Babies and Mapping the Pollution in People: EWG's HUMAN TOXOME PROJECT

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.

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

Miracle
OceanLab, Above and Beyond

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

Ancient Transporters: HDL and LDL Lipoproteins Carry Precious Cargo

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.'

~~~~~~~~~~~~~~~~~

LDL Affected by Apo E Alleles

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.




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


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.







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


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 

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


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.

Alsheikh-Ali AA, Maddukuri PV, Han H, Karas RH.

J Am Coll Cardiol. 2007 Jul 31;50(5):409-18.

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] 

Love, Carnivores, Big Brain Evolution, and Mating Systems (NSFW)

Conjure One
'Endless Dream' [click to listen]
Courtesy Youtube.com

"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."

~From Antoine de Saint-Exupery

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).

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?