By Professor Eric S. Kilpatrick, Consultant in Chemical Pathology
In the late 1990s, this article’s author worked in a large teaching hospital where around 40 vitamin D requests were received per month. In MFT in 2021 the average was approximately 3,500 requests per month. Few biochemistry tests, other than perhaps HbA1c, have seen such a transformation in requesting frequency over the past two decades. Primarily this is because vitamin D has become inextricably linked with the maintenance of bone health. Somewhat unusually, this general consensus crosses medical, lay and media boundaries and has been reinforced by the additional associations found between low vitamin D concentrations and a very wide spectrum of non-skeletal diseases.
This gave rise to the notion that, beyond avoiding severe deficiency, there could be benefit to vitamin D supplementation in preventing or treating many diseases and in the last decade numerous studies have been undertaken to investigate this possibility.
These studies are now reporting and, unfortunately, their results have not been encouraging. The largest study of its type, the Vitamin D and Omega-3 Trial (VITAL) has already shown in 25,781 US men and women averaging 67 years of age that supplementation with vitamin D3 (cholecalciferol , 2000 IU per day) did not prevent cancer or cardiovascular disease, prevent falls, improve cognitive function, reduce atrial fibrillation, change body composition, reduce migraine frequency, improve stroke outcomes, decrease age-related macular degeneration or reduce knee pain.1
The most recent VITAL publication is perhaps its most important and certainly its most unexpected. It found that a median period of 5.3 years vitamin D supplementation did not reduce the risk of total, hip or non-vertebral fractures, even amongst the 20% who also took calcium supplements. 2 Moreover, while it might be expected that subjects with the lowest initial vitamin D concentrations would gain most from supplementation, no such benefit was found, even amongst those with baseline vitamin D values below 30 nmol/L. Extensive subgroup analyses exploring possible benefits of supplementation according to factors such as age, sex, race or BMI also failed to show any positive signal. At least there were no safety concerns amongst those taking the study dose of vitamin D supplement.
So where do these study finding leave us? Certainly one swallow does not make a summer, but the fact that the results of the VITAL study were eagerly awaited – since they were likely to provide the most definitive evidence on vitamin D’s role in bone health – suggests its findings are of real importance. An accompanying strongly worded editorial associated with the paper did not pull its punches in advocating ‘providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements, and people should stop taking vitamin D supplements to prevent major diseases or extend life’ and suggesting that ‘use of the terms vitamin D “insufficiency” and “deficiency” should now be reconsidered’. 1
It is going to take some time for the findings from the VITAL study to filter through to current guidelines and perhaps this will allow sufficient time to ensure that the pendulum does not swing too far in the opposite direction, risking patients with rickets or osteomalacia remaining undetected, or particular patient groups, such as infants, immobile elderly, those who are pregnant or with severe kidney disease, not being properly considered. In the meantime, VITAL suggests that existing adult guidance such as that from NICE or GMMMG, which might previously have been regarded by some as being conservative in chiefly only recommending testing in symptomatic patients, may not have been overly cautious after all. Once the dust settles, I would not be surprised if we look back on this period of medicine as being ‘peak vitamin D’, both in regard to testing and supplementation.
1. Cummings SR, Rosen C. VITAL findings — a decisive verdict on vitamin D supplementation. NEJM 2022;387:368-370
2. LeBoff MS, Chou SH, Ratliff KA, Cook, NR et al. Supplemental Vitamin D and incident