What about Vitamin D?

Vitamin D, like vitamins A, E, and K, belongs to a group of fat-soluble vitamins. There are two forms of vitamin D: cholecalciferol and ergocalciferol. Cholecalciferol is produced in the skin of humans and animals under the influence of sunlight. Ergocalciferol is produced in some plants, provided that they have adequate exposure to the sun. Both cholecalciferol and ergocalciferol are forms that are not biologically active. Their activation occurs in two steps, the first of which takes place in the liver, while the second takes place in the kidneys.

Biological functions of vitamin D

The traditional function of vitamin D is to maintain an adequate level of calcium in serum within a very narrow range of 2.2-2.6 mmol/L or 9-10.5 mg/dl. This level is necessary for the proper functioning of the nervous system, as well as adequate growth and maintenance of strong bones and teeth. For this reason vitamin D plays a significant role in the prevention of health conditions related to bone development and deterioration, such as rickets in children, and osteopenia and osteoporosis in adults. Vitamin D actually stimulates absorption of other minerals, including phosphorus and iron. In addition, recent studies suggest that vitamin D plays an important role in the prevention of some cancers (especially breast, prostate, and colon cancer), cardiovascular diseases (including hypertension), and the proper functioning of the immune system. Also, vitamin D seems to influence mood and alters risk of depression. Vitamin D plays a significant role in fetal development, prevention of preterm birth, pregnancy-induced hypertension, and gestational diabetes. Some new studies indicate that inadequate levels of vitamin D may also be a factor in the development of autism, multiple sclerosis, and some other health conditions.

Vitamin D serum recommendations

Although vitamin D is stored in the body, recent studies suggest that its serum level during the autumn and winter months — periods of low sunlight exposure during which the reliance on the stored vitamin D is higher than in other time periods — may be insufficient to achieve benefits associated with adequate status of this nutrient. Elderly individuals who may not have adequate daily exposure to the sun may have a chronic suboptimal vitamin D level unless supplements are used. Vitamin D is measured in nanomoles per liter of blood (nmol/L) or as nanograms per milliliter (ng/ml). Until recently, the serum level considered adequate was in the range between 16 and 80 ng/ml (40 to 200 nmol/L). Results of more recent research suggest that higher low-normal cutoffs are associated with the best immune system function, cancer prevention, and other benefits. Table 1 (below) contains recommendations for vitamin D serum concentration issued by the Endocrine Society.

Table 1. The Endocrine Society’s recommendations for vitamin D serum concentration.

How many Americans have vitamin D deficiency?

Findings from the National Health and Nutrition Examination Survey (NHNES) 2005 to 2006 show that the overall prevalence of vitamin D below 20 ng/mL (<50 nmol/L) among 4,495 examined individuals was 41.6%. Black Americans had the highest prevalence rate (82.1%), followed by Hispanics (69.2%). Surprisingly, age specific analyses did not show significant variations between the prevalence of vitamin D deficiency. In another analysis from the NHNES data, American children and teenagers, ages 6 to 18, with vitamin D below 20 ng/mL (<50 nmol/L) reached 21%, 29%, 34%, and 49% in healthy-weight, overweight, obese, and severely obese participants respectively. The prevalence of vitamin D deficiency in severely obese White, Latino, and African-American children was 27%, 52%, and 87%, respectively. It must be pointed out that the NHNES study is considered representative of the entire United States population and that, as pointed out above, the level of serum vitamin D considered sufficient (30-44 ng/mL) is actually higher than the deficiency cutoff used in this study.

The data described above shows that vitamin D deficiency is prevalent in both American children and adults. Also, the data shows that weight status and ethnic background are risk factors for inadequate vitamin D concentration. Considering the role of vitamin D in growth, development, and disease prevention, it is accurate to conclude that vitamin D inadequacy is a major public health problem that affects individuals of all ages.

Vitamin D concentration and risk of selected health problems

A number of research manuscripts regarding the health impact of vitamin D have been published in professional journals. Many of them have shown that inadequate vitamin D concentration may increase the risk of several health conditions. Similarly, many research findings have shown beneficial effects of vitamin D supplement use. Also, several meta-analyses on the impact of vitamin D on different health conditions have been published. A meta-analysis is a statistical tool to evaluate the impact of more than one dataset on a given health condition. Thus, findings from a meta-analysis can be considered an overall take-home message of the impact of a risk factor on a health condition.

As indicated above, the traditional role of vitamin D has to do with absorption of minerals, such as calcium and phosphorus. Thus, vitamin D plays a role in bone development and maintenance. Findings of one meta-analysis show that vitamin D supplementation prevented non-vertebral fractures, including hip fractures. The analysis was based on 12 studies with 42,279 individuals 65 years of age and older. Researchers found that supplementation in the dose of 770 IU was associated with a 20 percent lower risk of non-vertebral fractures and an 18 percent lower risk of hip fractures. Lower supplemental dose was associated with a 14 percent lower risk for all non-vertebral fractures and a 9 percent lower risk of hip fractures.

Results of recent studies indicate that vitamin D plays a role in the prevention of heart disease. For example, results of the Health Professionals Follow-up Study with 18,225 male health professionals between 40 and 75 years of age showed that compared to individuals with a serum vitamin D level of 30 ng/mL or higher, those with a level of 15 mg/mL or lower had a 2.42 times higher risk of developing a heart attack. Those with an intermediate level of serum vitamin D had a 1.6 times higher risk in comparison to those with the highest vitamin D level.

Other studies show that adequate vitamin D is associated with reduced blood pressure. Since elderly individuals have the highest risk of heart disease of all age groups, and since age is a risk factor for hypertension, maintenance of an adequate serum vitamin D level may be helpful in reducing the risk of premature heart attacks and strokes in the elderly population more so than in younger individuals.

Another meta-analysis showed that a higher serum vitamin D level decreases the risk of developing certain cancers. Results of this meta-analysis indicated that for each 10 ng/mL increase in serum vitamin D level there was a 15 percent decrease in risk for colorectal cancer and an 11 percent decrease in risk for breast cancer.

A low level of Vitamin D concentration is associated with the occurrence of depression. Authors of a meta-analysis based on nine studies showed that individuals with the lowest serum vitamin D levels had a 31 percent higher risk of depression compared to those with the highest level. According to findings from another meta-analysis, an increase of 10 ng/ml of vitamin D was associated with an 8 percent decrease in depression in cohort studies (these are studies during which individuals are followed for a period of time; the Adventist Health Study 2 is an example of a cohort study) and 4 percent decrease in cross-sectional studies (these are studies in which an assessment is done at one time). The use of vitamin D supplements by some depressed individuals constitutes an effective treatment. According to yet another meta-analysis, the efficacy of using vitamin D supplements in a dose of 800 IU or more was similar to the treatment with anti-depressant medications.

In a meta-analysis based on 8 randomized studies with 2,426 individuals, researchers evaluated the risk of falls among vitamin D supplement users and nonusers. The results show that a dose of 700 to 1000 IU of vitamin D was associated with a higher serum vitamin D level, which reduced the risk of falls by 23 percent. According to the same analysis, supplementation with only 200 to 600 IU did not result in reduced risk of falls. Vitamin D, in addition to being essential in absorption of minerals, especially calcium, is associated with muscle strength and physical performance. Both of these factors play a role in preventing falls. It is estimated that individuals 65 years of age and older experience at least one fall each year. About 9 percent of these falls end up in emergency visits and about 5 percent result in fractures.

In addition to vitamin D being a factor in the development or prevention of adverse health conditions in adults, Canadian researchers found that children between 3 and 15 years of age whose serum vitamin D level was lower than 75 nmol/L had a 50 percent higher risk of viral respiratory tract infections compared to their peers with a higher level of vitamin D. Similarly, older teens with a vitamin D level lower than 30 ng/mL had a 36 percent higher risk of these infections compared to those with a level of ≥30 ng/mL.

How to obtain and maintain adequate vitamin D status

By far, the best way to provide the body with adequate doses of vitamin D is exposure to sunlight. Depending on geographic location, it is estimated that 20 to 30 minutes of sun bathing in the middle of the day in the period from mid-spring to mid-autumn may allow the skin of children and younger adults to produce significantly higher than the recommended amounts of vitamin D, provided that the face and forearms are exposed. This amount is not toxic because of the need for further activation of this vitamin in the body. Elderly individuals need somewhat longer exposure for reasons mentioned in the next paragraph. It should be noted that the International Agency for Research on Cancer, an agency of the World Health Organization, has classified solar radiation as a risk factor for skin cancer in humans. Therefore, it is a good idea to avoid prolonged sun exposure, especially in the summer.

Although the best way to maintain adequate vitamin D status, as indicated, is via sunshine exposure, experts on vitamin D research believe that during the winter months, individuals living north of Atlanta, Georgia, do not synthesize vitamin D. Thus, maintaining adequate vitamin D concentration in late fall, winter, and early spring in most parts of America is challenging for all people. The elderly are at the highest risk of a deficiency for several reasons. First, the elderly have a lower subcutaneous (under the skin) level of cholesterol, which is a substrate for vitamin D synthesis. Secondly, as people age they lose lean body mass and gain body fat. Vitamin D is a fat-soluble vitamin. Thus, higher body fat stores translate to higher area of vitamin D distribution (a sort of dilution effect), which decreases bioavailability and circulating level in the blood. Thirdly, the inactive form of vitamin D in circulation needs to be activated by the liver and the kidneys. Both of these organs, especially the kidneys, do not function as efficiently as they functioned earlier in life. Lastly, elderly individuals may have much lower sunshine exposure due to limited outdoor activity. This is especially true for institutionalized elderly and those with a disability.

There are not many foods that provide vitamin D. They include skim milk and soy milk, both of which are fortified with this vitamin. Some fatty fish contain relatively high vitamin D amounts. Vegetarians have even fewer options. Mushrooms exposed to sunshine can provide a significant amount of vitamin D. (Mushrooms contain ergosterol, which, when exposed to sunlight, is converted into an inactive vitamin D that can be activated in the body.) Table 2 contains dietary sources of vitamin D. Considering the limited food options that constitute significant sources of vitamin D, the best way to maintain adequate vitamin D status during periods of low sunshine exposure is to use vitamin D supplements.

Table 2. Dietary sources of vitamin D2

What is the appropriate dose of vitamin D supplements to maintain adequate vitamin D status?

The Endocrine Society recommends that individuals who are vitamin D deficient be treated with 50,000 IU of vitamin D weekly or 6000 IU daily for 8 weeks. The same organization suggests using a dose between 1500 to 2000 IU daily in order to maintain serum vitamin D above 30 ng/ml. Personally, in order to maintain adequate vitamin D concentration, I have recommended supplements in a dose of 800 to 2000 IU depending on age/lifecycle of individuals and their intake of vitamin D from foods. For example, children who like eating fatty fish may need considerably lower vitamin D supplements than elderly vegetarians. Also, I believe that correcting vitamin D status by using lower daily doses of supplements might be more effective than utilizing higher weekly doses.

Vitamin D2 vs. vitamin D3

Two different types of vitamin D are available in supplements: vitamin D2 and vitamin D3. Vitamin D2 is derived from mushrooms, while vitamin D3 is isolated from the skin of sheep. Vitamin D is synthesized when either ergosterol in mushrooms or dehydrocholesterol in animal skin are exposed to sunshine. According to the Endocrine Society, both treatment of vitamin D deficiency and maintenance of adequate serum vitamin D can be done by the use of either vitamin D2 or vitamin D3.

Should vitamin D supplement be used with or between meals?

Vitamin D is a fat-soluble compound, which means it is absorbed along with fat. Once fat is digested, fat particles (monoglycerides, fatty acids, phospholipids, cholesterol, fat-soluble vitamins, etc.) are used to form micelles. Micelles carry fat particles into enterocytes (small intestinal cells) where these particles are incorporated into chylomicrons. Fats, along with fat-soluble compounds, are transported via chylomicrons. Thus, vitamin D supplements need to be ingested along with some fat or oil. It is best to use vitamin D supplements along with a meal that contains some fat or oil.

Not-recommended ways of increasing vitamin D concentration

In America, the use of tanning salons has become increasingly popular. Although the synthesis of vitamin D by exposure to the radiation produced by tanning beds is possible, their potency is much lower than sunlight. This is because sunlight contains two types of UV rays: UVB and UVA. Of these, UVB rays are the most effective when it comes to production of vitamin D. Tanning beds or sunbeds, on the other hand, produce mainly UVA rays. In 2009, the International Agency for Research on Cancer identified tanning beds as a factor in causing cancer. The same organization found that the use of tanning beds carries risks similar to carcinogenic substances such as asbestos, tobacco, and arsenic.

The findings of a study that evaluated the impact of tanning beds on vitamin D synthesis show that the vitamin D levels among people using tanning salons an average of 6 to 12 minutes each day had increased from 11 nmol/L to 27 nmol/L after nine days. It should be noted, however, that people involved in this study experienced various unwanted side effects that are common among regular users of tanning salons. Therefore, taking also into account the fact that the use of tanning devices is associated with skin cancer, the authors of the study stated that, “Sunbed use as vitamin D source is, however, not generally recommendable due to the well-known carcinogenicity and high frequency of acute side effects.” A similar conclusion was reached by Dr. Woo and Dr. Eide, who evaluated scientific evidence of the impact of tanning beds on cancer and vitamin D: “Given the relative inefficiency of UVA-emitting tanning devices in increasing serum vitamin D levels, especially in those most at risk of vitamin D deficiency, indoor tanning is not recommendable as a way to achieve optimal vitamin D levels in the general public.”

Conclusion

Inadequate vitamin D concentration is a major public health issue. Individuals who want to achieve the most beneficial levels of vitamin D should spend a moderate amount of time in the sunlight during the late spring, summer, and early fall. During the other parts of the year, taking a daily dose of at least 800 and perhaps as much as 1500 to 2000 IU of vitamin D supplements would ensure an adequate serum level. Individuals with limited sun exposure should use supplements regardless of the time of the year. Regular intake of foods fortified with vitamin D will help in maintaining a sufficient level of this vitamin, but since the dose of fortification is relatively small, relying solely on fortified foods may not provide the best results in terms of ensuring optimal serum level of vitamin D.

Notes & References:

Bischoff-Ferrari H, Willett W., Wong J, Stuck A, Staehelin H, Orav E, Thoma A, Kiel D, Henschkowski J. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized control trials. Archives of Internal Medicine, 2009;169(6):551-561.

Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31(1):48-54.

Gandini S., Boniol M., Haukka J., Byrnes G., Cox B., Sneyd M., Mullie P., Autier P. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. International Journal of Cancer, 2011;128(6):1414–1424.

Giovannucci E, Liu Y, Hollis B, Rimm E. 25-hydroxyvitamin D and risk of myocardial infarction in men. Archives of Internal Medicine, 2008;168(11):1174-1180.

Grant W, Cross H, Garland C, Gorham E, Moan J, Peterlik M, Porojnicu A, Reichrath J, Zittermann A. Estimated benefit of increased vitamin D status in reducing the economic burden of disease in Western Europe. Progress in Biophysics and Molecular Biology, 2009;99(2−3):104−113.

International Agency for Research on Cancer Working Group on Artificial Ultraviolet (UV) Light and Skin Cancer. The association of use of sunbeds with cutaneous malignant melanoma and other skin cancers: a systematic review. International Journal of Cancer, 2007;120:1116–1122.

Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Retrieved from: http://www.iom.edu/Reports/2010/Dietary−Reference−Intakes−for−Calcium−and−Vitamin−D.aspx.

Ju S, Lee Y, Jeong S. Serum 25-hydroxyvitamin D levels and the risk of depression: a systemic review and meta-analysis. Journal of Nutrition, Health and Aging, http://link.springer.com/article/10.1007%2Fs12603-012-0418-0

Pawlak R. Forever young. Secrets of delaying aging and living disease free. Greenville, NC. 2nd edition. 2017.

Turer CB, Lin H, Flores G. Prevalence of Vitamin D Deficiency Among Overweight and Obese US Children. Pediatrics, 2013;131(1):e152-e161.

Tajalizadekhoob Y., Sharifi F., Fakhrzadeh H., Mirarefin M., Ghaderpanahi M., Badamchizade Z., Azimipour S. The effect of low-dose omega 3 fatty acids on the treatment of mild to moderate depression in the elderly: a double-blind, randomized, placebo-controlled study. European Archives of Psychiatry and Clinical Neuroscience, 2011;261:539–549.

Vitamin D Council. Understanding vitamin D cholecalciferol. http://www.vitamindcouncil.org/

Woo D., Eide M. Tanning beds, skin cancer, and vitamin D: an examination of the scientific evidence and public health implications. Dermatologic Therapy, 2010;23:61–71.

Roman Pawlak, Ph.D, RD is Associate Professor of Nutrition in the Department of Nutrition Science at East Carolina University.

Image credit: Pexels.com

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This is a companion discussion topic for the original entry at http://spectrummagazine.org/node/8720

You need to take K2 with D3 for it to work effectively. Why don’t any of these articles mention that?