#1

The following conclusions represent the official position of the ISSN:

  1. Athletes may be at a higher risk for ω-3 PUFA insufficiency.
  2. Diets rich in ω-3 PUFA, including supplements, are effective strategies for increasing ω-3 PUFA levels.
  3. ω-3 PUFA supplementation, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been shown to enhance endurance capacity and cardiovascular function during aerobic-type exercise.
  4. ω-3 PUFA supplementation may not confer a muscle hypertrophic benefit in young adults.
  5. ω-3 PUFA supplementation in combination with resistance training may improve strength in a dose- and duration-dependent manner.
  6. ω-3 PUFA supplementation may decrease subjective measures of muscle soreness following intense exercise.
  7. ω-3 PUFA supplementation can positively affect various immune cell responses in athletic populations.
  8. Prophylactic ω-3 PUFA supplementation may offer neuroprotective benefits in athletes exposed to repeated head impacts.
  9. ω-3 PUFA supplementation is associated with improved sleep quality.
  10. ω-3 PUFA are classified as prebiotics; however, studies on the gut microbiome and gut health in athletes are currently lacking.
1 Like
#2

I’ll be interviewing Dr Bill Harris of OmegaQuant about Omega 3 in a couple weeks. Any questions for Dr Harris?

Tópicos:

  • fatty15
  • pro resolving mediators
  • fish oil risks
  • fish oil supplement issues
  • others?
3 Likes
#3

I’m personally comfortable with algae omegas, but perhaps ask him about that option relative to fish oil because many of your listeners might not know that is a viable alternative.

1 Like
#4

When will you do the interview @Joseph_Lavelle ?

I asked OmegaQuant some questions by email and on Twitter in November 2024 but they never answered which makes me think that they are total bullshitters. So could you please ask him the following questions?

The last objection of the omega 3 proponents is that they should be taken in phospholipid or krill oil form. However, recent papers show that even these forms don’t work to increase brain levels:

Based on all the above, anyone should conclude that DHA supplementation is harmful. If Dr Bill Harris disagrees, is it because he has access to unpublished data that shows the benefits of DHA supplementation or is it because he makes money selling his BS Omega Index test and is therefore totally biased?

There’s also the question of different benefits in APOE4 carriers but PreventE4 showed that APOE4 carriers did not benefit from DHA supplementation. They might benefit from EPA (not DHA) though according to this trial: ω-3 PUFA for Secondary Prevention of White Matter Lesions and Neuronal Integrity Breakdown in Older Adults A Randomized Clinical Trial 2024: 3y, 975 mg EPA + 650 mg DHA, “neuronal integrity breakdown was reduced by ω-3 treatment in APOEE4 carriers […] Together these findings suggest that an EPA-dominant formula may provide some benefit in APOEE4 carriers with no dementia and WMLs, and DHA-dominant formulas may benefit noncarriers of APOE*E4 with mild-to-moderate AD.”

6 Likes
Omega 3 for neuroprotection: EPA vs DHA?
How much omega-3 do you need?
2g/day of DHA for 2 years has no impact on cognition or hippocampal volume
How much omega-3 do you need?
How much omega-3 do you need?
Predicting Alzheimers & Dementia (and minimizing risk)
How much omega-3 do you need?
Predicting Alzheimers & Dementia (and minimizing risk)
#5

Interesting connection between Omega 3 index and hba1c (longer lived red blood cells)… from Claude and I didn’t confirm. I will ask Dr Harris.

From Claude:

“ “A high omega index (which measures the levels of omega-3 fatty acids EPA and DHA in red blood cell membranes) does appear to be associated with longer-lived red blood cells, though the relationship is complex.

There are some studies that have examined the relationship between omega-3 fatty acids, red blood cell lifespan, and HbA1c values. Here are some relevant findings found by Claude:

  1. A 2011 study by Coban et al. found that omega-3 supplementation in diabetic patients was associated with a slight increase in HbA1c despite no change in fasting blood glucose, suggesting a possible effect on red blood cell lifespan.

  2. Research by Hou et al. (2016) demonstrated that DHA supplementation increased red blood cell deformability and potentially lifespan, which could theoretically affect HbA1c measurements.

  3. A small clinical study by Higuchi et al. observed that patients with higher omega-3 index had slightly higher HbA1c values relative to their average glucose measurements when compared using continuous glucose monitoring.

  4. The D2d trial (Vitamin D and Type 2 Diabetes Study) included secondary analyses that noted differences in HbA1c relative to average glucose in participants with varying levels of omega-3 fatty acids.

“A high omega index (which measures the levels of omega-3 fatty acids EPA and DHA in red blood cell membranes) does appear to be associated with longer-lived red blood cells, though the relationship is complex.

Red blood cells (erythrocytes) typically live for about 120 days in circulation. Their lifespan is influenced by membrane integrity and resistance to oxidative damage. Omega-3 fatty acids, particularly EPA and DHA, get incorporated into red blood cell membranes and can provide several benefits:

  1. Enhanced membrane fluidity - Omega-3s improve the flexibility of red blood cell membranes, which helps them navigate through narrow capillaries without damage.

  2. Reduced oxidative stress - Omega-3s have anti-inflammatory properties that can protect red blood cells from oxidative damage.

  3. Improved deformability - Red blood cells with more flexible membranes can change shape more easily, reducing mechanical stress and potentially extending lifespan.

  4. Decreased eryptosis (programmed red blood cell death) - Some research suggests omega-3s may help reduce premature red blood cell death.

The omega index itself is primarily used as a biomarker for cardiovascular health rather than a direct measure of red blood cell longevity. However, the membrane composition it measures does play a role in determining how long red blood cells survive.

3 Likes
#6

@adssx Good timing. My interview is tomorrow. I couldn’t possibly cover your entire note but I will ask about DHA and depression. I’ll also ask about detrimental effects of DHA. Thanks.

It’s important to know that EPA & DHA benefits are mostly from life long (or very long time) consumption. Omega 3 is a nutrient, not a drug. Short term effects are also real but are far harder to measure. This is hard to test in a study of weeks or a couple years but easier in epidemiological study which can be confounded by many things. Still, a recent paper showed that a higher omega index using Framingham samples was associated with lower ACM. I recall specifically heart disease and cancer. I don’t recall specifics on brain health. It did have a category for “all other” which included accidents, etc. Lower rates of death for higher omega index even though the highest quintile was only 6%-ish. The lowest was below 4% as I recall. I’ll find the paper to include in the podcast show notes.

Also….

RBC omega 3 (EPA / DHA) is a good proxy for organ Omega 3 except for brain. The brain is ½ fat, with a high percentage of DHA. The effect of diet and supplements on brain DHA is less known.

Sufficient Omega 3’s are a part of a healthy body that supports brain health. Omega 3’s can have standalone effects but they are harder to see in healthy subjects or subjects with sufficient omega 3’s already. More omega 3 can help but is harder to measure.

Thanks for the questions!

3 Likes
#7

We have Mendelian randomization for that: and they show that EPA and DHA are useless for cognition and that DHA might even be detrimental for CVD.

3 Likes
#8

Thanks a lot! If you also have time to ask him to comment on the PreventE4 trial results (here), it would be amazing: 2 g/day of DHA over 2y, combined with vitamin B and… nothing improved!

2 Likes
#9

Here is the Omega Index study referenced. It doesn’t speak to brain health other than as affects mortality. DHA and EPA both appear to be associated with lower ACM.

DHA has a bigger effect on omega index scoring than does EPA, FYI.

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

2 Likes
#10

Yes but since then Mendelian randomizations showed that this association was not causal for DHA.

4 Likes
#11

Both DHA and total Omega-3 increase risk of colerectal cancer by 24% in this study (per +1 SD increase) also found in tissues (@DeStrider)

We observed a positive [genetic] correlation between DHA and CRC, both in absolute levels (IVW: β = 0.218, P < .0001; WM: β = 0.266, P < .0001; MR-Egger: β = 0.290, P = .000384) and as a ratio to total fatty acids (IVW: β = 0.213, P = .00196; WM: β = 0.276, P < .0001; MR-Egger: β = 0.291, P = .00683). Similarly, we found a positive [genetic] correlation between omega-3 fatty acids and CRC, both in absolute levels (IVW: β = 0.174, P < .0001; WM: β = 0.225, P < .0001; MR-Egger: β = 0.220, P = .000637) and as a ratio to total fatty acids (IVW: β = 0.164, P = .000297; WM: β = 0.196, P < .0001; MR-Egger: β = 0.221, P = .000585).

Our study utilized data different from previous MR studies to validate the conclusion that omega-3 fatty acids enhance the risk of CRC. Several studies[24–27] have found that CRC tissue contains significantly higher levels of omega-3 PUFAs compared to adjacent normal tissue.

They didn’t write that they removed the SNP’s in the FADS region which are pleiotropic with e.g lipids, though.

FADS gene cluster again, hmm

The largest point estimates were observed for eicosapentaenoic acid (EPA), a long-chain omega-3 fatty acid (OREPA 0.92; 95% CI 0.88–0.96; p = 0.0002). The effect of omega-3 fatty acids was robust to MVMR models accounting for biologically correlated lipids. ‘Leave-one-out’ analyses highlighted the FADS gene cluster as a key driver of the effect.

I think if we choose to not believe there’s pleiotropy with FADS then DHA based on genetic studies causes a clinically relevant increase in aortic stenosis, depression, colorectal cancer, and lung cancer. Meanwhile EPA is protective with regards to depression.

So I’d say until we know more about that, I’d bet on the side of DHA being harmful.

5 Likes