Daily intake of a multivitamin supplement slightly slows biological ageing, according to a clinical trial

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.

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".

Stop spending your money on multivitamins. That is the most rational and straightforward conclusion from the recent article published in Nature Medicine. The paper is a complementary analysis 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 aim was to evaluate the effect of the daily consumption of Centrum, a pill containing more than 29 vitamins and minerals (100 % of the Recommended Daily Intake), compared with placebo. Participants who took Centrum had a higher risk of gastrointestinal bleeding as a side effect. However, Centrum consumption 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 for cancer mortality.

The rationale for the article published in Nature Medicine to use epigenetic aging clocks is that these markers are strongly associated with the main causes of mortality and morbidity. In a highly selected sample, the authors observed that Centrum consumption produced a small protective effect on these aging markers. However, the clinical relevance of these findings remains unknown, especially given that the COSMOS trial itself found no effect of Centrum consumption on the main causes of mortality and morbidity.

My personal advice is to stop taking multivitamins, whether in pills or gummies. Instead, follow a healthy, varied diet rich in fruits and vegetables—the main natural sources of vitamins and minerals—and do not spend your money on nutritional supplements. There are enormous commercial interests behind their consumption and a lack of solid clinical evidence supporting their benefits.

The study also shows no effects of cocoa supplementation. So you can eat chocolate if it gives you pleasure (and if you are not overweight or obese), but taking cocoa-based nutritional supplements does not make much sense either.

Save your money on supplements. Don’t distract yourself by taking pills thinking that this will “protect” you. Instead, focus on eating a diet rich in fruits and vegetables and low in ultra-processed foods. Your health, and your wallet, will thank you.

The work led by Howard Sesso, from Brigham and Women’s Hospital and Harvard Medical School, is part of the COSMOS clinical trial (COcoa Supplement and Multivitamin Outcomes Study). This clinical trial aims to evaluate the health effects of a commonly used multivitamin complex and a cocoa extract in over 20,000 participants. Previous results from this large-scale study had shown that cocoa reduced mortality from cardiovascular disorders and certain inflammatory markers, while the multivitamin complex, in a smaller sub-study, improved memory and attention and reduced brain ageing. To assess this, the authors used 'epigenetic clocks', increasingly popular tools that estimate an individual’s biological age by analysing DNA methylation changes that occur as people get older. After two years, supplementation with the multivitamin complex reduced the biological age of treated participants by 2.7 to 5.1 months compared with the control group. Regarding the cocoa extract, no significant effects were observed across the five epigenetic clocks analysed.

Although the study’s results are moderate, it is important to consider that ageing is an extremely complex process involving multiple molecular pathways, making it difficult for a single epigenetic clock to capture the biological state 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 may provide. For this reason, it is recommended to use as many clocks as possible, and even combine them with other measures based on different types of biological information that also change with age, such as gene activity, levels of certain blood components, or the composition of the gut microbiota.

In short, while it cannot be claimed that these supplements represent a definitive 'cure' for the biological decline associated with ageing, ensuring complete and balanced nutrition remains a fundamental pillar of self-care for maintaining a healthy lifestyle. This is especially relevant today, as ageing has become the main risk factor for the most significant diseases in our society, including cancer and cardiovascular and neurodegenerative conditions. For this reason, studies that use molecular methods to reliably and objectively measure 'biological age' are gaining increasing importance and are crucial in the scientific pursuit of improving human health and well-being.

Molecular alterations associated with ageing can be linked to various disorders and chronic diseases typical of older age. One such alteration, DNA methylation in blood, is used as an epigenetic clock to determine an individual’s biological age, which does not always correspond to their chronological age. Depending on multiple lifestyle factors, such as diet or physical activity, the rate of ageing can increase or decrease, and these changes are reflected in the DNA.

The authors investigated the effects of different treatments on these epigenetic clocks: MVM (a multivitamin and mineral supplement) and cocoa extract, as well as a placebo for the control group, over two years in a population of 482 women and 476 men with a mean age of 70. They measured the effects on five epigenetic clocks: PCHannum, PCHorvath, PCPhenoAge, PCGrimAge, and DunedinPACE.

In participants who, prior to the trial, showed accelerated ageing, treatment with MVM produced slight but significant improvements in two of the five epigenetic clocks measured. However, when the ageing markers did not show this accelerated profile, MVM treatment had no effect. Similarly, cocoa extract had no effect on any of the five epigenetic clocks, regardless of the participants’ baseline ageing status at the start of the trial.

As the authors note, further studies are needed to determine the relevance of these findings. Specifically, the impact of MVM use on the development of age-related diseases would require longer-term studies.

Nevertheless, the use of these techniques is important for determining individuals’ true biological age and for tailoring treatments accordingly, rather than relying solely on chronological age.