Vitamin D – How Important is it Really?

There is much confusion about Vitamin D…is it really a vitamin? Is it so important and if so, why? Do we need to get it from the sun or is it enough to supplement? Won’t sun exposure increase the risk of cancer? This month’s Health Insight hopes to address and answer these questions and more…so read on.

Vitamin D - What is it?

Vitamin D functions as a hormone in our bodies. The two major forms are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). The former (D2) is found in fungi, plants, and fortified foods/supplements; while the latter (D3) is synthesized in our skin when 7-dehydrocholesterol (in our skin) is exposed to UVB light in addition to being found in animals (oily fish) and fortified foods/supplements. The synthesis of vitamin D in the skin requires exposure to UVB light at wavelengths of 270-300nm, with peak incidence occurring between 295 and 300nm. Vitamin D is further processed in the liver to 25(OH)D and then again in the kidney to its final active form 1,25 dihydroxyvitamin D, (1,25(OH)2D) also known as calcitriol. Although some studies have found vitamin D3 to have longer lasting effects than vitamin D2, other studies have concluded that they are equally effective.

What does it do?

Vitamin D is responsible, directly and indirectly, for regulating over 200 genes in the human body. It activates genes by binding to the vitamin D receptor (VDR) in particular cells. Vitamin D receptors are found in cells all over the body (including the brain, heart, kidney, bone, intestine, skin, gonads, prostate, breast, parathyroid gland, and immune system) demonstrating how essential vitamin D is for the human body to function properly. Vitamin D functions range from regulating calcium and phosphorus levels in the blood (important for bone growth and remodeling) to acting as an immune modulator able to both suppress the immune system (to fight against conditions like Rheumatoid Arthritis, Lupus, and Multiple Sclerosis) and activate the immune system (to fight cancer as well as infections like Tuberculosis, Pneumonia, and Influenza) to decreasing Cardiovascular Risk  (Heart Attacks and Strokes) to preventing diabetes (by modifying the release of and response to insulin).

How is it measured?

To most accurately assess vitamin D status, its major circulating metabolite (the storage form prior to activation) calcidiol [25(OH)D] is measured. This measures both our intake and our production of vitamin D.  The activated form of vitamin D calcitriol [1,25(OH)2D] does not correlate well with overall vitamin D status and therefore the activated vitamin D level is not used for measurement purposes (our body keeps our activated vitamin D, calcitriol level, relatively constant no matter whether our stored vitamin D, calcidiol level, is low or high).

How much do we need?

Sources say normal vitamin D levels range between 30 to 70ng/mL with ideal levels being between 50 and 70 ng/mL.  Vitamin D deficiency is defined as a 25(OH)D level < 20ng/mL and vitamin D insufficiency as 21-29 ng/mL. Vitamin D levels often fluctuate due to geographic location, UV index, and temperature (skin exposure) so our goal should be a level close to 70ng/mL by the end of the summer (after maximum exposure) and ideally no lower than 50ng/mL by the end of the winter (after minimum exposure). Adequate exposure entails 50-75% of your skin exposed (shorts, sleeveless T-shirt, or swimsuit) between 10:30am and 2pm, about 3-4 times per week when your local UV index is 3 or higher. Early in the day and late in the day sunlight provides only UVA which does not help us make vitamin D but still can cause skin damage.

Adequate sun exposure also depends on the UV index (UVI) and your skin type:

Skin Type               UVI 0-2        UVI 3-5        UVI 6-7        UVI 8-10 & Tanning        UVI 11+

Always Burn,           None         10-15 min      5-10 min            2-8 min                      1-5 min

Never Tan            Produced 

Easily Burn,             None         15-20 min     10-15 min           5-8 min                      2-8 min

Rarely Tan           Produced

Occas. Burn,            None         20-30 min     15-20 min         10-15 min                   5-10 min

Slowly Tan           Produced

Rarely Burn,            None          30-40 min     20-30 min         15-20 min                 10-15 min

Rapidly Tan         Produced

Never Burn,             None          40-60 min     30-40 min         20-30 min                 15-20 min

Always Dark         Produced

*double exposure time if you are 50 or older

Where can we get it?

The best source of vitamin D is that which we make in our skin from sunlight exposure (when the UV index is 3 or greater). Most people can make up to 10,000 IU of vitamin D per day with maximum UVB exposure, after which the concentration of vitamin D precursors produced in the skin reaches an equilibrium and any additional vitamin D produced is just degraded. However, other sources include supplementation and to a smaller extent foods such as cod liver oil.

What is the UV index?

It is an international standard measurement of how strong the UV radiation from the sun is at a particular place on a particular day. It takes into account the UVA and UVB rays that penetrate the ozone layer with values ranging from 0 (nighttime) to as high as 17 (in areas where the ozone is depleted). It is a prediction of how strong the actual UV intensity will be at the sun's highest point in the day, which typically occurs during the two to four-hour period surrounding solar noon. Its purpose is to help people protect themselves from UV light. The UV index scale is linear so that one hour of sun exposure at a UV index of 10 is roughly equivalent to two hours of sun exposure at a UV index of 5. The balance of UVA and UVB from sunlight differs depending on the time of day. Early in the day and late in the day sunlight provides only UVA. The closer you get to solar noon the more UVB is available from sun exposure. Note that the balance of UVA/UVB changes with latitude, time of day, and season of year which is all reflected in the UV index. For example, in winter in Chicago for roughly 6 months all you get is UVA (note the UV index will respectively never get above 2), which damages skin without any UVB benefit. However, most people are covered up so they are protected from the UVA rays. For that reason you should not intentionally expose your skin when the UV index is less than 3. Whether reports often list the UV index and “The Weather Channel” application for the iPhone actually gives you a minute to minute update of your local weather report that includes the UV index for that specific time of day. You can also find out what your particular UV index is (for the hour surrounding solar noon) by plugging your zip code into the following website link:

http://www.epa.gov/sunwise/uvindex.html

What contributes to Vitamin D deficiency?

Lack of or inadequate sunlight exposure is the main issue. This may be due to geography (living above latitudes of 35 degrees – north of Los Angeles and Atlanta), skin color (darker skinned people need more time in the sun), application of sunscreen (SPF 15 sunscreen can block 99% of vitamin D synthesis by the skin), or personal preference (staying out of the sun for fear of sun damage). Inadequate intake (from fortified foods or supplements) and diseases of the liver and kidneys (which may affect conversion of vitamin D to its active form) also promote deficiency. Obesity promotes deficiency because vitamin D is a fat soluble hormone that is sequestered into fat cells, and as a result is not available for circulation. Finally, old age is a contributing factor as it is more difficult to synthesize vitamin D in the elderly, so much so that "after equal doses of sunlight exposure, a 70 year old person produces 25% less vitamin D3 than a 20 year old person." That is why people 50 or older should double their exposure time on the chart above.

How common is Vitamin D Deficiency?

More common than we would think. Up to 50% of young adults and children are vitamin D deficient. And 25-57% of adults in the United States are deficient reported The Third National Health and Nutritional Examination Survey (NHANES III). Likely even more people are deficient as vitamin D levels are not checked nearly as often as they should be.

What does Vitamin D deficiency lead to?

Low vitamin D levels have been associated with an increased rate of overall death, myalgias (nonspecific muscle aches and pains), cancer, diabetes, high blood pressure, congestive heart failure, impaired bone mineralization (leading to rickets in children, osteomalacia and osteoporosis in adults), several autoimmune conditions (including Rheumatoid Arthritis, Multiple Sclerosis, and Lupus), depression, and seasonal affective disorder among others. Note that it is absolutely essential to have normal vitamin D levels during pregnancy and early childhood to prevent infections, osteoporosis, autoimmune diseases, and cancer. Moreover, moms must have optimal vitamin D levels (50ng/mL or greater) to be able to provide ample amounts of vitamin D in their breast milk for their nursing babies.

In fact, a growing number of studies have been and continue to be published highlighting the benefits of vitamin D and the hazards of vitamin D deficiency. Usually they show that there is an association between different levels of Vitamin D and disease risk. A meta-analysis of five studies showed a 50% lower risk of colorectal cancer associated with a serum Vitamin D level of > or = 33ng/mL, compared to < or = 12 ng/mL. Other studies have shown similar improvements with breast cancer. The mechanism for this is believed to be vitamin D's affect on cell growth, differentiation, and death – all important components in the development of cancer. Other studies have demonstrated the positive role vitamin D plays in preventing heart disease. A study published in the Journal of Circulation looked at 1739 participants (average age 59) for five years and found that "those people with low levels of vitamin D (<15ng/mL) had a 53-80% higher risk of a cardiovascular event." Another study looked at 150 patients with nonspecific musculoskeletal pains and found that vitamin D levels were "insufficient in 93% of individuals and severely deficient in 28%." Low vitamin D levels have also been shown to correlate with increases in all-cause mortality. More specifically, using the National Health and Nutritional Examination Survey, that followed 13,331 adults older than 20, researchers found that levels of vitamin D <17.8ng/mL were associated with a 26% increased rate of all-cause mortality. Clearly vitamin D is an important factor in overall health and should be further studied.

Can we get Vitamin D toxicity?

The upper limit of vitamin D considered to be safe for a healthy adult is 250 micrograms (10,000 IU) daily. Symptoms of vitamin D toxicity result mostly from hypercalcemia (too much calcium in the blood) and include high blood pressure, nausea, vomiting, constipation, weakness, decreasing kidney function with increased urination, confusion, and lethargy. Overexposure to sunlight cannot cause toxicity because once vitamin D synthesis has reached an equilibrium or saturated state, the rest of the vitamin D is degraded. Supplementation, however, can lead to toxicity (although this is not very common) and should be administered with physician supervision.

What about cancer?

UV light can definitely damage cellular DNA which may lead to cancer; however, that does not mean that we should go to the other extreme either. Studies that looked at indoor workers versus outdoor workers versus mixed workers showed that mixed workers (those who worked partially indoors and partially outdoors) actually had the lowest risk of melanoma. This supports the idea that some sun exposure is actually protective against cancer. Burning is probably cancer promoting but clearly no sun exposure is cancer promoting too. One study pointed out that melanomas often show up on areas of skin that have not been damaged by the sun, suggesting that sunlight exposure to the skin is not the only important factor. We recommend people get their adequate sun exposure based on the UV index and their skin type (see chart above), and when that is completed to then use a barrier method of sun block (shirts, hats, etc.). Sun blocks are great at protecting us from burns and subsequent skin damage but do not clearly prevent against cancer.

What about tanning booths?

First of all, tanning booths are not the same across the board. Some use bulbs that emit only UVA light, some UVA and UVB light, and some UVA, UVB, and UVC light. UVC light is normally blocked by the ozone and very damaging, so it should be avoided at all costs. UVA light causes skin to tan quickly and therefore is preferred by tanning salons. However, UVA rays do not promote vitamin D production. The only wavelength that does promote vitamin D production is UVB light so only those bulbs that utilize UVB light will have any potential benefit. That being said the ratio of UVA to UVB light differs among bulbs and is often not measured or regulated. The ratio of UVA to UVB light from the sun is anywhere from 10 :1 to 20:1. But some tanning bulbs have a UVA to UVB ratio as high as 100:1. What this means as far as skin cancer risk is still not clear, but high levels of UVA exposure is probably a bad idea. There are some studies that show that those people who go tanning have increased rates of skin cancer. But it is not always clear what type of UV light they were using, what the UVA:UVB ratios were, or whether they were overexposing themselves (based on skin type) in those studies? Adequate sunlight exposure is your best bet for safe accumulation of vitamin D, but we still need to see a study that shows how tanning and supplements compare to sunlight. That being said, research does show that those people who frequent tanning salons have normal vitamin D levels, typically higher than 45ng/mL, which we know to be healthy. Ultimately, we just need more studies. No matter what you choose, be careful when tanning as those bulbs are very strong and have a UV index of approximately 7-8!

The verdict on supplementation?

Whenever possible, we should get our vitamin D from sunlight exposure. The sun has gotten a very bad rap but the reality is that studies show areas with greater sun exposure have reduced risks of cancers and heart disease. In addition, sunlight has been shown to have positive affects on rickets, osteomalacia, high blood pressure, depression, sleep disorders, ADHD, premenstrual syndrome, and acne. Having said that, we realize that, due to personal or geographical constraints, obtaining adequate sunlight exposure is not always possible. Therefore, in some situations (living in areas with little to no sun exposure) and/or for some people (elderly, nursing home or hospitalized patients) supplementation might not only be necessary but also recommended.

We know that people with optimum levels of vitamin D are much healthier than those with lower levels of vitamin D. We also know that a low level of vitamin D is really a sign of sunlight deficiency. At this point we cannot say for sure that raising vitamin D levels artificially with supplements will bring you to the same level of health as someone who raises their vitamin D level with sunlight. That being said we know that raising vitamin D levels from 20ng/mL to 40ng/mL doubles the calcium absorption ability of our intestine. We also know that parathyroid hormone (PTH) is elevated with vitamin D levels below 30ng/mL and we know that PTH normalizes when vitamin D levels reach 30ng/mL or higher. PTH is our backup system for when vitamin D levels are too low for adequate calcium absorption from the gut. Because calcium levels in our blood must remain relatively constant, PTH steps in and stimulates bone breakdown to get calcium into the blood to maintain those levels. It is very damaging to our bones to rely on our PTH backup system to normalize blood calcium levels. At this point in time, there are only two good randomized controlled intervention studies with therapeutic levels of vitamin D supplementation. The first investigated the effects of Vitamin D supplementation on depression in overweight and obese subjects. Although the study concluded that there seemed to be an association between low vitamin D levels (< 40 nmol L-1) and depression in overweight and obese subjects and that high levels of supplementation (up to 40.000 IU per week) may have a beneficial effect, the effect of other compounding variables (including supplementation with Calcium and level of physical activity) could not be excluded. As a result, “the main outcome of (this) study must be considered a negative.” The second study looked at over 1100 postmenopausal women and supplementation with 1100 IU of vitamin D3 (along with calcium). Most studies in the past were not randomized, placebo-controlled studies. The studies that were randomized, only used small amounts of vitamin D3 that barely raised vitamin D levels (1-2 ng/mL at best). This study used 1100 IU of vitamin D3 and increased vitamin D levels from 29ng/mL to 38ng/mL on average, actually showing about a 4-5% absolute risk reduction in total cancer by the end of 4 years. To answer our questions, we really need to see a long-term study on vitamin D without calcium (enough to raise levels to 50-70ng/mL) that is randomized to vitamin D supplementation versus sunlight versus placebo. If this hypothetical study showed a benefit on morbidity and/or mortality then we would have the much needed answers. However, no drug company will make money from that study so we will not hold our breath for the results. That being said, one theory right now is to use supplements (if we can't get enough sun) to get our vitamin D level to at least 30ng/mL, shutting off our PTH backup system and optimizing our intestinal calcium absorption, hopefully protecting our bones and improving our overall health.

The truth is that the average American probably needs about 20 to 25 IU of vitamin D per pound of body weight to get their levels up to 50-70ng/mL, and 10-15 IU per pound to get their level up to 30ng/mL. This is much more vitamin D than the current recommended daily intake. Keep in mind that one full day of adequate sunlight exposure (see chart above) can give you up to 10,000 IU’s of Vitamin D. Currently we would recommend people to get their levels up as high as they can with sun without getting sunburn. Then if levels are still below 30ng/mL, to use supplements to get their level to 30ng/mL. If still having significant symptoms that could possibly be due to suboptimal vitamin D levels (certain autoimmune diseases, fibromyalgia, seasonal affective disorder, particular musculoskeletal problems, etc.) then those patients may benefit from a trial of increased vitamin D supplementation. If symptoms don't improve despite vitamin D levels of 50-70ng/mL then they should decrease their supplementation to get back to a level of 30ng/mL. That being said, people should never grow complacent with supplementation. No matter what, you should always try to increase sun exposure (between 10:30am and 2pm with UV index of 3 or greater) whenever possible in an effort to decrease overall supplementation dependence.

Conclusion:

We hope we have been able to clear up some of the confusion regarding vitamin D.  The main take home points being:

*YES! vitamin D deficiency is a sign of sunlight deficiency.

*YES! Low vitamin D levels have been associated with cancer, heart disease, diabetes, rickets, osteomalacia, and osteoporosis among other diseases.

*YES! vitamin D is necessary and essential for proper and optimal functioning of many organ systems.

*YES! Just like plants, sunlight is essential for optimum health. And just as sprinkling vitamin D on the soil of plants won't effectively replace their sunlight requirement; neither should vitamin D replace human sunlight requirements!

On that note, for those of you who can, pack a picnic or grab your Frisbee and head out for some fun in the sun!

REFERENCES:

Dowd MD, James. "The Vitamin D Cure." John Wiley & Sons, Inc. Hoboken, New Jersey. 2008.

Garland CF, Gorham ED, Mohr SB, etal “Vitamin D and prevention of breast cancer: pooled analysis.”  J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):708-11.

Gorham ED, Garland CF, Garland FC et al. (2007). "Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis. Am J Prev Med. 32:210-216.

Holick, Michael F. MD, PhD "Vitamin D Deficiency: An Important, Common, and Easily Treatable Cardiovascular Risk Factor?" Journal of American College of Cardiology Vol. 52, No. 24, 2008

Holick MF. “Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease.”  Am J Clin Nutr. 2004 Dec;80(6 Suppl):1678S-88S.

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Jorde R, Sneve M., Figenschau Y., etal “Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial.”  J Intern Med. 2008 Dec;264(6):599-609.

Lappe JM, Travers-Gustafson D, Davies KM, et al. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr.  2007; 85(6):1586-91

Lee, John H. MD; O'Keefe, James H. MD; Bell, David MD; Hensrud, Donald D. MD,MPH;

Looker AC, Dawson-Hughes B, Calvo MS, Gunter EW, Sahyoun NR. Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. Bone 2002;30:771-7.

Melamed ML, Michos ED, Post W, Astor B. “25-hydroxyvitamin D levels and the risk of mortality in the general population.” Arch Intern Med. 2008 Aug 11;168(15):1629-37.

P J Nelemans, H Groenendal, L A Kiemeney “Effect of intermittent exposure to sunlight on melanoma risk among indoor workers and sun-sensitive individuals.” Environ Health Perspect. 1993 August; 101(3): 252–255.

Plotnikoff GA, Quigley JM. “Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain.” Mayo Clin Proc. 2003 Dec;78(12):1463-70.

Vitamin D, Merck Manual of Diagnosis and Therapy Professional Edition

www.uptodate.com – "Treatment of Vitamin D Deficient States." October, 2008.

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