May 5;1(8123):966-9.

Pascual J, Oterino A.
Cephalalgia. 2010 Jul;30(7):777-9.  

Levinsky RJ.
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Alpay K, Ertas M, Orhan EK, Ustay DK, Lieners C, Baykan B.
Cephalalgia. 2010 Jul;30(7):829-37. 

Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention ofmigraine like headaches.
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Nutr J. 2011 Aug 11;10:85.