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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:
Pilar Guallar Castillón, lecturer in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid, said:
“Stop spending your money on multivitamins is the most rational and direct conclusion of the recent article published in Nature Medicine. This is a complementary study to the COSMOS clinical trial. The COSMOS clinical trial was conducted in the United States with 21,442 participants, most of whom were white and highly educated. Its purpose was to assess the effect of daily consumption of Centrum, a tablet containing more than 29 vitamins and minerals (100% of the Recommended Daily Intake), compared to a placebo. Those who took Centrum had a higher risk of gastrointestinal bleeding as a side effect. However, taking Centrum did not improve overall mortality, nor did it reduce the incidence of acute myocardial infarction, stroke, or cardiovascular death. It also showed no benefit for cancer incidence (the primary outcome of the clinical trial) or cancer mortality.
“The rationale for using epigenetic ageing clocks, as published in Nature Medicine, is that they are strongly associated with the leading causes of mortality and morbidity. They found that, in a highly selected sample, Centrum consumption had a small protective effect on these markers of ageing. The clinical relevance of these findings is unknown, especially since COSMOS found no effect of Centrum consumption on the main causes of mortality and morbidity.
“My personal advice is to stop taking multivitamins, whether in pill or gummy form. Eat a healthy, varied diet rich in fruit and vegetables (the main natural source of vitamins and minerals), and do not waste your money on nutritional supplements. There are huge commercial interests in their consumption and a lack of clinical evidence.
“Nor do they show any effects of cocoa supplementation. So you can eat chocolate if it gives you pleasure (and you are not overweight or obese), but consuming nutritional cocoa supplements does not make much sense either.
“Save money on supplements, don’t be distracted by taking pills thinking that you are “protected”, and instead make an effort to eat a diet rich in fruit and vegetables and low in ultra-processed foods. Your health and your wallet will thank you”.
Víctor Celemín Capaldi, a researcher in the Department of Biochemistry and Molecular Biology at the University of Oviedo, said:
“The work led by Howard Sesso of Brigham and Women’s Hospital and Harvard Medical School is part of the COSMOS (COcoa Supplement and Multivitamin Outcomes Study) clinical trial. This clinical trial aims to evaluate the health effects of a commonly used multivitamin complex and a cocoa extract in more than 20,000 people. Previous results from this large-scale study had revealed that cocoa reduced mortality from cardiovascular disorders and some markers of inflammation, while the multivitamin complex, in a smaller sub-study, improved memory and attention and reduced brain ageing.
“To do this, the authors used “epigenetic clocks”, increasingly popular tools that estimate an individual’s biological age by analysing changes in DNA methylation that occur as they age. After two years, supplementation with the multivitamin complex reduced the biological age of the treated individuals by 2.7 to 5.1 months compared to the control group. With regard to the cocoa extract, no significant effects were observed in the five epigenetic clocks analysed.
“Although the study results are moderate, it should be noted that ageing is an enormously complex process involving multiple molecular pathways, making it difficult for a single “epigenetic clock” to capture the biological status of all of them. Therefore, the absence of detectable changes in some of these clocks does not necessarily invalidate the observed benefits that these supplements can generate. It is therefore advisable to use as many “clocks” as possible, and even to combine their use with different meters that employ other types of biological information that also changes with age, such as the activity of certain genes, the levels of certain blood components or the composition of the gut microbiota.
“In short, although it cannot be said that these supplements constitute a definitive “cure” for the biological decline of ageing, ensuring a complete and balanced diet remains a fundamental pillar of self-care for maintaining a healthy lifestyle. This is particularly relevant today, when ageing has become established as the main risk factor for the most significant diseases in our society, such as cancer, cardiovascular disease and neurodegenerative diseases. Therefore, studies such as these, which use molecular methods to measure “biological age” reliably and objectively, are becoming increasingly important and are crucial in the scientific race to improve human health and well-being”.
Rosa Arévalo García, full professor of Psychobiology at the University of La Laguna, said:
“The molecular alterations associated with ageing can be linked to various disorders and chronic diseases characteristic of advanced age. One of these alterations, blood DNA methylation, is used as an epigenetic clock to determine the biological age of subjects, which does not always correspond to their chronological age. Depending on multiple circumstances associated with lifestyle, such as diet or physical activity, the rate of ageing can increase or decrease, and this is recorded in the DNA.
“The authors studied the effects of different types of treatments on these epigenetic clocks: MVM (multivitamin and mineral supplement) and cocoa extract, in addition to a placebo for the control group, over two years in a population of 482 women and 476 men with an average age of 70.
“They determined the action on five epigenetic clocks: PCHannum, PCHorvarth, PCPhenoAge, PCGrimAge and DunedinPACE
“In subjects who showed accelerated ageing before the trial, treatment with MVM produced slight but significant improvements in two of the five epigenetic clocks measured. However, when the ageing markers did not show these characteristics of acceleration, treatment with MVM had no effect. Treatment with cocoa extract also had no effect on the five epigenetic clocks, regardless of the starting point at the beginning of the trial.
“As the authors point out, further studies are needed to determine the relevance of these results. Thus, the impact that the use of MVM would have on the development of age-related diseases would require longer-term studies.
“However, it is important to use these techniques to determine the actual biological age of subjects and tailor treatments without taking only chronological age into account”.
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 9th 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.
Pilar Guallar Castillón: No conflicts of interest.
Víctor Celemín Capaldi: No conflicts of interest.
Rosa Arévalo García: No conflicts of interest.