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?

Mitochondria: Fuel, Fluxxx and Heat (NSFW)

Buddha Bar (Sex Lounge)
Credit: Youtube.com

Fuel and Fluxxx...

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

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

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





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



CALORIES IN  ≠  CALORIES OUT

...we are not neat bomb-calorimeters, but open, conserved, networked metabolic and energy systems...

Photos credit: [2].













The Evolution of Body Heat?

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


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

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

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

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






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

Many obesity researchers appear to forget these multiple evolutionary and hormetic factors in their Big Pharma funded, tenure-track equations. One did not (though partly Joslin funded which is Big Pharma).


In a Nature article, Tseng et al discuss mechanisms to find a drug target to increase cellular bioenergetics and energy expenditure as an anti-obesity strategy [2]. (But... Drug targets are always silly, no?) They discuss PPAR-delta, AMPK and several other pathways with potential promise.  A succinct explanation of how mitochondria produce energy on demand by harnessing the energy from the formation of water in the cellular bioenergetics of mitochondrial metabolism of fuel is provided. They define bioenergetics as the 'Studies the flow of chemical bond energy within organisms. In a living cell, the principal reactions of fuel metabolism take place in the mitochondria, where food energy is released,oxygen is consumed, and water and carbon dioxide are produced.'

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

CO2 1/2 O2  =   one mole H2O (~18 grams water = 3.5 teaspoons)  =  286 kJ

Photo Credit: The Art, Mystery and Science of Water

Fuel Efficiency of Our Mitochondrial Cellular Respiration

With cellular respiration, instead of an enormous, exothermic explosion (like a hydrogen bomb), the electrons and protons are added step-wise on a gradient known as the electron transport chain (ECT) in plants and animals.  A biological mitochondrial 'battery' is created with the 'anode' on the inner mitochondrial membrane side and the 'cathode' on the other.  Heat is energy released when oxygen is the final proton acceptor and coupled to the enzyme (F1F0-ATPase) that forms ATP, the universal currency of cellular energy in the body. When the protons fall across the proton channel, ATP is formed.  We use ATP as fuel every minute every day for all cellular work, then recycled back to ADP.  In one day, it is estimated that our mitochondria may produce our own weight in ATP [5].

Efficiency of the theoretical transfer of energy from oxidizable fuel to ATP and heat is pretty darn good: 39% ATP and 61% heat [5]. Mitochondria are energy rockstars. Obviously many biolgical factors determine true efficiency: iron status (cytochromes are composed of heme), ubiquinol, oxidative and inflammatory state, thyroid, HPA axis function, hormones, etc.

Plants (chloroplasts) get 3-6% efficiency from transfer of solar energy to the energy bonds of plant starches and fatty acids. Particular C4 plants can get 7-8% (sugarcane) and one super cyanobacteria strain Chlorobaculum tepidum achieves 10%. Various modern fuel efficiencies are approximately -- for coal (~20-30s%) and solar (20%). Photo credit: [5].



References

1. Climate change and seasonal reproduction in mammals. Bronson FH.Philos Trans R Soc Lond B Biol Sci. 2009 Nov 27;364(1534):3331-40.

2. Cellular bioenergetics as a target for obesity therapy.Tseng YH, Cypess AM, Kahn CR. Nat Rev Drug Discov. 2010 Jun;9(6):465-82. [Free PDF here]

3. The Hot Brain: Survival, Temperature, and the Human BodyCarl V Gisolfi, Francisco Mora Teruel. MIT Press (Bradford Book), 2000. [Free SCRIBD text here]

4. Fungi and the rise of mammals.Casadevall A. PLoS Pathog. 2012 Aug;8(8):e1002808.  [PDF]

5. http://highered.mcgraw-hill.com/sites/dl/free/0073525502/930160/mad25502_ch08.pdf

Phat Fat Mitochondrial Energetics: Mobilization v. Accumulation

Adipose is Alive

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

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



All Organs Sync For Survival

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




Humans Killed for Fat

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




Fat Yields the Most Energy in Human/Mammalian Energy Systems

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

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



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


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


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

Prior animal pharm: Palmitate Utilized Between Meals




Mitochondrial Medicine

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

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

...FLUNKING your human SMOG TEST.

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

Phytanic Acid (Red Meat, Dairy, Seafood): Binds PPAR-α and RXR

'...Like all things come from the sun'
referencing all the food at the table,

daughter Natalie

ATB Sunset Girl

Courtesy: Youtube.com

Food, Sunlight and Nuclear Receptors

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

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





Phytanic Acid Generates Carnitine

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

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

Do butter and bison do a body good?

YESSSSSS.




Chlorophyll Is Biotransformed into Phytanic Acid by Fish and Mammals

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



Evolutionary Medicine: Mitochondrial Dysfunction

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

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





From Bacteria 4.5+ bya To Mitochondria

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

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


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





Health and Food Connection

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

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

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

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

Phytanic Acid (Cheese, Butter) Human RCT

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

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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