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

Posted Nov 04 2012 12:37am

'...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 Article Free 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.
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