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Discover what vitamin D means for you and your health status

How Common is Vitamin D Deficiency & Insufficiency? Who is at Risk?

Low vitamin D status is becoming more common worldwide. The prevalence of vitamin D deficiency (VDD) was found to be 28.9 % and vitamin D insufficiency (VDI) 41% in a subset of 26,010 US adults surveyed as part of the ongoing National Health and Nutrition Examination Survey (NHANES) 2001-2010. Those who were African American, less educated, of lower socioeconomic status, smokers, physically inactive, obese and infrequent milk consumers demonstrated a higher prevalence of VDD and VDI. 1 Worldwide, many countries report a high prevalence of low vitamin D status. The percentage of individuals with VDD or serum 25(OH)D <30 nmol/L (or 12 ng/ml) is estimated to be 7.4% in Canada, 2 13% in Europe3 and as high as >20% of the population in India, Tunisia, Pakistan and Afghanistan. 3,4 However, certain populations are more at risk for becoming deficient than others. For example, individuals with chronic diseases especially of the liver, kidney and heart, anyone with diseases that lead to malabsorption such as Crohn’s disease, hospitalized patients, and anyone with reduced exposure to sunlight. 5,6 Older adults, individuals with existing conditions, obese individuals, diabetics and those taking certain medications are particularly at risk. Older adults, especially those that are institutionalized, are at increased risk due to decreased sun exposure, decreased ability to synthesize vitamin D in the aging skin, 7 decreased intake and possibly a greater number of medications. Medications such as antiseizure medications, glucocorticoids, rifampin and supplements such as St. John’s Wort may increase the risk of vitamin D deficiency. 8 

  1. Liu X, Baylin A, Levy PD. Vitamin D deficiency and insufficiency among US adults: prevalence, predictors and clinical implications. British Journal of Nutrition. 2018;119(8):928-936.
  2. Sarafin K, Durazo-Arvizu R, Tian L, et al. Standardizing 25-hydroxyvitamin D values from the Canadian Health Measures Survey. Am J Clin Nutr. 2015;102(5):1044-1050.
  3. Cashman KD, Dowling KG, Škrabáková Z, et al. Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr. 2016;103(4):1033-1044.
  4. Cashman KD. Vitamin D Deficiency: Defining, Prevalence, Causes, and Strategies of Addressing. Calcified tissue international. 2020;106(1):14-29.
  5. Amrein K, Scherkl M, Hoffmann M, et al. Vitamin D deficiency 2.0: an update on the current status worldwide. European journal of clinical nutrition. 2020;74(11):1498-1513.
  6. MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest. 1985;76(4):1536-1538.
  7. Mandal AKJ, Baktash V, Hosack T, Missouris CG. Vitamin D status and COVID-19 in older adults. Aging clinical and experimental research. 2020;32(11):2425-2426.
  8. Wacker M, Holick MF. Vitamin D – effects on skeletal and extraskeletal health and the need for supplementation. Nutrients. 2013;5(1):111-148.

What is Vitamin D?

Vitamin D is a fat soluble vitamin that humans get from the diet, sunlight and supplements. It is not a single compound but is a family of similar compounds with slightly different side chains. There are two major forms of vitamin D: vitamin D2 and D3. Vitamin D2 or ergocalciferol is the most common form and an important dietary source that is synthesized by plants and also used to fortify foods like milk, orange juice and cereals. Most mammals can convert vitamin D2 to vitamin D3. Vitamin D3, also called cholecalciferol, is the form that can be made by the human body from cholesterol and is naturally found in cod liver oil, oily fish, and is often found in dietary supplements. D3 is the active part of 1,25-dihydroxycholecalciferol (1,25(OH)2D), which is responsible for the biological functions of vitamin D. 1 

With no supplementation, about 80% of vitamin D3 is synthesized in the skin and 20% is obtained from the diet. With regular sun exposure, a healthy diet, and healthy kidneys, many people can make the vitamin D they need. However, most people are not regularly exposed to the sun and diets vary. The absorption of Vitamin D from food sources is dependent upon the presence of long chain fats and bile salts. Dietary vitamin D first goes to the liver then the kidney converts it to its active form and distributes the active form throughout the body. Because it is synthesized and released from , the kidneys, and the fact that there are vitamin D receptors in many tissues makes vitamin D a “hormone-like” vitamin. 1 

Vitamin D is delivered throughout the body on vitamin D binding protein and must bond with a vitamin D receptor (VDR) to enact its biological effects. These receptors are located throughout the body and explain why vitamin D is important for so many functions in the body. 2 For example, VDR has been found in cells of the intestinal epithelium, renal tubules, parathyroid gland cells, skin (keratinocytes), mammary epithelium, pancreas (beta islet cells), pituitary gland, skeleton (osteoblasts and chondrocytes), immune system (monocytes, macrophages, and T-lymphocytes), and germ tissues. The tissues with the highest VDR content are intestine, kidney, parathyroid gland, and bone, all of which are associated with maintenance of calcium homeostasis. 3 

 

  1. Hewlings SJ, Medeiros DM. Nutrition: Real People, Real Choices. Pearson Prentice Hall; 2009.
  2. Sassi F, Tamone C, D’Amelio P. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients. 2018;10(11):1656.
  3. Wang Y, Zhu J, DeLuca HF. Where is the vitamin D receptor? Arch Biochem Biophys. 2012 Jul 1;523(1):123-33. doi: 10.1016/j.abb.2012.04.001. Epub 2012 Apr 6. PMID: 22503810.

Why is Vitamin D Important?

Vitamin D was first known for its role in bone development and maintenance. It plays a key role in the metabolism of calcium and phosphorus, two important minerals for bone integrity. Vitamin D stimulates the cells of the small intestine to produce a calcium binding protein called calbindin, which increases calcium absorption. When blood calcium levels decline, vitamin D stimulates the production of calbindin to increase calcium absorption from food. In addition, when blood levels of calcium fall, vitamin D stimulates the kidneys to conserve calcium by decreasing urinary excretion. Vitamin D has many other important functions. It plays a key role in maintaining immune health, oral health, muscle health and strength, for regulating gene transcription and promoting protein synthesis. 1 These functions have received more research attention in recent years due to the findings that vitamin D receptors (VDR) and the vitamin D activating enzyme 1-α-hydroxylase (CYP27B1) are found in many cells outside the bone and kidney including the muscles, the intestine and some immune cells. This suggests the biologically active form of vitamin D, 1,25(OH)2D, can influence immunity and health in multiple ways. 1-3 

  1. Wacker M, Holick MF. Vitamin D – effects on skeletal and extraskeletal health and the need for supplementation. Nutrients. 2013;5(1):111-148.
  2. Sassi F, Tamone C, D’Amelio P. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients. 2018;10(11):1656.
  3. Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients. 2013;5(7):2502-2521.

Vitamin D and Bone Health

While calcium is often associated with bone health, it is important to remember that vitamin D is also essential for healthy bones. In fact, the U.S. Food and Drug Administration (FDA) has authorized health claims that describe the relationship between vitamin D, calcium and osteoporosis risk [1]. For example, the FDA authorized health claim recognizes that adequate calcium and vitamin D throughout life, as part of a well-balanced diet, may reduce the risk of osteoporosis in later life [1]. Around the world, vitamin D is recognized for bone health and other non-U.S. government authorities, like Health Canada and the European Food Safety Authority (EFSA), also have authorized health claims,[1] including:

  • Vitamin D contributes to and helps develop/maintain/build strong bones and teeth [2-7]
  • Vitamin D helps with absorption/use of calcium/phosphorus and maintenance of blood calcium levels [2, 8]
  • Vitamin D and calcium may reduce the risk of developing osteoporosis when combined with healthy diet and regular exercise [2]
  • Vitamin D and calcium may reduce the loss of bone mineral (a risk factor for osteoporotic bone fractures) in post-menopausal women [9]

How Does Vitamin D Work in Bone Health?

The importance of vitamin D for bone health and strength is well-supported [10-15]. Vitamin D helps the body absorb and use calcium and assists the cells that re-structure and build bone through bone remodeling and bone mineralization [10-17]. 

Balance is key for bone health; the structure or scaffold of bone relies on normal bone mineralization, which requires balanced levels of calcium and phosphorus [13]. This is where vitamin D plays a vital role, via helping the body absorb calcium and phosphorus in the gastrointestinal tract and re-absorb calcium from the kidneys to keep it from being removed as waste [10, 14]. This role of vitamin D is regulated through actions of parathyroid hormone (PTH) which creates a feedback loop to keep vitamin D, calcium, and phosphorus all working together in concert [10, 12, 16]. When vitamin D levels are too low, less calcium is absorbed in the gastrointestinal tract [12, 17], leading to increases in PTH which causes the body to pull too much calcium from the bones, resulting in weaker bones over time [12, 17]. 

When thinking about bones, it may be easy to think of them as static after childhood and adolescence. But even in adults, bones are in a constant process of change as they turnover and remodel [10, 15, 17-19]. Bone cells, like osteoblasts and osteoclasts, work together in complex processes to digest old bone and replace it with new bone [10, 17, 18]. When vitamin D levels are too low, there can be an imbalance in this turnover, leading to more breakdown and less mineralization of the bone [12, 17]. 

Research on Vitamin D & Bone Health 

Numerous studies have demonstrated the role of vitamin D in bone health and maintenance [1-14, 16, 17, 20-31]. Its importance has been shown in different populations:    

  • Older adults: Aging can impact physiology and behaviors, which impacts vitamin D exposure and metabolism [23]. Vitamin D deficiency has been associated with hip fractures in older adults [28]. In women (≥65 years old) with osteoporosis in long term care facilities, as serum vitamin D levels increased, there were significant improvements in measurements of bone health and mobility performance [31]. 
  • Post-menopausal women: Vitamin D insufficiency was associated with increased bone remodeling and low bone mass in post-menopausal women [24]. Vitamin D supplementation, with or without calcium supplementation, reduce PTH in postmenopausal women [27]. 
  • Individuals with obesity: Obese adults generally have lower serum vitamin D levels which could impact their specific dosing needs, and particularly following bariatric surgery, bone density and microarchitecture can deteriorate [26]. 
  • Individuals with low vitamin D: Vitamin D intake is especially important for individuals with low serum vitamin D [13, 23, 27, 29, 30, 32, 33] and vitamin D supplementation may benefit bone mineral density over time in these individuals [13, 23, 29, 30]. 

Some clinical studies have found mixed results for bone mass density and risk of fractures [33, 34]. These results may be attributed to participants with sufficient vitamin D levels, or other factors impacting vitamin D levels, like sun exposure, dietary intake, and genetics [13, 14, 23, 27, 32, 33]. It is very important for individuals to know their personal vitamin D level as supplementation may be especially critical for people who have low or insufficient vitamin D levels [23, 27, 32, 33]. 

 Bone Health Risk 

According to the U.S. Department of Health, it is estimated that over 43 million people in the United States have low bone mass, which increases the risk for osteoporosis [35]. It is clear that severe vitamin D deficiency results in osteomalacia [30], but even vitamin D insufficiency may contribute to development of osteoporosis [10, 11]. Maintaining an ideal vitamin D level throughout the life span is important to ensure proper calcium absorption and bone health overall.

  1. 21 CFR 101.72(f), § 101.72 Health claims: calcium, vitamin D, and osteoporosis. Available online at: https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-101/subpart-E/section-101.72 (Accessed Sept. 07, 2023).
  2. Health Canada, Natural Health Product Monograph – Multivitamin/mineral. Available online at: https://webprod.hc-sc.gc.ca/nhpid-bdipsn/atReq.do?atid=multi_vitmin_suppl&lang=eng. 2023.
  3. EFSA, Scientific Opinion on the substantiation of health claims related to vitamin D and maintenance of bone and teeth (ID 150, 151, 158), absorption and utilisation of calcium and phosphorus and maintenance of normal blood calcium concentrations (ID 152, 157), cell division (ID 153), and thyroid function (ID 156) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. European Food Safety Authority (EFSA) Panel on Dietetic Products, Nutrition Allergies. EFSA Journal, 2009. 7(10): p. 1227.
  4. EFSA, Calcium and vitamin D and bone strength – Scientific substantiation of a health claim related to calcium and vitamin D and bone strength pursuant to Article 14 of Regulation (EC) No 1924/2006 – Scientific Opinion of the European Food Safety Authority (EFSA) Panel on Dietetic Products, Nutrition and Allergies. EFSA Journal, 2008. 6(10): p. 828.
  5. EFSA, Vitamin D and bone growth – Scientific substantiation of a health claim related to vitamin D and bone growth pursuant to Article 14 of Regulation (EC) No 1924/2006 – Scientific Opinion of the European Food Safety Authority (EFSA)Panel on Dietetic Products, Nutrition and Allergies. EFSA Journal, 2008. 6(10): p. 827.
  6. EFSA, Scientific Opinion on the substantiation of health claims related to calcium and vitamin D and maintenance of bone (ID 350) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Panel on Dietetic Products, Nutrition and Allergies. EFSA Journal, 2009. 7(10): p. 1272.
  7. EFSA, Scientific Opinion on the substantiation of health claims related to vitamin D and maintenance of bone and teeth (ID 150, 151, 158), absorption and utilisation of calcium and phosphorus and maintenance of normal blood calcium concentrations (ID 152, 157), cell division (ID 153), and thyroid function (ID 156) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Panel on Dietetic Products, Nutrition and Allergies. EFSA Journal, 2009. 7(10): p. 1227.
  8. EFSA, Scientific Opinion on health claims already evaluated (ID 215, 568, 674, 712, 1398, 1633, 1974, 4191, 4192, 4193, 4236, 4335, 4698, 4704) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Panel on Dietetic Products, Nutrition and Allergies. EFSA Journal, 2011. 9(6): p. 2203.
  9. EFSA, Calcium + Vitamin D3 chewing tablets and bone loss – Scientific substantiation of a health claim related to Calcium plus Vitamin D3 chewing tablets and reduction of the risk of osteoporotic fractures by reducing bone loss pursuant to Article 14 of Regulation (EC) No 1924/2006. European Food Safety Authority (EFSA). EFSA Journal, 2009. 7(8): p. 1180.
  10. LPI, Vitamin D. Linus Pauling Institue (LPI) – Oregon State University. Available online at: https://lpi.oregonstate.edu/mic/vitamins/vitamin-D (Accessed Sept. 01, 2023). 2017.
  11. NIH ODS, Vitamin D Fact Sheet. National Institute of Health (NIH) – Office of Dietary Supplements (ODS). Available online at: https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/ (Accessed Sept. 01, 2023). 2022.
  12. Laird, E., et al., Vitamin D and bone health: potential mechanisms. Nutrients, 2010. 2(7): p. 693-724.
  13. Reid, I.R. and M.J. Bolland, Calcium and/or Vitamin D Supplementation for the Prevention of Fragility Fractures: Who Needs It? Nutrients, 2020. 12(4).
  14. Portales-Castillo, I. and P. Simic, PTH, FGF-23, Klotho and Vitamin D as regulators of calcium and phosphorus: Genetics, epigenetics and beyond. Front Endocrinol (Lausanne), 2022. 13: p. 992666.
  15. IOM, Dietary Reference Intakes for Calcium and Vitamin D. 2010, Institute of Medicine of the National Academies: Washington, DC.
  16. Kužma, M., et al., Parathyroid Hormone-Related Changes of Bone Structure. Physiol Res, 2021. 70(Suppl 1): p. S3-s11.
  17. Bhattarai, H.K., et al., Vitamin D, Calcium, Parathyroid Hormone, and Sex Steroids in Bone Health and Effects of Aging. J Osteoporos, 2020. 2020: p. 9324505.
  18. Bolamperti, S., I. Villa, and A. Rubinacci, Bone remodeling: an operational process ensuring survival and bone mechanical competence. Bone Res, 2022. 10(1): p. 48.
  19. Allen, M.R. and D.B. Burr, Bone growth, modeling, and remodeling, in Basic and applied Bone biology. 2019, Elsevier. p. 85-100.
  20. Health Canada, Natural Health Product Monograph – Vitamin D (>1,000-2,500 IU). Available online at: https://webprod.hc-sc.gc.ca/nhpid-bdipsn/atReq.do?atid=vitamin.d.hd&lang=eng 2021.
  21. Yakabe, M., et al., Prescription of vitamin D was associated with a lower incidence of hip fractures. Sci Rep, 2023. 13(1): p. 12889.
  22. Kazemian, E., et al., Effect of supplemental vitamin D3 on bone mineral density: a systematic review and meta-analysis. Nutr Rev, 2023. 81(5): p. 511-530.
  23. Hill, T.R. and T.J. Aspray, The role of vitamin D in maintaining bone health in older people. Ther Adv Musculoskelet Dis, 2017. 9(4): p. 89-95.
  24. Mezquita-Raya, P., et al., Relation between vitamin D insufficiency, bone density, and bone metabolism in healthy postmenopausal women. J Bone Miner Res, 2001. 16(8): p. 1408-15.
  25. Owens, D.J., R. Allison, and G.L. Close, Vitamin D and the Athlete: Current Perspectives and New Challenges. Sports Med, 2018. 48(Suppl 1): p. 3-16.
  26. Walsh, J.S., S. Bowles, and A.L. Evans, Vitamin D in obesity. Curr Opin Endocrinol Diabetes Obes, 2017. 24(6): p. 389-394.
  27. Reis, A.R., et al., Supplementation of vitamin D isolated or calcium-associated with bone remodeling and fracture risk in postmenopausal women without osteoporosis: A systematic review of randomized clinical trials. Nutrition, 2023. 116: p. 112151.
  28. Matrangolo, M.R., et al., Predictor of hip fracture type: a systematic review. Acta Biomed, 2023. 94(S2): p. e2023047.
  29. Macdonald, H.M., et al., 25-Hydroxyvitamin D Threshold for the Effects of Vitamin D Supplements on Bone Density: Secondary Analysis of a Randomized Controlled Trial. J Bone Miner Res, 2018. 33(8): p. 1464-1469.
  30. Reid, I.R., et al., Effect of monthly high-dose vitamin D on bone density in community-dwelling older adults substudy of a randomized controlled trial. J Intern Med, 2017. 282(5): p. 452-460.
  31. Haeri, N.S., S. Perera, and S.L. Greenspan, The association of vitamin D with bone microarchitecture, muscle strength, and mobility performance in older women in long-term care. Bone, 2023: p. 116867.
  32. Fischer, C., et al., Additive Effects of Exercise and Vitamin D Supplementation (with and without Calcium) on Bone Mineral Density in Older Adults: A Systematic Review and Meta-Analysis. J Osteoporos, 2023. 2023: p. 5570030.
  33. Pilz, S., et al., Critical Appraisal of Large Vitamin D Randomized Controlled Trials. Nutrients, 2022. 14(2).
  34. LeBoff, M.S. and H.A. Bischoff-Ferrari, The Effects of Vitamin D Supplementation on Musculoskeletal Health: The VITAL and DO-Health Trials. J Gerontol A Biol Sci Med Sci, 2023. 78(Supplement_1): p. 73-78.
  35. U.S. Dept. Health and Human Services, Osteoporosis Workgroup. https://health.gov/healthypeople/about/workgroups/osteoporosis-workgroup.

Vitamin D and Muscle Health

Adequate vitamin D levels are necessary for muscle metabolism and muscle protein synthesis [1-4]. Vitamin D deficiency can cause muscle pain and weakness [2-4], which may impact mobility, stability, and posture. The European Food Safety Authority (EFSA) has authorized the following health claims[1] relevant for muscle health:

  • Vitamin D contributes to the maintenance of normal muscle function [3].
  • Vitamin D helps to reduce the risk of falling associated with postural instability and muscle weakness. Falling is a risk factor for bone fractures among men and women 60 years of age and older [5].

How Does Vitamin D Work in Muscle Health?

The role of vitamin D in muscle health starts with protein synthesis and muscle fiber metabolism to build up muscle [6-8]. Studies in muscle cells show that vitamin D plays important roles in cell signaling processes and gene expression that contribute to the growth, development, and function of muscle cells [6, 7, 9]. Further, vitamin D contributes to the cellular function and repair of muscle cells [6].

Research on Vitamin D and Muscle Health

There is a causal relationship between vitamin D levels and skeletal muscle health [9]. Evidence from human data supports an overall positive impact of vitamin D on muscle health, including [7, 9-19]:

  • In healthy adults, whey protein when combined with vitamin D supplementation improved lean muscle, muscle strength and physical mobility. As these muscle health improvements in healthy adults were not seen with whey protein supplementation alone, it is thought that correcting low or deficient vitamin D level was key to supporting muscle strength [7, 12].
  • In older Asian adults, low or deficient vitamin D levels have been associated with lower muscle health measures [15, 19].
  • In women (aged 74-89 years old) living in long term care facilities, increases in serum vitamin D levels were associated with better gait speed [16], a measurement of mobility and muscle strength [20].
  • Adolescents (aged 10-19 years old) with sufficient vitamin D levels had better grip strength measurements compared to their counterparts with vitamin D deficiency, suggesting a role of vitamin D for muscle health in adolescents [17].
  • In mobility-limited, vitamin D deficient women (aged 73-83 years old), vitamin D supplementation improved measurements of skeletal muscle fiber [18].

Muscle Health Risk

According to the U.S. Center for Disease Control, muscle strength decreases with age [21]. Skeletal muscle mass can decrease by 30% by age 80 [9]. An analysis that included U.S. adults aged 50 or older, found the prevalence of low muscle mass to be 17-23% and the prevalence of low muscle strength to be 19% [22]. Another analysis of Americans aged 65 or older found that 47-55% had weak muscles as defined by their grip strength, with 55% having slow gait speed [23]. The role of vitamin D in muscle health is one clear reason to maintain an ideal vitamin D level throughout all life stages.

[1] Health claims have specific conditions for use (e.g., require specific minimum levels of vitamin D) and specific wording of the claim – refer to the authorizing text for requirements mandated by the regulatory agency.

  1. NIH ODS, Vitamin D Fact Sheet. National Institute of Health (NIH) – Office of Dietary Supplements (ODS). Available online at: https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/ (Accessed Sept. 01, 2023). 2022.
  2. Natural Medicines, Vitamin D [monograph] (2023, July 25). http://naturalmedicines.therapeuticresearch.com. 2023.
  3. EFSA, Scientific Opinion on the substantiation of health claims related to vitamin D and normal function of the immune system and inflammatory response (ID 154, 159), maintenance of normal muscle function (ID 155) and maintenance of normal cardiovascular function (ID 159) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Panel on Dietetic Products, Nutrition and Allergies. EFSA Journal, 2010. 8(2):1468.
  4. LPI, Vitamin D. Linus Pauling Institue (LPI) – Oregon State University. Available online at: https://lpi.oregonstate.edu/mic/vitamins/vitamin-D (Accessed Sept. 01, 2023). 2017.
  5. EFSA, Scientific Opinion on the substantiation of a health claim related to vitamin D and risk of falling pursuant to Article 14 of Regulation (EC) No 1924/2006. EFSA Panel on Dietetic Products, Nutrition and Allergies. EFSA Journal, 2011. 9(9): p. 2382.
  6. Agoncillo, M., J. Yu, and J.E. Gunton, The Role of Vitamin D in Skeletal Muscle Repair and Regeneration in Animal Models and Humans: A Systematic Review. Nutrients, 2023. 15(20).
  7. Nasimi, N., et al., Whey Protein Supplementation with or without Vitamin D on Sarcopenia-Related Measures: A Systematic Review and Meta-Analysis. Adv Nutr, 2023. 14(4): p. 762-773.
  8. Kim, Y.C., et al., Recent Advances in Nutraceuticals for the Treatment of Sarcopenic Obesity. Nutrients, 2023. 15(17).
  9. Sutherland, J.P., A. Zhou, and E. Hyppönen, Muscle Traits, Sarcopenia, and Sarcopenic Obesity: A Vitamin D Mendelian Randomization Study. Nutrients, 2023. 15(12).
  10. Song, Z., et al., The effects of nutritional supplementation on older sarcopenic individuals who engage in resistance training: a meta-analysis. Front Nutr, 2023. 10: p. 1109789.
  11. Cochet, C., et al., The Role of Nutrition in the Treatment of Sarcopenia in Old Patients: From Restoration of Mitochondrial Activity to Improvement of Muscle Performance, a Systematic Review. Nutrients, 2023. 15(17).
  12. Voulgaridou, G., et al., Increasing Muscle Mass in Elders through Diet and Exercise: A Literature Review of Recent RCTs. Foods, 2023. 12(6).
  13. Beaudart, C., et al., The effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab, 2014. 99(11): p. 4336-45.
  14. Fox, F.A.U., et al., 25-hydroxyvitamin D level is associated with greater grip strength across adult life span: a population-based cohort study. Endocr Connect, 2023. 12(4).
  15. Lee, J.H., et al., Association between Vitamin D Deficiency and Clinical Parameters in Men and Women Aged 50 Years or Older: A Cross-Sectional Cohort Study. Nutrients, 2023. 15(13).
  16. Haeri, N.S., S. Perera, and S.L. Greenspan, The association of vitamin D with bone microarchitecture, muscle strength, and mobility performance in older women in long-term care. Bone, 2023: p. 116867.
  17. Orces, C.H., The Association between Vitamin D Status and Muscle Strength Among Adolescents. Int J Prev Med, 2022. 13: p. 146.
  18. Ceglia, L., et al., A randomized study on the effect of vitamin D₃ supplementation on skeletal muscle morphology and vitamin D receptor concentration in older women. J Clin Endocrinol Metab, 2013. 98(12): p. E1927-35.
  19. Yang, C., et al., Relationship of Serum 25-Hydroxyvitamin D Levels with Sarcopenia and Body Composition in Community-Dwelling Older Adults: A Paired Case-Control Study. J Am Med Dir Assoc, 2023. 24(8): p. 1213-1219.
  20. Stotz, A., D. Hamacher, and A. Zech, Relationship between Muscle Strength and Gait Parameters in Healthy Older Women and Men. Int J Environ Res Public Health, 2023. 20(7).
  21. CDC, Prevalence of Reduced Muscle Strength in Older U.S. Adults: United States, 2011–2012. Available online at: https://www.cdc.gov/nchs/products/databriefs/db179.htm. 2015.
  22. Li, R., et al., Associations of Muscle Mass and Strength with All-Cause Mortality among US Older Adults. Med Sci Sports Exerc, 2018. 50(3): p. 458-467.
  23. Duchowny, K.A., M.D. Peterson, and P.J. Clarke, Cut Points for Clinical Muscle Weakness Among Older Americans. Am J Prev Med, 2017. 53(1): p. 63-69.

Vitamin D & The Risk of Falls

Adequate vitamin D levels are necessary for muscle health, which is important for mobility, stability and posture [1-11]. As people get older, muscle weakness or muscle loss can increase the risk for frailty and falls, which can also lead to bone fractures [10, 12-14]. Vitamin D deficiency has been associated with increased falls and hip fractures in older adults [10, 12]. While fall risk involves many factors, including age, bone health, activity level, balance issues, underlying health conditions, and medication use [15-17], vitamin D is an important factor for reducing fall risk in older, vitamin D deficient populations because of its impact on muscle health [1-14]. 

How Does Vitamin D Work for Stability and Reducing Risk of Falls? 

Adequate muscle strength and mobility are associated with stability and a decreased risk of falling [1-10, 12-14, 18]. The role of vitamin D in reducing risk of falls starts with impacts on muscle strength and muscle metabolism. Vitamin D contributes to protein synthesis and muscle fiber metabolism, which is responsible for building and repairing muscle. Additionally, vitamin D is important for cell signaling processes and gene expression which contribute to the growth, development, function, and repair of muscle cells [5-8] 

Research on Vitamin D and Risk of Falls 

Evidence from human data, including observational data on vitamin D levels [13], interventional data [14, 16, 19-23], and meta-analyses of interventional data [6, 17, 18, 24-27], support an overall positive impact of vitamin D on stability, muscle health, and muscle function, which may impact the risk of falls, particularly for older adults who are vitamin D deficient or insufficient [17, 24, 25]. It should be noted that there have been inconsistent findings in vitamin D supplementation’s impact on fall risk [24, 28], resulting in conflicting recommendations [15, 17]. The inconsistent results might be attributed to some confounding factors, including differences in initial vitamin D status, dosing used, short study duration, and lack of individual dosing required to reach optimal levels [24] 

While more data is needed on vitamin D supplementation and falls [28], current evidence includes: 

  • Vitamin D supplementation alone has a benefit of reducing fall risk in older adults with vitamin D levels lower than 50 nmol/L [25]. The combination of vitamin D with calcium supplementation in this study involving older, vitamin D deficient adults reduced fall risk by 12% [25] 
  • Some studies suggest that consistent daily intake of vitamin D is associated with reduced risk of falls for those who are vitamin D deficient [24]. Studies also suggest that vitamin D intake amounts are important to consider and that higher amounts (≥1000 IU daily) may not show improvements in risk of falls compared to a daily intake of 200 IU [16, 19, 22, 23]. Together, the data highlights the importance of steady daily intake to maintain optimal vitamin D levels. 
  • In vitamin D deficient, elderly women, the combination of vitamin D and calcium supplementation reduced fall risk compared to calcium supplementation alone, which is partially attributed to improved balance control [14]. This suggests that vitamin D may impact fall risk through improved balance, muscle strength, and lower extremity function in this population [14]. 
  • Vitamin D has been linked to improved muscle health and mobility in vitamin D deficient healthy adults and older women [6, 13, 20, 29]. 
  • Individuals with conditions or chronic diseases impacting motor function or balance may also benefit from maintaining optimal vitamin D levels [21, 30]. 

Fall Risk 

According to the U.S. Centers for Disease Control and Prevention, falls are a leading cause of injury (fatal and non-fatal) among older adults who are 65 years or older [31]. Age-related decreases of muscle strength and skeletal muscle mass are some factors that can impact mobility and stability [8, 32, 33]. Older adults may not have sufficient knowledge about vitamin D, specifically relating to deficiency-associated risk of falls, which highlights the importance of educating the public [34]. While fall risk is associated with multiple factors [15-17], the role of vitamin D to support muscle health and potentially reduce risk of falls is one clear reason to maintain optimal vitamin D levels, particularly in advancing age. 

  1. Wu D, Lewis ED, Pae M, Meydani SN. Nutritional modulation of immune function: analysis of evidence, mechanisms, and clinical relevance. Frontiers in immunology. 2019;9:3160.
  2. Bilezikian JP, Bikle D, Hewison M, et al. MECHANISMS IN ENDOCRINOLOGY: Vitamin D and COVID-19. European journal of endocrinology. 2020;183(5):R133-r147.
  3. van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. The Journal of steroid biochemistry and molecular biology. 2005;97(1-2):93-101.
  4. Ginde AA, Mansbach JM, Camargo CA, Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Archives of internal medicine. 2009;169(4):384-390.
  5. Sassi F, Tamone C, D’Amelio P. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients. 2018;10(11):1656.
  6. Vetter V, Denizer G, Friedland LR, Krishnan J, Shapiro M. Understanding modern-day vaccines: what you need to know. Annals of medicine. 2018;50(2):110-120.

Vitamin D and the Immune System

Most days we go about our routines completely unaware that our immune systems are always working, recognizing, fighting and adapting to foreign invaders that might be bacteria, viruses, fungi .anything foreign to our bodies. However, in 2020 we likely became more aware than ever of the importance of our immune systems in health, well-being and survival. But what exactly is the immune system? Well, it is quite complex and impacts many aspects of illness and health. One researcher said it well, “The main functions of body’s immune system are to protect the host against infection from pathological microorganisms, to clear damaged tissues, and to provide constant surveillance of malignant cells that grow within the body. Additionally, the immune system develops appropriate tolerance to avoid unwanted response to healthy tissues of self or harmless foreign substances. There is considerable heterogeneity (differences) among individuals in the vigor of their immunological function, largely owing to factors such as genetics, environment, lifestyle, nutrition, and the interaction of these factors.” 1  

Vitamin D has profound effects on the immune system and has antibacterial and antiviral effects. 2 Vitamin D deficiency is associated with an increased risk of developing viral and bacterial infections. 3,4 The connection between vitamin D and immunity was first reported when it was identified that important immune cells like macrophages and dendritic cells, referred to as “antigen-presenting” cells, actually make the active form of vitamin D. Further studies demonstrated that epithelial cells like those found in skin, lung and the intestinal lining also convert vitamin D to its active form. This suggested that these cells could be influenced by vitamin D, which may be very important in respiratory diseases. 2 Overall, there are two parts to the immune system: the innate and adaptive immune responses which will be discussed below. The evidence is stronger for the role of vitamin D in the innate immune system, but promising for adaptive immune system function as well. 5 It is important to note that innate and adaptive immunity overlap and work together. For example, vaccines have been developed based on what scientists have learned about the complexities of our immune systems. Vaccines are designed to initiate an innate immune response, which then activates an antigen specific adaptive immune response. 6 It is important to clarify the difference, first let’s discuss innate immunity. 

  1. Wu D, Lewis ED, Pae M, Meydani SN. Nutritional modulation of immune function: analysis of evidence, mechanisms, and clinical relevance. Frontiers in immunology. 2019;9:3160.
  2. Bilezikian JP, Bikle D, Hewison M, et al. MECHANISMS IN ENDOCRINOLOGY: Vitamin D and COVID-19. European journal of endocrinology. 2020;183(5):R133-r147.
  3. van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. The Journal of steroid biochemistry and molecular biology. 2005;97(1-2):93-101.
  4. Ginde AA, Mansbach JM, Camargo CA, Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Archives of internal medicine. 2009;169(4):384-390.
  5. Sassi F, Tamone C, D’Amelio P. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients. 2018;10(11):1656.
  6. Vetter V, Denizer G, Friedland LR, Krishnan J, Shapiro M. Understanding modern-day vaccines: what you need to know. Annals of medicine. 2018;50(2):110-120.

Innate Immunity

Innate immunity is the human body’s first defense against infection. It includes physical barriers including the skin, mucus and lining of the lungs and intestines, as well as cells with receptors that quickly recognize pathogens. The role of Vitamin D in the regulation of this line of defense was initially discovered during research for the treatment of leprosy and tuberculosis. Vitamin D reinforces the barrier provided by epithelial cells, enhances the cell’s ability to produce 1,25 (OH)2D at the site of infection, increases other key defenses of innate immunity and decreases inflammatory markers. 1 Vitamin D is known to prevent the overproduction of certain inflammatory agents, cytokines, and enhances the bacterial fighting ability of a class of immune cells, called macrophages. 2

  1. Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients. 2013;5(7):2502-2521.
  2. Cannell JJ, Vieth R, Umhau JC, et al. Epidemic influenza and vitamin D. Epidemiology and infection. 2006;134(6):1129-1140.

Adaptive Immunity

The adaptive immune system is also called the acquired immune system. It is the body’s second defense against infection. Unlike the innate immune system, it fights against pathogens or antigens very specifically, but it takes longer to develop. It is activated by exposure to pathogens, and it is able to learn about the pathogen and adjust the immune response accordingly. It can be thought of as an immunological memory. It is the type of memory that is created by vaccines so that exposure to a specific pathogen causes our immune system to recognize and specifically target it. 1 1,25(OH)2D has an inhibitory, anti-inflammatory, effect on the adaptive immune system. 2 When cells of the adaptive immune system, called T and B cells, are activated by pathogens, the number of VDR on their surfaces is increased, which then upregulates up to 500 vitamin D responsive genes that influence the adaptive immune cell response. This is thought to play a protective role in autoimmune disorders and to decrease the inflammatory response. 3,4

  1. Vetter V, Denizer G, Friedland LR, Krishnan J, Shapiro M. Understanding modern-day vaccines: what you need to know. Annals of medicine. 2018;50(2):110-120.
  2. Hewlings SJ, Medeiros DM. Nutrition: Real People, Real Choices. Pearson Prentice Hall; 2009.
  3. Sassi F, Tamone C, D’Amelio P. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients. 2018;10(11):1656.
  4. Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients. 2013;5(7):2502-2521.

What Role Does Vitamin D Play in Respiratory Infections?

Observational studies report consistent independent associations between low serum concentrations of 25-hydroxyvitamin D (the major circulating vitamin D metabolite) and susceptibility to acute respiratory tract infection. In an analysis of 25 studies, vitamin D supplementation reduced the risk of acute respiratory tract infection among over 11,000 subjects who were supplemented. Daily or weekly supplementation benefitted the subjects more than just a large single dose. Those that were most deficient benefitted the most. 1

  1. Martineau A R, Jolliffe D A, Hooper R L, Greenberg L, Aloia J F, Bergman P et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data BMJ 2017; 356 :i6583 doi:10.1136/bmj.i6583.

What Role Does Vitamin D Play in COVID-19?

While scientists have not yet determined an exact answer to this question,  many studies suggest a potential connection between vitamin D and COVID-19 and 

While scientists have not yet determined an exact answer to this question, many studies suggest a potential connection between vitamin D and COVID-19 with several proposed mechanisms to explain the connection [1-12]. It is established that inflammation plays a critical role in COVID-19 patient outcomes [13-15]. A particularly severe reaction called “cytokine storm” can occur when the COVID-19 infection triggers the immune system and floods the bloodstream with inflammatory proteins called cytokines [13, 14, 16, 17]. This dramatic inflammatory reaction can kill cells and damage tissues and organs [13, 14, 16]. Vitamin D is involved in several molecular mechanisms that may protect the lungs from damage [18-20]. Recent publications suggest the following potential mechanisms:  

  • Vitamin D supports innate immunity functions, including the maintenance of physical barriers between cells to block the entry of pathogens into the body [21]. 
  • Vitamin D may decrease inflammatory stimuli in macrophages as part of the innate immune system [13, 21] 
  • Vitamin D supports the ability of macrophages (a type of white blood cell) to mature, which prevents them from releasing too many inflammatory molecules such as cytokines [16]. 
  • Vitamin D may downregulate pro-inflammatory cytokines [14, 16, 21] 
  • Vitamin D may have a protective effect on epithelial cells in the respiratory tract [13]. 
  • Vitamin D can also modulate the expression and concentration of certain genes and receptors and these functions may have a protective role against acute lung injury and acute respiratory distress syndrome [13, 16, 21, 22]. 
  • Vitamin D may exhibit antiviral effects by interfering with viral replication [15, 19] 
  • Vitamin D increases the production of peptides that have an antimicrobial effect [13, 16, 17]. 

The weight of the evidence suggests that vitamin D levels [12, 23-28] and vitamin D supplementation [1-7, 11, 28] plays an important role in COVID-19 susceptibility and/or severity, but there is variability across studies and not all the data agrees [6, 29-33]. Some factors that could influence the study findings include differences in study design [2, 3, 6, 33, 34], wide ranges of vitamin D supplementation, including single doses or very high doses [1, 3, 6, 28, 35], short study durations [1], differences in initial vitamin D status (e.g. deficient or replete) [1, 3, 4, 33], differences in determination of vitamin D levels [3, 6, 33, 34, 36, 37], and underlying conditions that could impact vitamin D status [33, 34]. Data also suggests that daily or weekly vitamin D supplementation is more effective than bolus doses. Bolus dosing, one time and very high doses of vitamin D, have lacked efficacy for respiratory tract infections, including COVID-19 [3, 28, 30, 31, 35, 38]. Together, the data suggests that a steady daily or weekly intake are associated with better outcomes. 

Clinical research evaluating vitamin D supplementation and COVID-19 outcomes is ongoing and more evidence will help further elucidate the role for vitamin D in COVID-19 [3, 36]. 

  1. Argano, C., et al., Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis. Pharmaceuticals (Basel), 2023. 16(1).
  2. Hosseini, B., A. El Abd, and F.M. Ducharme, Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis. Nutrients, 2022. 14(10).
  3. D’Ecclesiis, O., et al., Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis. PLoS One, 2022. 17(7): p. e0268396.
  4. Meng, J., et al., The role of vitamin D in the prevention and treatment of SARS-CoV-2 infection: A meta-analysis of randomized controlled trials. Clin Nutr, 2023. 42(11): p. 2198-2206.
  5. Pal, R., et al., Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis. J Endocrinol Invest, 2022. 45(1): p. 53-68.
  6. Zaazouee, M.S., et al., Hospital and laboratory outcomes of patients with COVID-19 who received vitamin D supplementation: a systematic review and meta-analysis of randomized controlled trials. Naunyn Schmiedebergs Arch Pharmacol, 2023. 396(4): p. 607-620.
  7. Sîrbu, A.C., et al., The Effect of Vitamin D Supplementation on the Length of Hospitalisation, Intensive Care Unit Admission, and Mortality in COVID-19-A Systematic Review and Meta-Analysis. Nutrients, 2023. 15(15).
  8. Barrea, L., et al., Vitamin D: A Role Also in Long COVID-19? Nutrients, 2022. 14(8).
  9. Oristrell, J., et al., Vitamin D supplementation and COVID-19 risk: a population-based, cohort study. J Endocrinol Invest, 2022. 45(1): p. 167-179.
  10. Seal, K.H., et al., Association of Vitamin D Status and COVID-19-Related Hospitalization and Mortality. J Gen Intern Med, 2022. 37(4): p. 853-861.
  11. Shah, K., et al., Does vitamin D supplementation reduce COVID-19 severity?: a systematic review. Qjm, 2022. 115(10): p. 665-672.
  12. Petrelli, F., et al., Vitamin D3 and COVID-19 Outcomes: An Umbrella Review of Systematic Reviews and Meta-Analyses. Antioxidants, 2023. 12(2): p. 247.
  13. Stafford, A. and N.D. White, Potential Benefit of Vitamin D Supplementation in COVID-19. Am J Lifestyle Med, 2023. 17(2): p. 202-205.
  14. Gotelli, E., et al., Understanding the immune-endocrine effects of vitamin D in SARS-CoV-2 infection: a role in protecting against neurodamage? Neuroimmunomodulation, 2023.
  15. Zabetakis, I., et al., COVID-19: The Inflammation Link and the Role of Nutrition in Potential Mitigation. Nutrients, 2020. 12(5).
  16. Murdaca, G., G. Pioggia, and S. Negrini, Vitamin D and Covid-19: an update on evidence and potential therapeutic implications. Clin Mol Allergy, 2020. 18(1): p. 23.
  17. Wimalawansa, S.J., Infections and Autoimmunity-The Immune System and Vitamin D: A Systematic Review. Nutrients, 2023. 15(17).
  18. Lauretani, F., et al., Relationship between Vitamin D and Immunity in Older People with COVID-19. Int J Environ Res Public Health, 2023. 20(8).
  19. Moukayed, M., A Narrative Review on the Potential Role of Vitamin D(3) in the Prevention, Protection, and Disease Mitigation of Acute and Long COVID-19. Curr Nutr Rep, 2023. 12(2): p. 215-223.
  20. Vasheghani, M., M. Rekabi, and M. Sadr, Protective role of vitamin D status against COVID-19: a mini-review. Endocrine, 2023. 79(2): p. 235-242.
  21. Tiwari, A.V. and S. Dangore-Khasbage, Vitamin D and COVID-19: An Update on Evidence and Potential Therapeutic Implications. Cureus, 2023. 15(9): p. e46121.
  22. Bilezikian, J.P., et al., MECHANISMS IN ENDOCRINOLOGY: Vitamin D and COVID-19. Eur J Endocrinol, 2020. 183(5): p. R133-r147.
  23. Teshome, A., et al., The Impact of Vitamin D Level on COVID-19 Infection: Systematic Review and Meta-Analysis. Front Public Health, 2021. 9: p. 624559.
  24. Szarpak, L., et al., A systematic review and meta-analysis of effect of vitamin D levels on the incidence of COVID-19. Cardiol J, 2021. 28(5): p. 647-654.
  25. Ghasemian, R., et al., The role of vitamin D in the age of COVID-19: A systematic review and meta-analysis. Int J Clin Pract, 2021. 75(11): p. e14675.
  26. Dissanayake, H.A., et al., Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis. The Journal of Clinical Endocrinology & Metabolism, 2021. 107(5): p. 1484-1502.
  27. Petrelli, F., et al., Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies. J Steroid Biochem Mol Biol, 2021. 211: p. 105883.
  28. Remy, D., et al., Vitamins for the Prevention and/or Treatment of COVID-19: An Umbrella Review. CAND Journal, 2023. 30(4): p. 15-31.
  29. Zhang, Y., et al., Effect of vitamin D supplementation on COVID-19 patients: A systematic review and meta-analysis. Front Nutr, 2023. 10: p. 1131103.
  30. Kümmel, L.S., et al., Vitamin D supplementation for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials. Front Immunol, 2022. 13: p. 1023903.
  31. Bassatne, A., et al., The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis. Metabolism, 2021. 119: p. 154753.
  32. Rawat, D., et al., Vitamin D supplementation and COVID-19 treatment: A systematic review and meta-analysis. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 2021. 15(4): p. 102189.
  33. Bignardi, P.R., et al., Is the vitamin D status of patients with COVID-19 associated with reduced mortality? A systematic review and meta-analysis. Arch Endocrinol Metab, 2023. 67(2): p. 276-288.
  34. Varikasuvu, S.R., et al., COVID-19 and vitamin D (Co-VIVID study): a systematic review and meta-analysis of randomized controlled trials. Expert Rev Anti Infect Ther, 2022. 20(6): p. 907-913.
  35. Zhong, Z., et al., High-dose vitamin D supplementation in patients with COVID-19: A meta-analysis of randomized controlled trials. Food Science & Nutrition, 2023.
  36. Hu, Y., et al., Effects of Vitamin D Serum Level on Morbidity and Mortality in Patients with COVID-19: A Systematic Review and Meta-Analysis. J Pharm Pharm Sci, 2022. 25: p. 84-92.
  37. Dissanayake, H.A., et al., Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis. J Clin Endocrinol Metab, 2022. 107(5): p. 1484-1502.
  38. Chandran, M., et al., Vitamin D in COVID – 19: Dousing the fire or averting the storm? – A perspective from the Asia-Pacific. Osteoporos Sarcopenia, 2020. 6(3): p. 97-105.

Vitamin D & Long COVID

In addition to vitamin D’s role in acute COVID-19 outcomes, scientists are also investigating the potential connection between vitamin D and symptoms that persist or return after the initial acute COVID-19 infection. These health issues are often referred to as long COVID, long-haul COVID, post-COVID-19 conditions, chronic COVID, or post-acute sequelae of SARS-CoV-2 (PASC) [1, 2]. Long COVID can cause various symptoms in different parts of the body, such as excessive fatigue and weakness, brain fog and mood changes, irregular heartbeats, pain and swelling, as well as symptoms similar to an acute COVID-19 infection that cannot be explained by an alternative diagnosis [1, 2]. These symptoms can be post-acute (generally persisting between 4-12 weeks after the acute infection) or longer (generally persisting beyond 12 weeks after the acute infection) [2] 

It is important to note that vitamin D and long COVID research is early stage, much is still unknown, and not all studies agree [3-5]. However, emerging observational data does suggest an association between long COVID and low vitamin D levels [4, 6-8]. For example, in small cohorts of COVID-19 survivors in Taiwan and Italy, low vitamin D levels were associated with higher occurrence of long COVID symptoms and delayed recovery from long COVID [6, 9, 10]. While more robust interventional research is needed, the preliminary data suggests that vitamin D levels may have an important role in post-COVID recovery [4, 6, 8]. More research on vitamin D supplementation is needed.  

Recent publications suggest that vitamin D has multiple mechanisms that may play a role in long COVID, including the following:  

  • Neuroimmunological: Vitamin D supports the function of immune and neurological cells such as dendritic cells, macrophages, lymphocytes, cerebral endothelial cells, pericytes, neurons, astrocytes, and microglia and may have a protective role in these cells and tissues [2]. 
  • Immune response: Micronutrient and vitamin D deficiencies are linked to a dysregulation of the host immune responses [2, 9, 10]. 
  • Antimicrobial: Vitamin D plays a role in innate immunity, which is responsible for producing antimicrobial peptides in immune cells like macrophages and monocytes [2]. 
  • Antioxidant system: Vitamin D acts as an antioxidant by reducing oxidative stress during the inflammation process and promoting cell survival [2, 9]. 
  • Inflammation: Vitamin D has anti-inflammatory effects through inhibition of pro-inflammatory cytokine production and upregulation of the anti-inflammatory receptors [2]. 

Clinical research evaluating vitamin D supplementation and COVID-19 outcomes is ongoing and more evidence will help further elucidate the role for vitamin D in COVID-19 [3, 36]. 

  1. NIH, Long COVID. National Institutes of Health (NIH) COVID-19 Research. Available online at: https://covid19.nih.gov/covid-19-topics/long-covid (Accessed Sept. 26, 2023). 2023.
  2. Chen, T.B., et al., Neuroimmunological Effect of Vitamin D on Neuropsychiatric Long COVID Syndrome: A Review. Nutrients, 2023. 15(17).
  3. Hikmet, R.G., C. Wejse, and J. Agergaard, Effect of Vitamin D in Long COVID Patients. Int J Environ Res Public Health, 2023. 20(22).
  4. Shetty, A.J., et al., Do vitamin D levels or supplementation play A role in COVID-19 outcomes?-a narrative review. Ann Palliat Med, 2023.
  5. Min, Y., X. Wei, and X. Peng, Letter to the Editor From Min et al: “Low Vitamin D Levels Are Associated With Long COVID Syndrome in COVID-19 Survivors”. The Journal of Clinical Endocrinology & Metabolism, 2023. 109(1): p. e434-e435.
  6. di Filippo, L., et al., Low Vitamin D Levels Are Associated With Long COVID Syndrome in COVID-19 Survivors. J Clin Endocrinol Metab, 2023. 108(10): p. e1106-e1116.
  7. di Filippo, L., S. Frara, and A. Giustina, Response to the Letter to the Editor From Min et al: Low Vitamin D Levels are Associated With Long COVID Syndrome in COVID-19 Survivors. The Journal of Clinical Endocrinology & Metabolism, 2023. 109(1): p. e438-e439.
  8. Gomaa, A.A., et al., Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy. Inflammopharmacology, 2023.
  9. Chen, K.Y., C.K. Lin, and N.H. Chen, Effects of vitamin D and zinc deficiency in acute and long COVID syndrome. J Trace Elem Med Biol, 2023. 80: p. 127278.
  10. di Filippo, L., et al., Lack of vitamin D predicts impaired long-term immune response to COVID-19 vaccination. Endocrine, 2023.

Vitamin D Status

Vitamin D goes through several transformations before the human body can use it. The first occurs in the liver where vitamin D is converted to 25-hydroxyvitamin D, also called calcidiol [25(OH)D]. The amount of 25(OH)D in the blood is a good indication of how much Vitamin D the body contains. Vitamin D status is determined by measuring serum levels of 25(OH)D. While there is not complete agreement on the exact levels to diagnose insufficiency, most experts agree that between 20 and 125 nmol/L is ideal for bone health. Levels higher than 150 nmol/L can be detrimental. Low concentrations of serum 25(OH)D (<30 nmol/L) are associated rickets and osteomalacia, conditions characterized by softened and weakened bone. Higher concentrations of serum 25(OH)D above the deficiency range, yet not sufficient, are associated with bone mineral depletion and susceptibility to fractures. 1,2,3 The National Academy of Medicine-recommends the following: at risk of deficiency [serum 25(OH)D <30 nmol/L (<12 ng/mL)], at risk of inadequacy [serum 25(OH)D 30–49 nmol/L (12–19 ng/mL)], sufficiency [serum 25(OH)D 50–125 nmol/L (20–50 ng/mL)], and concentrations of possible concern [serum 25(OH)D >125 nmol/L (>50 ng/mL)]. 4 Vitamin D deficiency can be caused by many factors including decreased intake, inadequate exposure to sunlight, living at high latitudes, winter season, having respiratory disease such as asthma, obesity, diabetes and even some medications can lead to deficiency. 5-7 Vitamin D deficiency is a major health concern because it has been linked to depression, fatigue, muscle aches, increased risk of respiratory infections, autoimmune disorders, osteoporosis, osteomalacia, osteoarthritis, increased risk of infection and some cancers. 5-7

  1. Sassi> F, >Tamone> C, >D’Amelio> P. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients. 2018;10(11):1656.>
  2. 2.Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients. 2013;5(7):2502-2521.> >
  1. Herrick KA, Storandt RJ, Afful J, et al. Vitamin D status in the United States, 2011-2014. Am J >Clin> Nutr>. 2019;110(1):150-157.>
  2. Del Valle HB, >Yaktine> AL, Taylor CL, Ross AC. Dietary reference intakes for calcium and vitamin D. 2011.>
  3. Holick MF. The vitamin D deficiency pandemic: a forgotten hormone important for health. >Public health reviews. >2010;32(1):267-283.>
  1. Amrein K, Scherkl M, Hoffmann M, et al. Vitamin D deficiency 2.0: an update on the current status worldwide. European journal of clinical nutrition. 2020;74(11):1498-1513.>
  2. 7>. MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest. 1985;76(4):1536-1538.>

How Do We Get Vitamin D?

Vitamin D comes from 3 potential sources: food, sunlight-dependent production in the skin and supplements. There are very few natural food sources; plants contain ergocalciferol (vitamin D2) and fatty fish (salmon, mackerel, sardines, cod liver oil) and some types of mushrooms (Shiitake), especially if sun-dried, contain cholecalciferol (vitamin D3). Because it is not easily obtained from food, manufacturers in many countries, including the US and Canada, have regulation that requires fortification of commonly consumed foods, such as milk, orange juice, other dairy products and cereals with vitamin D. Dietary supplements also contribute to intake and are of extra importance in the large population that is not regularly exposed to sunlight and/or who do not consume enough from food. 1

  1. Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients. 2013;5(7):2502-2521.

Making Vitamin D from Sunlight

One of the many unique characteristics of vitamin D is that the body can make it from sunlight. Cholesterol combines with ultraviolet rays from sunlight and is converted to a precursor form of vitamin D. Through a series of steps, it is ultimately converted to the active form of vitamin D. Even though humans can theoretically make all of the vitamin D they need, it is still advisable to consume vitamin D from food and/or dietary supplement sources because few people have sufficient exposure to sunlight. Anything that interferes with exposure to sunlight, especially UVB sunlight, can potentially impair sunlight-stimulated vitamin D production. UVB rays are not very strong at latitudes above 35 °N in the winter, so sufficient amounts of vitamin D cannot be made from sunlight exposure during the winter months at higher latitudes. Clothing, sunscreen and skin melanin levels also impair sunlight-induced vitamin D production. People with darker skin require longer exposure to the sun to make the same amount of vitamin D as individuals with less melanin. 1 Because the use of sunscreen is critical important for skin health, it is important to consider sources of vitamin D beyond sunlight as well.

  1. Tsiaras WG, Weinstock MA. Factors influencing vitamin D status. Acta dermato-venereologica. 2011;91(2):115-124.

Recommended Intake

The Institute of Medicine recommends a dietary intake of Vitamin D of 600 IU/day for all ages over 1 year (and for pregnant and lactating women), with increases to 800 IU/day for individuals over 71 years. 1 Few people are able to obtain enough vitamin D from food sources alone, therefore supplementation is very important. 2 How much to supplement is less clear and will vary based on vitamin D status. Deficient individuals will need a different supplemental strategy than those who are not deficient. As you read through the various studies and information regarding vitamin D, you will notice varying approaches to dosing individuals identified to be deficient. For many years it was common to provide what is called a bolus, or large single dose, it was easy and efficient, but it was determined to be less effective and to be associated with increased risk of falls and other issues. It then became more common to provide daily or weekly doses, and sometimes in individuals who are in intensive care or severely deficient, a large single dose is used along with daily or weekly supplementation. There is no agreed upon dose globally, recommendations typically range from 400-2000 IU/day and your doctor may recommend more. However, a common dose of 1000 IU or 25 μg of vitamin D3, has been identified to be safe and effective. 2 It has been reported that a daily vitamin D dose of 800 IU can achieve a target 25(OH)D level of at least 50 nmol/L (or 20 ng/mL) in most healthy individuals, and 2000 IU is sufficient to achieve a level of at least 75 nmol/L (or 30 ng/mL). 3

  1. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. The Journal of clinical endocrinology and metabolism. 2011;96(1):53-58.
  2. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77(1):204-210.
  3. Amrein K, Scherkl M, Hoffmann M, et al. Vitamin D deficiency 2.0: an update on the current status worldwide. European journal of clinical nutrition. 2020;74(11):1498-1513.

Toxicity

Toxicity is rare, and vitamin D is very safe at wide ranges of intake. However, growing consumer awareness of vitamin D has led to increased supplementation and intake making potential toxicity more of a possibility. In addition, there have been global public health campaigns to fortify common foods like dairy products, which increases total vitamin D consumption. High concentrations of serum 25(OH)D or free 1,25(OH)2D, when serum 25(OH)D exceeds 375 nmol/l (or 150 ng/ml), causes high calcium in the blood and urine and is typically associated with high calcium intake or genetic abnormalities in vitamin D metabolism. Vitamin D is a fat soluble vitamin so if levels increase to toxic levels, they will stay elevated for up to 18 months. Therefore, although it is very rare and one would have to consume a lot of vitamin D to reach toxic levels, it is advisable to stay within recommended intake ranges or follow the doses recommended by your healthcare practitioner. 1

  1. Amrein K, Scherkl M, Hoffmann M, et al. Vitamin D deficiency 2.0: an update on the current status worldwide. European journal of clinical nutrition. 2020;74(11):1498-1513.