Hey, Doc, Should I be Taking Vitamin D Capsules Just Like My Neighbor?

I take a modest dose (4000 units) of vitamin D every day after my primary care internist informed me that despite lots of sun exposure here in Arizona, my blood levels of this vitamin were low. Recently, a colleague asked me if this was an evidence-based decision. At the time, I had to admit that this intervention was certainly controversial, with some clinical reports showing benefit, while others have been negative. My colleague's question encouraged me to review the literature on vitamin D supplementation and its effects on multiple disease and health outcomes. Adequate blood levels of vitamin D play an important role in the endocrine system because this vitamin has an essential role in calcium homeostasis and bone metabolism. In addition, recent clinical investigation research has documented a diverse range of biological actions for this molecule, including induction of cell differentiation, inhibition of cell growth, modulation of the immune system, and control of other hormonal systems. Vitamin D itself is a prohormone that is metabolically converted to the active metabolite, 1,25-dihydroxyvitamin D [1,25(OH)(2)D].1Dusso AS Brown AJ Slatopolsky E Vitamin D.Am J Physiol Renal Physiol. 2005; 289: F8-F28Crossref PubMed Scopus (1094) Google Scholar Vitamin D and calcium supplementation are widely prescribed for patients with documented osteoporosis or osteopenia. However, clinical trial data showing that there is benefit in terms of reduced numbers of fractures or improved bone density are weak.2Reid IR Bolland MJ Grey A Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis.Lancet. 2014; 383: 146-155Abstract Full Text Full Text PDF PubMed Scopus (423) Google Scholar, 3Chakhtoura M Bacha DS Gharios C et al.Vitamin D supplementation and fractures in adults: a systematic umbrella review of meta-analyses of controlled trials.J Clin Endocrinol Metab. 2022; 107: 882-898Crossref PubMed Scopus (12) Google Scholar, 4Khazai N Judd SE Tangpricha V Calcium and vitamin D: skeletal and extraskeletal health.Curr Rheumatol Rep. 2008; 10: 110-117Crossref PubMed Scopus (157) Google Scholar Another area of musculoskeletal health where vitamin D supplementation has been tested involves attempts to increase muscular strength in athletes. Here, once again, clinical studies have not uniformly shown benefit.5Chiang CM Ismaeel A Griffis RB Weems S Effects of vitamin D supplementation on muscle strength in athletes: a systematic review.J Strength Cond Res. 2017; 31: 566-574Crossref Scopus (56) Google Scholar,6de la Puente Yagüe M Collado Yurrita L Ciudad Cabañas MJ Cuadrado Cenzual MA Role of vitamin D in athletes and their performance: current concepts and new trends.Nutrients. 2020; 12: 579Crossref Scopus (51) Google Scholar It has been suggested that vitamin D supplementation might decrease overall mortality because blood levels of this prohormone have been universally shown to be low in multiple epidemiological studies.7Zgaga L Theodoratou E Farrington SM et al.Diet, environmental factors, and lifestyle underlie the high prevalence of vitamin D deficiency in healthy adults in Scotland, and supplementation reduces the proportion that are severely deficient.J Nutr. 2011; 141: 1535-1542Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar,8Bjelakovic G Gluud LL Nikolova D et al.Vitamin D supplementation for prevention of mortality in adults.Cochrane Database Syst Rev. 2014; CD007470Google Scholar Other areas where therapeutic or preventive vitamin D supplementation has been suggested include cancer, cardiovascular diseases, metabolic disorders, infectious diseases, autoimmune diseases, renal failure, cystic fibrosis, and inflammatory bowel disease.9Lappe JM Travers-Gustafson D Davies KM Recker RR Heaney RP Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial.Am J Clin Nutr. 2007; 85: 1586-1591Abstract Full Text Full Text PDF PubMed Scopus (1186) Google Scholar, 10Wang TJ Pencina MJ Booth SL et al.Vitamin D deficiency and risk of cardiovascular disease.Circulation. 2008; 117: 503-511Crossref PubMed Scopus (1957) Google Scholar, 11Pittas AG Lau J Hu FB Dawson-Hughes B The role of vitamin D and calcium in type 2 diabetes: a systematic review and meta-analysis.J Clin Endocrinol Metab. 2007; 92: 2017-2029Crossref PubMed Scopus (1542) Google Scholar, 12Pittas AG Kawahara T Jorde R et al.Vitamin D and risk for type 2 diabetes in people with prediabetes. A systematic review and meta-analysis of individual participant data from 3 randomized clinical trials.Ann Intern Med. 2023; 176: 355-363Crossref PubMed Scopus (4) Google Scholar, 13Yamshchikov AV Desai NS Blumberg HM Ziegler TR Tangpricha V Vitamin D for treatment and prevention of infectious diseases: a systematic review of randomized controlled trials.Endocr Pract. 2009; 15: 438-449Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar, 14Merlino LA Curtis J Mikuls TR Cerhan JR Criswell LA Saag KG Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women's Health Study.Arthritis Rheum. 2004; 50: 72-77Crossref PubMed Scopus (634) Google Scholar, 15Cutolo M Otsa K Uprus M Paolino S Seriolo B Vitamin D in rheumatoid arthritis.Autoimmun Rev. 2007; 7: 59-64Crossref PubMed Scopus (195) Google Scholar, 16Jean G Souberbielle JC Chazot C Vitamin D in chronic kidney disease and dialysis patients.Nutrients. 2017; 9: 328Crossref Scopus (170) Google Scholar, 17Chesdachai S Tangpricha V Treatment of vitamin D deficiency in cystic fibrosis.J Steroid Biochem Mol Biol. 2016; 164: 36-39Crossref PubMed Scopus (41) Google Scholar, 18Maretzke F Bechthold A Egert S et al.Role of vitamin D in preventing and treating selected extraskeletal diseases–an umbrella review.Nutrients. 2020; 12: 969Crossref PubMed Scopus (57) Google Scholar Unfortunately, none of the clinical trials in these areas has been definitive, and all suffer from a variety of limitations. Of course, if convincing subsequent studies do indeed show clear benefit from supplemental vitamin D, this would be of considerable importance for public health in many countries because vitamin D deficiency has been shown to be highly prevalent in populations residing at high latitudes or living an indoor-oriented lifestyle. Because the scientific literature is often confusing or conflicted, and because meta-analyses have shown only modest benefit or negative results, how should clinicians advise their patients? Following my extensive literature review, as well as conversations with colleagues, here is my advice on vitamin D supplementation, knowing that this recommendation will result in many e-mails and letters because it is based on conflicting clinical trial results. I think that it is clinically reasonable to suggest moderate levels of vitamin D supplementation to patients with demonstrated low levels of the prohormone in their blood. This advice should be the result of shared decision-making because vitamin D supplementation can lead to an increase in painful renal stone formation. The clinical trials cited below did emphasize that there were very low levels of adverse events associated with vitamin D supplementation. This latter finding reassures me in making this recommendation. The cost of vitamin D supplementation is also modest. As always, I am happy to hear from readers at [email protected]