#41

Just to be clear: I said nothing about fish. I commented on DHA supplementation. Eating fish is probably good. Supplementing with DHA seems useless (or maybe even detrimental).

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#42

More on the negative: Omega-3 fatty acids are a risk factor for colorectal cancer

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#43

A small percentage of EPA gets converted to DHA in the liver, like 20%. Maybe that’s enough but we wouldn’t be doing that if there was no reason. The brain is made of DHA, sperm are made of DHA. You’re not saying it’s unnecessary, just that we have plenty and supplementation doesn’t always help. Probably right in most cases.

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#44

I say that DHA supplementation is detrimental as it seems to cause lung cancer, colorectal cancer, depression, atrial fibrillation, and cardiovascular disease, while it does not prevent dementia.

Of course, DHA is necessary for the body. Just that, unfortunately, supplementation doesn’t work.

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#45

Just checked the DrugAge database: fish oil led to a shorter median and max lifespan in mice (I guess that’s the ITP data?): Fish oil and its possible anti-ageing properties

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#46

You can cherry pick your studies all day long if you choose to. I’ll just keep working on my omega index to take advantage of whatever benefits omega 3’s bring to my body.

You do you.

But for those people here who are being swayed by oddly extreme opinions, here is the 17 study paper (again) covering 40,000 people followed for 5-32 years that associated higher omega 3 index (EPA / DHA) with lower all cause mortality as well as lower rates of death from CVD and cancer and everything else combined. It seems pretty clear to me that I want a higher omega index.

https://www.nature.com/articles/s41467-021-22370-2

It is always better to get nutrients from food rather than supplements. I’m the last person to disagree with that. But a higher omega index is the key even if supplements are the way to get there.

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#47

Yes, higher serum EPA and DHA is associated with a lower risk of many things. However, in the case of DHA, Mendelian randomization studies and RCTs found that this association was not causal. Worse, high-dose DHA supplementation seems detrimental for depression, some cancers, and maybe CVD.

This is not an “oddly extreme opinion”. It’s backed by all the latest research from the best research institutions in the world: Vitamin O (Omega 3) for athletes - #4 by adssx

So, if you aim for a high omega-3 index and cannot achieve it with food, then supplement with EPA only, not DHA. That’s it.

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#48

Harvard paper, just published, that cites the paper you mentioned: Non-Esterified Fatty Acid Profiles and Cause-Specific Mortality: The Cardiovascular Health Study 2025

The final population included 1996 participants with a mean age of 78 years. 60.5% were female. Over a median 11-year follow-up period, 1678 participants died. Total fasting NEFA was associated with higher risk of all-cause mortality (aHR per standard deviation: 1.17, 95% CI [1.10–1.23]). Total post-load NEFA was not associated with mortality. Among subclasses, only monounsaturated fatty acid (MUFA) was associated with total mortality (aHR 1.24, 95% CI [1.09–1.41]). For individual NEFAs, nervonic acid (aHR 1.06, 95% CI [1.01–1.12]), petroselaidic acid (aHR 1.21, 95% CI [1.03–1.42]) and eicosapentaenoic acid (aHR 0.90, 95% CI [0.82–0.99]) were associated with all-cause mortality.

Here as well, association with all-cause mortality for EPA, not DHA.

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#49

@adssx People on this forum respect you and listen to you so what you say matters. You are choosing to broadcast a very strong opinion about DHA (and fish oil to a lesser degree) based on a fraction of the deep scientific study over the last 40 years. Many of the studies you are highlighting were of people with advanced CVD. Do these results apply to healthy people? And don’t throw “Mendelian randomization” around like quotes from the Bible
a study is only as good as the design. This is why the body of work matters. Omega 3’s are one of the most research areas in nutritional science.

Omega 3’s are a nutrient. ALA is an “essential” nutrient. EPA and DHA are always found together in nature. EPA and DHA are only not considered “essential” (die without them) because the body can make a small amount from ALA. But the body will put more EPA and DHA into cells if added to the diet. Adding more is associated with lower all cause mortality. And lower inflammation. And faster recovery from exercise. And better immune function. And why wouldn’t we expect benefits from better functioning cells


I agree that no one should supplement only DHA but I see no reason to fear DHA. Get it by eating fish first or take fish oil that comes with EPA and DHA together as is found in fish. Algae sources can also work if fish is objectionable.

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#50

OK so disclaimer to our silent readers: I’m just a human being, and I often say dumb things, so I might be wrong on this! I actually hope I’m wrong because I supplemented with DHA for a long time (as I followed blindly the advice of some “influencers” without taking the time to properly look at the evidence, and also because the picture is getting worse and worse when you look at the latest evidence) and because I wish DHA could help. So if anyone has strong evidence against what I say: please post it!

Just based on all the latest research. Small low-quality trials or association studies from decades ago have no value when we have larger high-quality RCT (e.g., VITAL-DEP and PreventE4), high quality Mendelian randomization (didn’t exist until a few years ago), and higher quality association studies (adjusted for socio-economic status and comorbidities, with dose–response analysis, etc.).

Not at all. Please read the list again: Vitamin O (Omega 3) for athletes - #4 by adssx

  • PreventE4 was “365 cognitively unimpaired individuals between 55 and 80 (mean age 66)”.
  • VITAL was “20,000 U.S. men and women without cancer or CVD at baseline”. The mechanistic study is in all human being.
  • The Stanford + UCSD paper indeed looked at people “who underwent coronary angiography” so unhealthy. Still, if DHA is detrimental in these people, why would it be beneficial in healthy people? (it might be, but please prove it!)
  • Mendelian randomization studies apply to all people as well
  • The plasma study was done in “289 participants (103 AD patients, 92 MCI patients, and 94 controls)”, so not at all “people with advanced CVD”.
  • Same for the animal studies listed.

Yes, @Neo made good objections about MR studies here: Predicting Alzheimers & Dementia (and minimizing risk) - #623 by Neo

After checking, it seems that these MR studies were well done and that the results are sound (especially when an association, whether positive or negative, was found):

Yes, that’s why in my message I included various types of studies, all showing the null or detrimental effects of DHA supplementation: Vitamin O (Omega 3) for athletes - #4 by adssx

  • Randomized control trials
  • Meta-review of RCTs
  • Mendelian randomization studies
  • Association studies
  • Animal studies
  • Mechanistic studies on humans

Yes, and science moves forward. We should update our practice based on science.

I think one should fear DHA supplementation (dietary is OK, the amount are smaller) and supplement with EPA only if they want to supplement.

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#51

Are any of these studies involving DHA only supplementation? I’m not aware of any studies of DHA supplementation. I’ve only seen separate studies EPA compared to studies of EPA plus DHA, with inferences drawn about DHA. How many other differences were in the studies that could confound the possible “DHA offsets EPA benefits somewhat” hypothesis? It is far from clear.

EPA and DHA are found together in nature and the longest lived people have been eating it that way forever. Supplements are not ideal but better than nothing. That said I see no reason to take DHA only supplements or EPA only supplements. I eat fish. I also take fish oil to get a high omega index. That is what I think the science supports.

I have no idea about brain health effects from omega 3’s but lower chronic inflammation cannot be a bad thing for brain function. Omega 3’s are not a silver bullet to cure whatever is wrong with a person. Omega 3’s are a nutrient that the body expects and will use to function better. A high amount of EPA and DHA in RBC membranes has been shown to be associated with better health and longer life in humans. It s true that no one knows if it is causal but you got do what you can with what you have.

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#52

Please Joseph, just read: Vitamin O (Omega 3) for athletes - #4 by adssx

#53

As you like association studies @çșŠç‘Ÿć€«_æ‹‰ç»Žć°”: Novel Classification of Cardiovascular Disease Subtypes Reveals Associations Between Mortality and Polyunsaturated Fatty Acids: Insights from the United Kingdom Biobank Study 2024

They clustered people into 3 CVD subtypes based on some biomarkers:

Principal component analysis and k-means clustering were used to determine the CVD subtype. Variables included age, body mass index, waist–hip ratio, diastolic blood pressure, systolic blood pressure, total cholesterol, total triglycerides, high-density lipoprotein-cholesterol, apolipoprotein B:apolipoprotein A1, glycated hemoglobin, creatinine, albumin, C-reactive protein, white blood cell count, platelet count, and hemoglobin concentration.
Three distinct CVD subtypes were identified, with cluster 3 characterized by older age, male gender, and low high-density lipoprotein-cholesterol, having the highest risk of mortality. Clusters 2 and 3 had the highest DHA and ω-6/ω-3 ratios, respectively, compared with Cluster 1.
Cluster 1 consisted of the youngest individuals with elevated levels of ApoB:ApoA1, TC, TG, SBP, and DBP. Cluster 2 predominantly comprised females (77.9%) with the lowest BMI, WHR, TG, creatinine, C-reactive protein, WBC, and hemoglobin concentration, while having the highest levels of HDL-cholesterol. Cluster 3 primarily consisted of males (72.7%) who were older, with a higher BMI, WHR, and HbA1c, and a lower TC, HDL-cholesterol, and PLT.

They adjusted for:

  1. sociodemographic factors, including gender and household income (less than ÂŁ18,000, ÂŁ18,000 to ÂŁ30,999, ÂŁ31,000 to ÂŁ51,999, ÂŁ52,000 to ÂŁ100,000 and greater than ÂŁ100,000);
  2. socioeconomic status, including Townsend deprivation index;
  3. lifestyle habits, including smoking status (never, former, and current), alcohol status (never, former, and current), and physical activity (low, moderate, and high);
  4. comorbidities, including hypertension and diabetes; 5) drug use, including cholesterol-lowering medication use, antihypertensive drugs use, insulin treatment, and aspirin use.

Results:

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In multivariate models, we found significant nonlinear relationships between total PUFAs, ω-3, and DHA and risk of all-cause, CVD, and IHD mortality (all P for nonlinearity < 0.05). There was an inverse L-shaped exposure–response relationship between these PUFAs and risk of all-cause mortality, whereas there was a U-shaped exposure–response relationship for risk of CVD and IHD mortality. In the absence of these PUFAs, risk of the outcome increases. Within a specific range, higher ω-3 and DHA concentrations are associated with a reduced risk of outcomes [hazard ratio (HR) < 1.0]. However, once PUFAs reach a specific threshold level, risk stabilizes and no longer continues to decrease or even increase. Cluster 1 displayed the lowest HR under similar exposure levels in all-cause mortality (Figure 10).
We found significant linear relationships between ω-6 and LA and risk of the studied outcomes (all P for linearity < 0.05). High level of these PUFAs were associated with low risk of all-cause and CVD mortality but were associated with an increased risk of IHD mortality.
Our findings suggest that the mortality rates of ω-3 and DHA with CVD and IHD begin to trend upward at high intakes (fourth quartile array). The possible reason for this is that excess ω-3 and DHA may be predisposing factors for atrial fibrillation

So, even this association study confirms that higher might not be better, especially for DHA. The potential inconsistency with previous studies is, I guess, that this one adjusted for many factors, especially income and education. Rich people eat more fish, and if you don’t account for that, the omega-3 index is just a wealth index. Physical exercise might also help to absorb omega 3, so it’s good that this study adjusted for “physical activity (low, moderate, and high)”.

You also asked “Do these results apply to healthy people?”: here they “constructed a subtype model of cardiovascular patients” “according to patient baseline characteristics”. They identified 3 clusters that I would call “young unhealthy” (1), “healthy” (2, mostly females), and “old unhealthy” (3). The results were similar across these clusters.

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2g/day of DHA for 2 years has no impact on cognition or hippocampal volume
#54

As a rule of thumb, Dr. Stanfield has been recommending EPA to DHA in a 2:1 ratio. After looking at the results of these various studies, I may even want to try for a higher ratio of EPA to DHA. It does appear that DHA is the red-headed stepchild of the Omega 3 family. A bit of DHA is probably OK, but you want to limit supplementation to mostly EPA if possible. Eating fish is probably the best way to supplement Omega 3s.

I’m glad that @adssx has brought these facts up about DHA, but it seems like it’s become a crusade now. :wink:

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#55

I suspect that it’s partially designed to stimulate opposition. I do that myself sometimes - I will crusade on some issue, because I want people to challenge my idea/findings. Sometimes, if you just casually present something without really pushing it, it just gets ignored. And some ideas/findings are too important to be ignored, like EPA and DHA because it’s pushed so much by influencers and so many people supplement. It’s important to thoroughly discuss it, and hopefully reach some more justified practices with better evidence. For that it is useful to challenge people to present their best opposing arguments and findings. At least that’s how I take it :grin:.

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#56

That’s exactly the reason. I’m pushing for people to provide alternative explanations and challenge what started as a question ( Omega 3 makes me depressed: why? ) but what is now, I think, a fact: supplemental DHA is detrimental to your health. So far, no one has provided any valid objections. I hope one of the “influencers” I contacted will get back to me. I have low expectations.

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#57

I feel bad for @adssx for pulling together so much information and spending so much time on this, just for people to not read his posts thoroughly and instead just quickly criticize and keep to their pre-conceived notions of the what is right. I hope we can do better in the future.

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#58

I think many , like myself, find the information very helpful and will help guide my supplementation strategy.

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#59

A few people messaged me directly and told me switched to EPA-only or were considering doing so. That being said: I might be wrong. Mitchell Lee from Ora Biomedical made an intro to Matt Kaeberlein (his cofounder) to discuss EPA vs DHA so I hope Matt will get back to me. It would be good to know his thoughts.

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#60

I have not tried to analyse the information in any detail, but I have shifted to taking only EPA. As far as I can tell on a superficial scanning of the information there is clearly an argument against DHA supplementation.

My own personal results with fish oil is that I noticed a benefit from supplementation with a mixture a few years ago. Hence I have now stuck to an EPA only version possibly for a few months now. I have not checked exactly when I changed to EPA.

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