What Does The Research Say About Vitamin D and Immunity?
In this article:
- What is Vitamin D?
- Sunshine, Vitamin D, and Disease
- Vitamin D and Immune Function
- Vitamin D and Respiratory Tract Infections
- Vitamin D Trials and Other Immune Conditions
- Can You Take Too Much Vitamin D?
Improving your health is often related to your immune system. In cases with poor immune response, individuals may get sick more often. On the flip side, when the immune system is too aggressive or attacking the wrong targets, you can get experience inflammation, allergies, and autoimmune disease.
While inflammation is a healthy part of a normal immune response, it can become excessive and contribute to chronic disease. Some research even indicates that excessive inflammation is part of the aging process itself.
To maintain a proper balance of immune function the research suggests that several components can come into play. Examples include omega-3 fats for helping balance inflammatory responses, vitamin C as an antioxidant, and vitamin D.
Since its discovery, vitamin D has been recognized as an important factor in calcium metabolism and bone health. However, it wasn’t until the late 1990s that researchers started to uncover more of its effect on the immune system.
Vitamin D, often dubbed the sunshine vitamin, is actually misnamed. In the body, vitamin D is a prohormone. While we can get sparing amounts of vitamin D from food, most vitamin D is produced from sunlight and cholesterol in the skin. This creates the prohormone compound cholecalciferol, the same compound used in vitamin D capsules. Cholecalciferol is then converted into a hormone, referred to as active vitamin D, in the liver and kidneys.
In the 1990s, researchers started to notice significant correlations between numerous diseases and the latitude where people lived. Individuals living closer to the equator, who receive more sunlight, have decreased risks for many different chronic illnesses. Since people living near the equator get more sunshine, correlations emerged linking vitamin D as a potential reason why.
Similar findings for autoimmune conditions have also raised significant interest in vitamin D. Multiple sclerosis is more prevalent in northern climates with less sun exposure. Low vitamin D has also been shown to correlate with lupus and rheumatoid arthritis.
You also tend to get more sunlight during summertime wherever you live. For infectious diseases, differences from summer to winter have been noted for several different infections that appear to correlate with sunshine and vitamin D. Seasonal influenza has obvious correlations, although interestingly, so do some other infections, including tuberculosis and cholera.
The relationships between vitamin D and the above conditions are correlations. While the data is interesting, it’s worth asking the question if vitamin D is the cause of the differences seen. Some of the latest research on vitamin D and immune function suggests it’s a possibility.
Ongoing research into vitamin D is finding effects beyond those initially related to bone health. Vitamin D is critical for white blood cell production of antimicrobial compounds called cathelicidins. These compounds, found inside white blood cells, directly kill bacteria, viruses, and fungi, helping clear infections.
On the flip side, vitamin D appears to have direct anti-inflammatory activity, potentially helping calm overactive immune responses. In the body, vitamin D acts to reduce “toll-like receptors” (TLRs). These receptors are a key part of the inflammatory process. By reducing TLRs, vitamin D reduces numerous inflammatory cell signaling molecules.
This reduction appears to have real-world effects as a clinical trial of vitamin D combined with antibiotic treatment for tuberculosis resulted in a rapid drop of inflammation as compared with controls. Inflammation in tuberculosis is correlated with mortality, and the study authors suggest vitamin D might improve outcomes. This mechanism could be critical in other infections since an overaggressive inflammatory response is often responsible for tissue damage, which in extreme cases, can lead to death.
The latest data on vitamin D and respiratory tract infections provide some of the strongest evidence yet of potential benefits on immune function. A recent meta-analysis evaluating the research to date on vitamin D levels and acute upper respiratory infections (colds and flu) shows worse outcomes in individuals that are deficient in the vitamin. Individuals with higher levels of vitamin D decreased their risks of colds and flu by almost half. The study also reported a three times higher risk of death in individuals with the lowest levels of vitamin D.
Another recent meta-analysis looked at vitamin D supplementation for limiting colds and flu. The authors concluded that vitamin D may reduce upper respiratory infections by 70% in those that were most deficient in the vitamin. People that weren’t as deficient still saw a reduction of 25%. In addition, the authors noted that the evidence was of “high quality.” Interestingly, these benefits were not seen if vitamin D was given in large infrequent doses as compared to daily or weekly dosing.
Early evidence is also suggesting vitamin D supplementation might benefit other conditions. Clinical trials have also suggested some benefits in autoimmune conditions. While more research is needed, and benefits were modest, trials for rheumatoid arthritis, multiple sclerosis, and lupus all hint at some positive effects.
When supplementing with vitamin D, it is important to keep in mind that the vitamin is fat-soluble and can accumulate in tissues. As such, it is possible to get too much. To know if a person needs vitamin D, testing is typically necessary.
While up to 2000 international units (IU) are generally considered safe for adults, I’ve frequently encountered patients that needed higher doses to reach adequate levels. For anyone wishing to supplement, I highly recommend testing, both for initial levels and to verify changes over time. Blood levels come up slowly with supplementation taking about four to six months to plateau. Based on the research, I don’t recommend taking higher doses initially to try to raise levels more quickly.
The latest research suggests that vitamin D may have a potential place in helping balance some components related to immune function. While more research is necessary, based on the data, individuals with immune-based conditions might benefit from testing their vitamin D levels and treating deficiencies appropriately. It also appears likely that treating patients with vitamin D deficiencies will help reduce respiratory tract infections, including colds and flu.
- Pawelec G, Goldeck D, Derhovanessian E. Inflammation, ageing and chronic disease. Curr Opin Immunol. 2014;29:23-28. doi:10.1016/j.coi.2014.03.007
- Chiang N, Serhan CN. Specialized pro-resolving mediator network: an update on production and actions. Essays Biochem. 2020;64(3):443-462. doi:10.1042/EBC20200018
- Berretta M, Quagliariello V, Maurea N, et al. Multiple effects of ascorbic acid against chronic diseases: Updated evidence from preclinical and clinical studies. Antioxidants (Basel). 2020;9(12):E1182. Published 2020 Nov 26. doi:10.3390/antiox9121182
- Wheeler BJ, Snoddy AME, Munns C, Simm P, Siafarikas A, Jefferies C. A brief history of nutritional rickets. Front Endocrinol (Lausanne). 2019;10:795. Published 2019 Nov 14. doi:10.3389/fendo.2019.00795
- Holick MF. Cancer, sunlight and vitamin D. J Clin Transl Endocrinol. 2014;1(4):179-186. Published 2014 Oct 5. doi:10.1016/j.jcte.2014.10.001
- Ascherio A, Munger KL, Simon KC. Vitamin D and multiple sclerosis. Lancet Neurol. 2010;9(6):599-612. doi:10.1016/S1474-4422(10)70086-7
- Islam MA, Khandker SS, Alam SS, Kotyla P, Hassan R. Vitamin D status in patients with systemic lupus erythematosus (SLE): A systematic review and meta-analysis. Autoimmun Rev. 2019;18(11):102392. doi:10.1016/j.autrev.2019.102392
- Hajjaj-Hassouni N, Mawani N, Allali F, et al. Evaluation of vitamin D status in rheumatoid arthritis and its association with disease activity across 15 countries: "The COMORA Study". Int J Rheumatol. 2017;2017:5491676. doi:10.1155/2017/5491676
- Abhimanyu, Coussens AK. The role of UV radiation and vitamin D in the seasonality and outcomes of infectious disease. Photochem Photobiol Sci. 2017;16(3):314-338. doi:10.1039/c6pp00355a
- Charoenngam N, Holick MF. Immunologic effects of vitamin D on human health and disease. Nutrients. 2020;12(7):2097. Published 2020 Jul 15. doi:10.3390/nu12072097
- Chung C, Silwal P, Kim I, Modlin RL, Jo EK. Vitamin D-cathelicidin axis: at the crossroads between protective immunity and pathological inflammation during infection. Immune Netw. 2020;20(2):e12. Published 2020 Feb 11. doi:10.4110/in.2020.20.e12
- Coussens AK, Wilkinson RJ, Hanifa Y, et al. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proc Natl Acad Sci U S A. 2012;109(38):15449-15454. doi:10.1073/pnas.1200072109
- Pham H, Rahman A, Majidi A, Waterhouse M, Neale RE. Acute respiratory tract infection and 25-Hydroxyvitamin D concentration: A systematic review and meta-analysis. Int J Environ Res Public Health. 2019;16(17):3020. Published 2019 Aug 21. doi:10.3390/ijerph16173020
- Martineau AR, Jolliffe DA, Greenberg L, et al. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol Assess. 2019;23(2):1-44. doi:10.3310/hta23020
- Bhimani S, Khalid H, Khalid M, Ochani RK. Vitamin D and COVID-19: Does a deficiency point towards an unfavorable outcome?. Int J Endocrinol Metab. 2020;18(3):e107669. Published 2020 Aug 25. doi:10.5812/ijem.107669
- De Smet D, De Smet K, Herroelen P, Gryspeerdt S, Martens GA. Serum 25(OH)D level on hospital admission associated with COVID-19 stage and mortality [published online ahead of print, 2020 Nov 25]. Am J Clin Pathol. 2020;aqaa252. doi:10.1093/ajcp/aqaa252
- Entrenas Castillo M, Entrenas Costa LM, Vaquero Barrios JM, et al. "Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study". J Steroid Biochem Mol Biol. 2020;203:105751. doi:10.1016/j.jsbmb.2020.105751
- Murai IH, Fernandes AL, Sales LP, et al. Effect of vitamin D3 supplementation vs placebo on hospital length of stay in patients with severe COVID-19: A multicenter, double-blind, randomized controlled trial. medRxiv. 2020.11.16.20232397
- Manson JE, Bassuk SS, Buring JE; VITAL Research Group. Principal results of the VITamin D and OmegA-3 TriaL (VITAL) and updated meta-analyses of relevant vitamin D trials. J Steroid Biochem Mol Biol. 2020;198:105522. doi:10.1016/j.jsbmb.2019.105522
- Arnaout A, Robertson S, Pond GR, et al. Randomized window of opportunity trial evaluating high-dose vitamin D in breast cancer patients. Breast Cancer Res Treat. 2019;178(2):347-356. doi:10.1007/s10549-019-05392-9
- Yonaga H, Okada S, Akutsu T, Ohdaira H, Suzuki Y, Urashima M. Effect modification of vitamin D supplementation by histopathological characteristics on survival of patients with digestive tract cancer: Post hoc analysis of the AMATERASU randomized clinical trial. Nutrients. 2019;11(10):2547. Published 2019 Oct 22. doi:10.3390/nu11102547
- Chandrashekara S, Patted A. Role of vitamin D supplementation in improving disease activity in rheumatoid arthritis: An exploratory study. Int J Rheum Dis. 2017;20(7):825-831. doi:10.1111/1756-185X.12770
- Camu W, Lehert P, Pierrot-Deseilligny C, et al. Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE) [published correction appears in Neurol Neuroimmunol Neuroinflamm. 2019 Nov 15;7(1):]. Neurol Neuroimmunol Neuroinflamm. 2019;6(5):e597. Published 2019 Aug 6. doi:10.1212/NXI.0000000000000597
- Lima GL, Paupitz J, Aikawa NE, Takayama L, Bonfa E, Pereira RM. Vitamin D supplementation in adolescents and young adults with juvenile systemic lupus erythematosus for improvement in disease activity and fatigue scores: A randomized, double-blind, placebo-controlled trial. Arthritis Care Res (Hoboken). 2016;68(1):91-98. doi:10.1002/acr.22621