April 5, 2017

expert reaction to a study investigating the effect of monthly vitamin D supplementation on cardiovascular disease

In a new population-based cohort study, researchers publishing in JAMA Cardiology examine whether monthly high-dose vitamin D supplementation prevents cardiovascular disease.

Dr Benjamin Jacobs, Consultant Paediatrician, Royal National Orthopaedic Hospital, said:

“We know from other studies that Vitamin D can have cardiovascular effects, for example young babies with a severe lack of Vitamin D can get cardiomyopathy and heart failure. But this study did not show benefit in this population. That may well be because the population studied had much better Vitamin D levels than the UK population. Even the placebo group had a mean Vitamin D blood level above 65 nmol/L (26 ng/ml).”

Prof. Adrian Martineau, Clinical Professor of Respiratory Infection and Immunity, Queen Mary University of London (QMUL), said:

“This high quality study addresses the controversy relating to whether vitamin D supplementation could have a role in the prevention of cardiovascular disease. The study design – a double-blind randomised placebo-controlled trial – is the gold standard for evaluating effectiveness of interventions of this sort; bias and confounding were effectively eliminated. The authors recruited a sizeable population of older adults, and those randomised to the intervention arm of the trial received a generous dose of vitamin D, sufficient to cause a sustained boost in vitamin D levels over the course of three years. More than 85% of those who survived completed follow-up. The headline result is that no difference in risk of cardiovascular events was seen between arms.

“The study provides definitive evidence that monthly doses of vitamin D did not reduce the risk of cardiovascular disease in the study population. However, as the authors themselves acknowledge – and given the strength of suggestive evidence from observational studies – this trial does not rule out the possibility that vitamin D might have a role in reducing risk of cardiovascular disease if it were to be given in a different way or to a population with different characteristics. I say this for two reasons:

“1. Profound vitamin D deficiency (25-hydroxyvitamin D concentration <25 nmol/L) was relatively uncommon in the study population (around 10%). For other health outcomes (e.g. acute respiratory infections), vitamin D has been shown to be of greatest benefit  in people with these very low levels, and the same could be true for cardiovascular disease. Further trials in populations with lower baseline vitamin D status are needed to address this issue.

“2. The investigators gave vitamin D using a monthly dosing regimen: this can result in quite large fluctuations in vitamin D levels, which may impair the effectiveness of supplementation for some outcomes. Again, using the example of acute respiratory infections, daily or weekly supplementation has been shown to be effective in reducing risk, whereas more widely spaced dosing (e.g. monthly) is not protective.

“The bottom line is that the authors have conclusively shown that this dosing regimen of vitamin D, given to this population, did not prevent cardiovascular disease – and this is an important null finding. However, these results do not rule out a protective effect of daily/weekly dosing in people with low vitamin D levels.”

Dr Andrea Darling, Postdoctoral Research Fellow in the Department of Nutritional Sciences, University of Surrey, said:

“Although this is generally a well conducted study, shortcomings of this research has painted Vitamin D in an unfavourable light which may be misleading.

“Firstly, only half the sample group appeared to be at high risk of heart disease (e.g. current or previous smokers, had a previous heart disease related event, were sedentary and/or obese). This may explain the fewer than expected number of heart disease events occurring in the study. Vitamin D may show a greater effect in high heart disease risk people in contrast to low risk, so it is important that we study a high risk population to give vitamin D ‘a fair trial’.  Unfortunately, the subgroup analysis looking at only those who had history of heart related events is likely to contain too few people to be able to interpret the results meaningfully.

“Secondly, the study aimed to see a 20% reduction in risk of heart disease related events.  Twenty per cent is a very large effect to expect from a nutrient, considering statins have been found to reduce primary risk of cardiovascular disease by 27%(1). It is perhaps not surprising that vitamin D ‘cannot fill shoes this big’, whereby its role in heart disease may be smaller (e.g. 5%), but still of potential clinical relevance.

“As the study authors allude to in the discussion we should definitely be wary of discounting the benefits of Vitamin D in preventing cardiovascular disease on the basis of these results.”

(1)Taylor et al (2013) Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD004816

Prof. Metin Avkiran, Associate Medical Director at the British Heart Foundation said:

“The findings of this study mean we are still unclear about whether in the general population vitamin D supplements prevent cardiovascular disease, which is the cause of more than a quarter of all deaths in the UK. The study revealed that monthly doses provide no protection against cardiovascular disease, but more research is needed to understand if taking daily or weekly supplements is beneficial. However, it’s important that patients with a vitamin D deficiency, who have been prescribed supplements, continue to take them due to their established health benefits, such as improving bone strength.”

Dr Tim Chico, Reader in Cardiovascular Medicine & consultant cardiologist, University of Sheffield, said:

“This is an important and well conducted study that highlights many of the difficulties faced by researchers trying to work out the best way to prevent heart disease. We have known for a long time that people with low vitamin D levels have higher rates of heart disease, which has led to the suggestion that vitamin D supplementation may reduce these diseases. However, this study found no benefit of giving a monthly vitamin D supplement.

“What is clear from the results of this study is that there is no clear benefit in giving vitamin D in the dose and manner used in this trial. However, as always more questions are raised by these findings. It is possible giving people vitamin D more regularly, or in a different dose, or for longer, could lead to benefits, but this is purely speculation.

“This study adds to a large number of others that found disappointing or even harmful effects of vitamin supplementation on a range of diseases, including heart disease and cancer. Although low vitamin levels are “associated” with these diseases, it is likely that this is just a pointer to factors that lead to both low vitamin levels and these diseases.

“I see a lot of patients who take vitamin supplements in the expectation that this will reduce their risk of disease, and unfortunately I have to tell them that the evidence suggests they are a waste of time and money. The good news is that there are a range of cheap and effective commercially available products that boost your vitamin levels and definitely reduce heart disease, which are called vegetables.”

Dr Amitava Banerjee, Senior Clinical Lecturer in Clinical Data Science and Honorary Consultant Cardiologist, UCL, said:

“This is a high quality trial of monthly, high-dose vitamin D supplementation in over 5000 individuals, which shows that cardiovascular disease is not prevented by this regime of vitamin D. The association between low vitamin D levels and cardiovascular disease is well-documented, but previous trials of lower dose vitamin D supplements have had similar results. Therefore, although further research is required using daily or weekly regimens of vitamin D, it is very unlikely that vitamin D supplementation reduces the risk of cardiovascular disease, regardless of the other benefits.”

* ‘Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study’ by Scragg et al. will be published in JAMA Cardiology at 16:00 UK time on Wednesday 5 April, which is also when the embargo will lift. 

All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/?s=%22vitamin%20D%22&cat

Declared interests

Dr Benjamin Jacobs: No conflicts of interest to declare.

Prof Adrian Martineau: Prof Robert Scragg, the lead author of this study, is currently on sabbatical at my institution (Queen Mary University of London). However, we do not hold any joint research funding, and we do not have any joint publications.

Dr Andrea Darling: No conflicts of interest.

Prof. Metin Avkiran: No conflicts of interest.

Dr Tim Chico: Is a committee member and Treasurer of the British Atherosclerosis Society, a charity established in 1999 to promote UK atherosclerosis research. Dr Chico’s research group has previously examined the effect of vitamin D supplementation on heart disease, but he has not worked with the authors of this study, nor had any role in its funding or conduct.

Dr Amitava Banerjee: No conflicts of interest