PUFA: because this wouldn’t be a Ray Peat inspired blog without at least one post on PUFA

“The polyunsaturated fats are universally toxic to the energy producing system, and act as a “misleading signal” channeling cellular adaptation down certain self-defeating pathways.”

-Ray Peat

So just in case there are people reading this who don’t know what PUFA are, PUFA stands for polyunsaturated fatty acids, these are liquid oils, they’re liquid because they unsaturated (in 2 or more places), these include sunflower oil, safflower oil, canola /rapeseed oil, hemp seed oil, flax oil, chia seeds, and of course the current darling of the health supplement industry, fish oil. These are the oils commonly called essential fatty acids (EFAs), calling them essential is virtually meaningless as its near impossible to entirely avoid consuming at least some of these (I’ve tried, it requires eating a super boring F.A.D. diet), There is evidence which suggests that it may well be better to seek to avoid PUFA, both omega 6 and 3.

In 1938, a biochemist William Brown volunteered to go six months eating an extremely low-fat diet. He consumed a diet of defatted milk and cottage cheese, sucrose, potato starch, orange juice and some vitamin and mineral supplements. His blood lipids became more saturated and their concentrations of linoleic and arachidonic acids were cut in half. He experienced an absence of fatigue, his high blood pressure returned to normal, and migraines he had suffered from since childhood vanished, his metabolic rate increased and he lost weight, his respiratory quotient increased suggesting greater carbohydrate oxidation, lower respiratory quotients are associated with diabetes. The diet produced no deficiency, and likely corrected a PUFA excess. Six months on a specially prepared laboratory diet, no deficiency, if these fats are essential they’re essential in such tiny amounts that its almost meaningless to call them essential.

Hold on, are you saying we should avoid essential fatty acids?

Yes. “Essential” fatty acids are essentially toxic in warm-blooded oxygen respiring non-hibernating animals.

If you look at where the PUFA are found in nature you’ll find them associated with cold temperatures, for example in fish like sardines swimming around in icy-cold arctic waters, if the sardines had saturated fats they’d probably be solid and inflexible in such cold waters, fish found in the Amazon have highly saturated fats, low in PUFA. The other place you find PUFA in abundance is in nuts and seeds that have to germinate in cool spring after freezing winters. It has been shown that plants can vary the degree of the saturation or unsaturation of their fats in response to the climate they are grown in, soya grown in a tropical environment will have less PUFA than soya grown in a temperate environment (Wolf 1982), this is also why the tropical oils, coconut and palm are so highly saturated. A human being is a walking tropical environment, the fact that we don’t produce omega 3 and 6 PUFA might just be a good thing.

But, but…they’re called essential fatty acids, surely there must be studies that show they’re essential?

The studies that claim to demonstrate the essentiality of PUFA, were carried out around 1929, in rats, further at this time a number of vitamins were unknown, including B6, the need for zinc and some other trace elements was also unknown, Ray Peat has pointed this out, and further shown that the PUFA deficient rats demonstrate a higher metabolic rate and so would require greater amounts of these vitamins an minerals, the PUFA fed rats had lower metabolisms and so could survive on deficient diets. Further in experiments in the 1940’s the “fat deficiency” disease was cured with supplemental B6.

But, there’s thousands of studies in humans showing that fish oil is beneficial, that must mean its essential?

The vast majority of those studies are terrible, there is no adequate control group, typically one group are given fish oil whilst the other are likely eating a diet high in omega 6 PUFA, so yes the fish oil can produce some anti-inflammatory effects, but to really get an idea of what’s going on you’d need an additional group eating an essential fatty acid deficient diet (no omega 3 or 6), such studies are lacking although there are some indications that “essential” fatty acid deficiency produces less inflammation than fish oil supplementation as shown in this study in rats (Ling et al. 2012). Just because a study demonstrates an apparently beneficial pharmacological effect of fish oil does not make fish oil an essential nutrient, given the high intakes of omega 6 oils and their pro-inflammatory effects some short term benefit to fish oil is not surprising, but a similar anti-inflammatory immune suppressive effect can be produced from x-rays, if someone is presenting with chronic inflammation it might just be better to recommend the use of anti-inflammatory substances such as aspirin or herbs such as Salix alba which can inhibit COX and LOX enzymes preventing the formation of inflammatory prostaglandins and suggesting that the person reduce their total PUFA intake.

Ok, so maybe EFAs have been overhyped a little, but why should we avoid them, they’re natural?

Earlier I mentioned about how PUFAs are found in fish and plants living at low temperatures, and are less common in warmer environments, there’s a good reason for this whilst the double bonds (unsaturations) make the oils more flexible they also make them more prone to oxidation, with the highly unsaturated EPA (unsaturated in 5 places) and DHA (unsaturated in 6 places) being the most unstable. Traditionally oils such as flax / linseed and fish oil were used in painting and for making varnishes, their unsaturation makes them react easily with oxygen, heat and light increase this reactivity, and under such conditions they polymerize and harden, great for painting, not so great in your body as they can degrade into lipid peroxidation products such as acrolein, malondialdehyde, hydroxynonenal, crotonaldehyde, ethane, pentane, and the neuroprostanes, many of these are implicated in range of disorders including general mitochondrial inhibition, Alzheimer’s (guess fish oil isn’t so awesome for your brain), and cancer.

PUFA (omega 3 and 6) inhibit pyruvate dehydrogenase, a key enzyme that links glycolysis into the Kreb’s (TCA) cycle (Da Silva et al. 1993). Inhibition of pyruvate dehydrogenase is known to contribute to the Warburg effect, the aerobic glycolysis characteristic of cancer (McFate et al. 2008).

PUFA breakdown products (acrolein, malondialdehyde, hydroxynonenal, crotonaldehyde) inhibit mitochondrial respiration (Humphries et al. 1998, Picklo and Montine 2001).

PUFA (including fish oil) promote cancer (Griffini et al. 1998), high DHA is associated with prostate cancer (Brasky et al. 2011).

Linoleic acid (omega 6) is required for carcinogenesis in some animal models (Ip et al. 1985).

PUFA suppress metabolism, this can be seen most obviously in the elevated metabolisms of lab animals fed an “essential” fatty acid deficient diet, (Burr and Beber 1934), “essential” fatty acid deficiency is associated with increased activity of cytochrome oxidase a fundamental mitochondrial respiratory enzyme (Kunkel and Williams 1951).

Animals fed “essential” fatty acid sufficient diets gain more weight than deficient animals (Rafael et al. 1988).

PUFA inhibit thyroid hormone activity (Clarke and Hembree 1990).

PUFA, LA(omega 6), ALA (omega 3), AA (6), DHA(3) all cause brain swelling, oleic acid (MUFA) and palmitic acid (SFA) do not (Chan and Fishman, 1980).

PUFA cause nervous system damage and impair learning, (Harman et al. 1976).

Neuroprostanes breakdown products of DHA are implicared in Alzheimer’s, they are found in cerebrospinal fluid of Alzheimer’s patients at higher levels than age-matched controls (Roberts et al. 1998).

PUFA, both omega 3 and 6 are involved in atherosclerosis, a study examining fatty acid composition of aortic plaques found a positive association between omega 3 and 6 fatty acids of plaques with adipose tissue content, no association was found for saturated fatty acids (Felton et al. 1994).

PUFA, both omega 3 and 6 impair lung function (Wolfe et al. 2002).

PUFA interfere with insulin sensitivity and increase diabetes risk, a study looking at safflower and fish oil found that both increased fasting blood glucose, the fish oil group had higher blood glucose (Borkman et al. 1989).

PUFA promote liver cirrhosis, saturated fats and cholesterol are protective against liver cirrhosis (Nanji and French 1986). In another study fish oil promoted cirrhosis and saturated fat was found to reverse cirrhosis, whilst ethanol administration was ongoing!! So if you’re going out drinking make sure to eat lots of butter and coconut oil (Nanji et al. 2001).

Omega 3 fats lower endurance in rats (Ayre and Hulbert 1997).

Fish oil lowered mitochondrial activity and increased oxidative stress in… Atlantic Salmon, wow fish oil sucks even for fish (Kjaer et al. 2008).

Omega 3 and 6, especially 3 impair wound healing (Cardosso et al. 2004).

I noted a study above suggesting that essential fatty acid deficiency produces less inflammation than omega 3 supplementation, part of this effect occurs through inducing the synthesis of mead acid an omega 9 family PUFA (unsaturated in 3 places), the presence of mead acid is typically considered to be a marker of “essential” fatty acid deficiency, even when no pathology is present, its synthesis is inhibited by omega 3 and 6 PUFA, there are some animal studies showing anti-inflammatory effects from mead acid supplementation, mead acid because it is only unsaturated in 3 places is more stable than EPA or DHA (Yoshida et al. 2003).

There’s good evidence that PUFA especially the longer chain highly unsaturated AA and DHA accumulate with aging (Tamburini et al. 2004, Nourooz-Zadeh and Pereira 1999).

PUFA shorten lifespan, a number of animal studies show that the degree of unsaturation of tissue fatty acids corresponds inversely with maximum lifespan, i.e. eating lots of “essential” fatty acids will shorten your life (Bajra 2004). Naked mole-rats display unusual longevity for a rodent of their size they live around 28 years similarly sized mice live only 3-4 years. Mole-rats have low DHA (2-6%) in comparison to mice (27-57%), this low DHA means they are less susceptible to peroxidative damage (Mitchell et al. 2007).

In a study in Italy a high PUFA to saturated fat ratio was found to increase all-cause mortality (Solfrizzi et al. 2005).

So in summary PUFA inhibit metabolism, promote cancer, atherosclerosis, Alzheimer’s, diabetes, contribute to alcoholic liver disease, make you stupid, and generally kill you slowly, you might be thinking that’s not so bad, but wait it gets worse…. Much worse….

A recent study suggests that PUFA contribute to… male pattern baldness, yes prostaglandin D2 inhibits hair growth and is found in higher levels in bald men, its derived from Arachidonic acid (Garza et al. 2012).

I know its difficult to believe fish oil isn’t super-awesome, the stuff’s freakin’ delicious, every time I walk past a health food store it takes a herculean effort of will not to run in and eat a whole bottle of fish oil capsules, those things taste better than gummy bears. Weirdly cats don’t seem to like fish oil, tried feeding a cat some fish oil and she looked at me like I’d lost my mind, cats really like butter though, weird.

But we need essential fatty acids to have flexible cell membranes.

HUMBUG!! There’s likely no such thing as phospholipid bilayer membranes.

I’ll deal with the cell membrane nonsense in a later post.

YO-HO-HO-HO, I’m off to drink a barrel of rum, and eat a slab of butter (don’t worry I’m not serious, coconut oil is obviously the better choice, it has a higher saturation index, lower PUFA).

References

Ayre KJ, Hulbert AJ (1997), Dietary fatty acid profile affects endurance in rats, Lipids, 32(12), pp. 1265-1270.

Bajra G, (2004), Free radicals and aging, Trends Neurosci, 27(10), pp. 595-600.

Borkman M, Chisholm DJ, Furler SM, Storlien LH, Kraegen EW, Simons LA, Chesterman CN, (1989), Effects of fish oil supplementation on glucose and lipid metabolism in NIDDM, Diabetes, 38(10), pp. 1314-1319.

Brasky TM, Till C, White E, Neuhouser ML, Song X, Goodman P, Thompson IM, King IB, AlbanesD, Kristal AR, (2011), Serum Phospholipid Fatty Acids and prostate cancer risk: results from the prostate cancer prevention trial, Am J. Epidemiol, doi: 10.1093/aje/kwr027.

Burr GO, and Beber AJ, (1934), Metabolism studies with rats suffering from fat deficiency, Exp Biol Med, 31(8), pp. 911-912.

Cardosso CR, Souza MA, Ferro EA, Favoretto S Jr, Pena JD, (2004), Influence of topical administration of n-3 and n-6 essential and n-9 nonessential fatty acids on the healing of cutaneous wounds, Wound Repair Regen, 12(2), pp. 235-243.

Chan PH, and Fishman RA, (1980), Transient formation of superoxide radicals in polyunsaturated fatty acid-induced brain selling, J Neurochem, 35(4), pp. 1004-1007.

Clarke SD, and Hembree J, (1990), Inhibition of triiodothyronine’s induction of rat liver lipogenic enzymes by dietary fat, J Nutr, 120(6), pp. 625-630.

Da Silva LA, De Marcucci OL, Kuhnle ZR, (1993), Dietary polyunsaturated fats suppress the high-sucrose-induced increase of rat liver pyruvate dehydrogenase, Biochim Biophys Acta, 69(2), pp. 126-134.

Felton CV, Crook D, Davies MJ, Olivier MF, (1994), Dietary polyunsaturated fatty acids and composition of human aortic plaques, Lancet, 344(8931), pp. 1195-1196.

Garza LA, Liu Y, Yang Z, Alagesan B, Lawson JA, Norberg SM, Loy DE, Zhao T, Blatt HB, Stanton DC, Carrasco L, Ahluwalia G, Fischer SM, FitzGerald GA, Cotsarelis G, (2012), Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenic alopecia, Sci Transl Med, 4(126).

Griffini P, Fehres O, Klieverik L, Vogels IM, Tigchelaar W, Smorenburg SM, Van Noorden CJ, (1998), Dietary omega-3 polyunsaturated fatty acids promote colon carcinoma metastasis in rat liver, Cancer Res, 58(15), pp. 3312-3319.

Harman D, Hendricks S, Eddy DE, Seibold J, (1976), Free radical theory of aging: effect of dietary fat on central nervous system function, J Am Geriatr Soc, 24(7), pp. 301-307.

Humphries KM, Yoo Y, Szweda LI, (1998), Inhibition of NADH-linked mitochondrial respiration by 4-hydroxy-2-nonenal, Biochemistry, 37(2), pp. 552-557.

Ip C, Carter CA, Ip MM, (1985), Requirement of essential fatty acid for mammary tumorigenesis in the rat, Cancer Res, 45(5), pp. 1997-2001.

Kjaer MA, Todorcevic M, Torsten BE, Vegusdal A, Ruyter B, (2008), Dietary n-3 HUFA affects mitochondrial fatty acid beta-oxidation capacity and susceptibility to oxidative stress in Atlantic salmon, Lipids, 43(9), pp. 813-827.

Kunkel HO, and Williams JN Jr, (1951), The effects of fat deficiency upon enzyme activity in the rat, J Biol Chem, 189(2),pp. 755-761.

Ling PR, Malkan A, Le HD, Puder M, Bistrian BR, (2012), Arachidonic acid and docosahexaenoic acid supplemented to an essential fatty acid-deficient diet alters the response to endotoxin in rats, Metabolism, 61(3), pp. 395-406.

McFate T, Mohyeldin A, Lu H, Thakar J, Henriques J, Halim ND, Wu H, Schell MJ, Tsang TM, Teahan O, Zhou S, Califano JA, Jeoung NH, Harris RA, Verma A, (2008), Pyruvate dehydrogenase complex activity controls metabolic and malignant phenotype in cancer cells, J Biol Chem, 283(33), pp. 22700-22708.

Nanji AA, and French SW, (1986), Dietary factors and alcoholic liver cirrhosis, Alcohol Clin Exp Res, 10(3), pp. 271-273.

Nanji AA, Jokelainen K, Tipoe GL, Rahemtulla A, Dannenberg AJ, (2001), Dietary saturated fatty acids reverse inflammatory and fibrotic changes in rat liver despite continued ethanol administration, J Pharmacol Exp Ther, 299(2), pp. 638-644.

Nourooz-Zadeh J, and Pereira P, (1999), Age-related accumulation of free polyunsaturated fatty acids in human retina, Opthalmic Res, 31(4), pp. 273-279.

Picklo MJ, and Montine TJ, (2001), Acrolein inhibits respiration in isolated brain mitochondria, Biochim Biophys Acta, 1535(2), pp. 145-152.

Rafael J, Patzelt J, Elmadfa I, (1988), Effect of dietary linoleic acid and essential fatty acid deficiency on resting metabolism, nonshivering thermogenesis and brown adipose tissue in the rat, J Nutr, 118(5), pp. 627-632.

Roberts LJ, Montine TJ, Markesbery WR, Tapper AR, Hardy P, Chemtob S, Dettbarn WD, Morrow JD, (1998), Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosahexaenoic acid, J Biol Chem, 273(22), pp. 13605-13612.

Solfrizzi V, D’Introno A, Colacicco AM, Capsurso C, Palasciano R, Capurso S, Torres F, Capurso A, Panza F, (2005) Unsaturated fatty acids intake and all-causes mortality: a 8.5-year follow-up of the Italian longitudinal study on aging, Exp Gerontl, 40(4), pp. 335-343.

Tamburini I, Quartacci MF, Izzo R, Bergamini E, (2004), Effects of dietary restriction on age-related changes in the phospholipid fatty acid composition of various rat tissues, Aging Clin Exp Res, 16(6), pp. 425-431.

Wolf RB, (1982) Effect of temperature on soybean seed constituents,J Am Oil Chem Soc, 59: 230-2.

Wolfe RR, Martini WZ, Irtun O, Hawkins HK, Barrow RE, (2002), Dietary fat composition alters pulmonary function in pigs, Nutrition, 18(7-8), pp. 647-653.

Yoshida H, Soh H, Sando K, Wasa M, Takagi Y, Okada A, (2003), Beneficial effects of n-9 eicosatrienoic acid on experimental bowel lesions, Surg Today, 33(8), pp. 600-605.

Thanks: as always, Ray Peat.

Also Rob Turner of : http://www.functionalps.com/blog/  whose blog has an absolutely awesome collection of studies that support the work of Ray Peat.