Before I get into the meat of this post, first let me explain that this paper was written as part of my Lifestyle Medicine rotation. It was born out of my desire to truly seek whether or not the evidence supports various commonly-recommended supplements. It was written with the audience in mind of fellow medical students and physicians.

Vitamin D – A brief review of current recommendations and evidence

Among popular health advice is the recommendation to take daily vitamin D supplements. This advice is generally backed by reports of widespread deficiency in the fat-soluble vitamin and lists of bodily functions in which it participates. When coupled with statistics on the rarity of hypervitaminosis D and claims that few foods contain sufficient amounts, supplementation seems like the obvious conclusion. But is it? Perhaps a closer look is warranted.

A general principle of replacement therapy is to give supplementation only to patients who have documented deficiency so that therapy can be justified. The definition of vitamin D deficiency is generally considered less than 20 nanograms per milliliter [1]. The most commonly cited reason for deficiency is a lack of adequate sun exposure, which can occur by sun avoidance, sunscreen overuse, very modest clothing styles, darker skin tones or living too far away from the equator for optimal light angle. Other causes for deficiency include obesity, fat malabsorption syndromes, prior bariatric surgery, nephrotic syndrome & medications like anticonvulsants and antiretrovirals [2].

Even in the absence of these risk factors and conditions, many people are taking vitamin D supplementation regardless of clinically documented deficiency status [3, 4]. While vitamin D was not the only supplement turned to in the chaos of the recent coronavirus pandemic, the supplement business was a nearly $60 billion industry in 2021 and has been a very lucrative industry for decades [5], leading some to ponder the origins of claims regarding supplement benefits. Many of the claims circulating in popular culture about the benefits of vitamin D are based on the logical fallacy of the inverse, where one assumes that because an association has been seen between the presence of deficiency and the presence of a disease state, there must also be an association between the absence of deficiency and absence of said disease state. Many of these claims have now been well studied and found to be inaccurate, but some are of note to today’s health professionals.

Claims

Prevention of Fracture – While the physiology involved in the claim that vitamin D supplementation could prevent fractures is beyond the scope of this review, various resources on the topic are available to the curious reader [1, 2]. This claim is perhaps the most prevalent of those here examined, but the body of evidence does not support it. The recent randomized, controlled Vitamin D and Omega-3 Trial (VITAL trial) reported an ancillary study showing no decreased risk of fractures could be found between vitamin D supplementation and placebo groups in 25,871 generally healthy participants over 5 years of follow-up [6]. This trial is the largest to date, and it is considered by some to be the definitive answer on the subject of vitamin D supplementation benefits [7], but experts have predicted this outcome for some time now. The 2018 US Preventative Task Force (USPTF) published recommendations stating that there is inadequate evidence to support supplementation of vitamin D, calcium, or both to prevent fractures in general populations. The USPTF does specify doses of 400 IU of vitamin D and 1000 mg of calcium were studied and that this recommendation applies to premenopausal women and community-dwelling men in this edition of their report [8]. Part of the evidence base the 2018 USPTF had included a 2014 Cochrane review which found a  number needed to treat of 1000, indicating that supplementation with both vitamin D & calcium had little benefit to preventing fractures [9]. The USPTF reminds readers, though, that screening for osteoporosis to prevent fractures is recommended in both young women at risk and all post-menopausal women over the age of 65 [10].

Further analysis has gone into specifying if vitamin D supplementation could prevent falls, as a noted symptom of deficiency is muscle weakness [1]. While the USPTF found no benefit for vitamin D supplementation in preventing falls in the elderly, they did find B-level evidence that physical exercise interventions do have some benefit here [11].

Prevention of Cardiovascular Disease and Cancer – Although these two disease categories are distinct from each other, many observational studies looked at both endpoints. An ancillary report from the aforementioned VITAL study found that cholecalciferol (vitamin D3) at a dose of 2000 IU per day did not lower incidence of either invasive cancers or cardiovascular events compared to the placebo at 5 years [12]. Again, this is a strong, recent finding but was predictable from previous reviews and recommendations. A Cochrane review from 2014 stated that there was no firm evidence as to whether vitamin D supplementation increased or decreased cancer incidence [13] and the USPTF found insufficient evidence for any multivitamin to prevent cancer [14].

Prevention of Other Undesirable Conditions – Further claims that vitamin D supplementation can prevent infections in young children and dementia in aging adults were also examined and found wanting [15, 16].

Management of Known Conditions – With the recent coronavirus pandemic, there was an insurgence of vitamin D supplementation due to claims that it could mitigate the severity of COVID-19 infection, either prophylactically or for secondary prevention. However, there is still insufficient evidence to evaluate this claim [17].

Multiple sclerosis is noted to occur more commonly in people with vitamin D deficiency [18]. While no clinical trials have examined if vitamin D supplementation can prevent the disease, there are several examining management [19]. Although a 2018 Cochrane review found the evidence to be low quality, reviewers concluded that there was no difference from placebo [18].

Interestingly, there is some evidence for the management of asthma with vitamin D supplementation. While the evidence base is still growing and physicians are advised to wait before recommending it to patients [20], a few reviews have found reduced risk of asthma exacerbations leading to hospitalization [21] and incidence of acute respiratory infections in those with asthma and COPD with vitamin D supplementation compared to placebo [22]. Optimum dosing and further studies are still needed, but this is an interesting area for continued research.

In pregnancy, there is some evidence that vitamin D probably reduces the risk of preeclampsia, gestational diabetes and low birthweight, and may even reduce the risk of severe postpartum hemorrhage [23]. The USPTF recommends taking aspirin for prevention of preeclampsia [24]. Although vitamin D deficiency is common in both pregnant women and their neonates, insufficient evidence exists for giving vitamin D to neonates to improve bone health, either directly or through lactating mother [25].

So, should we supplement?

For select patients, the answer is absolutely. In the setting of clinical deficiency, treatment is often warranted. In children with documented deficiency, aggressive treatment may be needed to prevent rickets [2]. Those at risk for deficiency were listed above and should be screened regularly by their physicians. In the setting of chronic kidney disease, 25-hydroxyvitamin D levels should be measured annually [1]. In the setting of malabsorption, hepatic failure or chronic use of anticonvulsants, glucocorticoids or other drugs that activate the steroid & xenobiotic receptors repletion of vitamin D may require higher doses. Pregnant and lactating women are recommended to take 400 IU of vitamin D3 per day [1]. However, both USPTF and the Endocrine Society recommend against screening for vitamin D deficiency in those not considered at risk [26, 2].

It cannot be dismissed, however, that multiple undesirable conditions are associated with low vitamin D levels [19]. This knowledge may lead to the further question of, “is there anything to do, then?” There is room for improvement in a few areas of the standard American lifestyle.

As vitamin D is often called the “sunshine vitamin,” [27] it is commonly known that sun exposure can help prevent deficiency. Specifically, sunlight hitting the skin between 10am & 3pm during the spring, summer & fall that causes the skin to have a slight tone change for 24 hours after exposure provides ample production of the vitamin for most people. However, people who live above or below latitudes of 33 degrees may not be able to obtain enough sunlight. During the winter and in regions without enough sun, tanning beds used for 30-50% of the time used to tan can also help [1].

Other lifestyle changes to be made include weight loss, as adiposity is a risk factor for deficiency [28], and dietary modification. Despite popular confusion on optimum dietary parameters, there is a significant consensus in dietary evidence supporting that Americans need to eat fewer calories from solid (or saturated) fats, added sugars and refined grains and consume more fruits, vegetables and whole grains [29, 30]. This dietary pattern has been well-proven to decrease risk for CVD & multiple types of cancers, as compared to the lack of evidence supporting supplementation with Vitamin D to prevent the same [29]. Incorporating food items known to have significant amounts of vitamin D may help people achieve the recommended daily intake. For people between the ages of 1 & 70 years, the recommended dietary allowance is 600 IU [31]. Foods that are good sources of vitamin D include fish such as salmon, sardines, mackerel & tuna, mushrooms, egg yolks & fortified foods [1]. Most fortified foods are dairy products, including milk, yoghurt, cheese and butter, but plant-based sources include lichen & mushrooms [32].

While many of claims regarding vitamin D supplementation have been proven false, the persistence of an association between vitamin D deficiency and certain disease states presents a conundrum which popular logic solves by daily, safe-dosed supplementation. The symptoms of hypervitaminosis D are usually only seen at regular intakes far and above recommended daily intake and surveys point to less-than-adequate dietary intake of the vitamin [1, 31, 27, 19]. It seems pertinent to consider daily supplementation of 400-600 IU rather safe, so long as patients are not expecting the grandiose results promised by false claims. While benefits of daily supplementation are not supported by current literature, discussions where patients bring up vitamin D may provide an opportunity to discuss lifestyle-based methods of improving nutrition and health. Since human skin synthesizes vitamin D during sun exposure, increased vitamin D serum levels is a wonderful benefit to exercising outdoors. Since dietary intake of the vitamin is commonly low in Americans, increased fish & whole food intake are aligned both with the goal of increasing vitamin D and following well-proven diets like DASH and Mediterranean. Perhaps the best use of consultation time in discussion of the vitamin is simply promoting healthy lifestyle behaviors and not recommending potentially costly supplementation.

References

[1]	M. Holick, “Vitamin D Deficiency,” New England Journal of Medicine, no. 357, pp. 266-281, July 2007.
[2]	M. Holick, N. Binkley, H. Bischoff-Ferrari, C. Gordon, D. Hanley, R. Heaney, H. Murad and C. Weaver, “Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline,” J Clinical Endocrinology & Metabolism, vol. 96, no. 7, pp. 1911-1930, July 2011.
[3]	M. Rooney, L. Harnack and E. Michos, “Trends in Use of High-Dose Vitamin D Supplements Exceeding 1000 or 4000 International Units Daily, 1999-2014,” JAMA, vol. 317, no. 23, pp. 2448-2450, 2017.
[4]	K. Herrick, R. Storandt, J. Afful, C. Pfeiffer, R. Schleicher, J. Gahche and N. Potischman, “Vitamin D Status in the United States, 2011-2014,” Am J Clinical Nutrition, vol. 110, no. 1, pp. 150-157, 2019.
[5]	Nutrition Business Journal, “Supplement Business Report 2022,” New Hope Network, 2022. [Online]. Available: https://store.newhope.com/products/supplement-business-report-2022. [Accessed 22 September 2022].
[6]	M. LeBoff, S. Chou, K. Ratliff, N. Cook, B. Khurana, E. Kim, P. Cawthorn, D. Bauer, D. Black, C. Gallagher, M. Lee and J. Buring, “Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults,” NEJM, vol. 387, pp. 299-309, 2022.
[7]	S. Cummings and C. Rosen, “VITAL Findings – A Decisive Verdict on Vitamin D Supplementation,” NEJM, vol. 387, pp. 368-370, 2022.
[8]	US Preventative Task Force, “Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults,” JAMA, vol. 319, no. 15, pp. 1592-1599, 2018.
[9]	A. Avenell, J. Mak and D. O’Connell, “Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men,” Cochrane Database of Systematic Reviews, no. 4, 2014.
[10]	US Preventative Task Force, “Final Recommendation Statement on Osteoporosis to Prevent Fractures: Screening,” 26 June 2018. [Online]. Available: https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/osteoporosis-screening. [Accessed 21 September 2022].
[11]	USPTF, “Interventions to Prevent Falls in Community-Dwelling Older Adults,” JAMA, vol. 319, no. 16, pp. 1696-1704, 2018.
[12]	VITAL Research Group, “Vitamin D Supplements and Prevention of Cancer & Cardiovascular Disease,” NEJM, vol. 380, pp. 33-44, 2019.
[13]	G. Bjelakovic, L. Gluud, D. Nikolova, K. Whitfield, G. Krstic, J. Wetterslev and C. Gluud, “Vitamin D supplementation for prevention of cancer in adults,” Cochrane Database of Systemic Reviews, no. 6, 2014.
[14]	USPTF, “Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer,” JAMA, vol. 327, no. 23, pp. 2326-2333, 2022.
[15]	M. Yakoob, R. Salam, F. Khan and Z. Bhutta, “Vitamin D supplementation for preventing infections in children under five years of age,” Cochrane Database of Systematic Reviews, no. 11, 2016.
[16]	A. Rutjes, D. Denton, M. Di Nisio, L. Chong, R. Abraham, A. Al-Assaf, J. Anderson, M. Malik, R. Vernooij, G. Martinez, N. Tabet and J. McCleery, “Vitamin and mineral supplementation for preventing cognitive deterioration in cognitively healthy people in mid and late life,” Cochrane Database of Systematic Reviews, no. 12, 2018.
[17]	J. Stroehlein, J. Wallqvist, C. Iannizzi, A. Mikolajewska, M.-I. Metzendorf, C. Benstoem, P. Meybohm, M. Becker, N. Skoetz, M. Stegemann and V. Piechotta, “Vitamin D supplementation for the treatment of COVID-19: a living systematic review,” Cochrane Database of Systematic Reviews, no. 5, 2021.
[18]	V. Jagannath, G. Filippini, C. Pietrantonj, G. Asokan, E. Robak, L. Whamond and S. Robinson, “Vitamin D for the management of multiple sclerosis,” Cochrane Database of Systematic Reviews, no. 9, 2018.
[19]	National Institutes of Health Office of Dietary Supplements, “Vitamin D Fact Sheet for Health Professionals,” 12 August 2022. [Online]. Available: https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/. [Accessed 21 September 2022].
[20]	J. Qiu, “Vitamin D for the Management of Asthma,” American Family Physician, vol. 96, no. 5, pp. 290-291, 2017.
[21]	A. Martineau, C. Cates, M. Urashima, M. Jensen, A. Griffiths, U. Nurmatov, A. Sheikh and C. Griffiths, “Vitamin D for the management of asthma,” Cochrane Database of Systematic Reviews, no. 9, 2016.
[22]	D. Joliffe, C. Camargo, J. Sluyter, M. Aglipay and J. Aloia, “Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials,” The Lancet Diabetes and Endocrinology, vol. 9, no. 5, pp. 276-292, 2021.
[23]	C. Palacios, L. Kostiuk and J. Pena-Rosas, “Vitamin D supplementation for women during pregnancy,” Cochrane Database of Systematic Reviews, no. 7, 2019.
[24]	USPTF, “Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality,” JAMA, vol. 326, no. 12, pp. 1186-1191, 2021.
[25]	M. Tan, S. Abrams and D. Osborn, “Vitamin D supplementation for term breastfed infants to prevent vitamin D deficiency and improve bone health,” Cochrane Databse of Systematic Reviews, no. 12, 2020.
[26]	USPTF, “Screening for Vitamin D Deficiency in Adults,” JAMA, vol. 325, no. 14, pp. 1436-1442, 2021.
[27]	Academy of Nutrition and Dietetics, “Supplements for Breastfed Babies,” AND, June 2021. [Online]. Available: https://www.eatright.org/food/vitamins-and-supplements/dietary-supplements/supplements-for-breastfed-babies. [Accessed 22 September 2022].
[28]	S. Mallard, A. Howe and L. Houghton, “Vitamin D status and weight loss: a systematic review and meta-analysis of randomized and nonrandomized controlled weight-loss trials,” Am J of Clinical Nutrition, vol. 104, no. 4, pp. 1151-1159, 2016.
[29]	American College of Lifestyle Medicine, “A Family Physician’s Introduction to Lifestyle Medicine,” J Family Practice, vol. 71, no. 1, p. supplement, 2022.
[30]	L. Lesser, M. C. Mazza and S. Lucan, “Nutrition Myths and Healthy Dietary Advice in Clinical Practice,” American Family Physician, vol. 91, no. 9, pp. 634-638, 2015.
[31]	Institute of Medicine Committee to Reivew Dietary Reference Intakes for Vitamin D and Calcium, “Dietary Intake Assessment,” in Dietary Reference Intakes for Calcium and Vitamin D, Washington (DC), National Academies Press, 2011, p. Chapter 7.
[32]	W. Willett and D. Ludwig, “Milk and Health,” NEJM, vol. 382, pp. 644-654, 2020.