Vitamin D Review

07 Apr 2021 8:35 AM | Anonymous

By Angela Iovine, Pace University, 2021

Vitamin D is the most commonly used supplement in the U.S., and its popularity has further increased in recent months due to its perceived protective effect against the coronavirus.1  Both a vitamin and a hormone, Vitamin D helps maintain the balance of calcium and phosphorous within the body, which includes increasing the intestinal absorption of dietary calcium and keeping calcium in our bones.  It is therefore essential for strong bones and skeletal growth. Vitamin D may also have an immunomodulatory effect, and it appears to reduce all-cause mortality.2-5

Vitamin D from the Sun

Vitamin D is unique in that we can synthesize all that we need from exposure to the sun.  The precursor to vitamin D3 can be found evenly distributed along the surface of our skin.  When exposed to ultraviolet B (UVB) light, a component of sunlight, a molecule in our skin forms previtamin D3, which can then be converted into vitamin D3 in the body.  The amount of vitamin D3 produced from sun exposure is dependent on several factors, including:  how much skin is exposed, your latitude, air pollution and cloud cover, age, the color of your skin, and possibly use of sunscreen.  Clothing blocks UVB light from accessing the skin.  Glass also blocks UVB light, so sitting in the sun by a closed window will not help increase vitamin D production.  Those living above the 35th parallel (above Tennessee and North Carolina), generally receive less sunshine and fewer UVB rays, putting them at greater risk for deficiency.2,3 

Black Americans have been found to have lower levels of 25-hydroxyvitamin D3 (25-OH D), the form of vitamin D that is used to determine adequacy, than white Americans.  Although research in this field is limited, it is thought that the increased levels of melanin in darker skin can block some UVB light and result in less vitamin D activation.2,6  Black Americans also tend to have less vitamin D binding protein (VDBP), which may lead to more free-circulating vitamin D and explain why they generally have better bone density and lower fracture risk than white Americans despite having lower vitamin D levels.7 

The UVB rays that promote vitamin D synthesis can also cause sunburn, DNA damage to cells, and lead to skin cancer.  Some organizations, including the American Academy of Dermatology and the American Cancer Society, promote minimizing or avoiding sun exposure.3  Theoretically, sunscreen use could inhibit vitamin D production.  However, several studies have shown that lower SPF values still allow for vitamin D production in lighter-skinned individuals.  There is limited data on the effects of higher SPF values and the effect on darker-skinned people.8,9  For example, a study found that wearing SPF 15 sunscreen with a high UVA blocker was adequate to prevent sunburn while also allowing for vitamin D synthesis.  The study’s participants were all light-skinned people on vacation in the Canary Islands, and the UV index was very high.9 

Sunburn is not necessarily a marker for DNA damage, and damage can still occur without getting burnt.  Research suggests that exposing more skin to sunlight for shorter duration, or having short, but recurrent, periods of sun exposure may minimize UV-induced skin damage while maintaining vitamin D production.10   

Vitamin D in Food

            There is a relatively small number of foods that naturally contain vitamin D, most of which come from animals.  Eggs, liver, and fatty fish are good sources.  Smaller amounts can be found in butter and cheese.  Plant foods are generally poor sources of the vitamin, although mushrooms do contain some.  In the U.S., many foods are fortified with vitamin D to help reduce deficiency within the population.  Foods often fortified include orange juice, bread, cereal, milk, cheese, butter, margarine, and yogurt. 

Most often these foods are fortified with D3 (also known as cholecalciferol), although D2 (also known as ergocalciferol) is sometimes used.  The two forms are similar in structure, with some differences in their side chains, and are utilized within the body similarly.2 

Absorption of vitamin D in the digestive tract is not well understood, and there is much conflicting data on the subject.  Although vitamin D is better absorbed when taken with a meal that includes fat, it is not necessary for some absorption to take place.  The type of fat consumed does not matter, although this is open to debate.11  The overall amount of fat needed to optimize absorption is unclear; however, an older trial using a single bolus supplementation found some evidence that low-fat meals of about 11g of fat are superior.  Although after one month, regardless of fat intake, all participants had similar vitamin D levels.12

Vitamin D and COVID-19

Vitamin D appears to play a role in innate immunity and to exert an anti-inflammatory effect within the body, and it has been associated with improved outcomes for some viral infections, such as pneumonia.  Existing data suggests that vitamin D deficiency is not correlated with a greater risk of infection from coronavirus.  However, the severity of the deficiency is directly related to the severity of disease, hospitalization, and mortality from COVID-19, especially in the elderly.  Vitamin D may play a role in mediating cytokine activity associated with COVID-19 infections.3,13

There is limited data on this subject, and the studies that do exist tend to have significant limitations, including a high risk of bias due to convenience sampling and use of secondary data analysis.  Further, many of the patients who are hospitalized for COVID-19 infections also have comorbidities or are elderly.  These populations are inherently at greater risk for vitamin D deficiency.  Therefore, it is difficult to know if their vitamin D status played a role in their infection or if it was another factor. Until we have more data, maintaining adequate vitamin D levels and avoiding deficiency via sun exposure, consuming fortified foods, and supplementation as necessary seems the best course.13 

How is Vitamin D Status Measured?

Vitamin D status is obtained via a blood test that looks at concentrations of 25-OH D.  There is substantial variability in the laboratory methods used to determine a sample’s vitamin D level, and the same sample sent to different laboratories can yield markedly different results.  Translating these results can also be problematic, as several interpretations of serum levels also exist.  Regular testing is not recommended for individuals who are not at risk of deficiency, as vitamin D supplementation is generally considered a safe and effective way to improve status and testing results tend to be quite variable. 

Testing variability can also make it difficult to compare results across studies and develop clinical guidelines.  Some researchers have suggested that 25-OH D is not the best marker of the vitamin’s effect on the body, and that other markers should be used.7,14  The Institute of Medicine classifies serum 25-OH D concentrations less than 30 nmol/L as being indicative of deficiency and concentrations between 30-50 nmol/L as insufficiency.  Levels greater than 50 nmol/L are sufficient for most people.3  Levels between 50 – 80 nmol/L have been found to offer the most protection against all-cause mortality, with greater concentrations providing no additional benefit.4,5  Serum levels greater than 150 nmol/L have been linked to adverse events.3

Deficiency and Toxicity

About 40% of the U.S. population has either vitamin D insufficiency or  deficiency.  Unsurprisingly, vitamin D status varies by occupation, with up to 78% of people who work indoors having inadequate levels.15  The elderly are also commonly deficient due to being less efficient at making vitamin D and spending more time indoors.  Deficiency is also more common in those with fat-malabsorption disorders, liver or kidney dysfunction, infants who are breast-fed, those who are obese, nursing home residents and hospitalized patients.  Rickets in children and osteomalacia in adults result from severe vitamin D deficiency.2,3

Deficiency has also been implicated in a number of diseases, including cancer, cardiovascular disease, autoimmune diseases, and diabetes.  Recent evidence suggests that this role has been overstated.  Vitamin D supplementation appears not to have an effect on most non-skeletal conditions.  For example, it does not lower the incidence of cardiovascular events or invasive cancers, improve glucose metabolism, or help one lose weight.  The lower vitamin D status associated with these conditions is likely a product of poor health and not the cause of it.  Vitamin D does appear to play a role in overall cancer mortality and also death from respiratory diseases.  5,10,16,17

            Reaching toxic vitamin D levels due to too much sun exposure is not possible, as vitamin D levels in the body plateau with repeated exposure.  Toxicity via supplementation is possible, although it is quite rare.  It is not recommended to exceed the tolerable upper intake level for vitamin D of 4,000 IU (for adolescents and adults).  However, toxic levels are generally only seen with excessive intake, such as 50,000 IU per day taken for weeks or cumulative intakes of 240,000 IU or more.  The most common manifestations of toxicity include calcinosis and hypercalcemia, calcification of soft tissues, hypertension, hyperphosphatemia, nausea, weakness, headache, anorexia, renal disfunction, and it can sometimes result in death.2,14 

How Much Do We Need?

Recommending an adequate level of sun exposure is difficult due to the many confounding factors involved and the association between sun exposure and skin cancer.  Some studies attempt recommendations, however, there is significant variation across references on the amount of exposure needed to prevent vitamin D deficiency. 

The Dietary Guidelines for Americans acknowledge that it is difficult to get adequate vitamin D from dietary sources, and supplementation may be appropriate for individuals who get limited sunlight. The RDA for vitamin D is based on minimal sun exposure.  The recommendation is for 400 IU per day for infants under 1 year old, 600 IU per day for everyone from 1 – 70 years old, and 800 IU per day for those over 70 years old.18  Recommendations are confounded by the many factors that affect vitamin D status, and different countries and organizations have different recommendations for optimal intake.  Many researchers have proposed that the RDA is too low.  For example, the Endocrine Society recommends a minimum of 600 IU per day up to 2,000 IU per day to maintain adequacy in people aged 19-50.19,20

There appears to be consensus that 400 IU per day is adequate for infants, and there is no evidence to suggest that higher doses are beneficial.20,21 A meta-analysis of randomized controlled trials from Northern Europe found that intakes around 1,000 IU per day can maintain adequate vitamin D status in 97.5% of children and adults.4,22  Intakes as high as 2,000 IU per day are commonly recommended, are generally considered safe, and should keep vitamin D values well below the upper intake levels.3,14  Because vitamin D can be stored in fat cells, those who are overweight or obese may need more vitamin D to reach adequate levels.2  Intakes that are 1.5 times higher than recommendations may be appropriate for overweight individuals, while intakes 2-3 times higher may be appropriate for obese individuals.23 

            When thinking about adding an oral supplement, consider vitamin D intake from all sources, including fortified foods.  Children can maintain adequate vitamin D levels by consuming fortified foods, such as milk and cereal.24  Despite the vast body of research on vitamin D, there remains uncertainty around making recommendations.  There are many variables that contribute to one’s individual vitamin D status.  It is likely prudent to err on the side of caution and assess your individual circumstances when deciding on how to proceed.  Individuals should partner with a health professional, such as a registered dietitian nutritionist, when deciding to make dietary or lifestyle choices. 

 


References

1.         COVID Changed Supplement Popularity in 2020, ConsumerLab Survey Reveals. ConsumerLab Web site. https://www.consumerlab.com/news/covid-changed-supplement-popularity/02-26-2021/. Published February 26, 2021. Accessed March 27, 2021.

2.         Gropper S, Smith J. Advanced Nutrition and Human Metabolism. 6th ed. Belmont, CA: Wadsworth Cengage Learning; 2013.

3.         Matsui MS. Vitamin D Update. Current Dermatology Reports. 2020;9(4):323-330.

4.         Garland CF, Kim JJ, Mohr SB, et al. Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D. Am J Public Health. 2014;104(8):e43-50.

5.         Heath AK, Kim IY, Hodge AM, English DR, Muller DC. Vitamin D Status and Mortality: A Systematic Review of Observational Studies. Int J Environ Res Public Health. 2019;16(3):383.

6.         Young AR, Morgan KA, Ho T-W, et al. Melanin has a Small Inhibitory Effect on Cutaneous Vitamin D Synthesis: A Comparison of Extreme Phenotypes. Journal of Investigative Dermatology. 2020;140(7):1418-1426.e1411.

7.         Powe CE, Evans MK, Wenger J, et al. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. The New England journal of medicine. 2013;369(21):1991-2000.

8.         Neale RE, Khan SR, Lucas RM, Waterhouse M, Whiteman DC, Olsen CM. The effect of sunscreen on vitamin D: a review. British Journal of Dermatology. 2019;181(5):907-915.

9.         Young AR, Narbutt J, Harrison GI, et al. Optimal sunscreen use, during a sun holiday with a very high ultraviolet index, allows vitamin D synthesis without sunburn. British Journal of Dermatology. 2019;181(5):1052-1062.

10.       Lucas RM, Norval M, Neale RE, et al. The consequences for human health of stratospheric ozone depletion in association with other environmental factors. Photochemical & Photobiological Sciences. 2015;14(1):53-87.

11.       Silva MC, Furlanetto TW. Intestinal absorption of vitamin D: a systematic review. Nutr Rev. 2018;76(1):60-76.

12.       Dawson-Hughes B, Harris SS, Palermo NJ, Ceglia L, Rasmussen H. Meal conditions affect the absorption of supplemental vitamin D3 but not the plasma 25-hydroxyvitamin D response to supplementation. J Bone Miner Res. 2013;28(8):1778-1783.

13.       Pereira M, Dantas Damascena A, Galvão Azevedo LM, de Almeida Oliveira T, da Mota Santana J. Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2020:1-9.

14.       El-Hajj Fuleihan G, Bouillon R, Clarke B, et al. Serum 25-Hydroxyvitamin D Levels: Variability, Knowledge Gaps, and the Concept of a Desirable Range. Journal of Bone and Mineral Research. 2015;30(7):1119-1133.

15.       Sowah D, Fan X, Dennett L, Hagtvedt R, Straube S. Vitamin D levels and deficiency with different occupations: a systematic review. BMC Public Health. 2017;17(1):519.

16.       Manson JE, Cook NR, Lee IM, et al. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med. 2019;380(1):33-44.

17.       Autier P, Mullie P, Macacu A, et al. Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol. 2017;5(12):986-1004.

18.       U.S. Department of Health and Human Services, U.S. Department of Agriculture. 2015–2020 Dietary Guidelines for Americans. 8th Edition. Dietary Guidelines for Americans Web site. https://www.dietaryguidelines.gov/sites/default/files/2019-05/2015-2020_Dietary_Guidelines.pdf. Published December 2015. Accessed June 3, 2020.

19.       Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism. 2011;96(7):1911-1930.

20.       Bouillon R. Comparative analysis of nutritional guidelines for vitamin D. Nat Rev Endocrinol. 2017;13(8):466-479.

21.       Mimouni FB, Mendlovic J. Vitamin D requirements in infancy: an updated systematic review. Curr Opin Clin Nutr Metab Care. 2021;24(3):259-264.

22.       Cashman KD, Ritz C, Kiely M, Odin C. Improved Dietary Guidelines for Vitamin D: Application of Individual Participant Data (IPD)-Level Meta-Regression Analyses. Nutrients. 2017;9(5):469.

23.       Ekwaru JP, Zwicker JD, Holick MF, Giovannucci E, Veugelers PJ. The importance of body weight for the dose response relationship of oral vitamin D supplementation and serum 25-hydroxyvitamin D in healthy volunteers. PLoS One. 2014;9(11):e111265.

24.       Brandão-Lima PN, Santos BDC, Aguilera CM, Freire ARS, Martins-Filho PRS, Pires LV. Vitamin D Food Fortification and Nutritional Status in Children: A Systematic Review of Randomized Controlled Trials. Nutrients. 2019;11(11).



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