Thursday, August 4, 2011

Vitamin D its significance to human health

vitamin D
What can high-vitamin D foods do for you?
• Help optimize calcium metabolism
• Help optimize phosphorus metabolism
• Help prevent type 2 diabetes, insulin resistance, high blood pressure, heart attack, congestive heart failure, and stroke
• Help prevent falls and muscle weakness
• Help prevent osteoporosis while maintaining bone integrity
• Help regulate insulin activity and blood sugar balance
• Help regulate immune system responses
• Help regulate muscle composition and muscle function
• Help regulate blood pressure
• Lower risk of excessive inflammation
• Lower risk of some bacterial infections
• Support cognitive function, especially in older persons
• Support mood stability, especially in older persons
• Help prevent chronic fatigue
• Help prevent the following types of cancer: bladder, breast, colon, ovarian, prostate and rectal
What events can indicate a need for more foods rich in vitamin D?
• Muscle aches and muscle weakness
• Frequent falls, particularly among older persons
• Bone pain, frequent bone fractures, or soft bones
• Stunted growth in children
• Asthma in children (especially severe asthma)
• Impaired cognitive function, especially among older persons
• Lowered immunity
• Chronic low energy and fatigue
• Depression, particularly among older persons
• Presence of any autoimmune disorder
• Lack of exposure to sunlight for any reason, including geography, use of sunscreen, or wearing of protective clothing
Concentrated food sources of vitamin D include salmon, sardines, shrimp, milk, cod, and eggs. Among salmon, wild-caught fish have been shown to average significantly more vitamin D than non-organically farmed fish.

For serving size for specific foods, see Nutrient Rating Chart below at the bottom of this page.
• Description
• Function
• Deficiency Symptoms
• Toxicity Symptoms
• Cooking, storage and processing
• Factors that affect function
• Drug-nutrient interaction
• Nutrient interaction
• Health conditions
• Supplements
• Food Sources
• Public Recommendations
• References

Up until the mid-1990's, the answer to this question would have been fairly simple: vitamin D is a fat-soluble vitamin needed to prevent a bone disease in children called "rickets." Previous studies dating all the way back to the early 1800's had determined that cod liver oil could help to prevent and cure particular problems with bone development in children. In the early 1900's, a compound called "fat-soluble factor D" was isolated from cod liver oil, and this factor turned out to be the vitamin that we now refer to as "vitamin D." Scientific investigation of rickets helped establish the role of sunlight in providing us with vitamin D, and it also helped establish the role of vitamin D in bone health.
Beginning in the mid-1990's, however, our understanding of vitamin D began to change in a dramatic way. It would not be an exaggeration to say that the last 15 years have brought a revolution in our understanding of this vitamin! We now know that vitamin D is not simply a fat-soluble vitamin needed for healthy bones- it's also a hormone. When a substance functions like a vitamin, it participates in and regulates our metabolism, allowing it to function properly. And that is exactly what vitamin D does: it helps to regulate our bone development, our muscle function, our immune function, our insulin activity, our calcium balance, and our phosphorus balance. Just like for estrogen and cortisol, there are receptors for vitamin D (called VDRs, or vitamin D receptors) on the cell membranes of most cell types in the body. Instead of serving a very limited metabolic role in relationship to bone health, vitamin D plays a sweeping role in many diverse aspects of our health according to research conducted over the past 15 years.
There are two basic types of vitamin D. Ergosterol is the basic building block of vitamin D in plants. Cholesterol is the basic building block of vitamin D in humans. When ultraviolet light from the sun hits the leaf of a plant, ergosterol is converted into ergocalciferol, or vitamin D2. In just the same way, when ultraviolet light hits the cells of our skin, one form of cholesterol found in our skin cells-called 7-dehydrocholesterol-can be converted into cholecalciferol, a form of vitamin D3. (The revolution in our understanding of vitamin D has led to extensive research on both D2 and D3, and it is the overwhelming consensus of researchers that D3 is our best bet when supplementing with vitamin D. In fact, in 2006, the American Journal of Clinical Nutrition argued that D2 should no longer be considered as a nutrient "suitable for fortification or supplementation," given the strong hormonal advantages of D3. You'll find more about the issue of delivery form and supplementation in our section entitled "Form in Dietary Supplements.")
In the life of a plant, the ergocalciferol form of vitamin D2 serves to accomplish most of the desired purposes that were intended for this substance. In the life of a human, however, cholecalciferol is not the final intended form for this vitamin. In order for our bodies to come up with the fully active form of vitamin D3, further metabolism is required. A first step involves conversion of cholecalciferol into hydroxyvitamin D, also called 25-hydroxyvitamin D or 25(OH)D. Hydroxyvitamin D can be formed in the liver, kidney, lung, skin, prostate, brain, blood vessel linings, and macrophage cells of the immune system. An enzyme called CYP27A1 is required for formation of hydroxyvitamin D. A second step involves conversion of hydroxyvitamin D into dihydroxyvitamin D (also called 1,25-dihydroxyvitamin D or 25(OH)2D). This second step can take place in the lung, brain, liver, stomach, spleen, kidney, colon, thymus, lymph nodes, skin, placenta, and in the monocyte and dendritic cells of the immune system. An enzyme called CYP27B1 is required for formation of dihydroxyvitamin D. The different forms of vitamin D and their relationships are summarized in the chart below:
Form of Vitamin D Where Found What's Needed to Activate This Form of Vitamin D New Form of Vitamin D That Get's Created
7-dehydrocholesterol Skin UVB sunlight Cholecalciferol
cholecalciferol Many cell types CYP27A1 Hydroxyvitamin D 25(OH)D
25(OH)D Hydroxyvitamin D Many cell types CYP27B1 Dihydroxyvitamin D 25(OH)2D
25(OH)2D dihydroxyvitamin D Many cell types Already most active form No new form needed
Dihydroxyvitamin D (the only fully active hormonal form of vitamin D) does not last for very long in our body. The half-life of this hormone is between 2-3 weeks. For this reason, our vitamin D needs must be met on a fairly regular basis.
Before leaving this introductory description of vitamin D, it is important to note that our revolutionized understanding of vitamin D as a hormone found in a wide variety of cell types and responsible for the regulation of many different physiologic process has brought along with it a new understanding of how much we need. (You'll find more information on this topic in our section entitled "Public Health Recommendations.") There is a definite bottom line here: we need much more than we thought! When researchers had been limiting their research on vitamin D to bone health and rickets, they had been arriving at a clinical determination of about 15-20 ng/mL of vitamin D in our blood to keep us healthy. Once the research on vitamin D was expanded to include muscle health, immune health and other aspects of vitamin D function, this blood level of 15-20 ng/mL was clearly determined to be insufficient. Researchers quickly showed that blood levels of 30-50 ng/mL were needed to support these other health functions. In other words, our understanding of "normal vitamin D" has changed completely! Our blood levels need to be about twice as high as we previously thought, and it takes far more vitamin D intake than we previously thought to achieve those higher blood levels. (Once again, you will find more information on this topic in our sections entitled "Form in Dietary Supplements" and "Public Health Recommendations.")
How it Functions
What is the function of vitamin D?
The hormonal functions of vitamin D include regulation of bone health, regulation of muscle health (including both skeletal and heart muscle), regulation of immune response, regulation of insulin and blood sugar, and regulation of calcium and phosphorus metabolism. Further details about these functions are presented in the paragraphs below.
Regulation of bone health, calcium, and phosphorus
Bone composition involves many different substances, including collagen proteins, keratin proteins, and a variety of minerals including silicon, boron, and magnesium. But two especially critical bone components are the minerals calcium and phosphorus. These minerals form the bulk of a substance called hydroxyapatite, which accounts for over half of all bone composition.
The importance of hydroxyapatite in bone places a premium on calcium and phosphorus metabolism and their passage in and out of the body. While bone health is regulated by many different substances in the body-including growth hormone, testosterone, and estrogens-the importance of calcium and phosphorus in bone health also points to the special importance of two bone health regulators, namely parathyroid hormone (PTH) and vitamin D.
It's the job of our parathyroid glands to put out PTH whenever our blood calcium level gets too low. When that happens, PTH triggers release of calcium from our bones in order to boost our blood level back up to normal. PTH also triggers our kidneys to retain more calcium (keeping it available for our bloodstream) and excrete more phosphorus (thereby helping to create a more favorable ratio of calcium to phosphorus in our blood). If there is too much PTH released from our parathyroid glands, however, we may end up removing too much calcium from our bones and leaving too much in our blood, compromising both our cardiovascular and our bone health. Research has shown vitamin D deficiency to be a key risk factor for overproduction of PTH and optimal levels of vitamin D to be associated with healthy parathyroid function (and desirable PTH levels). Like PTH, vitamin D helps the intestines absorb more calcium from our food, and it also helps our kidneys hang on to calcium. But unlike PTH, vitamin D also helps our kidneys retain phosphorus. The two hormones work together in order to assure proper balances of calcium and phosphorus in our bloodstream and in our bones. Interestingly, PTH "knows" that it must act in partnership with vitamin D because it triggers conversion of hydroxyvitamin D into dihydroxyvitamin D (the hormonally active form).
Regulation of immune function
It would be very difficult to overestimate the importance of recent discoveries about vitamin D and the immune system. Vitamin D's role in immune regulation has revolutionized research in this area to such a degree that it is virtually impossible to investigate an autoimmune disease without considering the possible role of vitamin D. This statement holds true for health conditions like rheumatoid arthritis, multiple sclerosis, Crohn's disease, systemic lupus erythematosus, and numerous other autoimmune conditions.
Discovery of vitamin D's critical role in immune function was aided by the discovery of vitamin D receptors (VDRs) on the immune system's macrophage and dendritic cells in the past 15 years. Once triggered by vitamin D, macrophage cells are capable of releasing antibacterial peptides (parts of protein) like cathelicidin, and these antibacterial proteins play a critical role in the immune system's prevention of infection. Of special interest in this area has been infection by Mycobacterium tuberculosis (responsible for tuberculosis) and Mycobacterium leprae (responsible for leprosy). Vitamin D deficiency has emerged as a clear risk factor for these diseases.
Autoimmune conditions remain an extremely active area of vitamin D research. In current research on multiple sclerosis, for example, clinicians are experimenting with vitamin D doses up to 40,000 IU, and in research on rheumatoid arthritis, doses up to 100,000 IU are being used in some clinical trials. (To get some perspective on these vitamin D supplementation levels, they can be compared to the current adult Dietary Reference Intake recommendations for vitamin D, which range from 200-600 IU.)
Regulation of blood pressure and cardiovascular health
Vitamin D plays a direct role in regulating our blood pressure by inhibiting the activity of a system called the renin-angiotensin system. It's the job of the renin-angiotensin system to help increase our blood pressure whenever it gets too low. (The renin-angiotensin system accomplishes this task by helping our body retain sodium and water-thus providing more fluid in our blood vessels-and by causing our blood vessels to constrict and thereby increasing the pressure inside them.) We need optimal levels of vitamin D to hold this system in check, and to prevent it from raising our blood pressure under inappropriate circumstances.
Vitamin D deficiency has been shown to be a significant risk factor for high pressure in a variety of studies, and risk of high blood pressure during pregnancy (called pre-ecclampsia) has also been associated with maternal deficiency of vitamin D. In one interesting study on a group of individuals with high blood pressure, those whose UVB exposure was increased by using tanning beds (30 min/3 times a week) increased their vitamin D levels by 180% and decreased their blood pressure by about 5%. (Ultraviolet B light is the type of light required to convert 7-dehydrocholesterol in the skin into cholecaliferol, a preliminary form of vitamin D.)
The key role played by vitamin D in regulation of calcium metabolism has opened the door to research about broad cardiovascular benefits of vitamin D not limited to its role in regulation of blood pressure. Overloading of cells with calcium is a problem for heart tissue, and it is associated with increased risk of oxidative stress and tissue damage. By triggering unwanted release of PTH, vitamin D deficiency can result in precisely this situation of cellular calcium overload. In several studies, the ability of heart tissue to heal after an event like heart attack has been shown to suffer significantly in the absence of optimal vitamin D.
Regulation of insulin and blood sugar
While researchers are not entirely clear about the exact mechanisms for vitamin D regulation of insulin metabolism and blood sugar balance, there is no doubt that vitamin D plays an important role in this area of body function. Vitamin D deficiency is clearly a risk factor for development of type 2 diabetes, and vitamin D levels have been associated with insulin secretion by the beta cells of the pancreas as well as insulin activity once released into the bloodstream. Interestingly, when vitamin D is deficient in the body and parathyroid hormone (PTH) is released in inappropriately large amounts, too much calcium can accumulate in the cells. When too much calcium accumulates in fat cells, these cells can end up producing too much cortisol, a hormone that counteracts the effectiveness of insulin. Similarly, too much accumulation of calcium in our fat and muscle cells can inhibit the formation of a protein called GLUT-4. This protein helps carry sugar (glucose) out of our bloodstream and into our cells, and it is designed to perform this function whenever directed to do so by insulin. Without sufficient vitamin D, too little GLUT-4 is formed, and insulin lacks one of the proper tools to do its job.
Regulation of muscle composition and muscle function
Research in this area of vitamin D function has expanded enormously in the past ten years, and vitamin D deficiency has been shown to play a key role in prevention of muscle weakness and prevention of falls, especially in older persons. Interestingly, vitamin D deficiency has been associated with too much accumulation of fat throughout muscle tissue, in such a way that muscle strength is decreased and physical performance is compromised. In one study in California on healthy young women, decreased muscle strength was not only associated with vitamin D deficiency but also found to be independent of muscle mass. In other words, women with deficient vitamin D intake were found to have less muscle strength even when their muscles were the same size as the muscles of other women. Some of the research on vitamin D deficiency and risk of falling has also stepped outside of muscle function per se and looked at the broader issue of neuromuscular function and the relationship of muscle movement to nerve activity. Since vitamin D is a key regulator of calcium metabolism, and calcium is known to play a key role in nerve firing and nerve triggering of muscle contraction, this broader research focus may turn up important information about vitamin D and its role in reducing risk of falls.
Prevention of cancer
The role of vitamin D in cancer prevention is a lively area of current research, and the mechanisms linking vitamin D to cancer prevention are not completely evident. Nevertheless, research has shown a clear role for vitamin D in prevention of the following types of cancer: bladder cancer, breast cancer, colon cancer, ovarian cancer, prostate, and rectal cancer. In certain situations, vitamin D may also play a role in cancer treatment. Vitamin D analogs (vitamin-D like substances synthesized in the laboratory) are actively being tests as anticancer agents, especially with respect to breast and prostate cancers.
Other functions of vitamin D
The presence of vitamin D receptors (VDRs) in so many different tissue types-including the brain and skin-has left the door open to a wide variety of vitamin D functions. There is considerable research underway in the area of vitamin D deficiency and cognitive function, especially in aging persons. Senile dementia and Alzheimer's disease are two areas where vitamin D deficiency is under active investigation. Mood disorders-especially depression in older persons-is also an area of active research with respect to vitamin D deficiency. Due to its role in immune regulation and the known presence of VDRs in skin, vitamin D is a particularly good candidate for investigation in a skin-related autoimmune disease like psoriasis. Research in this area is also well underway.
Deficiency Symptoms
What are deficiency symptoms for vitamin D?
Bone pain, frequent bone fractures, and softening of the bones can all be symptoms of vitamin D deficiency. So can muscle aches and muscle weakness since vitamin D helps to regulate muscle composition and prevent too much fat accumulation alongside of muscle tissue. In this context, especially in older persons, frequent falls can point to deficiency of this vitamin. The key role of vitamin D in regulation of immune response means that lowered immunity can be a symptom of vitamin D deficiency, as can the presence of any autoimmune disorder. In older persons, cognitive problems (disturbances in thought processes) and depression can be symptomatic of vitamin D deficiency, and in children, stunted growth and severe asthma have also been shown to have vitamin D deficiency as potential causes.
Toxicity Symptoms
What are toxicity symptoms for vitamin D?
Excessive intake of vitamin D can be toxic, and toxicity of vitamin D can come from either its plant-based (D2) or animal-based (D3) form. Symptoms of toxicity include loss of appetite, nausea, vomiting, high blood pressure, kidney malfunction, and failure to thrive. However, it is also important to note that vitamin D deficiency poses a far greater risk to the vast majority of individuals than vitamin D toxicity and that vitamin D toxicity from food intake is extremely unlikely. Less than one-third of all persons in the U.S. meet the Dietary Reference Intake level for vitamin D, and are far from consuming anything close to potentially toxic levels.
In 2010, the National Academy of Sciences set Tolerable Upper Intake Levels (ULs) for vitamin D as follows:
• infants, 0-6 months: 25 micrograms (1,000 IU) per day
• infants, 6-12 months: 38 micrograms (1,500 IU) per day
• children, 1-3 years: 63 micrograms (2,500 IU) per day
• children, 4-8 year: 75 micrograms (3,000 IU)per day
• children and adolescents, 9-18 years: 100 micrograms (4,000 IU) per day
• adults, 19 years and older: 100 micrograms (4,000 IU) per day
• pregnant and lactating women, 100 micrograms (4,000 IU) per day.
While these toxicity limits are based on credible data, they do not attempt to address the issue that is posed by higher vitamin D intake amounts potentially needed to offset chronic deficiency of this vitamin. Clinical research has clearly shown that vitamin D supplementation in the range of 1,000-2,000 IU per day is unable to restore optimal vitamin D levels in many individuals with chronic vitamin D deficiency. In many cases, individuals with chronic vitamin D deficiency will need to exceed the vitamin D Upper Limits established by the National Academy of Sciences in order to bring the levels of hydroxyvitamin D in their blood up to optimal levels. Remedy of chronic vitamin D deficiency will also typically require supplementation of vitamin D since everyday food intake is typically unable to provide deficiency-offsetting amounts of this vitamin. Steps to remedy chronic vitamin D deficiency should always be taken in consultation with a licensed healthcare provider who is able guide and monitor changes in blood levels of vitamin D.
Individuals with primary hyperparathyroidism (overactivity of the parathyroid gland not caused by vitamin D deficiency) are at increased risk for vitamin D toxicity and should not take supplemental vitamin D without consulting a physician.
Impact of Cooking, Storage and Processing
How do cooking, storage, or processing affect vitamin D?
Since cow's milk-containing foods are an important source of vitamin D in the United States, and since most dairy products are not only fortified with vitamin D but also pasteurized prior to retail sale, there is good research data on the stability of vitamin D under different heating and storage conditions. Researchers have found virtually no loss of vitamin D following pasteurization of processed cheese under normal commercial conditions. They have also found a vitamin D loss of about 25-30% when cheese is exposed to an oven temperature of 450°F (232°C) for approximately 5 minutes. Since foods like frozen cheese pizzas are often cooked in the oven at temperatures between 400-450°F (204-232°C) for approximately 20 minutes, this research tells us that we can expect at least one-fourth of the vitamin D to be lost during the pizza re-heating process. This percentage of vitamin loss is still relatively low, however, in comparison to similar heating of other foods and loss of other vitamins (especially less heat-stable vitamins, like vitamin C).
Storage of cheese over a 9-month period at temperatures ranging from 39-84°F (4-29°C) have shown virtually no loss of vitamin D, also underscoring the relative stability of this vitamin.
Factors that Affect Function
What factors might contribute to a deficiency of vitamin D?
Insufficient sun exposure
By far the most important D-deficiency contributing factor faced worldwide is insufficient exposure to sunlight. More specifically, it is ultraviolet B sunlight in the range of 290-300nm that is needed to convert 7-dehydrocholesterol found in our skin cells into cholecalciferol (the preliminary form of vitamin D3).
Although the task of "getting enough sunlight" may seem like a fairly straightforward one, the relationship between our vitamin D status and our time in the sun is not nearly as simple as many people might think. First, there is the fluctuating nature of UVB light. UVB light-the kind needed for skin synthesis of vitamin D-is not always present with the same intensity just because there is visible sunlight. The intensity of UVB light varies dramatically with geographical location (latitude), time of year, time of day, degree of cloud cover, and other factors. In other words, there are times when your eyes might leave you thinking that you are getting good intensity UVB light and synthesizing optimal amounts of vitamin D in your skin cells, but you actually are not. In addition, there is the issue of latitude, angle of sunlight, and time of day. In higher-latitude countries across the globe, UVB light in the range of 290-300nm wavelengths may not be available except for a few hours in the middle of the day. In those countries, being outside on a "bright and sunny day" would not be enough to guarantee adequate skin synthesis of vitamin D. Skin pigmentation also plays an important role in skin synthesis of vitamin D. Darker skin pigmentation means less vitamin D synthesis per minute exposure to UVB light. (In the United States, for example, it is estimated that African American adults are 2-3 times more likely to have vitamin D insufficiency than Caucasian adults.) As all of these examples indicate, even when common sense tells you that you are getting good sun exposure and must be synthesizing plenty of vitamin D, you might not be, for a variety of reasons.
Some lifestyles and occupations provide unusual amounts of sun exposure. Individuals who work outdoors throughout the day in warmer climates have a great chance of getting good exposure to UVB light and synthesizing adequate amounts of vitamin D. Under optimal circumstances, our skin can synthesize between 10,000-20,000 IU of vitamin D (cholecalciferol) in 30 minutes. Yes, all of the practical factors still have to line up correctly (like angle of the sun, time of day, degree of cloud cover, etc.), but when people spend generous amounts of times outdoors in the sun on a regular basis, their chances of adequate vitamin D synthesis are greatly increased. At the other end of the spectrum, if an individual typically wears clothing that blocks a lot of the skin from exposure to sunlight, or typically uses sunblock, or works in a job that keeps him or her indoors throughout the day, chances of adequate vitamin D synthesis are greatly decreased.
Based on all of the factors listed above, we believe that the majority of U.S. adults are unlikely to be getting enough exposure to UVB sunlight in the 290-300nm wavelength required to allow for optimal skin synthesis of vitamin D. In addition, we believe that many people may assume that they get plenty of sunlight and have plenty of vitamin D synthesis in their skin cells when they actually do not. Except in cases where lifestyle and/or occupation makes exposure to sunlight an issue that is free from debate, we encourage individuals to avoid assumptions about the adequacy of their sunlight exposure and to treat their vitamin D needs as a matter for special focus and potential reason for follow-up healthcare consultation.
The importance of sunlight for vitamin D health has been the subject of longstanding research. The term "vitamin D winter" was coined several decades ago to summarize the impact of this lower-sunlight season on potential compromise in vitamin D status. More recently, the idea of a "vitamin D winter" has been revisited to include a look at diseases which are related to vitamin D deficiency. Researchers are discovering that many autoimmune conditions have greater severity in winter versus summer, and they are investigating possible links with vitamin D deficiency under these circumstances. Similarly, there has been a strong research trend for studying the occurrence of vitamin D-related diseases at different latitudes on the earth. Over the past 10 years, researchers have found "South to North" trends for increased occurrence of multiple sclerosis, Crohn's disease, and type 1 diabetes. In other words, there is lesser incidence of these vitamin D deficiency-related diseases at lower latitudes (closer to the equator) where UVB light exposure is presumably higher, and greater incidence of these vitamin D deficiency-related diseases at higher latitudes (farther from the equator).
Breastfeeding and pregnancy
Since nursing mothers must help supply their infants with vitamin D, breastfeeding can pose a challenge both to mothers and infants in terms of vitamin D status. The American Academy of Pediatrics (AAP) and the Canadian Pediatric Society (CPS) have both recommended vitamin D supplementation for both mothers and infants for this reason. (See the section on "Public Health Recommendations" for more information.)
Insufficient dietary fat or inability to absorb dietary fat
Since vitamin D is a fat-soluble vitamin, a diet that is extremely low in fat and/or the presence of certain medical conditions that cause a reduction in the ability to absorb dietary fat may cause vitamin D deficiency. These medical conditions include pancreatic enzyme deficiency, Crohn's disease, celiac sprue, cystic fibrosis, surgical removal of part or all of the stomach, gall bladder disease, and liver disease. Symptoms of fat malabsorption include diarrhea and greasy stools.
Health conditions that involve the parathyroid gland or kidney
Under certain circumstances, the conversion of inactive forms of vitamin D to calcitriol is impaired. For example, diseases that affect the parathyroid gland, liver, and/or kidney impair the synthesis of the active form of vitamin D.
The production of vitamin D precursors in the skin decreases with age. Additionally, with age the kidneys and many other organ systems and cell types are less able to convert vitamin D to its active hormone form.
Genetic susceptibility
Some individual's genetic inheritance includes genetic polymorphisms that result in the production of vitamin D receptors (VDR) that don't work very well. To help compensate for such VDR defects, these individuals need more vitamin D than would normally be necessary.
Drug-Nutrient Interactions
What medications affect vitamin D?
The following medications impact the absorption, utilization, and/or activation of vitamin D:
• Anticonvulsant medications, including Dilantin, are used to control seizure activity in people with epilepsy and brain cancer, and those who have suffered head trauma through injury or stroke. These medications decrease the activity of vitamin D.
• Bile acid sequestrants (Cholestyramine, Colestipol) are a class of drugs used to lower cholesterol levels. These drugs may reduce the intestinal absorption of the fat-soluble nutrients, including vitamins A, D, E, and K.
• Cimetidine (Tagamet and Tagamet HB) prevents the release of hydrochloric acid into the stomach and is used to treat the symptoms associated with stomach and duodenal ulcers and acid reflux. This drug may reduce vitamin D activation by the liver.
• Hormone replacement therapy may increase blood levels of vitamin D.
• The corticosteroids are a family of anti-inflammatory drugs, including hydrocortisone and prednisone, that are commonly used in the treatment of autoimmune and inflammatory diseases, such as asthma, rheumatoid arthritis, and ulcerative colitis. These drugs reduce the activation of vitamin D.
• Heparin, an anticoagulant prescription medication used to prevent blood clots after surgery, may interfere with vitamin D activation.
Vitamin D impacts the following medications:
• Vitamin D may interfere with the effectiveness of calcium channel-blockers, a class of drugs used to treat chest pain, irregular heart beat, and high blood pressure.
• Taking supplemental vitamin D and calcium along with thiazide diurectics can cause blood levels of calcium to increase above normal levels.
Nutrient Interactions
How do other nutrients interact with vitamin D?
Vitamin D plays a role in maintaining normal blood levels of calcium. As a result, vitamin D impacts the absorption and storage of calcium. Vitamin D also stimulates the absorption of phosphorus.
Vitamin D helps to regulate the production of certain calcium-binding proteins that function in the bones and kidneys. Because these binding proteins are also dependent on vitamin K, interrelationships between vitamin D and vitamin K have become the subject of active research investigation.
Health Conditions
What health conditions require special emphasis on vitamin D?
Vitamin D may play a role in the prevention and/or treatment of the following health conditions:
• Asthma (severe childhood)
• Atherosclerosis
• Bladder cancer
• Breast cancer
• Chronic fatigue syndrome
• Colon cancer
• Congestive heart failure
• Crohn's disease
• Ovarian cancer
• Depression
• Epilepsy
• Fibromyalgia
• Heart attack
• Hypertension
• Inflammatory bowel disease
• Insulin resistance
• Kidney disease
• Leprosy
• Liver disease
• Metabolic syndrome
• Multiple sclerosis
• Myofascial pain syndrome
• Osteoporosis
• Periodontal disease
• Preeclampsia
• Psoriasis
• Rectal cancer
• Rheumatoid arthritis
• Senile dementia
• Stroke
• Tinnitus
• Tuberculosis
• Type 2 diabetes
• Ulcerative colitis
Form in Dietary Supplements
What forms of vitamin D are found in dietary supplements?
The two forms of vitamin D used in dietary supplements are ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Ergocalciferol is sometimes considered a vegetarian source of vitamin D since it can be plant-derived. However, yeast is also commonly used as a source of D2 as are other fungi (like ergot). Some individuals would regard these microbially produced forms of D2 as animal-based, while others would not. There's also one "synthetic versus natural" issue involved with supplemental vitamin D. When the plant building block for vitamin D2 (ergosterol) is used to produce vitamin D2 (ergocalciferol), it's usually irradiated in a chemistry lab in order to produce this D2 form.
Cholecalciferol, the D3 form of the vitamin, can be obtained from animal or microbial sources. One practice for generating the D3 found in supplements involves sheep's wool. Sheep (and many other animals) have sebaceous glands in their skin that secrete a complex variety of substances, including cholesterol (in the form of 7-dehydrocholesterol). The secretions from the sebaceous glands naturally find their way into the animal's fur. A supplement manufacturer wanting to produce vitamin D3 supplements can remove the secretions from the fur (in this case sheep's wool), process and purify the 7-dehydrocholesterol, expose it to UVB (ultra-violet B) light, and thereby convert it into cholecalciferol.
From our perspective, very few individuals will benefit from supplementation with vitamin D2 versus vitamin D3. Although we might not go as far as the American Journal of Clinical Nutrition-which argued in 2006 that D2 should no longer be considered as a nutrient "suitable for fortification or supplementation" given the strong hormonal advantages of D3-we believe that the vast majority of unwanted consequences from vitamin D deficiency stem from deficiency of the hormonally active, dihydroxyvitamin D form of this nutrient. For this reason, we believe that D3 is the delivery form of choice when supplementing with vitamin D.
Within the category of D3 supplements, the most common form for vitamin D3 delivery is gel caps containing D3 in liquid form (and often dispersed in flax oil or olive oil). D3 is also available in powdered form in D3 capsules, in powdered form involving pressed tablets, and in unencapsulated liquid form (D3 drops). We have not seen non-proprietary, peer-reviewed studies comparing these various delivery forms of vitamin D3. In general, we have seen more problems with absorption of powdered vitamins from tablets versus capsules due to problems in digestive track breakdown of pressed tablets. For this reason, we favor use of vitamin D3 capsules over vitamin D3 tablets when selecting from dry powder versions of vitamin D3. However, with respect to encapsulated powders versus encapsulated liquids (or liquid drops in unencapsulated form), we believe that your most important consideration is reliability of the manufacturer and quality control/ assurance provided by that manufacturer.
Vitamin D is often measured in International Units (IU) or micrograms. One microgram of cholecalciferol is equal to 40 IU of vitamin D.
Food Sources
What foods provide vitamin D?
Excellent sources of vitamin D include salmon while very good sources include sardines, shrimp and vitamin-D fortified milk.
Good food sources of vitamin D include cod and eggs.

Introduction to Nutrient Rating System Chart
In order to better help you identify foods that feature a high concentration of nutrients for the calories they contain, we created a Food Rating System. This system allows us to highlight the foods that are especially rich in particular nutrients. The following chart shows the World's Healthiest Foods that are either an excellent, very good, or good source of vitamin D. Next to each food name, you'll find the serving size we used to calculate the food's nutrient composition, the calories contained in the serving, the amount of vitamin D contained in one serving size of the food, the percent Daily Value (DV%) that this amount represents, the nutrient density that we calculated for this food and nutrient, and the rating we established in our rating system. For most of our nutrient ratings, we adopted the government standards for food labeling that are found in the U.S. Food and Drug Administration's "Reference Values for Nutrition Labeling."Read more background information and details of our rating system.
Food Serving
Size Cals Amount
(%) Nutrient
Density World's
Foods Rating
Salmon, chinook, baked/broiled World's Healthiest Foods ranked as quality sources of:
vitamin D 261.9 411.00 102.8 7.1 excellent
Shrimp, steamed/boiled 4 oz-wt 112.3 162.39 40.6 6.5 very good
Sardines 3.25 oz can 191.4 250.24 62.6 5.9 very good
Cow's milk, 2% 1 cup 121.2 97.60 24.4 3.6 very good
Shiitake Mushrooms, raw 1 cup 49.3 29.00 7.2 2.6 good
Cod, baked/broiled 4 oz-wt 119.1 63.50 15.9 2.4 good
Egg, whole, boiled 1 each 68.2 22.88 5.7 1.5 good
World's Healthiest
Foods Rating Rule
excellent DV>=75% OR Density>=7.6 AND DV>=10%
very good DV>=50% OR Density>=3.4 AND DV>=5%
good DV>=25% OR Density>=1.5 AND DV>=2.5%
Public Health Recommendations
What are current public health recommendations for vitamin D?
In 2010, the Institute of Medicine at the National Academy of Sciences established revised Dietary Reference Intake (DRI) recommendations for vitamin D based on new research in this area. The following Adequate Intake (AI) levels for vitamin D were established in 2010 for infants:
• Infants 0-6 months: 10 micrograms (400 IU) per day
• Infants 6-12 months: 10 micrograms (400 IU) per day
The following Recommended Dietary Allowances (RDAs) were established for children, teenagers, and adults:
• Children 1-13 years: 15 micrograms (600 IU)
• Teenagers 14-18 years: 15 micrograms (600 IU)
• Adults 19-70 years: 15 micrograms (600 IU)
• Adults above 70 years: 20 micrograms (800 IU)
• Pregnant and lactating women: 15 micrograms (600 IU)
While we were glad to see the the National Academy of Sciences making revised public health recommendations in 2010 for increased intake of vitamin D, we do not believe that all health and lifestyle factors evaluated in research studies on vitamin D research were fully addressed in the revised recommendations. Over the past 15 years, more than 10,000 studies on vitamin D have been published in research journals. These studies have convincingly shown that: (1) we need much more vitamin D than we previously thought; (2) lifestyle trends have significantly reduced our exposure to sunlight; (3) prevalence of vitamin D deficiency is far greater than previously estimated, and (4) more vitamin D is required to remedy deficiency than can be obtained in a standard diet.
In studies on infants and toddlers, between 40-65% have been shown to be vitamin D insufficient with blood levels of hydroxyvitamin D below 30 ng/mL in several countries throughout the world, and in studies in the U.S., including a recent study in Massachusetts. Insufficiency has also been shown in U.S. teens, at a level of approximately 60% (once again, using the standard of 30 ng/mL or less for hydroxyvitamin D in the blood). Similar percentages have been determined for insufficiency in older individuals. Among young adults and middle-aged individuals, the prevalence of vitamin D insufficiency has been estimated to range from a minimum of about 50% to a maximum of perhaps 75% or greater. It's important to note that "insufficiency" is a looser standard than "deficiency" and generally refers to a blood level of hydroxyvitamin D below 30 ng/mL rather than a blood level below 20 ng/mL. While this lower blood level has traditionally been used to diagnose vitamin D deficiency, it is no longer appears relevant for determining the amount of vitamin D needed for optimal hormonal regulation of many body processes by vitamin D. Realization of this greater level of vitamin D needed in our bloodstream is one result of the revolution that has taken place in our understanding of vitamin D over the past 15 years.
Just as we now realize that more vitamin D is needed in our blood, we also realize that it takes higher levels of vitamin D intake to bring blood levels up to a healthy standard. For example, in situations where sunlight is limited, we know that at least 1,000 IU of vitamin D are needed to increase blood levels of vitamin D from 20ng/mL to 30 ng/mL or higher. For prevention of bone loss in persons at risk for osteoporosis, we know that a minimum of 700 IU is required and that no prevention results have been demonstrated at levels of intake below 400 IU. Under circumstances involving autoimmune problems like rheumatoid arthritis or multiple sclerosis, experimental supplemental doses of vitamin D range not in 100s of IUs, but in 1,000s or 10,000s of IUs.
Since personal health history and personal exposure to sunlight play such an important role in determining each individual's vitamin D needs, it is very difficult to make a firm and fast public health recommendation for vitamin D that is guaranteed to meet the optimal requirements of each individual. For this reason, we like the basic two-fold approach taken by the Harvard School of Public Health, which can be found here.
On a first level, even though there is not yet conclusive research evidence available, daily supplementation with vitamin D in the range of 1,000 - 2,000 IU may provide important health benefits for many individuals. If your routine diet does not include plentiful amounts of vitamin D-rich foods, you may want to target the higher side of this range (while also increasing your intake of D-rich foods). If your diet already includes ample amounts of foods that are rich in vitamin D, you may want to target the lower side of this range when deciding on a supplementation level.
On a second level, if you are an individual who might be at higher risk for vitamin D deficiency (for example, because you have very limited exposure to sunlight), we encourage you to consult with your healthcare provider, schedule a blood test for vitamin D, and determine (in consultation with your healthcare provider) an appropriate level of vitamin D supplementation. Depending on the results of your blood test, you may very possibly need a greater level of vitamin D supplementation that is greater than the 4,000 IU Tolerable Upper Limit set by the National Academy of Sciences. Blood testing can definitely help to remove the "guesswork" factor here. You'll be able to determine the actual level of hydroxyvitamin D in your blood and see the actual amount of increase following supplementation at whatever level you and your healthcare provider determine to be appropriate. When supplementing with vitamin D, we support the position of the Harvard School of Public Health (and many other public health organizations) in recommending supplementation with vitamin D3 (cholecalciferol) rather than D2 (ergocalciferol)."
What is our bottom line with respect to food versus supplemental intake of vitamin D? Based on studies showing the impact of supplemental D3 intake on blood levels of hydroxyvitamin D, we believe that the vast majority of U.S. adults and children will not be able to achieve optimal vitamin D status from food intake alone. Exactly how much D3 supplementation each individual may need-and the form of this supplementation-should be determined with the help of a healthcare provider. That healthcare provider can not only evaluate personal health history factors but can also monitor the impact of vitamin D supplementation of blood levels of this vitamin.
Despite this likely need for supplemental vitamin D, we also believe that it is important to maximize food intake of vitamin D. Intake of foods rich in vitamin D still remains a natural lifestyle option for obtaining this vitamin, even if this option is not sufficient all by itself to offset lack of sunlight exposure and other factors that have combined to compromise our vitamin D status.
With respect to women who are breastfeeding, the American Academy of Pediatrics (AAP) and the Canadian Pediatric Society (CPS) have both recommended vitamin D supplementation for both mothers and infants. The APP has recommended 200 IU of vitamin D per day for all infants 2 months and older, and 400 IU for newborns during the first days of life. These APP recommendations are generally consistent with the revised 2010 Adequate Intake (AI) levels for vitamin D set by the National Academy of Sciences (NAS). The NAS recommends 400 IU of vitamin D for newborns and infants up to 12 months of age. It is worth pointing out that direct vitamin D supplementation for the infant is separate and apart from any vitamin D supplementation that the mother herself might need. Given the special challenges posed by breastfeeding for vitamin D sufficiency, the guidance of a healthcare provider is highly recommended to determine the steps needed for optimal vitamin D intake in this situation. Like breastfeeding, pregnancy poses a special challenge for vitamin D sufficiency. Once again, given the widespread nature of vitamin D deficiency, the DRIs may be unable to provide optimal guidelines for many pregnant women. For this reason, pregnant women are encouraged to work out a vitamin D sufficiency plan with their healthcare provider.
The National Academy of Sciences set Tolerable Upper Intake Levels (ULs) for vitamin D as follows:
• infants, 0-6 months: 25 micrograms (1,000 IU) per day
• infants, 6-12 months: 38 micrograms (1,500 IU) per day
• children, 1-3 years: 63 micrograms (2,500 IU) per day
• children, 4-8 year: 75 micrograms (3,000 IU)per day
• children and adolescents, 9-18 years: 100 micrograms (4,000 IU) per day
• adults, 19 years and older: 100 micrograms (4,000 IU) per day
• pregnant and lactating women, 100 micrograms (4,000 IU) per day.

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