Is Omega-3 Fish Oil Bad?

[nwo2012]

Nice rhyme, I should use that as my signature

Haha. Nice.

 

[Travis]

Omega−6 fatty acids are not essential and never were, and of course should be strictly avoided. However, humans do have a requirement for trace amounts of either DHA (22∶6ω−3) or its precursor α-linolenic acid (18∶3ω−3). Failing to discriminate between individual fatty acids is not helpful, and making sweeping statements about all polyunsaturated fatty acids is dubious in every instance. Even when speaking about peroxidation, things such as conjugation and bis-allyl hydrogens need to be considered. The differences between the hormonal and chemoattractant properties of each fatty acid subtype is even more extreme. We can make polyunsaturated ω−9 fatty acids de novo—i.e. Mead acid (20∶3ω−9)—and we desaturate stearic acid all the time. I would never recommend fish oil, but without DHA we would all most certainly be dead. These are facts.

 

[nwo2012]

Omega−6 fatty acids are not essential and never were, and of course should be strictly avoided. However, humans do have a requirement for trace amounts of either DHA (22∶6ω−3) or its precursor α-linolenic acid (18∶3ω−3). Failing to discriminate between individual fatty acids is not helpful, and making sweeping statements about all polyunsaturated fatty acids is dubious in every instance. Even when speaking about peroxidation, things such as conjugation and bis-allyl hydrogens need to be considered. The differences between the hormonal and chemoattractant properties of each fatty acid subtype is even more extreme. We can make polyunsaturated ω−9 fatty acids de novo—i.e. Mead acid (20∶3ω−9)—and we desaturate stearic acid all the time. I would never recommend fish oil, but without DHA we would all most certainly be dead. These are facts.

Saying it were so, surely the likes of grass-fed beef, liver and low fat sea-food provide enough without seeking any supplementation. So it's a non-issue on a RP style eating lifestyle anyways.

 

[Travis]

Saying it were so, surely the likes of grass-fed beef, liver and low fat sea-food provide enough without seeking any supplementation. So it's a non-issue on a RP style eating lifestyle anyways.

Yes: Getting enough α-linolenic acid (18∶3ω−3) is a total non-issue, and experiments show that only about 1% of dietary lipids need to be either α-linolenic acid (18∶3ω−3) or DHA—and these have been conducted on quickly-growing rats. The main issue is actually ω−6 fatty acids occupying DHA-elongating enzymes and displacing them—with arachidonic acid (20∶4ω−6)—from cell membranes, thus increasing the requirement while introducing a potentially carcinogenic lipid. There is enough trace α-linolenic acid (18∶3ω−3) in milk, beef, and leaves to make all the DHA a person needs. Neither fish oil nor the animal in which its derived need ever be consumed. As α-linolenic acid (18∶3ω−3) is the precursor for EPA (20∶5ω−3), which in turn is the precursor for prostaglandin E₃ and leukotriene B₅, too much could be pathological. Eicosapentaenoic acid (20∶5ω−3) is also found in fish.

 

[Kartoffel]

I would never recommend fish oil, but without DHA we would all most certainly be dead. These are facts.

Where are these facts? In this thread you posted a study where they used a PUFA control group to show that another PUFA is essential. Feeding rats two horrible seed oils, and seeing that one of them is worse than the other doesn't prove the essential status of any fatty acid. They didn't use a control group w/o any PUFA, and inferring some essential function of DHA for the brain from the difference in cognitive performance in this study is simply not valid.
Regarding DHA supposed essential status for humans, you posted a horrible study without any control group in the last thread, where the researcher just a gave a bunch of Zellweger's kids some DHA, and attributed any positive cognitive development to the fatty acid. I explained in more detail why this is bad science, and showed you the studies where DHA compared to a control group didn't provide any positive effects for Zellweger's.
So, if there are so many facts on the essentiality of PUFA, and DHA in particular, why do you only cite these junk studies instead of showing us the good stuff?

 

[Travis]

Where are these facts? In this thread you posted a study where they used a PUFA control group to show that another PUFA is essential. Feeding rats two horrible seed oils, and seeing that one of them is worse than the other doesn't prove the essential status of any fatty acid. They didn't use a control group w/o any PUFA, and inferring some essential function of DHA for the brain from the difference in cognitive performance in this study is simply not valid.
Regarding DHA supposed essential status for humans, you posted a horrible study without any control group in the last thread, where the researcher just a gave a bunch of Zellweger's kids some DHA, and attributed any positive cognitive development to the fatty acid. I explained in more detail why this is bad science, and showed you the studies where DHA compared to a control group didn't provide any positive effects for Zellweger's.
So, if there are so many facts on the essentiality of PUFA, and DHA in particular, why do you only cite these junk studies instead of showing us the good stuff?

You're an insult to the authors of those studies, myself, children with Zellweger's disease, and to reason itself. I can tell by your comments that you hadn't even read the study, and also that you have zero comprehension of DHA deficiency disease.

[1] Ahmad, Aneeq. "Decrease in neuron size in docosahexaenoic acid-deficient brain." Pediatric neurology (2002)​

What happens without DHA or its precursor α-linolenic acid? This is by no mean mysterious, and the answer can be found in dozens of published studies. Without DHA or its precursor α-linolenic acid, omega−6 fatty acids will preferentially become incorporated into the cell membrane. Since we're dealing with DHA-deficient Kartoffel here, I'll highlight the two most pertinent lipid species from the above-cited study: Docosahexaenoic acid (22∶6ω−3) is shown in dark blue, while osbond acid (22∶5ω−6) gets lighter shade of same (or is that purple?):

Now Kartoffel, what is the longest ω−9 fatty acid shown in the chart? and how prevalent is it? Since mammals cannot synthesize either ω−3 nor ω−6 fatty acids, what would happen if a person were to avoid both? If you had to pick between one or the other, which one would you choose and why?

As it turns out, this extra double bond of DHA and its position affords this lipid the greatest ability to exclude cholesterol from cell membranes. This has been confirmed in dozens of in vitro studies, many of which can be found in the citation section of this article:

[2] Wassall, Stephen. "Order from disorder, corralling cholesterol with chaotic lipids: The role of polyunsaturated lipids in membrane raft formation." Chemistry and physics of lipids (2004)

'Of special importance is the ω−3-PUFA docosahexaenoic acid (DHA), with 22 carbons and six double bonds that constitute the most highly unsaturated fatty acid naturally occurring. Our experiments target the membrane as a likely site of action and focus upon the interaction of cholesterol with PUFA-containing phospholipids. They support the idea that steric incompatibility of the rigid steroid moiety for highly disordered PUFA chains promotes lateral segregation of lipids into PUFA-rich/sterol-poor and PUFA-poor/sterol-rich regions. Solid state ²H NMR and X-ray diffraction demonstrate that the solubility of cholesterol is low in polyunsaturated bilayers.' ―Wassall​

Is Kartoffel going to read this article before mocking it? of course he's won't. Watch Kartoffel insinuate that all this is 'bad science' regardless.

The enhanced cholesterol-excluding property of DHA compared to all other membrane lipids becomes apparent in MRI images of patients with Zellweger's disease. Just like ω−3-deficient rats, the brains of Zellweger's patients are also enriched ω−6 fatty acids in an amount corresponding to the DHA-displaced:

[3] Martinez, Manuela. "MRI evidence that docosahexaenoic acid ethyl ester improves myelination in generalized peroxisomal disorders." Neurology (1998)

[4] Martinez, Manuela. "MRI evidence that docosahexaenoic acid ethyl ester improves myelination in generalized peroxisomal disorders." Neurology (1998)​

​

With the loss of only one double bond: cholesterol, pregnenolone, and progesterone transgress into grey matter cell membranes. The increased affinity of the DHA-deficient grey matter for sterols leads to a higher density membrane, reduced glucose flux, and impaired myelination: Pregnenolone and progesterone form a substantial component of myelin, essential steroids accounting for nearly half its mass. Do you really think that Mead acid alone, the most unsaturated membrane lipid we can make ourselves, can ensure proper brain function? Mead acid has merely three double bonds, and even osbond acid—having five of these—fails to maintain proper brain function.

Just as with hydrophilicity, volume also decreases as a function of unsaturation. A cell membrane of lower volume is more glucose-permeant, and besides promoting proper myelination it can also be argued that DHA promotes intelligence by increasing glucose flux.

[5] Kim, Jeffrey. "Dietary DHA reduces downstream endocannabinoid and inflammatory gene expression and epididymal fat mass while improving aspects of glucose use in muscle in C57BL/6J mice." International journal of obesity (2016)​

 

[General Orange]

I come from native decent. The native people have been eating food sources like salmon since before the white man even came over to North America. I noticed years ago when I stopped taking wild salmon fish oil or even cut out PUFAs all together because of anabolic men that lots of things became harder. Simple taskes harder, socializing became harder it's like my brain was trying 10 times harder to do things came natural before. It wasn't until I emailed a smart guy called area1255 for a problem and one his suggestions was adding omega 3s in my diet.

It's been like 2 weeks of supplementing wild salmon fish oil, instead of real salmon only because I live in the city now and everything has become easier. Emotional control, socializing, ******* adding and ***t had become easier. It's all natural to me like when I was a kid eating salmon religiously. I was told omega 3 were only bad IF they raise inflammation.

But also I'd say I'm more genetically adapted to take in omega 3s just like how the white man is more adapted to take in alcohol lol. Say what you guys want I'm probably never going to stop eating wild salmon or even supplementing with its omega 3 oil.

To me this omega-3 dependency, seems like a state of high oxidative stress, that increases brain activity in an inflammatory way, much the same as serotonin SSRI could increase memory allocation but to put it bluntly it just makes the brain work hotter. So missing the omega-3, for you, could mean that there is practically a genetic adaption for lower activity of "receptors" so impaired functioning from abstinence of omega-3 could only be treated with certain orthomolecular neuro repartitioning stimulants on a mRNA level.

 

[Travis]

[1] Stillwell, William. "Docosahexaenoic acid: membrane properties of a unique fatty acid." Chemistry and physics of lipids (2003)

'These experiments saw no strong correlation between cholesterol-induced condensation and acyl chain unsaturation.' ―Stillwell

'Despite qualitative similarity in behaviour, a major distinction with DHA exists. High conformational disorder of the multiple double bond-containing chain deters close contact with the rigid steroid moiety.' ―Stillwell

'The interaction of cholesterol with DHA-containing PE [phosphatidylethanolamine] has received much less attention than the equivalent PC [phosphotidylcholine]. Poor affinity between sterol and polyunsaturated acyl chain is again in evidence. Whereas the solubility of cholesterol in 16∶0-18∶1 PE bilayers is ∼51 mol%, in 16∶0-22∶6 PE the value is reduced to 32 mol% (Shaikh et al., unpublished data). These results demonstrate that unlike in PC bilayers where a marked reduction in solubility requires polyunsaturation at sn-1 and sn-2 positions, DHA at the sn-2 position with a saturated sn-1 chain is sufficient in PE to trigger exclusion of the sterol.' ―Stillwell

'Finally, Demel et al. (1972) showed that DHA incorporated into the sn-2 position of PC [phosphotidylcholine] increased permeability to glucose, erythritol and glycerol. The increase, however, was lateral pressure-dependent as similar glucose permeability for oleic acid and DHA-containing bilayers was observed at high, biologically relevant, pressures' ―Stillwell

'In the plasma membrane of most animal cells, the major polar lipid is not a phospholipid but instead is cholesterol. In these membranes DHA must be exposed to cholesterol and the interaction between these two species may profoundly affect membrane structure and function. There is a strong correlation between various membrane properties and the degree of unsaturation and cholesterol present (Shinitzky, 1984). For example, in synaptic membranes PUFAs and cholesterol are the major determinants of membrane molecular order (Hibbeln and Salem, 1995). Early experiments showed that DHA-containing PCs were far less affected by cholesterol than were many other PCs (Finegold, 1993; Shinitzky, 1984). These results showed that cholesterol demonstrated little monolayer “condensation” and bilayer permeability with DHA-containing PCs and suggested that cholesterol may exhibit poor solubility in these membranes. Arriving at a similar conclusion by a completely different method, Dusserre et al. (1995) reported cholesterol efflux from plasma membranes remained the same after incorporation of oleate, linoleate or arachidonate but increased with EPA and DHA. They suggested that incorporation of DHA into the membrane inner leaflet forces cholesterol into outer leaflet where it is more readily lost from the membrane. While it is beyond the scope of this review, many differential scanning calorimetry experiments have demonstrated cholesterol-induced phase separations in PC bilayers (Shinitzky, 1984; Ghosh et al., 1973; Stillwell et al., 1996).' ―Stillwell

'At 15 mol% or more 18∶0-22∶6 PE in SM, a plateau region was observed in the pressure–area isotherms indicating “squeeze out” of 18∶0-22∶6 PE from the monolayers. Addition of cholesterol to equimolar amounts of SM and 18∶0-22∶6 PE further increased the size of the plateau regions supporting the concept of fluid–fluid phase separation into a cholesterol- and SM-rich liquid ordered phase and a 18∶0-22:6 PE-rich liquid disordered phase.' ―Stillwell

'A simple elimination of one double bond from DHA producing DPA (22∶5, omega-6) results in the loss of several behavioural features in animals (Eldho et al., 2003; Ward et al., 1996).' ―Stillwell
​

[2] Demel, R. A. "The properties of polyunsaturated lecithins in monolayers and liposomes and the interactions of these lecithins with cholesterol." Biochimica et Biophysica Acta (BBA)-Biomembranes (1972)

'SUMMARY:

1. The force-area characteristics of monolayers of synthetic lecithins with one to six double bonds in one acyl chain have been studied.

2. The area per molecule increases stepwise. The most significant increase is observed after the introduction of the first double bond. The subsequent introduction of two, three or four double bonds or polyunsaturated chains at both ester positions produces some further increase.

3. The interaction with cholesterol depends on the unsaturation and the distribution of the double bonds between the acyl chains.

[...]

5. No significant differences in behavior are found for the two structural isomers with a mono- or disaturated chain at the 1- or 2-position.

6. The permeability of liposomes, derived from the above mentioned lecithins, to glucose, erythritol and glycerol increases in the same order as the area per molecule at the air-water interface.

7. The presence of cholesterol reduced the permeability to glucose, erythritol, glycerol only for the lecithins which showed a condensation effect. 8. The unsaturation and the distribution of the dbbuble bonds appear to be of critical importance for the barrier properties of lecithins and for the interaction with cholesterol.' ―Demel

'Liposomes showed an increased permeability for glycerol, erythritol, and glucose, when the fatty acid constituents of the lecithin molecule showed an increase in unsaturation.' ―Demel

​

'The results compiled in Figs. 3A–3C demonstrate that the permeability of pure lecithin liposomes towards glucose increases with increasing unsaturation of the fatty acid constituents. Monolayer studies showed already that increasing unsaturation increases the area per molecule (Figs. 1A–1C). The permeability of lecithin liposomes to glucose is particularly increased when the unsaturation is increased from one to two double bonds, (1-stearoyl-2-oleoyl)-3-lecithin versus (1-palmitoyl-2-linoleoyl)-3-lecithin. Comparable permeability rates are observed for (1-palmitoyl-2-linoleoyl)-3-lecithins, (1-linoleoyl-2-palmitoyl)-3-lecithin, (1-palmitoyl-2-linolenoyl)-3-lecithin and (1-palmitoyl-2-arachidonoyl)-3-lecithin (Figs. 3A and 3B). A further increase in permeability is observed for (1-palmitoyl-2-docosahexaenoyl)-3-lecithin and particularly for the lecithins with two unsaturated fatty acid chains (1,2-dilinoleoyl)-3-lecithin and (1,2-dilinolenoyl)-3-lecithin.' ―Demel

'The data on the interfacial properties of a great number of synthetic lecithin species demonstrate that the area per molecule is increased with increasing unsaturation of the acyl moiety.' ―Demel

'Unsaturation to two, three, four or six double bonds in one acyl chain effects a further but smaller area increase.' ―Demel

'The noticed increase in permeability for glycerol, erythritol and glucose with increasing unsaturation in synthetic lecithins is also noticed for lecithins from natural origins. Natural products containing high amounts of polyunsaturated fatty acids showed also a high permeability for glucose. Egg lecithin containing 4o % docosahexaenoic acid and soya bean lecithin containing 67 % linoleic acid, the latter containing an appreciable amount of (1,2-dilinoleoyl)-3-lecithin, give rise to a glucose leak of 65 % (Fig. 7).' ―Demel

​

'The studies with unsaturated lecithin species in model membranes demonstrate the importance of the degree of unsaturation with respect to the permeability properties of the lipid barrier. The unsaturation and the distribution of the double bonds is also of critical importance for the interaction with cholesterol,' ―Demel​

 

[MrSmart]

Since we're dealing with DHA-deficient Kartoffel here

That made my day.

 

[General Orange]

So, when intake of DHA is high via diet, does the body get lazy in converting DHA from ALA?

 

[General Orange]

I would like to add, the intake of DHA via diet is normally not needed when Peating, but could be useful when PUFA is high:

The use of ALA labelled with radioisotopes suggested that with a background diet high in saturated fat conversion to long-chain metabolites is approximately 6% for EPA and 3.8% for DHA. With a diet rich in n-6 PUFA, conversion is reduced by 40 to 50%.

Under the circumstances of experiencing Brain shivers or zapps from excessive serotonin or MDMA or SSRI withdrawal, it helps to increase DHA via for example salmon or stable fish-oil supplements.

Curcumin boosts DHA in the brain: implications for the prevention of anxiety disorders

Curcumin (diferuloylmethane), which is a principal component of the spice turmeric, complements the action of DHA in the brain, and this study was performed to determine molecular mechanisms involved. We report that curcumin enhances the synthesis of DHA from its precursor, α-linolenic acid (C18: 3n-3; ALA) and elevates levels of enzymes involved in the synthesis of DHA such as FADS2 and elongase 2 in both liver and brain tissue.

edit
Dietary Stearidonic Acid Is a Long Chain (n-3) Polyunsaturated Fatty Acid with Potential Health Benefits

The therapeutic and health-promoting effects of (n-3) long-chain PUFA (LCPUFA) from fish are well known, although these same benefits may not be shared by their precursor, α-linolenic acid (ALA). World-wide agencies and scientific organizations (i.e. FDA, AHA, International Society for the Study of Fatty Acids and Lipids, Institute of Medicine, WHO, etc.) have made similar dietary recommendations for (n-3) LCPUFA; however, due to concerns regarding the safety of consuming fish, alternative sources of (n-3) LCPUFA are being investigated. One such lipid is stearidonic acid (SDA), a naturally occurring (n-3) PUFA that may have similar biological properties to eicosapentaenoic acid (EPA), a major (n-3) PUFA in fish oil. ...

 

[MrSmart]

So, when intake of DHA is high via diet, does the body get lazy in converting DHA from ALA?

The direct conversion rate seems to consistent across all dietary intakes, however, high α-linolenic acid increases human cell membrane composition of ALA (18:3n−3), EPA (20:5n−3), and DPA (22:5n−3), with no changes to DHA¹. It was even reduced in some other studies. The de-novo synthesis from ALA in humans is rather low, but increasing ALA intake will reliably improve absolute levels of DHA, up to a point. Still, the conversion levels vary in the range of 0.05-0.1%, whether or not that is enough to support brain function is debatable. Our brains have around 5g of DHA, most of it accumulated at very early years, including prenatally, the recycling of such is close to the amount we can normally synthesize².

(1) Goyens, Petra LL, et al. "Conversion of α-linolenic acid in humans is influenced by the absolute amounts of α-linolenic acid and linoleic acid in the diet and not by their ratio–." The American journal of clinical nutrition 84.1 (2006): 44-53.
(2) Domenichiello, Anthony F., Alex P. Kitson, and Richard P. Bazinet. "Is docosahexaenoic acid synthesis from α-linolenic acid sufficient to supply the adult brain?." Progress in lipid research 59 (2015): 54-66.

 

[Kartoffel]

You're an insult to the authors of those studies, myself, children with Zellweger's disease, and to reason itself. I can tell by your comments that you hadn't even read the study, and also that you have zero comprehension of DHA deficiency disease.

Of course I read the study, you should have done the same before you cited it as evidence for you grand claim. This paper doesn't prove any essentiality of anything. Period. The paper has not only been criticized by me but by his peers, so there is no need to insult anyone here. Just for you I will quote this paragraph from Paker et al. again:

"In previous open studies [here they reference Martinez], it had been stated that DHA supplementation was associated with improvements in vision and growth of these children. In a similar fashion, we also noticed improvement in vision, weight, and height in both groups, but these effects were not related to DHA supplementation because they were present also in the untreated group." [...] In light of these findings of maturational effects in untreated individuals, other alleged benefits, including changes in myelin, are suspect without a comparison group. (Paker et al. 2010)

The enhanced cholesterol-excluding property of DHA compared to all other membrane lipids becomes apparent in MRI images of patients with Zellweger's disease.

No it doesn't! And my claim stands: The Martinez paper is bad sciene with terrible methodology. I will ask again: what is that Martinez paper supposed to prove? What are those MRI images supposed to prove? Paker et al. 2010 showed that the same things happened to Zellweger's children without any DHA in their control group! It's amazing how you can continue to ignore the fact that this study didn't use a control group, and still present it as some kind of evidence for DHA's essentiality. If DHA is essential,`and the central problem in Zellweger's, then why doesn't DHA supplementation improve the development of Zellweger's? Why can PUFA or DHA deficiency be cured by supplementing other nutrients, and not the missing fatty acids?As long as you can't answer those simple questions on the in vivo level, you can make all the arguments abouts it's essential role in membranes that you want, it won't discard the more basic, and more clear, evidence.

Since mammals cannot synthesize either ω−3 nor ω−6 fatty acids, what would happen if a person were to avoid both? If you had to pick between one or the other, which one would you choose and why?

Since the consumption of high ω-3 oils like fish oil shortens life span the most in long lived animals (Lopez-Dominguez et al. 2014; Schroder and Brunet 2015) , I would probably go for avoiding them instead of a little oil high in ω-6 , but there isn't enough data for me to make a reasonable choice. Both should be avoided as much as possible, but I think in the long-term a little ω-6 is better than a little ω-3.

I will read and consider all the material you posted (as I always do since most of your stuff is really good), but I suggest you calm down a little and try to respond to reasonable criticism without insulting others and labeling them your intelectual inferiors simply because you can't stand having your arguments questioned.

 

[sunraiser]

Of course I read the study, you should have done the same before you cited it as evidence for you grand claim. This paper doesn't prove any essentiality of anything. Period. The paper has not only been criticized by me but by his peers, so there is no need to insult anyone here. Just for you I will quote this paragraph from Paker et al. again:

"In previous open studies [here they reference Martinez], it had been stated that DHA supplementation was associated with improvements in vision and growth of these children. In a similar fashion, we also noticed improvement in vision, weight, and height in both groups, but these effects were not related to DHA supplementation because they were present also in the untreated group." (Paker et al. 2010)




No it doesn't! And my claim stands: The Martinez paper is bad sciene with terrible methodology. I will ask again: what is that Martinez paper supposed to prove? What are those MRI images supposed to prove? Paker et al. 2010 showed that the same things happened to Zellweger's children without any DHA in their control group! It's amazing how you can continue to ignore the fact that this study didn't use a control group, and still present it as some kind of evidence for DHA's essentiality. If DHA is essential,`and the central problem in Zellweger's, then why doesn't DHA supplementation improve the development of Zellweger's? Why can PUFA or DHA deficiency be cured by supplementing other nutrients, and not the missing fatty acids?As long as you can't answer those simple questions on the in vivo level, you can make all the arguments abouts it's essential role in membranes that you want.

.....

I know you were arguing a specific point, but to bring a human and common sense thought and perhaps provide practical suggestions to this topic...

Surely this just highlights the transience of health. Your (and RP's) theory is as follows:

Optimal nutritional status = no DHA need therefore we should avoid DHA.

But from your post that isn't what I believe should be taken from the argument. I would suggest the following :

Suboptimal health = DHA required to varying levels while moving towards health.

You cannot just ignore the process. Health is transient and DHA can provide an important function while a given deficiency or metabolic challenge is present. Living life generally presents these challenges regardless so total avoidance to mimic the needs of a theoretical ideal scenario doesn't make sense.

Annnd just for some anecdote: i eat mackerel or salmon once or twice a week based on cravings. Cravings for non stimulant whole foods are the most relevant and intelligent guide to your PERSONAL current needs, imo.

Not to derail your argument about the paper, more to highlight an idea that may or may not further discussion :)

tldr: another case of correlation ! = causation. o3 rich foods reducing lifespan may just mean these people never reached metabolic optimum and therefore the best possible health they could achieve was by meeting their o3 needs. Living life is often going to mean optimal lab conditions aren't achievable!

 

[MrSmart]

Animals fed n-3 deficient diets literally have missing parts of the brain. Not all FA can substitute their properties. Unsaturation in brain tissue is a must, how is this even debatable.

I think the problem here is that people often take things to the extreme. Yes PUFAs are bad to include in your diet, but to absolutely deny their complete existence in the human body as redundant is just madness.

I think if asked, Ray will tend to agree.

 

[Kartoffel]

I know you were arguing a specific point, but to bring a human and common sense thought and perhaps provide practical suggestions to this topic...

Surely this just highlights the transience of health. Your (and RP's) theory is as follows:

Optimal nutritional status = no DHA need therefore we should avoid DHA.

But from your post that isn't what I believe should be taken from the argument. I would suggest the following :

Suboptimal health = DHA required to varying levels while moving towards health.

You cannot just ignore the process. Health is transient and DHA can provide an important function while a given deficiency or metabolic challenge is present. Living life generally presents these challenges regardless so total avoidance to mimic the needs of a theoretical ideal scenario doesn't make sense.

Annnd just for some anecdote: i eat mackerel or salmon once or twice a week based on cravings. Cravings for non stimulant whole foods are the most relevant and intelligent guide to your PERSONAL current needs, imo.

Not to derail your argument about the paper, more to highlight an idea that may or may not further discussion :)

tldr: another case of correlation ! = causation. o3 rich foods reducing lifespan may just mean these people never reached metabolic optimum and therefore the best possible health they could achieve was by meeting their o3 needs. Living life is often going to mean optimal lab conditions aren't achievable!

I was making a specific point about that paper, but a general one about DHA's supposed essentiality - where is the evidence that DHA is essential? I think the papers Travis has presented here don't support any claim like this. The argument that a highly unsaturated fatty acid like DHA is needed for "membrane fluidity", and proper exclusion and/or influx of different substances has been around for decades, and I think Peat has talked sufficiently about why this view isn't supported by anthing resembling real science. I am not rejecting this idea because I don't want it to be true, I just don't objectively see any evidence. I don't reject Travis's evidence because I dislike him, but because I think these studies are genuinely terrible. A good professor would smack you with a thick book, if you presented him a study like this without a control group and then even made such outrageous claims.
Food cravings are of course important to tell you that something is missing, but how can you know that it is PUFA that you are craving and not something else present in fish? @haidut posted a study not long ago showing that parvalbumin found in fish strongly protects the brain, and might be a more reasonable candidate explaining the beneficial effects of fish.

 

[Dave Clark]

Is squalene or alkyglycerols beneficial, or they as bad as fish oil? In fact, are they even PUFAs, that is something I am not clear on? I thought I read somewhere that squalene was a different type of omega fat, but I can't seem to get any information clarifying whether it is a fat or not.

 

[nwo2012]

Ok and I did get a good laugh at some of this:

Me to RP

[1] Ahmad, Aneeq. "Decrease in neuron size in docosahexaenoic acid-deficient brain." Pediatric neurology (2002)

What happens without DHA or its precursor α-linolenic acid? This is by no mean mysterious, and the answer can be found in dozens of published studies. Without DHA or its precursor α-linolenic acid, omega−6 fatty acids will preferentially become incorporated into the cell membrane. Since we're dealing with DHA-deficient Kartoffel here, I'll highlight the two most pertinent lipid species from the above-cited study: Docosahexaenoic acid (22∶6ω−3) is shown in dark blue, while osbond acid (22∶6ω−6) gets lighter shade of same (or is that purple?):

Now Kartoffel, what is the longest ω−9 fatty acid shown in the chart? and how prevalent is it? Since mammals cannot synthesize either ω−3 nor ω−6 fatty acids, what would happen if a person were to avoid both? If you had to pick between one or the other, which one would you choose and why?

As it turns out, this extra double bond of DHA and its position affords this lipid the greatest ability to exclude cholesterol from cell membranes. This has been confirmed in dozens of in vitro studies, many of which can be found in the citation section of this article:

[2] Wassall, Stephen. "Order from disorder, corralling cholesterol with chaotic lipids: The role of polyunsaturated lipids in membrane raft formation." Chemistry and physics of lipids (2004)

'Of special importance is the ω−3-PUFA docosahexaenoic acid (DHA), with 22 carbons and six double bonds that constitute the most highly unsaturated fatty acid naturally occurring. Our experiments target the membrane as a likely site of action and focus upon the interaction of cholesterol with PUFA-containing phospholipids. They support the idea that steric incompatibility of the rigid steroid moiety for highly disordered PUFA chains promotes lateral segregation of lipids into PUFA-rich/sterol-poor and PUFA-poor/sterol-rich regions. Solid state ²H NMR and X-ray diffraction demonstrate that the solubility of cholesterol is low in polyunsaturated bilayers.' ―Wassall

Is Kartoffel going to read this article before mocking it? of course he's won't. Watch Kartoffel insinuate that all this is 'bad science' regardless.

The enhanced cholesterol-excluding property of DHA compared to all other membrane lipids becomes apparent in MRI images of patients with Zellweger's disease. Just like ω−3-deficient rats, the brains of Zellweger's patients are also enriched ω−6 fatty acids in an amount corresponding to the DHA-displaced:

[3] Martinez, Manuela. "MRI evidence that docosahexaenoic acid ethyl ester improves myelination in generalized peroxisomal disorders." Neurology (1998)

[4] Martinez, Manuela. "MRI evidence that docosahexaenoic acid ethyl ester improves myelination in generalized peroxisomal disorders." Neurology (1998)

With the loss of only one double bond: cholesterol, pregnenolone, and progesterone transgress into grey matter cell membranes. The increased affinity of the DHA-deficient grey matter for sterols leads to a higher density membrane, reduced glucose flux, and impaired myelination: Pregnenolone and progesterone form a substantial component of myelin, essential steroids accounting for nearly half its mass. Do you really think that Mead acid alone, the most unsaturated membrane lipid we can make ourselves, can ensure proper brain function? Mead acid has merely three double bonds, and even osbond acid—having five of these—fails to maintain proper brain function.

Just as with hydrophilicity, volume also decreases as a function of unsaturation. A cell membrane of lower volume is more glucose-permeant, and besides promoting proper myelination it can also be argued that DHA promotes intelligence by increasing glucose flux.

[5] Kim, Jeffrey. "Dietary DHA reduces downstream endocannabinoid and inflammatory gene expression and epididymal fat mass while improving aspects of glucose use in muscle in C57BL/6J mice." International journal of obesity (2016)

"With the institutions of research and education controlled by pharmaceutical, military and industrial interests for their own benefit, fundamental progress in knowledge is a threat to the system." ―Ray Peat

https://raypeatforum.com/community/threads/is-omega-3-fish-oil-bad.24798/page-3#post-354962
Hii Ray,
What do you make of this argument. I dont buy it personally,

RP

What argument? Who is making those comments? Does he sell fish oil? Which Kartoffel is he addressing?

Me

That is forum member Travis making the argument that DHA is essential as it kerps cholesterol out of the cell membrane and claims we would die without out. But does not recommend fish oil and that we get enough from milk and beef. Kartoffel is saying Travis is wrong and they've been arguing in a few different threads.

RP

The idea about cholesterol and lipid bilayer membranes was very popular when I was a graduate student in the late ‘60s, but by the early ‘70s most biologists and biochemists realized that the in vitro models had nothing to do with physiology. A physicist in Indiana is carrying on about the interactions of DHA and cholesterol, making really ignorant comments about its biological implications. Cholesterol is associated with the cytoskeletal proteins all through the cytoplasm and nucleus. DHA is one of the most disruptive fatty acids.

Molecules 2018, 23(7), 1531; https://
α-Synuclein and Polyunsaturated Fatty Acids: Molecular Basis of the Interaction and Implication in Neurodegeneration
Chiara Fecchio 1, Luana Palazzi 2and Patrizia Polverino de Laureto 2,* [OrcID]
1Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy
2Department of Pharmaceutical and Pharmacological Sciences, CRIBI, University of Padova, 35131 Padova, Italy
(This article belongs to the Special Issue The Multiple Roles of Fatty Acids)
View Full-Text
Abstract
α-Synuclein (α-syn) is a 140-amino acid protein, the physiological function of which has yet to be clarified. It is involved in several neurodegenerative disorders, and the interaction of the protein with brain lipids plays an important role in the pathogenesis of Parkinson’s disease (PD). Polyunsaturated fatty acids (PUFA) are highly abundant in the brain where they play critical roles in neuronal membrane fluidity and permeability, serve as energy reserves and function as second messengers in cell signaling. PUFA concentration and composition in the brain are altered with age when also an increase of lipid peroxidation is observed. Considering that PD is clearly correlated with oxidative stress, PUFA abundance and composition became of great interest in neurodegeneration studies because of PUFA’s high propensity to oxidize. The high levels of the PUFA docosahexaenoic acid (DHA) in brain areas containing α-syn inclusions in patients with PD further support the hypothesis of possible interactions between α-syn and DHA. Additionally, a possible functional role of α-syn in sequestering the early peroxidation products of fatty acids was recently proposed. Here, we provide an overview of the current knowledge regarding the molecular interactions between α-syn and fatty acids and the effect exerted by the protein on their oxidative state. We highlight recent findings supporting a neuroprotective role of the protein, linking α-syn, altered lipid composition in neurodegenerative disorders and PD development.

 

[Kartoffel]

Ray said:

Does he sell fish oil?

That made my day :)

 

[MrSmart]

Ok and I did get a good laugh at some of this:

Me to RP

Among the different FAs present in the brain, omega-6 (n-6) and omega-3 (n-3) are essential; therefore, they must be obtained from food [28]. These PUFAs are abundant in neuronal membranes and exert several important effects (Figure 1). Notably, DHA and AA deficiencies lead to severe problems in the brains, since n-3 such as DHA is required for brain development and function, while n-6 such as AA yields essentials metabolic products. Increasing evidence suggests that a balanced dietary intake of these PUFAs has beneficial effects in maintaining the health state of the brain [16]. In particular, dietary intake of DHA strongly influences DHA levels in different tissues, in a faster way than it happens for AA [29,30].

The presence of PUFAs guarantees membrane fluidity and plasticity, providing a more dynamic environment due to the high number of double bonds, even if in a different extent between n-3 and n-6 fatty acids [10]. As a consequence, not only the presence of PUFAs, but also the balance between n-3 and n-6 PUFAs influences different processes on membranes, such as trafficking and vesicle budding and fusion [28].

PUFAs act also on vesicles formation and fusion in an active manner, contributing to an efficient release of neurotransmitters and hormones or neurite outgrowth [23,31]. Indeed, PUFAs activate with high specificity a protein localized on the plasma membrane, syntaxin, pushing it to enter the SNARE complex [32], which is essential for vesicle trafficking [31,33,34]. When phospholipases induce the release of PUFAs, typically occupying the sn-2 position in phospholipids, they become available to directly contribute to many processes or to be converted into eicosanoids [35]. PUFAs can activate syntaxin, and PUFA metabolites can either activate or inhibit vesicle fusion processes [32].

Among other important functions, PUFAs act also on the apoptosis pathway [36]. Apoptosis is a tightly-controlled process bringing cells to death without causing an inflammatory response. A recognized signal triggering of this process is the accumulation of phospholipase-released free PUFAs [37]. On the other side, also cell proliferation is influenced by lipids [38].

Finally, a major role in brain health involves the pro- or anti-inflammatory effect of molecules deriving from the catabolism of n-6 or n-3 PUFAs, respectively [28]. Several actions derived from PUFA metabolites have opposite effects depending on their n-3 or n-6 FA derivation [28]. DHA and AA, de-esterified by PLA-2 enzymes, can be metabolized through different pathways, but generally, metabolites of n-3, such as DHA or eicosapentaenoic acid (EPA), show anti-inflammatory properties, while those deriving from AA show opposite effects [39,40]. Notably, COX2, which facilitates the formation of prostaglandin E2 from AA, is expressed at a higher level in neurons than in any other tissue. AA may also be converted to other metabolites, usually conducible to pro-inflammatory activity [41]. On the contrary, DHA metabolites are less clearly identified, but the main known products include 17S-hydroxy-DHA, 14-hydroxy-DHA and LOX-induced resolvin D5, maresin 1 and neuroprotectin D1 [42]. These molecules, at variance with AA products, are reported to act as “pro-resolving” mediators [26], since they are involved in an active mechanism of inflammation resolution. The discovery of mediators with anti-inflammatory or “pro-resolving” effects derived from n-3 PUFAs highlighted the presence of active pathways for inflammation resolution other than a “dilution effect”, able to actively compete with AA metabolites [26], underlining the importance of such protective mechanisms in the brain.

To exert their functions, n-3 metabolites have been reported to inhibit NF-κB(nuclear factor kappa-light-chain-enhancer of activated B cells), thus controlling several cytokines [43], and to bind the peroxisome proliferator-activated receptor (PPAR) family of transcription factors more efficiently than n-6-derived metabolites [44]. Given their different and sometimes opposite effects, the importance of a strict controlled ratio between n-6 and n-3 accumulation and metabolism in the brain becomes clear.

Fecchio, C., L. Palazzi, and P. P. de Laureto. "α-Synuclein and Polyunsaturated Fatty Acids: Molecular Basis of the Interaction and Implication in Neurodegeneration." Molecules (Basel, Switzerland) 23.7 (2018).

And here we are presented with a similar issue that is due to a natural imbalance rather than a presence itself. This is why taking DHA is better than not taking it on a high LA diet, but maybe more detrimental if n-6 intake is very low. Lipid peroxidation will still be an issue in this case, but it's not the only issue with the PUFA biochemistry. This is one of the few areas where I disagree with Ray. Keeping the absolute amounts is critical no doubt, but the ideal balance in the subject tissue at any level is even more critical.