Are omega-6's healthy, or really bad? Or does it depend on how they're processed and D6D genotype?

[Alex K Chen]

Highly unsaturated omega-6 PUFAs (eg linoleic acid/corn oil/seed oils) may not be as bad in humans (or long-lived organisms) as they are in rodents

 

https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2002.tb02118.x

 

Quote

The presence of constitutively low desaturase activities in long-lived animals can
explain why feeding corn oil (rich in LA) to primates increases mainly LA (to 30%
of total fatty acids) instead of AA (only to 10% of total) in their tissues,51 whereas
in short-lived rodents dietary LA leads to strong increases in AA. Similarly to those
primates, human monastic communities that chronically consume only corn oil as
the main dietary fat source (67% rich in LA) have lipid profiles with around 30% LA
but only 9% AA in their lipoproteins.52 Also, standard diets of mammals (i.e., rats,
mice, cows, and horses) and even of birds contain the precursors in the n-6 and n-3
PUFA families LA and LNA at similar levels (35–41% and 1–2%, respectively, in
the four species) and do not contain DHA (this extremely unsaturated fatty acid is
not added to commercial diets because it oxidizes too easily to be stable at room temperature). However, tissue DHA reached 10% in mice and 3.6% in rats, whereas it
was below 0.6–0.3% in cows and horses, which also showed low AA/LA ratios.
The low DBI of long-lived animals is based in a redistribution between types of
PUFAS without any alteration in the total (%) PUFA content or in the average chain
length. This is an elegant evolutionary strategy, since it allows the reduction of sensitivity to lipid peroxidation and lipoxidation-derived damage to cellular macromolecules without altering fluidity/microviscosity, a fundamental property of cellular
membranes for the proper function of receptors, ion pumps, and transport of metabolites, among other functions. This occurs because membrane fluidity is known to increase strongly with the formation of the first and (less) with the second double bonds
by means of their introduction of “kinks” in the fatty acid molecule, whereas additional (the third and subsequent) double bonds cause few further variations in fluidity.53 This is so because the kink has a larger impact on fluidity when the double bond
is situated near the center of the fatty acid chain (first double bond) than when it is
situated progressively nearer to its extremes (next double bond additions). In the case
of sensitivity to lipid peroxidation, however, double bonds increase it irrespective of
being situated at the center or laterally on the fatty acids. Thus, by substituting fatty
acids with four or six double bonds with those having only two (or sometimes three)
double bonds, the sensitivity to lipid peroxidation is strongly decreased in long-lived
animals; whereas the fluidity of the membrane is essentially maintained. We call this
phenomenon, reminiscent of membrane acclimation to temperature at PUFA level in
poikilotherms, the homeoviscous longevity adaptation in homeotherms.

Also rlevant https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544151/

 

Quote

 

Interestingly, within the top ten markers predictive of human epigenetic age, four are localized in the CpG islands in the regulatory element of the ELOVL2 gene, accounting for over 70% of the one “methylation clock” model [8]. Consequently, methylation of the ELOVL2 regulatory region has been shown in many studies to correlate strongly with the biological age of individuals [9–12], as well as in rodents [7].

ELOVL2 is an enzyme that elongates long-chain omega-3 and omega-6 polyunsaturated fatty acids (LC-PUFAs), precursors of 22:6n-3, docosahexaenoic acid (DHA) and very-long-chain PUFAs (VLC-PUFAs), all playing important role in retina biology [13]. The fatty acids composition in the retina is unique - the retina is particularly enriched in PUFAs, with DHA constitutes 40–50% of the total fatty acids in the photoreceptor outer disc membranes [14]. VLC-PUFAs account for a unique ~5% of the total fatty acids in the disk membranes of photoreceptors, the second highest level in the body after testis. These features result in a highly fluid photoreceptors disc membranes that permit efficient conformational changes and signaling dynamics for visual chromophore necessary for the continuous detection of light [15–17].

 

https://academic.oup.com/jcem/article/104/12/6207/5540968

PUFA decreases ceramides

==

related

Do Seed Oils Make You Sick?

Critics say they raise your risk for weight gain, heart issues, and more. But the science doesn’t support those claims.

https://www.consumerreports.org/health/healthy-eating/do-seed-oils-make-you-sick-a1363483895/ 3

Edited October 6, 2023 by InquilineKea

[Alex K Chen]

https://neurosciencenews.com/soybean-oil-genetics-asd-15505/

Someone calls this a questionable study

[Alex K Chen]

fireinabottle is anti-ppargamma (b/c it comes from unsaturated fatty acids)

it may cause you to gain fat, but that is not always a bad thing (this reduces lipotoxicity)

https://en.wikipedia.org/wiki/Peroxisome_proliferator-activated_receptor_gamma

Quote

PPARγ may be the most widely studied PPAR isoform. To date, several studies have evaluated the role of PPARγ in major metabolic tissues and cell types, including liver, adipocytes, pancreas, macrophages, skeletal muscle, and colonocytes, among others (Willson et al., 2001). An alteration in this ligand-activated transcription factor is associated with metabolic disorders, such as atherosclerosis (Lefebvre et al., 2006), obesity (Evans et al., 2004), metabolic syndrome and dyslipidemias (Barter and Rye, 2008), type 2 diabetes (Jay and Ren, 2007), and cancer (Grommes et al., 2004). Like PPARα, the implication of PPARγ in these prevalent diseases makes it a potential target of pharmacotherapies (Ahmadian et al., 2013). There is evidence that PPARγ may also contribute to the anti-inflammatory property of polyunsaturated fatty acids (PUFAs), as n3 PUFA enhanced hepatic regulatory T (Treg) cell generation by upregulating PPARγ and transforming growth factor beta (TGF-β) expression, thus regulating inflammatory processes in the liver (Lian et al., 2015). Along these lines, PPARγ is a target of other PUFA-derived compounds and arachidonic acid (AA), such as 15-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2), the most recently discovered anti-inflammatory eicosanoid of which numerous beneficial effects on health are known (Marion-Letellier et al., 2016). Recent studies in rat colonic inflammation support the hypothesis of cooperation among eicosanoid prostaglandin and PPARγ, correlating the levels of 15d-PGJ2 and PPARγ expression with improved symptoms (Ponferrada et al., 2007). In this sense, antinociceptive and antiedematogenic activities of fenofibrate, an agonist of PPARα, and pioglitazone, a synthetic TZD agonist of PPARγ, have also been observed (Oliveira et al., 2007).

Quote

The mice eating a low LA diet were producing 50% more PPAR alpha than they were PPAR gamma.  The dys-regulated mice were producing 2.5 TIMES as much PPAR gamma as PPAR alpha!!  Going over 5-6% of LA in your diet seems to be a switch that turns on PPAR gamma and turns off PPAR alpha.  This is likely useful to a hibernating bear eating acorns to fatten up for winter but likely less useful for you.  I suspect Native Americans were aware of the metabolic changes associated with LA overconsumption and that is why they replaced acorn oil with low-PUFA, spring-collected bear grease.

I mean, who binges on PUFAs as more than 50% of their diet? (I have done it occasionally twice last week just b/c there wasn't much available other than hemp hearts, but I quit b/c it induced torpor)

Edited July 16, 2023 by InquilineKea

[Alex K Chen]

https://pubmed.ncbi.nlm.nih.gov/36711941/

[Alex K Chen]

Not sure how credible but I've always been somewhat concerned about the mass of pro-omega-3 papers

https://triumphtraining.com/blogs/blog/14885549-the-fallacy-of-fish-oil-part-1

[Ron Put]

13 hours ago, InquilineKea said:

Not sure how credible but I've always been somewhat concerned about the mass of pro-omega-3 papers

Bombastic, and poorly argued. Plus, it was retracted, in part because the author is a promoter of patented PUFA supplements and in part because he lacks the credentials he claims.

Having said that, I have also come to the general conclusion that the mostly industry-sponsored marine oil research is poor and that it makes little sense once one peeks behind the headlines, in my opinion, at least. I have posted some of my thoughts on the subject of marine Omega-3 supplementation in another thread here: Omega-3 to Omega-6 Ratio Experiment - General Health and Longevity - CR Society Forum

P.S. Here is a link to the original retracted article, which I am posting because some of the references are valid and may be interesting to some here:

Why Fish Oil Fails: A Comprehensive 21st Century Lipids-Based Physiologic Analysis - PMC (nih.gov)
 

Edited July 25, 2023 by Ron Put

[Alex K Chen]

 

[Alex K Chen]

https://twitter.com/hubermanlab/status/1704199971011186720

 

Edited September 26, 2023 by InquilineKea

[Alex K Chen]

Inflammation isn't everything though.. cell composition changes are more worrying

https://www.lesswrong.com/posts/DHkkL2GxhxoceLzua/thoughts-on-seed-oil

Edited April 21 by InquilineKea