Here is a rather interesting study of rate of aging in the older demographic of 70+. The interventions were daily omega 3, vitamin D and Simple Home Exercise either singly or in combination, with separate arms and controls. Both men and women. Pace of aging was using epigenetic clocks, but in a fairly sophisticated way with good analysis of biomarkers - the clocks were tested individually and collectively.

The biggest impact was omega 3. Adding vitamin D and exercise had a signal in only one clock. The DO-HEALTH study itself had some interesting findings, with important benefits against rate of infections (13%), (pre)frailty (39%), invasive cancer (61%) and falls (10%).

I’m generally skeptical of epigenetic clocks, but here I found the discussion of the clocks of different generations and mode of utilization quite illuminating.

Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial

https://www.nature.com/articles/s43587-024-00793-y

“While observational studies and small pilot trials suggest that vitamin D, omega-3 and exercise may slow biological aging, larger clinical trials testing these treatments individually or in combination are lacking. Here, we report the results of a post hoc analysis among 777 participants of the DO-HEALTH trial on the effect of vitamin D (2,000 IU per day) and/or omega-3 (1 g per day) and/or a home exercise program on four next-generation DNA methylation (DNAm) measures of biological aging (PhenoAge, GrimAge, GrimAge2 and DunedinPACE) over 3 years. Omega-3 alone slowed the DNAm clocks PhenoAge, GrimAge2 and DunedinPACE, and all three treatments had additive benefits on PhenoAge. Overall, from baseline to year 3, standardized effects ranged from 0.16 to 0.32 units (2.9–3.8 months). In summary, our trial indicates a small protective effect of omega-3 treatment on slowing biological aging over 3 years across several clocks, with an additive protective effect of omega-3, vitamin D and exercise based on PhenoAge.”

In the DO-HEALTH trial including all 2,157 participants, we reported that omega-3 alone reduced the rate of infections by 13% (ref. 22) and the rate of falls by 10% (ref. 23), and all three interventions combined had a significant additive benefit on reducing prefrailty by 39% (ref. 24) and incident invasive cancer by 61% (ref. 25) over a 3-year follow-up.

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I’m a big fan of all 3 interventions. It would have been nice if they threw in magnesium as that helps vitamin D absorption but overall it’s a great result.

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They used: “1 g per day of omega-3s (330 mg EPA plus 660 mg DHA from marine algae)”

We know that DHA causes depression, so there’s a tradeoff here? (Sources: Omega 3 makes me depressed: why? )

The DO-HEALTH trial sample does not reflect the general population of adults aged 70 years and older. DO-HEALTH preselected generally healthy and active adults aged 70 years and older; within the Swiss subgroup, more than 50% met the Nurses’ Health Study criteria for healthy agers at baseline. Our subgroup analyses suggested a stronger benefit of omega-3 in participants who started with lower baseline omega-3 (DHA plus EPA) blood levels. Notably, the Swiss subgroup had lower baseline blood omega-3 levels than the total DO-HEALTH population, possibly reflecting the landlocked geography of Switzerland (Extended Data Table 1), which may have supported the benefit of omega-3 supplementation on biological aging in this subsample of DO-HEALTH.

Do I understand correctly Extended Data Fig. 3 that the effects are null in men? (or even borderline detrimental?)

So basically the results is only valid for old (>70yo) women with low serum DHA+EPA?

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What struck me is that the biggest problem for men was SHEP. Note, that no matter the other agent, vit. D or omega 3, the moment you combine them with SHEP, there is detriment. Of course the worst is SHEP by itself. Strange.

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https://x.com/drjohnm/status/1887249671837368644#m

Does these effects compound (so if you eat omega-3 for a long time = higher risk of afib onset?)

Until this is addressed I’m unsure how to make sense of appropriate Omega-3 (EPA/DHA) intake.

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