Vitamin D insufficiency is a major health problem worldwide with over one billion people affected across all ethnicities and age groups. Even those living in tropical countries with lots of sun exposure, or in developed countries where vitamin D fortification of foods is prevalent, deficiency exists. 1, 2
Over the last few decades, understanding of vitamin D has changed from merely a vitamin involved in bone metabolism, to a more complex micronutrient with multiple physiological functions, including the modulation of cell growth, inflammation, neuromuscular and immune functions. 3, 4, 5, 6
WE ALL NEED A LITTLE SUNSHINE
We can obtain vitamin D from diet, or from synthesis in the skin by exposure to ultraviolet B (UVB) irradiation from the sun.
Dietary sources of vitamin D include fatty fish, cod liver oil, eggs, milk, mushrooms, liver, and fortified foods. Exposure to UVB solar radiation, however, is the main source of vitamin D for the majority of the population. 5, 6, 7
WHY IS THE FLU SEASONAL?
We all know that colds and flu tend to occur in the winter months. In 1981, a British doctor, Robert Edgar Hope-Simpson, proposed that a “seasonal stimulus” directly associated with solar radiation may explain the seasonality of epidemic influenza.
This association was highlighted a quarter of century later when studies found that vitamin D status may be the “seasonal stimulus” for influenza.10, 21
Wintertime vitamin D deficiency, due to lack of sun exposure on bare skin, has profound effects on the immune system, and thus on susceptibility to infectious diseases. 10
Surprisingly, the immune-enhancing effects of UVB radiation had been recognized more than a century ago. Unknowingly, vitamin D was used to treat tuberculosis before antibiotics for tuberculosis were discovered. People with tuberculosis were treated with sun therapy.16 Cod liver oil (a rich source of vitamin D) was also used to treat tuberculosis, as well as to increase resistance to infections.16
Recently studies have proved this link between tuberculosis and deficiency of vitamin D.22, 23, 24, 25, 26 Clinical trials found that vitamin D supplementation could reduce the risk of tuberculosis infection, and high doses of vitamin D with antibiotic treatment may help tuberculosis patients recover faster.17, 29
WHAT DO SCIENTIFIC STUDIES SHOW?
Using Third National Health and Nutrition Examination Survey (NHANES III) data, researchers found that upper respiratory tract infection was reported by 40 percent more individuals deficient in vitamin D compared to individuals with adequate vitamin D status.18
Another study found that soldiers with lower levels of serum 25-hydroxyvitamin D had a 63% increased risk of absence from duty due to respiratory tract infections than did soldiers with higher 25-hydroxyvitamin D levels. 20
Studies proved that vitamin D supplementation may help protect against infections. 25-hydroxyvitamin D supports the synthesis of antimicrobial peptides in response to both viral and bacterial infection. 9, 10, 12, 13, 14, 15
A review of 25 trials showed that vitamin D supplementation may boost immunity and cut rates of respiratory tract infections.9
One study found 70 % less incidence of cold and influenza symptoms were reported by those receiving 800 to 2000 IU of vitamin D daily during a 3-year follow-up, compared with the control group. Only one subject had cold/influenza symptoms while taking high doses of vitamin D (2000IU/day). 21, 30
Source: (Aloia et al., 2007), (Aloia et al., 2005)
Official recommendations for adults: 31
Recommended Dietary Allowance (RDA) for adults 19-70 years by the Institute of Medicine (US)
600 IU (15 mcg)/day
Recommended Dietary Allowance (RDA) for adults over 70 years by the Institute of Medicine (US)
800 IU (20 mcg)/day
Adequate Intake (AI) by the European Food Safety Authority (EFSA)
600 IU (15 mcg)/day
In the Endocrine Society Clinical Practice Guideline, researchers suggested “that all adults who are vitamin D deficient be treated with 50,000 IU of vitamin D2 or vitamin D3 once a week for 8 weeks or its equivalent of 6000 IU of vitamin D2 or vitamin D3 daily to achieve a blood level of 25-hydroxyvitamin D above 30 ng/ml, followed by maintenance therapy of 1500–2000 IU/d.” 33, 34
According to Institute of Medicine (US) (similarly to the European Food Safety Authority EFSA) a tolerable upper intake level for adults is up to 4000 IU.31, 35
Endocrine Practice Guidelines Committee recommends for patients at risk for vitamin D deficiency to set a UL of 10,000 IU/day.31, 33
(Tolerable upper intake level (UL) is the maximum level of total chronic daily intake of a particular nutrient judged to be unlikely to pose a risk of adverse health effects.)
- Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? The Journal of steroid biochemistry and molecular biology. 2014;144PA:138-145. doi:10.1016/j.jsbmb.2013.11.003.
- Kaddam IM, Al-Shaikh AM, Abaalkhail BA, et al. Prevalence of vitamin D deficiency and its associated factors in three regions of Saudi Arabia: A cross-sectional study. Saudi Medical Journal. 2017;38(4):381-390. doi:10.15537/smj.2017.4.18753.
- Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-281. doi: 10.1056/NEJMra070553
- Pfotenhaur, K. Shubrook, J. Vitamin D Deficiency, It’s Role in Health and Disease, and Current Supplementation Recommendations. The Journal of the American Osteopathic Association, May 2017, Vol. 117, 301-305. doi:10.7556/jaoa.2017.055
- Spiro A, Buttriss JL. Vitamin D: An overview of vitamin D status and intake in Europe. Nutrition Bulletin / Bnf. 2014;39(4):322-350. doi:10.1111/nbu.12108.
- Nair R, Maseeh A. Vitamin D: The “sunshine” vitamin. Journal of Pharmacology & Pharmacotherapeutics. 2012;3(2):118-126. doi:10.4103/0976-500X.95506.
- Calvo MS, Calvo MS, Whiting SJ, et al. Vitamin D intake: a global perspective of current status. The Journal of Nutrition. 2005;135:310–316.
- Lofgren E, Fefferman NH, Naumov YN, Gorski J, Naumova EN.: Influenza seasonality: underlying causes and modeling theories. J Virol. 2007 Jun;81(11):5429-36. Epub 2006 Dec 20.
- Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. The BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583.
- Cannell JJ, Vieth R, Umhau JC, et al. Epidemic influenza and vitamin D. Epidemiology and Infection. 2006;134(6):1129-1140. doi:10.1017/S0950268806007175.
- Jolliffe DA, Griffiths CJ, Martineau AR. Vitamin D in the prevention of acute respiratory infection: systematic review of clinical studies. J Steroid Biochem Mol Biol 2013;136:321-9.
- Hansdottir S, Monick MM, Hinde SL, Lovan N, Look DC, Hunninghake GW. Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol 2008;181:7090-9. doi:10.4049/jimmunol.181.10.7090 pmid:18981129.
- Olliver M, Spelmink L, Hiew J, Meyer-Hoffert U, Henriques-Normark B, Bergman P. Immunomodulatory effects of vitamin D on innate and adaptive immune responses to Streptococcus pneumoniae. J Infect Dis 2013;208:1474-81. doi:10.1093/infdis/jit355 pmid:23922371.
- Greiller CL, Martineau AR. Modulation of the immune response to respiratory viruses by vitamin D. Nutrients 2015;7:4240-70. doi:10.3390/nu7064240 pmid:26035247.
- Hewison M. Vitamin D and the immune system: new perspectives on an old theme. Endocrinology and metabolism clinics of North America. 2010;39(2):365-379. doi:10.1016/j.ecl.2010.02.010
- Aranow C. Vitamin D and the Immune System. Journal of investigative medicine : the official publication of the American Federation for Clinical Research. 2011;59(6):881-886. doi:10.231/JIM.0b013e31821b8755.
- Coussens AK, Wilkinson RJ, Hanifa Y, et al. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(38):15449-15454. doi:10.1073/pnas.1200072109.
- Ginde AA, Mansbach JM, Camargo CA. 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. doi:10.1001/archinternmed.2008.560.
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA): 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 Journal 2010; 8(2):1468. DOI: 10.2903/j.efsa.2010.1468
- Laaksi I, Ruohola JP, Tuohimaa P, Auvinen A, Haataja R, Pihlajamäki H, Ylikomi T.: An association of serum vitamin D concentrations < 40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr. 2007 Sep;86(3):714-7.
- Aloia JF, Li-Ng M. Correspondence. Epidemiology and Infection. 2007;135(7):1095-1098. doi:10.1017/S0950268807008308
- Sita‐Lumsden A, Lapthorn G, Swaminathan R, Milburn HJ. Reactivation of tuberculosis and vitamin D deficiency: the contribution of diet and exposure to sunlight. Thorax. 2007;62(11):1003-1007. doi:10.1136/thx.2006.070060.
- Davies PD, Brown RC, Woodhead JS.: Serum concentrations of vitamin D metabolites in untreated tuberculosis. Thorax. 1985 Mar; 40(3):187-90.
- Chan T Y. Vitamin D deficiency and susceptibility to tuberculosis. Calcif Tissue Int 200066476–478.
- Grange J M, Davies P D, Brown R C. et al Vitamin D levels in Indonesian patients with untreated pulmonary tuberculosis. Tubercle 198766187–191.
- Balcells ME, García P, Tiznado C, et al. Association of vitamin D deficiency, season of the year, and latent tuberculosis infection among household contacts. Subbian S, ed. PLoS ONE. 2017;12(4):e0175400. doi:10.1371/journal.pone.0175400.
- Adams JS, Liu PT, Chun R, Modlin RL, Hewison M. Vitamin D in defense of the human immune response. Ann N Y Acad Sci. 2007;1117: 94–105. doi: 10.1196/annals.1402.036
- Gombart AF. The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Future Microbiol. 2011;4: 1151–1165.
- Ganmaa D, Giovannucci E, Bloom BR, Fawzi W, Burr W, Batbaatar D, Sumberzul N, Holick MF, Willett WC.: Vitamin D, tuberculin skin test conversion, and latent tuberculosis in Mongolian school-age children: a randomized, double-blind, placebo-controlled feasibility trial. Am J Clin Nutr. 2012 Aug; 96(2):391-6.
- Aloia JF, Talwar SA, Pollack S, Yeh J.: A randomized controlled trial of vitamin D3 supplementation in African American women. Arch Intern Med. 2005 Jul 25; 165(14):1618-23.
- Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, et al., editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011.
- EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2016. Scientific opinion on Dietary Reference Values for vitamin D. EFSA Journal 2016;volume(issue):NNNN, 179 pp. doi:10.2903/j.efsa.2016.NNN
- Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30. doi: 10.1210/jc.2011-0385. Epub 2011 Jun 6.
- Pramyothin P, Holick MF.: Vitamin D supplementation: guidelines and evidence for subclinical deficiency. Curr Opin Gastroenterol. 2012 Mar;28(2):139-50. doi: 10.1097/MOG.0b013e32835004dc.
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA);Scientific Opinion on the Tolerable Upper Intake Level of vitamin D. EFSA Journal 2012;10(7):2813. [45pp.] doi:10.2903/j.efsa.2012.2813