March 9, 2026

expert reaction to RCT on the effects of daily multivitamin–multimineral and cocoa extract supplementation on epigenetic aging clocks

A randomised controlled trial published in Nature Medicine looks at multivitamin cocoa extract supplementation and biological ageing.

Dr Laura Sinclair, Lecturer in Healthcare & Postdoctoral Researcher, said:

On the press release:

“The press release reflects the science. I would specify “DNA modification patterns” rather than “DNA patterns” as the latter would mean genetic (and not epigenetic) patterns to me.”

On the paper/wider implications:

“This study is a large, randomised-controlled, commercially funded trial. The authors have conclusions backed up by their robust data, adjusted for confounders such as age, sex, diet and lifestyle, and recognised the limitations of their study.

“Epigenetic clocks are powerful tools to measure biological ageing, but they are only one piece of the ageing puzzle. We know that ageing is underpinned by the “Hallmarks of Ageing”, mechanisms that contribute to biological ageing. “Epigenetic alterations” was one of the nine originally recognised hallmarks, although there are now more. Other hallmarks, things like DNA damage, changes in proteins, and problems in cellular communication, also play a role in ageing. If we want to really know if supplements can slow biological ageing, we need to look at the full picture.

“This study uses five clocks to measure epigenetic age in blood samples, only two of which measure a difference with multivitamin-multiminerals, and no difference with flavanols. This is interesting because there is lots of evidence that multivitamin-multiminerals and flavanols may slow biological ageing, but how they affect ageing isn’t fully understood yet. This study can only comment on its epigenetic snapshot of ageing in the blood. Other tissues in the body may have different epigenetic ages – for example, your liver may “age” faster than your blood.

“This study doesn’t recommend going out and buying supplements. If a person eats a nutritionally balanced diet, then many dietary supplements would probably be superfluous to their individual requirements. However, most adults in the UK are actually not eating a nutritionally balanced diet and so probably would benefit from a multivitamin-multimineral. Indeed, the UK government suggests that UK adults should consider a vitamin D supplement in autumn and winter.

From our friends at the Spanish SMC:

Carmen Romero Ferreiro, Doctor of Biology and Vice Dean of Research at Francisco de Vitoria University, said:

“This study examines whether daily supplementation with a multivitamin complex or cocoa extract can influence biological ageing as measured by epigenetic clocks. These clocks are biomarkers based on patterns of DNA methylation (small chemical modifications that regulate how genes are expressed) and allow researchers to estimate a person’s biological age, that is, how ‘aged’ their cells are compared with their chronological age.

“The research is based on a randomised clinical trial involving more than 900 adults followed over a two-year period, which represents a robust methodological design for assessing the potential effects of these nutritional interventions.

“The results show that multivitamin supplementation is associated with a slight reduction in the rate of biological ageing according to some of the epigenetic clocks analysed. However, this effect is not observed across all the markers evaluated, and its magnitude is small. In fact, the detected changes correspond to roughly a few months’ difference in the estimated biological age.
With regard to cocoa extract, the study finds no evidence that supplementation has a protective effect on these ageing markers.

“This finding is noteworthy because cocoa and flavanols have been associated in other research with cardiovascular benefits, yet these effects do not necessarily appear to translate into detectable changes in the epigenetic biomarkers of ageing examined in this study.

“As with any research, several limitations should be considered. The follow-up period was two years, which is relatively short for assessing processes as complex and cumulative as biological ageing. In addition, although epigenetic clocks are promising tools for estimating biological age, they remain indirect biomarkers. It is still being investigated to what extent changes observed in these indicators translate into clinically meaningful improvements in health or longevity.

“Overall, this work provides evidence on the potential role of multivitamin supplementation in biological ageing, although the effects observed are limited. Within the broader context of diet and lifestyle, these results suggest that its impact would likely be complementary within wider strategies for promoting health and healthy ageing, rather than a stand-alone intervention with a decisive effect”. 

Jordi Pérez-Tur, Research scientist at the Public Research Organisation (PRO) at the Institute of Biomedicine of Valencia of the Spanish National Research Council (CSIC) and principal investigator at CIBERNED, said:

Summary of the study

“This study investigates the potential association between the consumption of multivitamin–multimineral supplements (MVM) with cocoa extract and biological ageing. The authors followed a cohort of 958 individuals aged over 60 (men) and 65 (women) who had no previous chronic diseases. The cohort was divided into four groups that, for two years, followed specific instructions regarding whether or not to consume cocoa extract and MVM supplements.

“Participants were monitored periodically, analysing changes that accumulate in specific regions of DNA and that have been linked to ageing. These changes allow researchers to estimate a ‘biological age’, which may differ from chronological age. There are several methods for measuring biological age, and the study used five different approaches.

“The study concludes that taking MVM supplements for two years appears to slow the rate of biological ageing according to two of these measures, known as ‘biological clocks’. In addition, participants who showed faster ageing before the intervention experienced a greater slowing of the ageing rate after taking MVM and cocoa extract. No significant effects were observed for cocoa extract consumption alone. The researchers also examined the impact of the dietary intervention on certain inflammatory markers and, from a cognitive perspective, on the functioning of specific brain domains. These results were again interesting for some of the biological clocks analysed. However, the subgroup analysed for these outcomes was even smaller than the overall study population, so the findings should be considered preliminary and useful mainly as a basis for future studies”.

Quality of the study

“As the authors themselves note in the abstract, further studies are needed to confirm and better define these results, particularly the clinical relevance of these supplements and their potential benefits for chronic diseases associated with ageing. A statistically significant result does not necessarily mean that the effect is biologically meaningful. In this study, only two of the five measures of ageing rate showed an effect, and the magnitude of that effect was relatively small (equivalent to only a few months).

“Moreover, the study design can only demonstrate an association: the consumption of MVM supplements coincided with a modest reduction in the rate of ageing. The molecular mechanisms linking these observations remain unknown and cannot be addressed within the scope of this study. In other words, correlation does not imply causation (although it does not rule it out either)”.

Implications and fit with existing evidence

“At present, the implications are limited because this is a relatively preliminary study. Although it provides interesting results, further complementary research will be needed to confirm them. Nevertheless, it provides a rationale for conducting such studies”.

Limitations

“As mentioned above, the main limitation is that the observed effect is relatively small. This may partly reflect the size of the study groups, which included around 250 individuals each. Detecting effects of this magnitude may require larger populations.

“In addition, the authors did not include other variables in their analyses that could influence the results, such as the participants’ diet or their level of physical activity, both of which can also affect the DNA modifications analysed in the study.

“Finally, due to the study design, the participants were limited to older adults of Caucasian (European) origin. As a result, it is not possible to determine whether this simple dietary intervention would produce similar effects in other populations or age groups”.

General comments

“This is an interesting study that may serve as a foundation for larger investigations. Overall, and bearing in mind the limitations of the study, the findings suggest that a simple intervention such as taking multivitamin supplements could potentially contribute to healthier ageing.

“However, further research will be needed before firm conclusions can be drawn, and we must wait for the continuation of the project to determine whether these findings can be confirmed”.

From our friends from the Australian SMC:

Professor Luigi Fontana is a Professor of Medicine and Nutrition and the Leonard P Ullman Chair in Translational Metabolic Health at The University of Sydney. He is also Scientific Director and Director of the Healthy Longevity Research and Clinical Program at the Charles Perkins Centre, said:

“This is a well-conducted trial, but the interpretation of the findings needs to be cautious. The study reports that a daily multivitamin slightly slowed two of five DNA-based ‘epigenetic clocks’ used as markers of biological ageing in older adults. However, the magnitude of the effect is extremely small, and the effect was not consistent across all the ageing measures tested.

“Another important issue is that several ageing markers were analysed, and the statistical tests were not adjusted for multiple comparisons. When many outcomes are tested simultaneously, it becomes more likely that some apparently ‘positive’ results will appear simply by chance.

“It is also important to remember that epigenetic clocks are still research tools rather than validated clinical endpoints. While they can respond to lifestyle or pharmacological interventions, we do not yet know whether small changes in these biomarkers translate into meaningful reductions in disease risk, disability or mortality.

“Participants in this study were generally healthy older adults rather than people with clear nutritional deficiencies. If the effect is real, it may simply reflect correction of mild micronutrient insufficiencies in some individuals rather than a fundamental slowing of the biological ageing process.

“Overall, the findings are scientifically interesting, but they do not provide convincing evidence that taking a daily multivitamin meaningfully slows human ageing.”

‘Effects of daily multivitamin–multimineral and cocoa extract supplementation on epigenetic aging clocks in the COSMOS randomized clinical trial’ by Howard Sesso et al. was published in Nature Medicine at 16:00 UK Time Monday the 9^th March. 

DOI: https://doi.org/10.1038/s41591-026-04239-3

Declared interests

Dr Laura Sinclair: “Dr Sinclair leads the Phyto Ageing study team at the University of Exeter. The Phyto Ageing study is an early-stage, feasibility study investigating the effects of a plant-derived dietary supplement on ageing in the hands.

Dr Sinclair is in the academic team of Prof Lorna Harries. Prof Harries’ academic team works alongside Prof Harries’ spin-out company, Senisca Ltd.

Dr Sinclair is a Trustee of the British Society for Research on Ageing.”

Carmen Romero Ferreiro: No conflicts of interest. 

Prof Luigi Fontana: No conflicts of interest. 

Jordi Pérez-Tur: No conflicts of interest.