Vitamin D

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 Sun exposure. 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 other one, 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, osteopenia and osteoporosis in adults. Vitamin D actually stimulates absorption of other minerals, including phosphorus and iron. In addition, recent studies suggested 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 developing autism, multiple sclerosis and some other health conditions.
Vitamin D serum recommendations
Although vitamin D is stored in the body, recent studies suggested 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 Sun exposure 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 suggested 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.

Severe deficiency associated with rickets and osteomalacia < 25nmol/L < 10ng/mL
Deficiency associated with long-term adverse health problems < 50nmol/L < 20ng/mL
Insufficiencyassociated with increased parathyroid hormone concentration < 75nmol/L < 30ng/mL
Sufficiencyassociated with the best outcomes 75-110nmol/L 30 - 44ng/mL
Toxicityassociated with hypercalcemia> 250nmol/L > 100ng/mL

How many Americans have vitamin D deficiency?
Findings from the National Health and Nutrition Examination Survey (NHNES) 2005 to 2006 showed that the overall prevalence of vitamin D below 20 ng/mL (<50 nmol/L) among 4495 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 with American 6 to 18-year old children and teenagers 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, sufficiently high level of serum vitamin D (30-44 ng/mL) is actually higher than the deficiency cutoff used in this study.
The data described above showed that vitamin D deficiency is very prevalent in both American children and adults. Also, the data showed 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 health impact of vitamin D have been published in professional journals. Many of them have shown that inadequate vitamin D concentration may increase risk of several health conditions. Similarly, many research findings have shown beneficial impacts of using vitamin D supplements. Also, several meta-analyses on the impact of vitamin D and 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 conditions. Thus, findings from a meta-analysis can be considered an overall take home message of an 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 showed 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 indicated that vitamin D plays a role in 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 in comparison to individuals with serum vitamin D level of 30 ng/mL or more those with a level of 15 mg/mL or less 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 highest vitamin D level.
Other studies showed that adequate vitamin D was 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 adequate serum vitamin D level may be helpful in reducing risk of premature heart attacks and strokes in the elderly population more so than in younger individuals.
Another meta-analysis showed that 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 risk for colorectal cancer and 11 percent decreased risk for breast cancer.
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 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 8 percent decrease in depression in cohort studies (cohort studies 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 (cross-section studies 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 supplements users and nonusers. The results showed that a dose 700 to 1000 IU of vitamin D was associated with a higher serum vitamin D level, which reduced 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, it 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 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 development or prevention of adverse health conditions in adults, Canadian researchers showed 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 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 the 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, as indicated, the best way to maintain adequate vitamin D status is via the sunshine exposure, experts on vitamin D research believe that in the winter months, individuals living north of Atlanta, Georgia have no synthesis of vitamin D. Thus, maintaining adequate vitamin D concentration in late fall, winter, and early spring in most parts of America, including North and South Carolina, is challenging for all people. The elderly are at the highest risk of a deficiency for several reasons. First, the elderly have 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 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 or soymilk, both of which are fortified with this vitamin. Some fatty fish contain relatively high vitamin D amounts. Vegetarians have even fewer options. Mushrooms that are exposed to the sunshine (mushrooms contain ergosterol, which, when exposed to sunlight is converted into an inactive vitamin D that can be activated in the body) can provide a significant amount of vitamin D. Table 2 contains dietary sources of vitamin D. Considering the limited food options that constitute significant sources of vitamin D, during periods of low sunshine exposure the best way to maintain adequate vitamin D status is to utilize vitamin D supplements.

Table 2. Dietary sources of vitamin D2 (amount in IU/3.5 oz.).

Portabella mushrooms exposed to ultraviolet lightraw 1120
Mushroom maitakeraw 1120
Mushrooms whiteraw 1040
Portabella mushrooms exposed to ultraviolet lightgrilled 520
Mushrooms Chanterelleraw 200
Mushrooms Morelraw 200
Mushrooms shiitakedried 160
Soymilkfortified with vitamin D 40

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 are 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 dose.
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 either by the use of vitamin D2 or vitamin D3.
Should vitamin D supplement be used with or between meals?
Vitamin D is a fat-soluble compound. As other fat soluble substances, it is absorbed along with absorption of fat. Once fat is digested fat particles (monoglycerides, fatty acids, phospholipids, cholesterol, fat soluble vitamin, 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 thus best to use vitamin D supplement 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 exposure to sunlight. This is because sunlight contains two types of UV rays: UVB and UVA. Of these, UVB rays are most effective when it comes to production of vitamin D. Tanning or sun beds, 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 other carcinogenic substances such as asbestos, tobacco and arsenic.
Findings of a study that evaluated the impact of tanning beds on vitamin D synthesis showed 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.”
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 just on fortified foods may not provide the best results in terms of ensuring optimal serum level of vitamin D.

Roman Pawlak, PhD, RD
Associate Professor
Department of Nutrition Science
East Carolina University

Selected 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:−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,
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.
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.

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