MoonDragon's Health & Wellness
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VITAMIN D DESCRIPTION
THE SUNSHINE VITAMIN
Vitamin D, a fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement. It is required for the absorption and utilization of calcium and phosphorus by the intestinal tract and maintaining adequate serum calcium and phosphate concentrations to enable normal mineralization of bone and prevent hypocalcemic tetany. It is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts. Without sufficient Vitamin D, bones can become thin, brittle, or misshapen. Vitamin D sufficiency prevents rickets in children and osteomalacia in adults.
It is necessary for growth and development of bones and teeth in children. Together with calcium, Vitamin D also helps protect older adults from osteoporosis. It protects against muscle weakness and is involved in regulation of the heartbeat. It is also important in the prevention and treatment of osteoporosis and hypocalcemia, enhances immunity, and is necessary for thyroid function and normal blood clotting.
Vitamin D has other roles in human health, including modulation of neuromuscular and immune function and reduction of inflammation. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D. Many laboratory-cultured human cells have vitamin D receptors and some convert 25(OH)D to 1,25(OH)2D. It remains to be determined whether cells with vitamin D receptors in the intact human carry out this conversion.
The form of Vitamin D that we get from food or supplements is not fully active. It requires conversion by the liver, and then by the kidneys, before it becomes fully active. This is why people with liver or kidney disorders are at a higher risk for osteoporosis. When the skin is exposed to the sun's ultraviolet rays, triggering vitamin D synthesis, a cholesterol compound in the skin is transformed into a precursor of vitamin D.
Vitamin D obtained from sun exposure, food, and supplements is biologically inert and must undergo two hydroxylations in the body for activation. The first occurs in the liver and converts vitamin D to 25-hydroxyvitamin D [25(OH)D], also known as calcidiol. The second occurs primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as calcitriol. Exposing the face and arms to the sun for 15 minutes 3 times a week is an effective way to ensure adequate amounts of vitamin D in the body.
Severe deficiency of Vitamin D can cause rickets in children and osteomalacia, a similar disorder, in adults. Lesser degrees of deficiency may be characterized by loss of appetite, a burning sensation in the mouth and throat, diarrhea, insomnia, visual problems, and weight loss.
MoonDragon's Health & Wellness: Rickets & Osteomalacia (Vitamin D Deficiency)
Serum concentration of 25(OH)D is the best indicator of Vitamin D status. It reflects vitamin D produced cutaneously and that obtained from food and supplements and has a fairly long circulating half-life of 15 days. However, serum 25(OH)D levels do not indicate the amount of vitamin D stored in other body tissues. Circulating,25(OH)2D is generally not a good indicator of vitamin D status because it has a short half-life of 15 hours and serum concentrations are closely regulated by parathyroid hormone, calcium, and phosphate. Levels of 1,25(OH)2D do not typically decrease until vitamin D deficiency is severe.
There is considerable discussion of the serum concentrations of 25(OH)D associated with deficiency (e.g., rickets), adequacy for bone health, and optimal overall health (Table 1). A concentration of less than 20 nanograms per milliliter (ng/mL) (or less than 50 nanomoles per liter [nmol/L]) is generally considered inadequate.
Table 1: Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health* ng/mL** nmol/L** Health Status
Less than 11
Less than 27.5
Associated with vitamin D deficiency and rickets in infants and young children.
Less than 10 to 15
Less than 25 to 37.5
Generally considered inadequate for bone and overall health in healthy individuals.
More than or equal to 30
More than or equal to 75
Proposed by some as desirable for overall health and disease prevention, although a recent government-sponsored expert panel concluded that insufficient data are available to support these higher levels.
Consistently greater than 200
Consistently greater than 500
Considered potentially toxic, leading to hypercalcemia and hyperphosphatemia, although human data are limited. In an animal model, concentrations less than or equal to 400 ng/mL (less than or equal to 1,000 nmol/L) demonstrated no toxicity.
* Serum concentrations of 25(OH)D are reported in both nanograms per milliliter (ng/mL) and nanomoles per liter (nmol/L).
** 1 ng/mL = 2.5 nmol/L.
Intake reference values for vitamin D and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of The National Academies (formerly National Academy of Sciences). DRI is the general term for a set of reference values used to plan and assess nutrient intakes of healthy people. These values, which vary by age and gender, include:
- Recommended Dietary Allowance (RDA): average daily level of intake sufficient to meet the nutrient requirements of nearly all (97-98 percent) healthy people.
- Adequate Intake (AI): established when evidence is insufficient to develop an RDA and is set at a level assumed to ensure nutritional adequacy.
- Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects.
The FNB established an AI for vitamin D that represents a daily intake that is sufficient to maintain bone health and normal calcium metabolism in healthy people. AIs for vitamin D are listed in both micrograms (mcg) and International Units (IUs); the biological activity of 1 mcg is equal to 40 IU (Table 2). The AIs for vitamin D are based on the assumption that the vitamin is not synthesized by exposure to sunlight.
Table 2: Adequate Intakes (AIs) for Vitamin D Age Children Men Women Pregnancy Lactation Birth to 13 Years 5 mcg
14 to 18 Years 5 mcg
19 to 50 Years 5 mcg
51 to 70 Years 10 mcg
70-Plus Years 15 mcg
In 2008, the American Academy of Pediatrics (AAP) issued recommended intakes for vitamin D that exceed those of FNB. The AAP recommendations are based on evidence from more recent clinical trials and the history of safe use of 400 IU/day of vitamin D in pediatric and adolescent populations. AAP recommends that exclusively and partially breastfed infants receive supplements of 400 IU/day of vitamin D shortly after birth and continue to receive these supplements until they are weaned and consume greater than or equal to 1,000 mL/day of vitamin D-fortified formula or whole milk. (All formulas sold in the United States provide greater than or equal to 400 IU vitamin D-3 per liter, and the majority of vitamin D-only and multivitamin liquid supplements provide 400 IU per serving.) Similarly, all non-breastfed infants ingesting less than 1,000 mL/day of vitamin D-fortified formula or milk should receive a vitamin D supplement of 400 IU/day. AAP also recommends that older children and adolescents who do not obtain 400 IU/day through vitamin D-fortified milk and foods should take a 400 IU vitamin D supplement daily.
VITAMIN D INTAKES & STATUS
In 1988 to 1994, as part of the third National Health and Nutrition Examination Survey (NHANES III), the frequency of use of some vitamin D-containing foods and supplements was examined in 1,546 non-Hispanic African American women and 1,426 non-Hispanic white women of reproductive age (15 to 49 years). In both groups, 25(OH)D levels were higher in the fall (after a summer of sun exposure) and when milk or fortified cereals were consumed more than three times per week. The prevalence of serum concentrations of 25(OH)D equal to or less than 15 ng/mL (equal to or less than 37.5 nmol/L) was 10 times greater for the African American women (42.2 percent) than for the white women (4.2 percent).
The 2000-2004 NHANES provided the most recent data on the vitamin D nutritional status of the U.S. population. Generally, younger people had higher serum 25(OH)D levels than older people; males had higher levels than females; and non-Hispanic whites had higher levels than Mexican Americans, who in turn had higher levels than non-Hispanic blacks. Depending on the population group, 1 to 9 percent had serum 25(OH)D levels less than 11 ng/mL (less than 27.5 nmol/L), 8 to 36 percent had levels less than 20 ng/mL (less than 50 nmol/L), and the majority (50 to 78 percent) had levels less than 30 ng/mL (less than 75 nmol/L). Among adults in the United Kingdom, nationally representative data collected between 1992 and 2001 show that 5 to 20 percent in most age groups on average had serum 25(OH)D levels less than 10 ng/ml (less than 25 nmol/L); the prevalence of deficiency was greater (range 20 to 40 percent) for older people greater than 65 years of age in residential care homes and among women greater than 85 years. Among all adults, 20 to 60 percent had levels equal to or less than 20 ng/ml (equal to or less than 50 nmol/L) and 90 percent had levels equal to or less than 32 ng/ml (equal to or less than 80 nmol/L).
VITAMIN D DEFICIENCY
Nutrient deficiencies are usually the result of dietary inadequacy, impaired absorption and use, increased requirement, or increased excretion. A vitamin D deficiency can occur when usual intake is lower than recommended levels over time, exposure to sunlight is limited, the kidneys cannot convert vitamin D to its active form, or absorption of vitamin D from the digestive tract is inadequate. Vitamin D-deficient diets are associated with milk allergy, lactose intolerance, and strict vegetarianism.
Rickets and osteomalacia are the classical vitamin D deficiency diseases. In children, vitamin D deficiency causes rickets, a disease characterized by a failure of bone tissue to properly mineralize, resulting in soft bones and skeletal deformities. Rickets was first described in the mid-17th century by British researchers. In the late 19th and early 20th centuries, German health care providers noted that consuming 1 to 3 teaspoons of cod liver oil per day could reverse rickets. In the 1920s and prior to identification of the structure of vitamin D and its metabolites, biochemist Harry Steenbock patented a process to impart antirachitic activity to foods. The process involved the addition of what turned out to be precursor forms of vitamin D followed by exposure to UV radiation. The fortification of milk with vitamin D has made rickets a rare disease in the United States. However, rickets is still reported periodically, particularly among African American infants and children. A 2003 report from Memphis, for example, described 21 cases of rickets among infants, 20 of whom were African American.
Prolonged exclusive breastfeeding without the AAP-recommended vitamin D supplementation is a significant cause of rickets, particularly in dark-skinned infants breastfed by mothers who are not vitamin D replete. Additional causes of rickets include extensive use of sunscreens and placement of children in daycare programs, where they often have less outdoor activity and sun exposure. Rickets is also more prevalent among immigrants from Asia, Africa, and the Middle East, possibly because of genetic differences in vitamin D metabolism and behavioral differences that lead to less sun exposure.
In adults, vitamin D deficiency can lead to osteomalacia, resulting in weak muscles and bones. Symptoms of bone pain and muscle weakness can indicate inadequate vitamin D levels, but such symptoms can be subtle and go undetected in the initial stages.
MoonDragon's Health & Wellness: Rickets
GROUPS AT RISK OF VITAMIN D INADEQUACY
Obtaining sufficient Vitamin D from natural food sources alone can be difficult. For many people, consuming Vitamin D-fortified foods and being exposed to sunlight are essential for maintaining a healthy Vitamin D status. In some groups, dietary supplements might be required to meet the daily need for vitamin D.
- Breastfed Infants: Vitamin D requirements cannot be met by human milk alone, which provides only about 25 IU/L. A recent review of reports of nutritional rickets found that a majority of cases occurred among young, breastfed African Americans. The sun is a potential source of Vitamin D, but AAP advises keeping infants out of direct sunlight and having them wear protective clothing and sunscreen. As noted earlier, AAP recommends that exclusively and partially breastfed infants be supplemented with 400 IU of Vitamin D per day.
- Older Adults: Americans aged 50 and older are at increased risk of developing Vitamin D insufficiency. As people age, skin cannot synthesize vitamin D as efficiently and the kidney is less able to convert Vitamin D to its active hormone form. As many as half of older adults in the United States with hip fractures could have serum 25(OH)D levels less than 12 ng/mL (less than 30 nmol/L).
- People With Limited Sun Exposure: Homebound individuals, people living in northern latitudes (such as New England and Alaska), women who wear long robes and head coverings for religious reasons, and people with occupations that prevent sun exposure are unlikely to obtain adequate Vitamin D from sunlight.
- People With Dark Skin: Greater amounts of the pigment melanin result in darker skin and reduce the skin's ability to produce Vitamin D from exposure to sunlight. Some studies suggest that older adults, especially women, with darker skin are at high risk of developing Vitamin D insufficiency. However, one group with dark skin, African Americans, generally has lower levels of 25(OH)D yet develops fewer osteoporotic fractures than Caucasians (see section below on osteoporosis).
- People With Fat Malabsorption: As a fat-soluble vitamin, Vitamin D requires some dietary fat in the gut for absorption. Individuals who have a reduced ability to absorb dietary fat might require Vitamin D supplements. Fat malabsorption is associated with a variety of medical conditions including pancreatic enzyme deficiency, Crohn's disease, cystic fibrosis, celiac disease, surgical removal of part of the stomach or intestines, and some forms of liver disease.
MoonDragon's Health & Wellness: Celiac Disease
MoonDragon's Health & Wellness: Cystic Fibrosis
MoonDragon's Health & Wellness: Crohn's Disease
MoonDragon's Health & Wellness: Pancreatitis
MoonDragon's Health & Wellness: Malabsorption Disorders
- People Who Are Obese: Individuals with a body mass index (BMI) equal to or greater than 30 typically have a low plasma concentration of 25(OH)D. This level decreases as obesity and body fat increase. Obesity does not affect skin's capacity to synthesize Vitamin D, but greater amounts of subcutaneous fat sequester more of the vitamin and alter its release into the circulation. Even with orally administered Vitamin D, BMI is inversely correlated with peak serum concentrations, probably because some vitamin D is sequestered in the larger pools of body fat.
MoonDragon's Womens Health Information: Obesity
VITAMIN D & HEALTH
Optimal serum concentrations of 25(OH)D for bone and general health throughout life have not been established and are likely to vary at each stage of life, depending on the physiological measures selected. The three-fold range of cut points that have been proposed by various experts, from 16 to 48 ng/mL (40 to 120 nmol/L), reflect differences in the functional endpoints chosen (e.g., serum concentrations of parathyroid hormone or bone fractures), as well as differences in the analytical methods used. The numerous assays for 25(OH)D provide differing results. One reason for these issues of precision and variability is that no standard reference preparations or calibrating materials are available commercially to help reduce the variability of results between methods and laboratories. Efforts are underway to standardize the quantification of 25(OH)D to measure Vitamin D status.
In March 2007, a group of Vitamin D and nutrition researchers published a controversial and provocative editorial contending that the desirable concentration of 25(OH)D is equal to or greater than 30 ng/mL (equal to or greater than 75 nmol/L). They noted that supplemental intakes of 400 IU/day of Vitamin D increase 25(OH)D concentrations by only 2.8-4.8 ng/mL (7-12 nmol/L) and that daily intakes of approximately 1,700 IU are needed to raise these concentrations from 20 to 32 ng/mL (50 to 80 nmol/L).
More than 25 million adults in the United States have or are at risk of developing osteoporosis, a disease characterized by fragile bones that significantly increases the risk of bone fractures. Osteoporosis is most often associated with inadequate calcium intakes (generally less than 1,000 to 1,200 mg/day), but insufficient Vitamin D contributes to osteoporosis by reducing calcium absorption. Although rickets and osteomalacia are extreme examples of the effects of Vitamin D deficiency, osteoporosis is an example of a long-term effect of calcium and Vitamin D insufficiency. Adequate storage levels of vitamin D maintain bone strength and might help prevent osteoporosis in older adults, non-ambulatory individuals who have difficulty exercising, post-menopausal women, and individuals on chronic steroid therapy.
MoonDragon's Womens Health Information: Osteoporosis
Normal bone is constantly being remodeled. During menopause, the balance between these processes changes, resulting in more bone being resorbed than rebuilt. Hormone therapy with estrogen and progesterone might be able to delay the onset of osteoporosis. However, some medical groups and professional societies recommend that post-menopausal women consider using other agents to slow or stop bone resorption because of the potential adverse health effects of hormone therapy.
MoonDragon's Womens Health Information: Menopause - HRT Therapy
Most supplementation trials of the effects of Vitamin D on bone health also include calcium, so it is not possible to isolate the effects of each nutrient. The authors of a recent evidence-based review of research concluded that supplements of both Vitamin D-3 (at 700 to 800 IU/day) and calcium (500 to 1,200 mg/day) decreased the risk of falls, fractures, and bone loss in elderly individuals aged 62 to 85 years. The decreased risk of fractures occurred primarily in elderly women aged 85 years, on average, and living in a nursing home. Women should consult their health care providers about their needs for Vitamin D (and calcium) as part of an overall plan to prevent or treat osteoporosis.
African Americans have lower levels of 25(OH)D than Caucasians, yet they develop fewer osteoporotic fractures. This suggests that factors other than Vitamin D provide protection. African Americans have an advantage in bone density from early childhood, a function of their more efficient calcium economy, and have a lower risk of fracture even when they have the same bone density as Caucasians. They also have a higher prevalence of obesity, and the resulting higher estrogen levels in obese women might protect them from bone loss. Further reducing the risk of osteoporosis in African Americans are their lower levels of bone-turnover markers, shorter hip-axis length, and superior renal calcium conservation. However, despite this advantage in bone density, osteoporosis is a significant health problem among African Americans as they age.
CANCER & VITAMIN D
Laboratory and animal evidence as well as epidemiologic data suggest that Vitamin D status could affect cancer risk. Strong biological and mechanistic bases indicate that Vitamin D plays a role in the prevention of colon, prostate, and breast cancers. Emerging epidemiologic data suggest that Vitamin D has a protective effect against colon cancer, but the data are not as strong for a protective effect against prostate and breast cancer, and are variable for cancers at other sites. Studies do not consistently show a protective effect or no effect, however. One study of Finnish smokers, for example, found that subjects in the highest quintile of baseline Vitamin D status have a three-fold higher risk of developing pancreatic cancer.
Vitamin D emerged as a protective factor in a prospective, cross-sectional study of 3,121 adults aged equal to or greater than 50 years (96 percent men) who underwent a colonoscopy. The study found that 10 percent had at least one advanced cancerous lesion. Those with the highest vitamin D intakes (greater than 645 IU/day) had a significantly lower risk of these lesions. However, the Women's Health Initiative, in which 36,282 post-menopausal women of various races and ethnicities were randomly assigned to receive 400 IU Vitamin D plus 1,000 mg calcium daily or a placebo, found no significant differences between the groups in the incidence of colorectal cancers over 7 years. More recently, a clinical trial focused on bone health in 1,179 post-menopausal women residing in rural Nebraska found that subjects supplemented daily with Calcium (1,400 to 1,500 mg) and vitamin D-3 (1,100 IU) had a significantly lower incidence of cancer over 4 years compared to women taking a placebo. The small number of cancers reported (50) precludes generalizing about a protective effect from either or both nutrients or for cancers at different sites. This caution is supported by an analysis of 16,618 participants in NHANES III, where total cancer mortality was found to be unrelated to baseline vitamin D status. However, colorectal cancer mortality was inversely related to serum 25(OH)D concentrations; levels greater than 80 nmol/L were associated with a 72 percent risk reduction than those less than 50 nmol/L.
Further research is needed to determine whether Vitamin D inadequacy in particular increases cancer risk, whether greater exposure to the nutrient is protective, and whether some individuals could be at increased risk of cancer because of Vitamin D exposure.
MoonDragon's Health & Wellness: Cancer
ALZHEIMER'S DISEASE & VITAMIN D
Adults with Alzheimer's disease have increased risk of hip fractures. This may be because many Alzheimer's patients are homebound, and frequently sunlight deprived. Alzheimer's disease is more prevalent in older populations, so the fact that the ability of skin to convert Vitamin D to its active form decreases as we age also may contribute to increased risk of hip fractures in this group. One study of women with Alzheimer's disease found that decreased bone mineral density was associated with a low intake of Vitamin D and inadequate sunlight exposure. Health care providers evaluate the need for Vitamin D supplementation as part of an overall treatment plan for adults with Alzheimer's disease.
MoonDragon's Health & Wellness: Alzheimer's Disease
OTHER HEALTH CONDITIONS
A growing body of research suggests that Vitamin D might play some role in the prevention and treatment of type 1 and type 2 diabetes, hypertension, glucose intolerance, multiple sclerosis, and other medical conditions. However, most evidence for these roles comes from in vitro, animal, and epidemiological studies, not the randomized clinical trials considered to be more definitive. Until such trials are conducted, the implications of the available evidence for public health and patient care will be debated.
A recent meta-analysis found that use of Vitamin D supplements was associated with a reduction in overall mortality from any cause by a statistically significant 7 percent. The subjects in these trials were primarily healthy, middle aged or elderly, and at high risk of fractures; they took 300 to 2,000 IU/day of vitamin D supplements.
VITAMIN D USES, HEALTH BENEFITS, & SCIENTIFIC EVIDENCE
Vitamin D is one of several substances called vitamins, which the body needs to grow and develop normally. Vitamin D is famous for its role in helping the body absorb the calcium needed for strong bones and in maintaining an adequate level of calcium in the blood. A deficiency of vitamin D leads to a softening of the bones that in children is called rickets and in adults osteomalacia.
Vitamin D also plays a role in promoting cell growth, in building our immune function, and in reducing inflammation. New research is studying the role these activities may play in the development of several chronic diseases, including heart disease, multiple sclerosis, and diabetes. Checking the patientís vitamin D status is becoming a common laboratory test ordered by health care providers, and levels less than 30 nanomoles per liter (nmol/l) of blood indicates a deficiency.
VITAMIN D - BONE & MUSCLE STRENGTH
Several studies link low vitamin D levels with an increased risk of fractures in older adults, and they suggest that vitamin D supplementation may prevent such fractures - as long as it is taken in a high enough dose. A summary of the evidence comes from a combined analysis of 12 fracture prevention trials that included more than 40,000 elderly people, most of them women. Researchers found that high intakes of vitamin D supplements - of about 800 IU per day - reduced hip and non-spine fractures by 20 percent, while lower intakes (400 IU or less) failed to offer any fracture prevention benefit.
Vitamin D may also help increase muscle strength, which in turn helps to prevent falls, a common problem that leads to substantial disability and death in older people. Once again, vitamin D dose matters: A combined analysis of multiple studies found that taking 700 to 1,000 IU of vitamin D per day lowered the risk of falls by 19 percent, but taking 200 to 600 IU per day did not offer any such protection.
A recent vitamin D trial drew headlines for its unexpected finding that a very high dose of vitamin D increased fracture and fall risk in older women. The trial's vitamin D dose - 500,000 IU taken in a once-a-year pill - was much higher than previously tested in an annual regimen. After up to 5 years of treatment, women in the vitamin D group had a 15 percent higher fall risk and a 26 percent higher fracture risk than women who received the placebo. It is possible that giving the vitamin D in one large dose, rather than in several doses spread throughout the year, led to the increased risk. The study authors note that only one other study - also a high-dose, once-a-year regimen - found vitamin D to increase fracture risk; no other studies have found vitamin D to increase the risk of falls. Furthermore, there is strong evidence that more moderate doses of vitamin D taken daily or weekly protect against fractures and falls - and are safe.
A reasonable conclusion would be to continue taking moderate doses of vitamin D regularly, since these have a strong safety record, but to avoid extremely high single doses. This recent finding does present a challenge to scientists who will work to understand why the extreme single dose appears to have adverse effects.
VITAMIN D & HEART DISEASE
The heart is basically a large muscle, and like skeletal muscle, it has receptors for vitamin D. So perhaps it is no surprise that studies are finding vitamin D deficiency may be linked to heart disease. The Health Professional Follow-Up Study checked the vitamin D blood levels in nearly 50,000 men who were healthy, and then followed them for 10 years. They found that men who were deficient in vitamin D were twice as likely to have a heart attack as men who had adequate levels of vitamin D. Other studies have found that low vitamin D levels were associated with higher risk of heart failure, sudden cardiac death, stroke, overall cardiovascular disease, and cardiovascular death. There is evidence that vitamin D plays a role in controlling blood pressure and preventing artery damage, and this may explain these findings. Still, more research is needed before we can be confident of these benefits.
VITAMIN D & CANCER
Nearly 30 years ago, researchers noticed an intriguing relationship between colon cancer deaths and geographic location: People who lived at higher latitudes, such as in the northern U.S., had higher rates of death from colon cancer than people who live closer to the equator. Many scientific hypotheses about vitamin D and disease stem from studies that have compared solar radiation and disease rates in different countries. These can be a good starting point for other research but do not provide the most definitive information. The sun's UVB rays are weaker at higher latitudes, and in turn, people's vitamin D levels in these high latitude locales tend to be lower. This led to the hypothesis that low vitamin D levels might somehow increase colon cancer risk.
Since then, dozens of studies suggest an association between low vitamin D levels and increased risks of colon and other cancers. The evidence is strongest for colorectal cancer, with most (but not all) observational studies finding that the lower the vitamin D levels, the higher the risk of these diseases. Vitamin D levels may also predict cancer survival, but evidence for this is still limited. Yet finding such associations does not necessarily mean that taking vitamin D supplements will lower cancer risk.
The VITAL trial will look specifically at whether vitamin D supplements lower cancer risk. It will be years, though, before it releases any results. It could also fail to detect a real benefit of vitamin D, for several reasons: If people in the placebo group decide on their own to take vitamin D supplements, that could minimize any differences between the placebo group and the supplement group; the study may not follow participants for a long enough time to show a cancer prevention benefit; or study participants may be starting supplements too late in life to lower their cancer risk. In the meantime, based on the evidence to date, 16 scientists have circulated a call for action on vitamin D and cancer prevention: Given the high rates of vitamin D deficiency in North America, the strong evidence for reduction of osteoporosis and fractures, the potential cancer-fighting benefits of vitamin D, and the low risk of vitamin D supplementation, they recommend widespread vitamin D supplementation of 2000 IU per day.
VITAMIN D & IMMUNE FUNCTION
Vitamin D's role in regulating the immune system has led scientists to explore two parallel research paths: Does vitamin D deficiency contribute to the development of multiple sclerosis, type 1 diabetes, and other so-called "autoimmune" diseases, where the body's immune system attacks its own organs and tissues? And could vitamin D supplements help boost our body's defenses to fight infectious disease, such as tuberculosis and seasonal flu? This is a hot research area and more findings will be emerging.
- Vitamin D & Multiple Sclerosis: Multiple sclerosis (MS) rates are much higher far north (or far south) of the equator than in sunnier climes, and researchers suspect that chronic vitamin D deficiencies may be one reason why. One prospective study to look at this question found that among white men and women, those with the highest vitamin D blood levels had a 62 percent lower risk of developing MS than those with the lowest vitamin D levels. The study did not find this effect among black men and women, most likely because there were fewer black study participants and most of them had low vitamin D levels, making it harder to find any link between vitamin D and MS if one exists.
- Vitamin D & Type 1 Diabetes: Type 1 diabetes is another disease that varies with geography. A child in Finland is about 400 times more likely to develop it than a child in Venezuela. Evidence that vitamin D may play a role in preventing type 1 diabetes comes from a 30-year study that followed more than 10,000 Finnish children from birth: Children who regularly received vitamin D supplements during infancy had a nearly 90 percent lower risk of developing type 1 diabetes than those who did not receive supplements. Other European case-control studies, when analyzed together, also suggest that vitamin D may help protect against type 1 diabetes. No randomized controlled trials have tested this notion, and it is not clear that they would be possible to conduct.
- Vitamin D, the Flu, & the Common Cold: The flu virus wreaks the most havoc in the winter, abating in the summer months. This seasonality led a British doctor to hypothesize that a sunlight-related seasonal stimulus triggered influenza outbreaks. More than 20 years after this initial hypothesis, several scientists published a paper suggesting that vitamin D may be the seasonal stimulus. Among the evidence they cite:
- Vitamin D levels are lowest in the winter months.
- The active form of vitamin D tempers the damaging inflammatory response of some white blood cells, while it also boosts immune cells' production of microbe-fighting proteins.
- Children who have vitamin D-deficiency rickets are more likely to get respiratory infections, while children exposed to sunlight seem to have fewer respiratory infections.
- Adults who have low vitamin D levels are more likely to report having had a recent cough, cold, or upper respiratory tract infection.
A recent randomized controlled trial in Japanese school children tested whether taking daily vitamin D supplements would prevent seasonal flu. The trial followed nearly 340 children for four months during the height of the winter flu season. Half of the study participants received pills that contained 1,200 IU of vitamin D; the other half received placebo pills. Researchers found that type A influenza rates in the vitamin D group were about 40 percent lower than in the placebo group; there was no significant difference in type B influenza rates. This was a small but promising study, and more research is needed before we can definitively say that vitamin D protects against the flu. But donít skip your flu shot, even if vitamin D has some benefit.
- Vitamin D & Tuberculosis: Before the advent of antibiotics, sunlight and sun lamps were part of the standard treatment for tuberculosis (TB). More recent research suggests that the sunshine vitamin may be linked to TB risk. Several case-control studies, when analyzed together, suggest that people diagnosed with tuberculosis have lower vitamin D levels than healthy people of similar age and other characteristics. Such studies do not follow individuals over time, so they cannot tell us whether vitamin D deficiency led to the increased TB risk or whether taking vitamin D supplements would prevent TB. There are also genetic differences in the receptor that binds vitamin D, and these differences may influence TB risk. (49) Again, more research is needed.)
VITAMIN D & RISK OF PREMATURE DEATH
A promising report in the Archives of Internal Medicine suggests that taking vitamin D supplements may even reduce overall mortality rates: A combined analysis of multiple studies found that taking modest levels of vitamin D supplements was associated with a statistically significant 7 percent reduction in mortality from any cause. The analysis looked at the findings from 18 randomized controlled trials that enrolled a total of nearly 60,000 study participants; most of the study participants took between 400 and 800 IU of vitamin D per day for an average of five years. Keep in mind that this analysis has several limitations, chief among them the fact that the studies it included were not designed to explore mortality in general, or explore specific causes of death. More research is needed before any broad claims can be made about vitamin D and mortality.
VITAMIN D DOSAGE INFORMATION
The Institute of Medicine (IOM) released guidelines suggesting that most Americans and Canadians get enough vitamin D, and recommending modest doses of vitamin D supplements. The new treatment guidelines point to new data suggesting that the IOM recommendations may be inadequate. The new guidelines recommend different doses of vitamin D for those at risk of vitamin D deficiency:
Age 0 to 1 year: 400 to 1,000 International Units (IU) daily Age 1 to 18 years: 600 to 1,000 IU daily All adults over age 18: 1,500 to 2,000 IU daily Pregnant or nursing women under age 18: 600 to 1,000 IU daily Pregnant or nursing women over age 18: 1,500 to 2,000 IU daily Because fat stores vitamin D, obese people may need to take two or three times the usual dose of vitamin D.
The guidelines recommend much larger doses of vitamin D, for a very limited time, for people trying to get their vitamin D levels back up to 30 ng/mL. Such doses should be taken under a health care provider's supervision.
FOOD SOURCES OF VITAMIN D
Sources of Vitamin D include fish liver oils, fatty saltwater fish, dairy products, and eggs all contain Vitamin D. It is found in butter, cod liver oil, dandelion greens, egg yolks, halibut, liver, milk, oatmeal, salmon, sardines, sweet potatoes, tuna, and vegetable oils. Vitamin D is also formed by the body in response to the action of sunlight on the skin. Herbs that contain Vitamin D include Alfalfa, Horsetail, Nettle, and Parsley.
Very few foods in nature contain Vitamin D. The flesh of fish (such as salmon, tuna, and mackerel) and fish liver oils are among the best sources. Small amounts of Vitamin D are found in beef liver, cheese, and egg yolks. Vitamin D in these foods is primarily in the form of Vitamin D-3 (cholecalciferol) and its metabolite 25(OH)D-3. Some mushrooms provide Vitamin D-2 (ergocalciferol) in variable amounts.
Fortified foods provide most of the Vitamin D in the American diet. For example, almost all of the U.S. milk supply is fortified with 100 IU/cup of Vitamin D (25 percent of the Daily Value or 50 percent of the AI level for ages 14 to 50 years). In the 1930s, a milk fortification program was implemented in the United States to combat rickets, then a major public health problem. This program virtually eliminated the disorder at that time. Other dairy products made from milk, such as cheese and ice cream, are generally not fortified. Ready-to-eat breakfast cereals often contain added Vitamin D, as do some brands of orange juice, yogurt, and margarine. In the United States, foods allowed to be fortified with Vitamin D include cereal flours and related products, milk and products made from milk, and calcium-fortified fruit juices and drinks. Maximum levels of added Vitamin D are specified by law.
Several food sources of Vitamin D are listed in the following table.
Table 3: Selected Food Sources of Vitamin D Food IUs per Serving* Percent DV**
Cod liver oil, 1 tablespoon
Salmon, cooked, 3.5 ounces
Mackerel, cooked, 3.5 ounces
Tuna, canned in oil, 3 ounces
Sardines, canned in oil, drained, 1.75 ounces
Milk, nonfat, reduced fat, and whole, vitamin D-fortified, 1 cup
Margarine, fortified, 1 tablespoon
Ready to eat cereal, fortified with 10 percent of the DV for vitamin D, 3/4 to 1 cup (more heavily fortified cereals might provider more of the DV. Read the label.
Egg, 1 whole (vitamin D is found in yolk)
Liver, beef, cooked, 3.5 ounces
Cheese, Swiss, 1 ounce
*IUs = International Units.
**DV = Daily Value. DVs are reference numbers based on the Recommended Dietary Allowance (RDA). They were developed by the U.S. Food and Drug Administration (FDA) to help consumers compare the nutrient contents of products within the context of a total diet. The DV for vitamin D is 400 IU for adults and children age 5 and older. The percent DV (%DV) listed on the nutrition facts panel of food labels tells adults what percentage of the DV is provided by one serving. Percent DVs are based on a 2,000-calorie diet. Your Daily Values may be higher or lower depending on your calorie needs. Foods that provide lower percentages of the DV will contribute to a healthful diet. Food labels, however, are not required to list vitamin D content unless a food has been fortified with this nutrient. Foods providing 20 percent or more of the DV are considered to be high sources of a nutrient.
The U.S. Department of Agriculture's Nutrient Database lists the nutrient content of many foods; relatively few have been analyzed for vitamin D content.
VITAMIN D & HEALTHFUL DIETS
According to the 2005 Dietary Guidelines for Americans, "nutrient needs should be met primarily through consuming foods. Foods provide an array of nutrients and other compounds that may have beneficial effects on health. In certain cases, fortified foods and dietary supplements may be useful sources of one or more nutrients that otherwise might be consumed in less than recommended amounts. However, dietary supplements, while recommended in some cases, cannot replace a healthful diet."
The Dietary Guidelines for Americans describes a healthy diet as one that use these recommendations.
- Emphasizes a variety of fruits, vegetables, whole grains, and fat-free or low-fat milk and milk products.
- Milk is fortified with vitamin D, as are many ready-to-eat cereals and a few brands of yogurt and orange juice.
- Cheese naturally contains small amounts of vitamin D.
- Sources includes lean meats, poultry, fish, beans, eggs, and nuts.
- Fish such as salmon, tuna, and mackerel are very good sources of vitamin D.
- Small amounts of vitamin D are also found in beef liver and egg yolks.
- Is low in saturated fats, trans fats, cholesterol, salt (sodium), and added sugars.
- Vitamin D is added to some margarines.
- Stays within your daily calorie needs.
For more information about building a healthful diet, refer to the Dietary Guidelines for Americans and the U.S. Department of Agriculture's food guidance system, My Pyramid.
Most people meet their Vitamin D needs through exposure to sunlight. Ultraviolet (UV) B radiation with a wavelength of 290 to 315 nanometers penetrates uncovered skin and converts cutaneous 7-dehydrocholesterol to previtamin D-3, which in turn becomes Vitamin D-3. Season, geographic latitude, time of day, cloud cover, smog, skin melanin content, and sunscreen are among the factors that affect UV radiation exposure and Vitamin D synthesis. The UV energy above 42 degrees north latitude (a line approximately between the northern border of California and Boston) is insufficient for cutaneous Vitamin D synthesis from November through February; in far northern latitudes, this reduced intensity lasts for up to 6 months. Latitudes below 34 degrees north (a line between Los Angeles and Columbia, South Carolina) allow for cutaneous production of Vitamin D throughout the year.
Complete cloud cover reduces UV energy by 50 percent; shade (including that produced by severe pollution) reduces it by 60 percent. UVB radiation does not penetrate glass, so exposure to sunshine indoors through a window does not produce Vitamin D. Sunscreens with a sun protection factor of 8 or more appear to block vitamin D-producing UV rays, although in practice people generally do not apply sufficient amounts, cover all sun-exposed skin, or reapply sunscreen regularly. Skin likely synthesizes some vitamin D even when it is protected by sunscreen as typically applied.
The factors that affect UV radiation exposure and research to date on the amount of sun exposure needed to maintain adequate Vitamin Dlevels make it difficult to provide general guidelines. It has been suggested, for example, that approximately 5 to 30 minutes of sun exposure between 10 AM and 3 PM at least twice a week to the face, arms, legs, or back without sunscreen usually lead to sufficient vitamin D synthesis and that the moderate use of commercial tanning beds that emit 2 to 6 percent UVB radiation is also effective. Individuals with limited sun exposure need to include good sources of Vitamin D in their diet or take a supplement.
Despite the importance of the sun to Vitamin D synthesis, it is prudent to limit exposure of skin to sunlight. UV radiation is a carcinogen responsible for most of the estimated 1.5 million skin cancers and the 8,000 deaths due to metastatic melanoma that occur annually in the United States. Lifetime cumulative UV damage to skin is also largely responsible for some age-associated dryness and other cosmetic changes. It is not known whether a desirable level of regular sun exposure exists that imposes no (or minimal) risk of skin cancer over time.
In supplements and fortified foods, Vitamin D is available in two forms, D-2 (ergocalciferol) and D-3 (cholecalciferol). Vitamin D-2 is manufactured by the UV irradiation of ergosterol in yeast, and vitamin D-3 is manufactured by the irradiation of 7-dehydrocholesterol from lanolin and the chemical conversion of cholesterol. The two forms have traditionally been regarded as equivalent based on their ability to cure rickets, but evidence has been offered that they are metabolized differently. Vitamin D-3 could be more than three times as effective as vitamin D-2 in raising serum 25(OH)D concentrations and maintaining those levels for a longer time, and its metabolites have superior affinity for vitamin D-binding proteins in plasma. Because metabolite receptor affinity is not a functional assessment, as the earlier results for the healing of rickets were, further research is needed on the comparative physiological effects of both forms. Many supplements are being reformulated to contain vitamin D-3 instead of vitamin D-2. Both forms (as well as vitamin D in foods and from cutaneous synthesis) effectively raise serum 25(OH)D levels.
VITAMIN D SAFETY, CAUTIONS & INTERACTIONS
Do not take vitamin D without calcium. Toxicity may result from taking amounts over 65,000 IU over a period of years.
Intestinal disorders and liver and gallbladder malfunctions interfere with the absorption of vitamin D. Some cholesterol-lowering drugs, antacids, mineral oil, and steroid hormones (cortisone) also interfere with absorption. Thiazide diuretics such as chlorothiazide (Diuril) and hydrochlorothiazide (Esidrix, HydroDIURIL, Oretic) disturb the body's calcium/vitamin D ratio.
HEALTH RISKS FROM EXCESSIVE VITAMIN D
There is a high health risk associated with consuming too much Vitamin D. Vitamin D toxicity can cause non-specific symptoms such as nausea, vomiting, poor appetite, constipation, weakness, and weight loss. More seriously, it can also raise blood levels of calcium, causing mental status changes such as confusion and heart rhythm abnormalities. The use of supplements of both Calcium (1,000 mg/day) and Vitamin D (400 IU/day) by post-menopausal women was associated with a 17 percent increase in the risk of kidney stones over 7 years in the Women's Health Initiative. Calcinosis, the deposition of calcium and phosphate in the kidneys and other soft tissues, can also be caused by excessive Vitamin D levels. A serum 25(OH)D concentration consistently greater than 200 ng/mL (greater than 500 nmol/L) is considered to be potentially toxic. In an animal model, concentrations equal to or less than 400 ng/mL (equal to or less than 1,000 nmol/L) were not associated with harm.
Excessive sun exposure does not result in Vitamin D toxicity because the sustained heat on the skin is thought to photodegrade previtamin D-3 and vitamin D-3 as it is formed. High intakes of dietary Vitamin D are very unlikely to result in toxicity unless large amounts of cod liver oil are consumed; toxicity is more likely to occur from high intakes of supplements.
Long-term intakes above the UL increase the risk of adverse health effects (Table 4). Substantially larger doses administered for a short time or periodically (e.g., 50,000 IU/week for 8 weeks) do not cause toxicity. Rather, the excess is stored and used as needed to maintain normal serum 25(OH)D concentrations when Vitamin D intakes or sun exposure are limited.
Table 4: Tolerable Upper Intake Levels (ULs) for Vitamin D Age Children Men Women Pregnancy Lactation Birth to 12 Months 25 mcg
1 to 13 Years 50 mcg
14-Plus Years 50 mcg
A daily intake above the UL increases the risk of adverse health effects and is not advised.
Several nutrition scientists recently challenged these ULs, first published in 1997. They point to newer clinical trials conducted in healthy adults and conclude that the data support a UL as high as 10,000 IU/day. Although Vitamin D supplements above recommended levels given in clinical trials have not shown harm, most trials were not adequately designed to assess harm. Evidence is not sufficient to determine the potential risks of excess Vitamin D in infants, children, and women of reproductive age.
INTERACTIONS WITH MEDICATIONS
Vitamin D supplements have the potential to interact with several types of medications. A few examples are provided below. Individuals taking these medications on a regular basis should discuss Vitamin D intakes with their healthcare providers.
Corticosteroid medications such as prednisone, often prescribed to reduce inflammation, can reduce calcium absorption and impair Vitamin D metabolism. These effects can further contribute to the loss of bone and the development of osteoporosis associated with their long-term use.
Both the weight-loss drug orlistat (brand names Xenical and Alli) and the cholesterol-lowering drug cholestyramine (brand names Questran, LoCholest, and Prevalite) can reduce the absorption of Vitamin D and other fat-soluble vitamins. Both phenobarbital and phenytoin (brand name Dilantin), used to prevent and control epileptic seizures, increase the hepatic metabolism of Vitamin D to inactive compounds and reduce calcium absorption.
Disorders that may contribute to malabsorption problems of Vitamin D and other important nutrients include:
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VITAMIN D SUPPLEMENTS & RELATED PRODUCTS
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VITAMIN D SUPPLEMENT PRODUCTS
Vitamin D is necessary for proper immune function, aids in Calcium uptake and is necessary for healthy bones and teeth and is also needed for adequate blood levels of insulin. People in northern latitudes or those who do not drink adequate milk, at risk of osteoporosis, have dark skin, live in a cloudy environment, or get out in the sun very much will require more vitamin D-3 supplementation than people who live closer to the equator or sunbathe frequently. Vitamin D is made in our bodies when sunlight converts a chemical in the skin into a usable form of the vitamin. Due to the perils of too much sunlight, concerns have been raised about a decrease in Vitamin D levels particularly in at-risk groups. A deficiency of vitamin D may not only have an impact on bone health, but also immune function, mood and birth weight. Alongside calcium, vitamin D is considered one of the big 3required nutrients together with folic acid and omega 3-fatty acids. Vitamin D deficiency is more common in strict vegetarians (who avoid vitamin D-fortified dairy foods), dark-skinned people, alcoholics, and people suffering intestinal malabsorption disorders such as celiac disease, reduced liver or kidney function. A daily intake of 400 to 1000 IU daily of a Vitamin D supplement may help to prevent or alleviate deficiency.
STARWEST BOTANICALS PRODUCTS
Starwest Botanicals: Vitamin D (Cholecalciferol) Tablets, 1000 IU, With Calcium, 120 mg, 100 Tabs.
Starwest Botanicals: Vitamin D (Cholecalciferol), 1000 IU, With Calcium, 120 mg, 500 Tabs.
Starwest Botanicals: Vitamin D (D-3 Cholecalciferol), 5000 IU, 100 Softgels
Starwest Botanicals: Vitamin D (D-3 Cholecalciferol), 5000 IU, 500 Softgels
HerbsPro: Vitamin D-3 Liquid Drops, Natural Raspberry Flavor, Child Life Essentials, 1 fl. oz. (80557)
HerbsPro: Vitamin D-3 Liquid Drops, Citrus Flavor, BlueBonnet Nutrition, 400 IU, 1 fl. oz. (100537)
HerbsPro: Vitamin D-3 Liquid Drops, Citrus Flavor, BlueBonnet Nutrition, 1000 IU, 1 fl. oz. (100538)
HerbsPro: Vitamin D-3 Liquid Drops, Citrus Flavor, BlueBonnet Nutrition, 2000 IU, 1 fl. oz. (100539)
HerbsPro: Liquid Vitamin D-3 (Cholecalciferol), Orange Flavor, Solgar, 5000 IU, 2 fl. oz. (100288)
HerbsPro: Vitamin D-3 Liquid, Cherry Flavored, Country Life, 5000 IU, 16 fl. oz. (85127)
HerbsPro: Vitamin D-3 Liquid, Trace Minerals, 16 fl. oz. (85049)
HerbsPro: Vitamin D-3 Animal-Shaped Chews, Mixed Berry, Rainforest Animalz, 400 IU, 90 Tabs (100489)
HerbsPro: Vitamin D-3 Cholecalciferol, Solgar, 400 IU, 250 Softgels (36863)
HerbsPro: Vegan Vitamin D, Deva Vegan Vitamins, 800 IU, 90 Tabs (78608)
HerbsPro: Vitamin D-3, High Potency, Sundown Naturals, 1000 IU, 60 Caps (102719)
HerbsPro: Dry Vitamin D-3, Country Life, 1000 IU, 100 Tabs (37552)
HerbsPro: Vitamin D-3, Country Life, 1000 IU, 100 Softgels (79190)
HerbsPro: Best Vitamin D-3, Doctors Best, 1000 IU, 180 Softgels (79251)
HerbsPro: Vitamin D-3, Country Life, 1000 IU, 200 Softgels (79192)
HerbsPro: Vitamin D-3, NOW Foods, 1000 IU, 360 Softgels (77530)
HerbsPro: Kyolic Vitamin D-3, Immune Support, Wakunaga Kyolic, 2000 IU, 80 Caps (104755)
HerbsPro: Vitamin D-3 Chewables, Earthsweet Raspberry Flavor, BlueBonnet Nutrition, 2000 IU, 90 Tabs (100534)
HerbsPro: Vitamin D-3, Bluebonnet Nutrition, 2000 IU, 90 VCaps (100517)
HerbsPro: Vitamin D-3 Chewables, Chocolate, Enzymatic Therapy, 2000 IU, 90 Chew Tabs (82028)
HerbsPro: Best Vitamin D-3, Doctors Best, 2000 IU, 180 Softgel (79252)
HerbsPro: Vitamin D-3, NOW Foods, 2000 IU, 240 Softgels (77531)
HerbsPro: Vitamin D-Pak, Lemon Lime, Trace Minerals, 2500 IU, 30 Packs (85067)
HerbsPro: Vitamin D-3, Country Life, 2500 IU, 200 Softgels (79191)
HerbsPro: Vitamin D-3, Olympian Labs, 3000 IU, 100 Caps (92799)
HerbsPro: RAW Vitamin D-3, Garden of Life Vitamin Code, 5000 IU, 60 Caps (94342)
HerbsPro: Vitamin D-3, Country Life, 5000 IU, 200 Softgels (85126)
HerbsPro: Best Vitamin D-3, Doctors Best, Doctors Best, 5000 IU, 360 Softgels (86810)
HerbsPro: Vitamin D-3 Cholecalciferol, Solgar, 10,000 IU, 120 Softgels (100294)
Kalyx: Vitamin D Fish Liver Oil, Thompson, 400 IU, 30 Softgels: K
Kalyx: Vitamin D Cholecalciferol, Thompson, 400 IU, 30 Tabs: K
Kalyx: Vitamin D Fish Liver Oil, Thompson, 400 IU, 30 Softgels: K
Kalyx: Yummi Bears Vitamin D, Hero Nutrition, 600 IU, 60 Count: K
Kalyx: Vitamin D Gummy Slices, Slice of Life, Natural Lemon Flavor, 1000 IU, 60 Slices: K
Kalyx: Dry Vitamins D Cholecalciferol, Solaray, 1000 IU, 90 Tabs: K
For Fat-Restricted Diets.
Kalyx: Vitamin D-3 Plus Fish Oil, Heart & Immune Support, Natrol, 1000 IU, 90 Softgels: K
Kalyx: Vitamin D Sunny Gummies, Rainbow Light, Lemon Flavor, 1000 IU, 100 Count: K
Kalyx: Vitamin D Gummy Vitamins for Adults, Nutrition Now, 2000 IU, 75 count: K
Available in Blackberry, Peach & Strawberry.
Kalyx: Vitamin D-3. Fast Dissolve Wild Cherry, Natrol, 2,000 IU, 90 Mini Tabs: K
Kalyx: Vitamin D-3, Thompson Nutritional, Lemon Flavored, 2,500 IU, 90 Chewable Tabs: K
Kalyx: Vitamin D-3, Maximum Strength, Natrol, 10,000 IU, 60 Tabs: K
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