Clinical trials reveal benefits of exercise, vitamin D3 and omega-3 on healthy ageing

Hi 🙏

This week, I'm excited to dive into the DO-HEALTH trial, a landmark clinical trial that just delivered some powerful new insights into the biology of ageing.

At its core, the DO-HEALTH trial was a massive, 3-year clinical trial conducted across five European countries (Switzerland, Germany, Austria, France, and Portugal).

It recruited 2,157 healthy adults, all aged 70 or older, who were living active and independent lives.

The study was designed as a 2×2×2 factorial trial, a clever way to test the individual and combined effects of three simple interventions:

• High-dose Vitamin D₃ supplementation
• ω−3 fatty acid (omega-3) supplementation
• A simple home exercise program

Participants were divided into groups to receive one, two, or all three of these interventions, or a placebo/control.

Initially, the trial focused on endpoints like cancer risk and found that taking all these supplements reduced the risk of cancer >60% when compared to controls.

Then, a recent, extended analysis has revealed something even more fundamental about the ageing process itself.

How can we measure "biological age"?

Before we get to the exciting results, we need to ask a crucial question. How do you even measure ageing?

We all have a chronological age (the number of candles on our birthday cake), but our biological age (how old our cells and tissues are functionally) can be quite different.

While there is no single "gold standard" for measuring biological age, scientists have developed a powerful tool called epigenetic clocks.

Epigenetics refers to the chemical marks or tags that attach to the DNA and tell your genes when to switch on or off.

One common type of mark is called DNA methylation. As we age, the patterns of these marks change in predictable ways. Epigenetic clocks are sophisticated algorithms that analyze these patterns from a blood sample to calculate a person's biological age.

The DO-HEALTH researchers used several well-established clocks to get a comprehensive picture, including Horvath’s multitissue clock, Hannum's blood-based clock, PhenoAge4, GrimAge2, and DunedinPACE (which measures the pace of ageing).

These are not just theoretical concepts; numerous previous studies have shown they are strong indicators of cellular and biological ageing.

A trio for healthy ageing?

So, what happened when the researchers analyzed the epigenetic clocks of the DO-HEALTH participants after three years?

The results were striking.

The analysis showed a significant slowing of biological ageing specifically in the group that received all three interventions combined: Vitamin D₃, ω−3s, and the exercise program.

This suggests a powerful synergy.

While each component is known to be beneficial, their combined effect on these fundamental markers of ageing was greater than the sum of their parts.

The interventions literally appeared to slow the ticking of the participants' internal, biological clocks.

Why is this important?

Ageing is the number one risk factor for the top human diseases and new proposals among scientists is to treat ageing to combat these diseases.

Towards these proposals, the DO-HEALTH trial is a significant boost.

First, it suggests that therapeutic intervention can slow down ageing.

Second, it also suggests a reduction in cancer risk (important to note that it is the risk of cancer that was reduced but not already developed cancer).

Finally, it provides strong evidence that we have a degree of control over how we age, and that a multi-pronged approach spread over nutrition, supplementation, and physical activity could be an effective strategy.

References

For the curios lot, here are the links to the trial and the flagship research papers.

• https://clinicaltrials.gov/study/NCT01745263
• https://doi.org/10.3389/fragi.2022.852643
• https://doi.org/10.1038/s43587-024-00793-y

🧠Word of the day

Epigenetics - the study of heritable changes in gene expression that occur without altering the underlying DNA sequence.

For instance, chemical modifications (methylation of DNA bases). This alters how genes are expressed.

Like DNA sequence, epigenetic marks may also be heritable 🤯.

Environment (food, weather, etc) can influence epigenetics.