Cardiologist Ananda Raja does not have a long memory of an association between vitamin D and heart disease in medical literature. “I have been practising for about 18 years,” he says, “but I started hearing about vitamin D and heart disease only about five years ago.”In his own practice at the All India Institute of Medical Sciences in Delhi and now in his private clinic in Pondicherry, he had noticed that many heart patients had low vitamin D. But he could not conclude that low vitamin D levels increased the risk of heart disease.Which was why Raja did not raise an eyebrow when he heard last week about a paper in the New England Journal of Medicine, which found that there was no evidence to say that vitamin D supplements reduced the risk of heart disease or cancer. The paper reported the largest and longest study in the world on vitamin D and omega-3 fatty acids, following 25,871 participants over five years at least.Their conclusion: Vitamin D was no better than placebo for lowering the risk of heart disease and cancer. There were similar conclusions for omega-3 fatty acid supplements, which people consume as fish oil For a long time, Vitamin D had been prescribed for treating and preventing fractures in the elderly, as well as improving bone density in adult population. In recent times, physicians in the US and the Europe had started looking at vitamin D supplementation as a possible way of preventing cardiovascular disease and cancer, and the use of vitamin supplements has increased four times in the last decade. This was because observational evidence showed that fewer people had heart disease in areas — in the US — where it was easier to get sunlight.This and other laboratory evidence had made doctors prescribe vitamin D supplements as a preventive strategy for heart disease and cancer.Such observations were quickly translated to the rest of the world. In India, tests began to show that the majority of the population was deficient in blood vitamin D levels as it was defined in the West. The vitamin D supplement industry began to boom around the world, as physicians began prescribing supplements to anyone who showed even mildly low blood levels of the vitamin, or even to people who had normal levels.Last year, a report by the research firm Markets and Markets had predicted a global market of $2.5 billion for vitamin D supplements in 2020, a combined aggregate growth rate of 11% since 2014. The Asia-Pacific market was predicted to have one of the largest increases.The medical community now has the first serious evidence that large-scale vitamin D supplementation may not protect against serious diseases.“This is an eyeopener,” says Prasad Narayan, medical oncologist at the Cytecare Cancer Hospital in Bengaluru. “It proves beyond doubt that there is no reduction in cancer rates if we give vitamin D supplements.” When combined with other recent studies on vitamin D, there is enough evidence to even question regular vitamin D testing and supplementation in the general population.“Routine vitamin D supplementation has proven to have no benefits,” says Mark Bolland, associate professor at the University of Auckland and the author of a large study on Vitamin D last year. “So it shouldn’t be prescribed.”Last year, Bolland analysed 81 clinical trials involving 53,000 participants. He found that vitamin D supplementation did not prevent falls or fractures in the elderly, or improve bone density by a meaningful amount. This year, a Chinese study on 33 trials with over 50,000 participants, published in the Journal of American Medical Association , found similar results. Calcium and vitamin D supplements did not reduce fractures in the elderly compared with placebo or no treatment.These studies present a U-turn in the evidence for vitamin D and omega-3 fatty acid supplementation, and raise questions about what to do in a general population with deficiencies in vitamin D and omega-3 acids. In India, it raises deeper questions about how to define deficiencies, and how to translate test results into decisions about keeping the general population healthy. The question is complicated by the fact that data about the Indian population are still scarce, and that vegetarian cuisine is the foundation of the diets of a substantial part of the population.Low vitamin D level is considered a major health issue in recent times in India, since doctors started testing regularly for the vitamin. In the last few years, people even started testing for vitamin D as part of a general health check. Studies that looked at evidence for deficiencies presented an alarming picture. Two years ago, a paper published in the Indian Journal of Clinical Biochemistry spoke of major deficiencies across the country. It was an assessment of hospital-based studies, consisting of 26,346 healthy individuals, enrolled for annual health checks at Medanta in Gurgaon. Vitamin D deficiency was found in 93% of these otherwise healthy individuals.This year, another paper published in the Journal of Family Medicine and Primary Care found vitamin D deficiencies - based on hospital data - of between 37% and 99%, in people who are otherwise healthy. Other studies in children also showed deficiencies.Yet there was no consensus on what these deficiencies meant for the general Indian population. There were not enough studies on correlations between low vitamin D levels and serious diseases in the country. Indian doctors were transplanting data from the west to India. Absence of clear data has made several medical practitioners sceptical about the utility of routine vitamin D supplementation in healthy individuals, even if some deficiencies are spotted, and have welcomed the results in the New England Journal of Medicine. "It is a watershed moment," says Charit Bhograj, cardiologist at Vikram Hospital, Bengaluru. "It is a study that provides an important message." The message has been loud and clear for some time: supplements provide no benefit for healthy individuals.Absence of data from India has been noticed by those who conducted the large metaanalyses. "Almost all the trials were done in Europe or America," said Bolland in an email."There were no trials in India, surprisingly. Regionally, the closest trials were conducted in Sri Lanka and Bangladesh."However, a closer examination of these studies provides fascinating clues about sub-groups. In the trial results published last week, secondary data have thrown up new lines of argument among scientists and doctors.As the journal noticed in a commentary, there was compelling evidence that eating fish was associated with protection against cardiovascular disease. Some fatty fish also have high levels of vitamin D (See Sources of Vitamin D). The American Heart Association recommended consuming omega-3 fatty acids as protection against heart attacks, although evidence came only in a sub-group that had a recent heart attack. Now the current study, called the VITAL study, showed there was no benefit for the general healthy population in consuming omega-3 fatty acids either.The VITAL study itself noted some studies that showed that vitamin D protected against cancer. The vitamin is also known to suppress cell proliferation in laboratory studies. The vitamin D receptor is known to be important for initiating several metabolic pathways, including for providing immunity. And yet, the larger combined study provided no benefit for vitamin D as a protection against heart disease or cancer.The Indian vitamin D level data were intriguing for doctors. "Every person is deficient," says Harit Chaturvedi, head of oncology at Max Healthcare in Delhi. "It includes even those who are outdoors."Hospital-based studies report vitamin D deficiencies even in the rural population, which generally gets plenty of sun. The reason for such low levels is not clear. Have Indians always had low levels? Those with darker skin do not synthesise the vitamin well even in sunlight, and there is a chance that Indians may not need the same levels of the vitamin as those with fair skin in the West.Are Indians deficient in vitamin D because of increasing pollution, which is known to reduce ultraviolet light and interfere with vitamin D synthesis in the skin? Is heavy clothing a factor? Are there different factors at work in urban and rural India? Urban India because of lack of sun exposure and rural India because of consumption of plants that reduce vitamin D absorption?Scientists say that clear answers to these questions are necessary before associating vitamin D with any disease in the country. Meanwhile, most of them recommend using supplements with caution, and only when absolutely necessary. "It is important to use clinical judgment while prescribing vitamin D," says Bhograj.This usually means symptoms like aches and pains, fatigue, or probably low bone density.The last word hasn't been told on this topic. "We don't really know what levels put individuals at risk of complications that can be prevented with vitamin D supplementation," says Bolland, "partly because very few trials have been done in individuals with clearly low levels of vitamin D."Almost all Indians are good candidates for such trials.In the absence of studies on Indian patients, it is common to use western studies as evidence for decision-making in Indian healthcare. No one knows whether Indians should have the levels of vitamin D — or most vitamins — defined as normal for the western population. Indian doctors have no choice but to take that western values hold true for Indian population as well. What should they do when faced with a reverse situation, when a supplement is not seen to be beneficial for the western population?The VITAL study, which looked at the benefits of vitamin D and omega-3 supplements, hints at what can be done in such circumstances.The study looked at benefits of fish oil for cardiovascular disease and found no benefits. The disease group had heart attacks, strokes and other heart-related deaths. But when it looked at heart attacks alone, it found a 28% reduction in risk in general for those who take fish oil, 40% for those who do not eat fish regularly, and 77% for African Americans.“A 28% reduction is significant,” says Kumar Kothapalli, associate professor at University of Texas, specialising in the medical genetic basis of disease.Kothapalli had researched the Indian population and found that the Indian genetic make-up is different from that of the western population, specifically in the way Indians use up fatty acids in the body. “Most Indians have low levels of omega-3 in the body due to genetics and high intake of omega-6 fatty acids.”Human beings evolved to maintain a balance of 1:1 between omega-6 and omega-3 acids, but modern vegetable oils have skewed the ratio towards the pro-inflammatory omega-6 acids.One way to maintain a balance is to reduce omega-6 acids in the diet, and the other way is to increase the consumption of omega-3. Considering that most Indians do not eat fatty fish, would Indians see a reduction of heart attack risk by consuming fish oil? Only an Indian study will provide a clear answer.