Author's response
I appreciate the letter from Dr. Grant in response to my previous Practice Alert, as it provides an opportunity to make some important points about assessment of scientific evidence and drawing conclusions based on sound methodology. There is an overabundance of scientific literature published, much of which is of questionable quality, meaning a “study” or 2 can be found to support any preconceived point of view.
In 2011, the Institute of Medicine (now the National Academy of Medicine) published a series of recommendations on how trustworthy recommendations and guidelines should be produced.1,2 Key among the steps recommended is a full assessment of the totality of the literature on the subject by an independent, nonconflicted panel. This should be based on a systematic review that includes standard search methods to find all pertinent articles, an assessment of the quality of each study using standardized tools, and an overall assessment of the quality of the evidence. A high-quality systematic review meeting these standards was the basis for my review article on vitamin D.3
To challenge the findings of the unproven benefits of vitamin D, Dr. Grant cited 4 studies to support the purported benefit of achieving a specific serum 25(OH)D level to prevent cardiovascular disease, diabetes, cancer, and COVID-19. After reading these studies, I would not consider any of them a “game changer.”
The first study was restricted to those with prediabetes, had limited follow-up (mean of 2.5 years), and found different results for those with the same 25(OH)D concentrations in the placebo and treatment groups.4 The second study was a large, well-conducted clinical trial that found no benefit of vitamin D supplementation in preventing cancer and cardiovascular disease.5 While Dr. Grant claims that benefits were found for some subgroups, I could locate only the statistics on cancer incidence in Black participants, and the confidence intervals showed no statistically significant benefit. It is always questionable to look at multiple outcomes in multiple subgroups without a prior hypothesis because of the likely occurrence of chance findings in so many comparisons. The third was a retrospective observational study with all the potential biases and challenges to validity that such studies present.6 A single study, especially 1 with observational methods, almost never conclusively settles a point.
The role of vitamin D in the prevention or treatment of COVID-19 is an aspect that was not covered in the systematic review by the US Preventive Services Task Force. The study on this issuecited by Dr. Grant was a large retrospective observational study that found an inverse relationship between serum 25(OH)D levels and SARS-CoV-2 positivity rates.7 This is 1 observational study with interesting results. However, I believe the conclusion of the National Institutes of Health is currently still the correct one: “There is insufficient evidence to recommend either for or against the use of vitamin D for the prevention or treatment of COVID-19.”8
With time and further research, Dr. Grant may eventually prove to be correct on specific points. However, when challenging a high-quality systematic review, one must assess the quality of the studies used while also placing them in context of the totality of the literature.
Doug Campos-Outcalt, MD, MPA
Phoenix, AZ
References
1. Institute of Medicine. Finding What Works in Health Care. The National Academy Press, 2011.
2. Institute of Medicine. Clinical Practice Guidelines We Can Trust. The National Academy Press, 2011.
3. Kahwati LC, LeBlanc E, Weber RP, et al. Screening for vitamin D deficiency in adults; updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2021;325:1443-1463. doi: 10.1001/jama.2020.26498
4. Dawson-Hughes B, Staten MA, Knowler WC, et al. Intratrial exposure to vitamin D and new-onset diabetes among adults with prediabetes: a secondary analysis from the Vitamin D and Type 2 Diabetes (D2d) Study. Diabetes Care. 2020;43:2916-2922. doi: 10.2337/dc20-1765
5. Manson JE, Cook NR, Lee I-M, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380:33-44. doi: 10.1056/NEJMoa1809944
6. Acharya P, Dalia T, Ranka S, et al. The effects of vitamin D supplementation and 25-hydroxyvitamin D levels on the risk of myocardial infarction and mortality. J Endocr Soc. 2021;5:bvab124. doi: 10.1210/jendso/bvab124
7. Kaufman HW, Niles JK, Kroll MH, et al. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS One. 2020;15:e0239252. doi: 10.1371/journal.pone.0239252
8. National Institutes of Health. Vitamin D. COVID-19 treatment guidelines. Updated April 21, 2021. Accessed November 18, 2021. www.covid19treatmentguidelines.nih.gov/therapies/supplements/vitamin-d/