PUFA Accumulation & Aging

Also see:
Unsaturated Fats and Longevity
Vitamin E Needs Increases with PUFA Consumption and Greater Unsaturation
“Curing” a High Metabolic Rate with Unsaturated Fats
Fat Deficient Animals – Activity of Cytochrome Oxidase
Dietary PUFA Reflected in Human Subcutaneous Fat Tissue
Toxicity of Stored PUFA
PUFA, Development, and Allergy Incidence
PUFA, Aging, Cytochrome Oxidase, and Cardiolipin
Calorie Restriction, PUFA, and Aging
Your MUFA + PUFA Intakes Determine Your True Vitamin E Requirements – N-3s are the Worst Offenders + Even MUFAs Need Buffering | Tool to Calculate Your Individual Needs
The Dangers of Fat Metabolism and PUFA: Why You Don’t Want to be a Fat Burner

Quotes by Ray Peat, PhD:
“Long ago, people knew that polyunsaturated fats blocked proteolytic enzymes. The first effect of too much PUFA is to block the ability of the thyroid gland to secrete the hormone by breaking down the thyroid globulin. If the thyroid does manges to secrete it, the transport of it on proteins in the blood is inhibited in proportion to the unsaturation. Fish oils with 5 and 6 unsaturated double bonds are the most powerful, almost total inhibitors of thyroid transport. Linolenic acid (omega -3) fats with 3 double bonds inhibits about 50%, linoleic acid (omega -6) with 2 double bonds inhibits about 30%. So the inhibition is proportional to the amount of double bonds. The responsiveness of the cell to thyroid is inhibited in proportion to the amount of unsaturated fats. Carotene is highly unsaturated and it has the same effect of interfering with thyroid function because of this series of unsaturations. The accumulated unsaturated fats in the body turn on other anti-thyroid processes, so it isn’t all immeidate and direct. They make you more susceptibel to turning on prostaglandins which promote inflammation and increase the tendency to produce lactic acid, and they interfere with the mitochondrial oxidative energy production. After you are 30 or 40 years old almost everyone has accumulated enough PUFA to cause a whole range of metabolic problems.”

“Since stored fats are usually mostly polyunsaturated, the thyroid gland will keep being suppressed as long as weight is being lost, since the PUFA are being released into the blood stream. If a person has enough cholesterol, thyroid, and vitamin A, and keeps estrogen low, progesterone supplements shouldn’t be needed, but since adipose tissue is a source of estrogen synthesis when there’s inflammation, stress, or low thyroid, the need for progesterone is likely to recur. Aspirin helps to inhibit estrogen synthesis.”

“Heavy drinking inhibits cellular respiration and sets up an inflammatory process, involving iron, which will still be harmful, but less so than in the presence of PUFA. If absolutely none of the dietary PUFA were in the body, no one really knows what that metabolic stress would do, maybe nothing cumulative.”

“The use of adequate protein and saturated fats during pregnancy will prevent many of the problems of pregnancy and infancy, but since the unsaturated fats remain stored in the tissues for many years, and are mobilized during stress, it’s important to eat correctly long before pregnancy. The requirement for vitamin E remains high for years after the diet has contained an excess of the polyunsatured fats. The diet which protects the developing fetus happens to be the diet that protects adults from all sorts of stress, and prevents many of the worst symptoms of aging.”

“In a young person, good food, sunlight, and a high altitude can often overcome severe and progressive inflammatory conditions. In an older person, whose tissues contain larger amounts of polyunsaturated fats and their breakdown products, it takes more environmental support to get out of the inflammatory pattern.”

“To reverse this process, it’s necessary to avoid doing the things that caused the problem to develop. The accumulation of heavy metals and of the unstable unsaturated fats (linoleic, linolenic, and arachidonic acids) can be slowed or reversed by careful dietary choices. The calorie restricted diets that slow the aging process reduce the accumulation of the unstable fats and the heavy metals. Vitamin E reduces the vascular leakiness and the free radical peroxidation that are so closely involved in fibrosis. Since serotonin and nitric oxide are involved in these processes, they should be minimized by keeping carbon dioxide production high (by optimizing thyroid function), and by eating protein that have a safe balance of the amino acids. Too much arginine increases nitric oxide formation, and too much tryptophan increases serotonin production. Too much glutamic acid, aspartic acid, and cysteine can be directly excitotoxic, and the metabolites of cysteine include proinfiammatory homocysteine, which can disrupt collagen structure.”

“All phases of development, from gestation to aging, are altered by the presence of the unsaturated fats, and these effects correspond closely to the loss of regenerative capacity, the ability to replenish and restore tissues.”

“But many very useful drugs that already existed, including cortisol and aspirin, were found to achieve some of their most important effects by inhibiting the formation of the prostaglandins. It was the body’s load of polyunsaturated fats which made it very susceptible to inflammation, stress, trauma, infection, radiation, hormone imbalance, and other fundamental problems, and drugs like aspirin and cortisone, which limit the activation of the stored “essential fatty acids,” gain their remarkable range of beneficial effects partly by the restraint they impose on those stored toxins.”

“Sugars, if they are consumed in quantities beyond the ability to metabolize them (and that easily happens in the presence of PUFA) are converted into saturated fatty acids, which have antistress, antiinflammatory effects. Many propaganda experiments are set up, feeding a grossly excessive amount of polyunsaturated fat, causing sugar to form fat, specifically so they can publish their silly diet recommendations, which supposedly explain the obesity epidemic, but the government figures I cited show that vegetable fat consumption has increased, sugar hasn’t. My articles have a lot of information on the mechanisms, such as the so-called ‘Randle cycle,’ in which fatty acids shut down the ability to oxidize sugar. Polyunsaturated fats do many things that increase blood sugar inappropriately, and my articles review several of the major mechanisms. Several years ago, medical people started talking about the harmful effects of insulin, such as stimulating fat production, so ‘insulin resistance’ which keeps a high level of insulin from producing obesity would seem to be a good thing, but the medical obesity culture really isn’t thinking very straight. One factor in the ‘insulin resistance’ created by PUFA involves estrogen—chronic accumulation of PUFA in the tissues increases the production of estrogen, and the polyunsaturated free fatty acids intensify the actions of estrogen, which acts in several ways to interfere with glucose oxidation.”

“Our innate immune system is perfectly competent for handling our normal stress induced exposures to bacterial endotoxin, but as we accumulate the unstable fats, each exposure to endotoxin creates additional inflammatory stress by liberating stored fats. The brain has a very high concentration of complex fats, and is highly susceptible to the effects of lipid peroxidative stress, which become progressively worse as the unstable fats accumulate during aging.”

“EFA Deficiency” found in Newborns:
The fatty acids of newborn humans, and other non-ruminants, reflect their mothers’ diets more closely, but Mead acid is still present in human newborns (Al, et al., 1990). -Ray Peat, PhD

Early Hum Dev. 1990 Dec;24(3):239-48.
Biochemical EFA status of mothers and their neonates after normal pregnancy.
Al MD, Hornstra G, van der Schouw YT, Bulstra-Ramakers MT, Huisjes HJ.
The essential fatty acid (EFA) status of neonates was compared with that of their mothers by determining the fatty acid compositions of phospholipids (PL), isolated from umbilical arterial and venous tissue, blood cells (BC) and plasma, from maternal venous plasma and BC, and from non-infarcted placental tissue. The PL of umbilical arterial tissue (efferent fetal vessels) contained fewer fatty acids of the (n-6) family and more of the (n-9) family than umbilical venous tissue (afferent fetal vessel). The relative amounts of (n-6) and (n-3) fatty acids were less in arterial than in venous plasma. Mead acid, 20:3(n-9), the presence of which indicates a poor EFA status, was 5 times higher in the efferent than in afferent cord vessels. In neonatal plasma and BC it was twice as high as compared with maternal levels. In general, the fatty acid composition of the placenta PL showed a comparable pattern as neonatal venous plasma PL. These findings demonstrate that the biochemical EFA status of neonates after a normal pregnancy is not optimal. The significant correlations between neonatal and maternal EFAs indicate that the neonatal EFA status depends on the EFA content of the maternal diet.

At birth, the baby’s mitochondria contain a phospholipid, cardiolipin, containing palmitic acid, but as the baby eats foods containing polyunsaturated fatty acids, the palmitic acid in cardiolipin is replaced by the unsaturated fats. As the cardiolipin becomes more unsaturated, it becomes less stable, and less able to support the activity of the crucial respiratory enzyme, cytochrome oxidase.-Ray Peat, PhD

The respiratory activity of the mitochondria declines as the polyunsaturated oils replace palmitic acid, and this change corresponds to the life-long decline of the person’s metabolic rate. -Ray Peat, PhD

Physiol Bohemoslov. 1990;39(2):125-34.
Proportion of individual fatty acids in the non-esterified (free) fatty acid (FFA) fraction in the serum of laboratory rats of different ages.
Smídová L, Base J, Mourek J, Cechová I.
In experiments on Wistar strain rats of both sexes, aged 5, 10 and 14 days and adult (90-120 days), of their own breed, the authors determined the quantitative proportion of individual fatty acids in the serum free non-esterified fatty acid (FFA) fraction, using mixed blood (obtained by decapitation) and the titration method of Trout et al. (1960). The proportion of the individual fatty acids was then determined in this fraction by gas chromatography (Base 1978) and their concentration (in mumol.1-1) was determined by simple calculation from the relative chromatogram data. Animals in the first three age groups were killed in the morning, directly from the nest; in adult rats the FFA fraction was measured after a 20 h fast. It was demonstrated that the increase in the proportion of monoenoic acids was highly statistically significant (about fivefold) during ontogenesis and that there was also a marked increase in the quantitative expression of polyenic acids, especially in group (n-6). The n-6/n-3 acid index in the FFA fraction altered during maturation (despite some fluctuation it basically rose from 4.3 in 5-day-old young to 10.0 in adult rats). It was further demonstrated that the concentration of fatty acids with a very short chain fell significantly during development, so that C 8:0, for example, could be detected only in the first two age groups, but not in 14-day-old and adult rats. The concentration of the saturated fatty acids C 15:0 to C 18:0 in the serum FFA fraction showed a statistically significant increase, while the index expressing the ratio of saturated to unsaturated fatty acids displayed a downward trend during development.

The phospholipids of mitochondria and microsomes become more unsaturated with aging (Laganiere and Yu, 1993, Lee, et al., 1999). -Ray Peat, PhD

Gerontology. 1993;39(1):7-18.
Modulation of membrane phospholipid fatty acid composition by age and food restriction.
Laganiere S, Yu BP.
Phospholipids from liver mitochondrial and microsomal membrane preparations were analyzed to further assess the effects of age and lifelong calorie restriction on membrane lipid composition. Results showed that the major phospholipid classes, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol and cardiolipin did not vary significantly with age or diet. The fatty acid composition of the phospholipids was determined in PC and PE and ages of 6, 12 and 24 months. The data revealed characteristic patterns of age-related changes in ad libitum (AL) fed rats: membrane levels of long-chain polyunsaturated fatty acids, 22:4 and 22:5, increased progressively, while membrane linoleic acid (18:2) decreased steadily with age. Levels of 18:2 fell by approximately 40%, and 22:5 content almost doubled making the peroxidizability index increase with age. In addition, levels of 16:1 and 18:1 decreased significantly with age, indicating a possible change in delta 9-desaturase activity coefficient. Food restriction resulted in a significant increase in levels of essential fatty acids while attenuating levels of 22:4, 22:5, 22:6 and peroxidizability. We concluded that the membrane-stabilizing action of long-term calorie restriction relates to the selective modification of membrane long-chain polyunsaturated fatty acids during aging.

Free Radic Biol Med. 1999 Feb;26(3-4):260-5.
Modulation of cardiac mitochondrial membrane fluidity by age and calorie intake.
Lee J, Yu BP, Herlihy JT.
The aim of the present study was to determine the effects of dietary restriction (DR) on the age-related changes in membrane fluidity, fatty acid composition and free radical damage of mitochondrial membranes obtained from the rat left ventricle. Mitochondrial membrane preparations were obtained from the left ventricles of 6- and 24-month-old, male, Fischer 344 rats that were allowed to eat throughout their life either ad lib (Group A) or only 60% of the amount consumed by the ad lib fed group (Group B). Our results show that the membrane fluidity of the 24 month Group A hearts was less than that of the 6 month group A hearts. No differences in membrane fluidity were observed between the 6 and 24 month DR groups. The fatty acid composition of the mitochondrial membranes of the two ad lib fed groups differed: the long-chain polyunsaturated 22:4 fatty acid was higher in the older group, although linoleic acid (18:2) was lower. DR eliminated the differences. No statistically significant difference in the overall polyunsaturated fatty acid content was noted. However, the peroxidizability index was higher in the membranes of the 24 month Group A hearts but not in the 24 month Group B hearts. Finally, the degree of lipid damage, as assessed in vitro by the induced production of reactive oxygen species, was elevated in the 24 month Group A hearts. No difference was observed between the young and old DR groups. Considered together, these results suggest that DR maintains the integrity of the cardiac mitochondrial membrane fluidity by minimizing membrane damage through modulation of membrane fatty acid profile.

Biochem Biophys Res Commun. 1987 Jun 30;145(3):1185-91.
Anti-lipoperoxidation action of food restriction.
Laganiere S, Yu BP.
Chronic food restriction inhibited the age-related increase of malondialdehyde production and lipid hydroperoxides in liver mitochondrial and microsomal membranes of ad libitum fed Fischer 344 rats. The anti-lipoperoxidation action of food restriction could not be attributable to the changes in membrane lipid content nor vitamin E status. Restricting calories modified membrane fatty acid composition by increasing linoleic acid and decreasing docosapentaenoic acid content in both membranes. The significance of the fatty acid modification was discussed in terms of anti-lipoperoxidation and membrane fluidity.

Aging Clin Exp Res. 2004 Dec;16(6):425-31.
Effects of dietary restriction on age-related changes in the phospholipid fatty acid composition of various rat tissues.
Tamburini I, Quartacci MF, Izzo R, Bergamini E.
Polyunsaturated fatty acids (PUFAs) are essential components of the cell lipid bilayer and are involved in membrane fluidity and normal functioning, but they are vulnerable to free radical attack. Given the role of oxidative stress in the aging process, age-related changes in phospholipid fatty acid (PLFA) composition in rat liver, kidney and heart were assessed in 3-, 12- and 24-month-old rats fed either ad libitum but only every other day, or daily but only 60% of the quantity normally consumed by age-matched controls.
Lipids were extracted and phospholipids (PLs) were separated using the solid phase extraction technique, then transesterified and assayed by gas-liquid chromatography.
Saturated fatty acids (FAs) did not change significantly with age; mono- and bi-unsaturated FAs decreased in the liver and heart, and the ratio of the former to the latter increased in the liver, kidney and heart. PUFAs increased in the liver and heart. As regards individual FAs, 20:1(n-9) decreased in all organs, 14:1 and 18:1(n-7) increased in the kidney and heart, 18:1(n-9) increased in the kidney, 20:2(n-6), 18:2(n-6) and 22:5(n-3) decreased in the liver and heart, 20:3(n-6) decreased in the kidney and increased in the heart. The most abundant PUFAs, 20:4(n-6) and 22:6(n-3), either remained the same or increased with age. The N-9 family increased in the kidney, the N-7 family increased in the kidney and heart, the N-6 family decreased in all three organs, and the N-3 family increased in the liver and kidney. Dietary restriction (DR) significantly counteracted most of these changes, but changes in some FAs [20:2(n-6) in the heart] were magnified by DR and may not be age-related.
Most age-related changes (that occurred in the rat liver, kidney and heart and were counteracted by the two different types of DR) may be involved in the mechanism of aging.

In the human retina there is a similar accumulation of PUFA with aging (Nourooz-Zadeh and Pereira, 1999), which implies that the aged retina will be more easily damaged by light. -Ray Peat, PhD

Ophthalmic Res. 1999;31(4):273-9.
Age-related accumulation of free polyunsaturated fatty acids in human retina.
Nourooz-Zadeh J, Pereira P.
The present study reports composition of free (nonesterified) as well as total (sum of free and esterified) fatty acids (FAs) in human retina (n = 13). For free fatty acid (FFA) analysis, retina tissue was homogenized, total lipids were partitioned with ethyl acetate and subsequently applied onto a aminopropyl (NH2) cartridge to isolate FFAs from the bulk of other lipids. FFAs were converted to methyl ester derivatives and analysed by gas chromatography using flame ionization detector. Analysis of FFAs revealed that the mean percentage composition of the major components including palmitic acid (PA), stearic acid (SA), oleic acid (OA), arachidonic acid (AA) and docosahexaenoic acid (DHA) were 17.2, 36.7, 15.6, 8.8 and 14.2%, respectively. There were significant correlations between age of the donors’ and the content of both free AA and DHA (rPearson = 0.69, p = 0.005, and rPearson = 0.64, p = 0.009). The mean percentage of total PA, SA, OA, AA and DHA were 22.6, 23.2, 17.7, 11.4 and 21.9%, respectively. There was no association between age and any of the major FAs. The present study provides the first evidence for the presence of FFAs in the human retina as well as an age-related accumulation of polyunsaturated fatty acids (PUFAs). The latter finding suggests an alteration in the metabolism of retinal PUFAs which can be due to an increase of oxidative stress and/or decrease of antioxidant defences during ageing.

This progressive increase [in PUFA] with age can be seen already in early childhood (Guerra, et al., 2007). -Ray Peat, PhD

Ann Nutr Metab. 2007;51(5):433-8. Epub 2007 Nov 20.
Three-year tracking of fatty acid composition of plasma phospholipids in healthy children.
Guerra A, Demmelmair H, Toschke AM, Koletzko B.
The fatty acid composition of plasma phospholipids reflects the dietary fatty acid intake as well as endogenous turnover. We aimed at investigating the potential tracking of plasma phospholipid fatty acid composition in children that participated in a prospective cohort study.
26 healthy children participated in a longitudinal study on health risks and had been enrolled after birth. All children were born at term with birth weights appropriate for gestational age. Follow-up took place at ages 24, 36 and 60 months. At each time point a 24-hour dietary recall was obtained, anthropometric parameters were measured and a blood sample for phospholipid fatty acid analysis was taken.
Dietary intake of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids at the three time points were not correlated. We found lower values for plasma MUFA and the MUFA/SFA ratio at 60 months compared to 24 months. In contrast, total PUFA, total n-6 and n-6 long-chain polyunsaturated fatty acids (LC-PUFA) were higher at 60 months. Significant averaged correlation coefficients (average of Pearson’s R for 24 versus 36 months and 36 versus 60 months) were found for n-6 LC-PUFA (r = 0.67), n-6/n-3 LC-PUFA ratio (r = 0.59) and arachidonic acid/linoleic acid ratio (r = 0.64). Partial tracking was found for the docosahexaenoic acid/alpha-linolenic acid ratio (r = 0.33). Body mass index and sum of skinfolds Z-scores were similar in the three evaluations.
A significant tracking of n-6 LC-PUFA, n-6 LC-PUFA/n-3 LC-PUFA ratio, arachidonic acid/linoleic acid ratio and docosahexaenoic acid/alpha-linolenic acid ratio may reflect an influence of individual endogenous fatty acid metabolism on plasma concentrations of some, but not all, fatty acids.

Ann Nutr Metab. 1989;33(6):315-22.
Adipose tissue levels of fatty acids and tocopherol in young and old women.
Schäfer L, Overvad K, Thorling EB, Velander G.
Tocopherol concentration and fatty acid composition were determined in samples of subcutaneous adipose tissue from 33 young and 28 old women. Young women exhibited more saturated fatty acids and less monounsaturated fatty acids than old women (p less than 0.01). Adipose tissue tocopherol correlated with plasma tocopherol, with r = 0.49 and p less than 0.01, when the data for young and old were combined. A negative association was found between adipose tissue tocopherol and the n-3/n-6 fatty acid ratio in the old women (r = 0.42; p less than 0.05), suggesting that the tocopherol content of adipose tissue is determined not only by the intake of the nutrient but also by the tissue fatty acid composition.

Adv Nutr November 2015 Adv Nutr vol. 6: 660-664, 2015
Increase in Adipose Tissue Linoleic Acid of US Adults in the Last Half Century
Stephan J Guyenet and Susan E Carlson
Linoleic acid (LA) is a bioactive fatty acid with diverse effects on human physiology and pathophysiology. LA is a major dietary fatty acid, and also one of the most abundant fatty acids in adipose tissue, where its concentration reflects dietary intake. Over the last half century in the United States, dietary LA intake has greatly increased as dietary fat sources have shifted toward polyunsaturated seed oils such as soybean oil. We have conducted a systematic literature review of studies reporting the concentration of LA in subcutaneous adipose tissue of US cohorts. Our results indicate that adipose tissue LA has increased by 136% over the last half century and that this increase is highly correlated with an increase in dietary LA intake over the same period of time.

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