Vitamin D

Other common name(s):

calcitriol, calciferol, ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), 1,25-D, the sunshine vitamin

Scientific/medical name(s):

1,25 dihydroxycholecalciferol, 25 hydroxycholecalciferol, 1,25 dihydroxyvitamin D

Description

Vitamin D is an important vitamin the body needs to regulate the amount of calcium and phosphorus in the body. It is best known for its role in using calcium to help build bones and keep them strong. Vitamin D affects many other tissues in the body, including the kidneys, intestines, and parathyroid glands.

Vitamin D is found in salmon, mackerel, tuna, and sardines, as well as in cod liver oil. Beef liver, cheese, and egg yolks contain small amounts. Most of the milk supply in the United States has vitamin D added to it, as do some breakfast cereals, orange juices, and milk substitutes (such as soy milk). Experts note that vitamin D acts more like a hormone than a vitamin, in part because the body can make its own vitamin D if the skin gets enough ultraviolet (UV) rays from sunlight.

Overview

Vitamin D is needed to keep a balance between calcium and phosphorus in the body. It controls how much of these nutrients are absorbed from foods or even taken from bones. While known for its role in building bones and keeping them strong, the exact function of vitamin D in other cells and organs is not fully known. It has a role in nerve, muscle, and immune function, and affects inflammation as well as cell growth and death.

After fairly brief exposure to sunlight, the body can make vitamin D for several hours. But the amount of sun it takes to make enough vitamin D depends on several factors (see "What does it involve?"). Because UV light exposure is linked to skin cancer and other diseases, safety is a concern when sunlight is used to meet vitamin D requirements. Most people can get enough vitamin D from foods and supplements, if they are used properly. Foods and vitamin D supplements have the advantage of not causing skin cancer and other unwanted effects on the skin that can be caused by UV light.

Some studies suggest that risk of developing some types of cancer is lower for people who have higher levels of vitamin D in the body. But more studies are needed to find out whether vitamin D is the reason for this decreased risk, or if there is another reason. If there is a link, researchers would still have to find out whether vitamin D deficiency raises a person's cancer risk. They would also need to know whether taking in more vitamin D than the recommended daily value lowers this risk. The possible role of vitamin D in treating cancer is still being studied.

How is it promoted for use?

Vitamin D is promoted by mainstream clinicians mainly for its role in balancing calcium and phosphorus and keeping bones healthy. Some other practitioners further claim that vitamin D is an immune system booster that can be used to prevent many problems, including autism, type I diabetes, schizophrenia, mood disorders, infectious diseases, cancer, and other illnesses. Others say it helps with weight loss. In orthomolecular medicine and some other forms of alternative medicine, large doses of vitamin D may be used along with other vitamins to treat cancer (see Orthomolecular Medicine). Researchers are also looking into using Vitamin D along with chemotherapy as a possible part of standard cancer treatment.

What does it involve?

The body can make vitamin D after exposure to UV rays or it can be obtained through some foods or supplements. The amount of vitamin D made when the skin is exposed to sunlight depends on several factors, including:

• Age
• Skin color
• How much skin is exposed
• Time of year
• Time of day
• Cloud cover
• Smog, dust, or haze
• Length of exposure
• Geographic location

Latitudes further away from the equator do not get much UV light through the earth's atmosphere in the winter months. This can be a problem for people who live in the northern United States and Canada and who do not take in much vitamin D in foods. Darker-skinned people need somewhat longer UV exposures to trigger their bodies to make vitamin D, and older people do not make as much vitamin D as younger people in response to sunlight. Sunscreen also blocks UV rays, which reduces the body's ability to produce vitamin D.

Even in a sunny climate, sunlight's effects can be hard to predict. One study looked at 93 adults in Hawaii who reported several hours of sun exposure each week for at least 3 months. The researchers found that half of them had low vitamin D levels in their blood. Closer analysis showed no predictable link between vitamin D levels and age, lightest or darkest skin colors, or hours of sun exposure without sunscreen. Clearly, there is no "one size fits all" prescription for a reliable minimum amount of sun exposure to meet the vitamin D requirements of every person.

The body stores several forms of vitamin D. Vitamin D3 is the form that is made in the skin. Vitamin D2 (calciferol) or D3 (cholecalciferol) can be absorbed from food. All must be changed into 25 hydroxyvitamin D (25 hydroxycholecalciferol), a form that can last for several weeks in the blood. This is the vitamin D level that doctors generally check.

The liver and kidneys change vitamin D into calcitriol (also called 1,25 dihydroxycholecalciferol or 1,25 dihydroxyvitamin D), which helps the intestine absorb more calcium and phosphorus.

The Institute of Medicine was able to set a recommended daily allowance (RDA) for vitamin D in 2010. The RDA of vitamin D for infants, children, and men and women up through age 70 is 15 micrograms (equal to 600 International Units or IU) per day. The RDA is 20 micrograms (800 IU) a day for adults older than 70. The safe upper limit for adults was set at 100 micrograms (4,000 IU) per day.

Blood tests can now measure the body's stores of vitamin D, and many people have unexpectedly low levels. For those with low levels, there are questions about how much vitamin D it takes to raise the body's stores of it to healthy levels.

Because vitamin D occurs naturally in very few foods, some adults may not get enough from their everyday diet. After vitamin D started being added to milk and other breakfast foods, many people have been able to get more of it. For instance, 1 cup of fortified milk contains half of the current adequate intake (AI) of vitamin D (see below) for an adult between the ages of 19 and 50. But that same cup supplies only one-quarter of the AI for an adult aged 51 to 70, and about one-sixth of the AI for a person 71 or older.

This means that fortified foods and/or vitamin D supplements may be needed by some people:

• People age 50 and older, whose skin cannot make as much vitamin D and/or whose kidneys are less able to convert vitamin D to its active form
• People with limited sun exposure; for instance, those who are homebound, who live in northern areas such as New England and Alaska, women who wear robes and head coverings for religious reasons, and people whose work prevents sun exposure, if they are unable to consume enough vitamin D in foods
• Adults with darker skin. Some studies suggest that older adults with dark skin, especially women, are at even higher risk of vitamin D deficiency if they do not consume enough vitamin D in foods
• People who do not absorb fat well. This is linked to several medical conditions:
• Deficiency of pancreatic enzymes
• Crohn's disease
• Cystic fibrosis
• Sprue or celiac disease (gluten intolerance)
• Certain types of liver disease
• Surgical removal of all or part of the stomach or intestine
• Children and teens who are not exposed to sun and who do not drink at least 2 cups of fortified milk per day
• People who are lactose intolerant, allergic to milk, or who avoid milk products for any reason
• Infants who are breast-fed only. Formula is fortified with vitamin D. An infant who consumes 2 cups of formula per day takes in adequate vitamin D.
• People who are overweight or obese. The more body fat a person has, the more vitamin D is needed to increase blood levels of the vitamin

Vitamin D supplements are most often taken as pills although cod liver oil is also still used. Supplements are available at drugstores, grocery stores, health food stores, and on the Internet.

What is the history behind it?

Rickets, a disease of weak bones and other deformities, was first described in the mid-1600s as a major problem among city children. Even though there were reports that rickets could be cured by sunbathing or cod liver oil, the disease was still widespread in northern Europe in the early twentieth century. After vitamin A was discovered in 1913 by Elmer McCollum as a cure for night blindness, a British doctor named Edward Mellanby induced rickets in dogs and then cured the condition using cod liver oil. He assumed that the vitamin A in the cod liver oil had cured the dogs. To test Mellanby's theory, McCollum devised a way to inactivate the vitamin A in cod liver oil. As expected, the oil no longer cured night blindness. To nearly everyone's surprise, however, it still cured rickets, which proved that another substance besides vitamin A was responsible. McCollum published these findings in 1922, calling this substance vitamin D. Soon after, a program to add vitamin D to milk was started in the United States, and rickets was nearly wiped out. Cod liver oil has remained a home remedy ever since.

Even though vitamin D was named and put to wide use, scientists in the early twentieth century knew almost nothing about what it was or how it worked. It took years of study and discoveries by a number of researchers to learn that there were several forms of vitamin D, and how they work in the body.

German researcher Adolf Windaus first discovered 3 forms of the vitamin, which he called D1, D2, and D3. (Because it was later learned that the product Windaus named vitamin D1 was a mixture of compounds rather than a pure vitamin D product, the term D1 is no longer used.) In the early 1950s, Arvid Carlsson found that vitamin D can remove calcium from the bones when the body needs it for other uses. Ragnar Nicolaysen, a dietary researcher, discovered that the amount of calcium absorbed from food is guided by an internal factor that tells the intestine how much the body needs. In 1975, another researcher named Mark Haussler confirmed that the intestines have a receptor protein that only binds to active vitamin D.

Today, vitamin D is still added to most milk sold in the United States, although it is not added to all milk products like cheese and ice cream. Some companies also add it to cereal, soy milk, rice milk, and orange juice, usually along with calcium. It is now understood that rickets is the product of long-standing and severe vitamin D deficiency, and that milder cases of deficiency may have no symptoms.

Since a few studies in the early 2000s have suggested higher levels of vitamin D may be linked to lower cancer risk, more studies have begun to look at this possibility.

What is the evidence?

Laboratory and animal studies and observational epidemiologic studies suggest that higher levels of vitamin D in the body may be linked to lower cancer risk. Observational studies only look at people without changing anything they do, so it is hard to know the role of the vitamin D.

The studies suggest that the risk for some forms of cancer is lower in those who get more calcium and vitamin D (which may include vitamin D from foods as well as sunlight). Higher vitamin D levels in the blood have also been linked to lower risk for some types of cancer, especially colorectal cancers. One researcher who analyzed 60 such studies noted that calcium intake appeared more protective than vitamin D against colon and rectal cancer. Because of the way vitamin D works with calcium, it may be hard to separate these effects.

Vitamin D seemed to be a bigger factor in a study of more than 3,000 adults (mostly men) who had colonoscopies between 1994 and 1997 to look for polyps or cancer. Those with the highest vitamin D intake were less likely to have advanced cancer than those with low intake. Although all of this sounds promising, observational epidemiologic studies cannot prove that other unknown factors may have caused the outcome of lower cancer risk.

Randomized clinical trials, which offer much stronger evidence than observational studies, are also studying the role vitamin D may play in cancer prevention. A Women's Health Initiative study published in 2006 put more than 36,000 menopausal women into 2 groups: half got vitamin D with calcium and half got a placebo (sham pill). After 7 years, the researchers looked at colorectal cancer risk in the 2 groups. Cancer risk was not lower in the group that took vitamin D. Critics of the study noted that the dose given (400 IU per day) may have been too low to make a difference, and that many women were not taking their pills at all. The average vitamin D and calcium intake of the women at the start of the study was also about twice as high as the national average, and close to the doses used in the study. And finally, women in the study were allowed to take extra vitamin D and calcium if they wished. This means that many women who were thought to be on placebo may have taken the same or higher doses as those who were in the test group. These factors may have limited the ability of the study to find any differences. Interestingly, colorectal cancer risk was lower in women who had higher levels of vitamin D in their blood at the start of the study. Researchers will keep watching the women until late 2010, so there may be more information at that time. A report on this study from 2009 showed no difference in death rates between the test group (women given vitamin D and calcium supplements) and those who were not given them.

A 4-year study published in 2007 looked at 1,179 healthy women over age 55 who were randomly chosen from rural Nebraska. The researchers gave a third of the women 1,400 to 1,500 milligrams of calcium each day. Another third received calcium plus 1,100 IU of vitamin D3 each day, while the rest got a placebo. The women who took calcium and vitamin D had significantly less risk for all types of cancer combined, as did the women who had higher vitamin D levels when the study started. This sounds promising, but it was only one study, so it is hard to be certain the vitamin D and calcium caused the difference. It is possible that other differences between the groups may have accounted for the lower cancer rates. Before this information can be used to recommend increased supplements of vitamin D and calcium, it needs to be confirmed by other studies. For one thing, it needs to be shown that the findings hold true in other groups of people. For another, doctors would want to know if these higher doses raise the risk of other problems, and whether there are unexpected side effects. For instance, more kidney stones have been reported in women taking vitamin D and calcium.

Well-designed clinical trials are needed to confirm whether low levels of vitamin D raise cancer risk and to find out if taking more vitamin D (with or without extra calcium) reduces cancer risk. Until such studies are completed, it is too early to advise people to take vitamin D supplements for cancer prevention.

The International Agency for Research on Cancer, a part of the World Health Organization, reviewed this topic and concluded in a 2008 report that vitamin D may reduce risk of colorectal cancer, but not prostate cancer, and that the evidence is weak regarding a link with breast cancer.

A 2010 analysis of data from 10 studies did not find any association of vitamin D levels and 6 less common types of cancer -- endometrial, esophageal, gastric, kidney, non-Hodgkin lymphoma, and ovarian. And, people with the highest vitamin D levels seemed to have an higher, rather than lower, chance of developing pancreatic cancer.

Some researchers are interested in whether vitamin D can play a role in cancer treatment. A few small studies have looked at vitamin D along with standard treatment for prostate cancer. In one study of 16 men with metastatic prostate cancer, 1 in 4 had less bone pain and 1 in 3 had stronger muscles after taking 2,000 IU of vitamin D each day for 12 weeks. However, nearly half of the patients were deficient in vitamin D at the start of the study, which could have affected the results.

Another study looked at the effects of vitamin D3 on blood levels of prostate-specific antigen (PSA) in men whose prostate cancer had come back after treatment. PSA is a substance produced by normal and cancerous prostate cells, and high levels are considered to be a sign of cancer growth. After treatment with radiation or surgery, the men took daily doses of vitamin D3 for a period of between 6 and 15 months. The researchers observed that in 6 of 7 patients, their PSA levels increased more slowly than before they started the vitamins. However, the men began to lose calcium in their urine, which limited the amount of vitamin D they could safely take. This was a small pilot study that called for further testing.

A 2003 study of 22 men with recurrent prostate cancer used larger weekly doses of vitamin D3. The researchers observed that the weekly dose was safe. However, while the rate of PSA increase in men slowed to some extent, more studies are needed to find out whether vitamin D has a significant role in slowing the growth of prostate cancer. Studies could also help find out if it helps people live longer or feel better.

Women who are vitamin D–deficient give birth to children with very little vitamin D in their bodies. In addition, past testing has shown that human breast milk contains very little vitamin D. This finding has led to the recommendation that infants who are fed only breast milk be given vitamin D supplements. However, recent small early studies in breast-feeding women have found that women with high blood levels of vitamin D have adequate amounts in their breast milk. In order to reach these levels, though, researchers had to give the women very high doses of vitamin D each day. More research is needed to find out about safety and side effects, use of blood tests to measure vitamin D status, and the healthiest blood levels of the vitamin.

Researchers are also testing whether vitamin D can help make some chemotherapy drugs work better. Lab studies and early human studies in prostate cancer were encouraging, so a more careful randomized, double blind clinical trial was done. The findings that came out in 2008 did not show that taxotere plus vitamin D worked any better than taxotere alone in prolonging the lives of men with advanced prostate cancer.

Researchers are also testing deltanoids—compounds chemically related to vitamin D—for cancer prevention and for treatment. These are being tested alone and in combination with other cancer drugs.

Vitamin D can prevent and treat some bone problems such as rickets in children and osteomalacia in adults. Vitamin D deficiency, which is often seen in older people, can lead to osteoporosis and is linked to an increased risk for broken hips. Studies of the effect of vitamin D supplements on hip fracture risk among older people have had conflicting results. More information is needed before any recommendations can be made for older people at risk of hip fracture.

Although low vitamin D levels seem to be linked to several diseases, further study is needed to learn whether the disease causes the low levels of vitamin D, the vitamin deficiency increases the risk for disease, or there is some other relationship between the two.

Are there any possible problems or complications?

This product is sold as a dietary supplement in the United States. Unlike companies that produce drugs (which must be tested before being sold), the companies that make supplements are not required to prove to the Food and Drug Administration that their supplements are safe or effective, as long as they don't claim the supplements can prevent, treat, or cure any specific disease.

Some such products may not contain the amount of the herb or substance that is on the label, and some may include other substances (contaminants). Actual amounts per dose may vary between brands or even between different batches of the same brand. In 2007, the FDA wrote new rules to improve the quality of manufacturing for dietary supplements and the proper listing of supplement ingredients. But these rules do not address the safety of the ingredients or their effects on health.

Most such supplements have not been tested to find out if they interact with medicines, foods, or other herbs and supplements. Even though some reports of interactions and harmful effects may be published, full studies of interactions and effects are not often available. Because of these limitations, any information on ill effects and interactions below should be considered incomplete.

Vitamin D is considered safe as part of a normal healthy diet. Too much vitamin D can cause nausea, vomiting, poor appetite, constipation, weakness, and weight loss. It can also raise blood calcium levels, causing changes in mental status such as confusion. High blood calcium can also cause abnormal heart rhythms. Too much vitamin D over a long time can cause depression, headaches, sleepiness, and weakness, as well as calcium and bone loss. It can also cause the arteries and other soft tissues of the body (such as kidneys, heart, lungs) to become hardened and lined with layers of calcium, a condition known as calcinosis.

Getting vitamin D through sunlight may not work for some and may cause problems for others. Besides the danger of sunburn, exposure to ultraviolet light can cause skin cancer; wrinkled, sagging skin; damage to the eyes, including cataracts; and can impair the immune system. Reflective surfaces make UV exposure more intense and can worsen these effects. Water, snow, and sand reflect the most. While sun exposure can cause other problems, it has never been reported to produce toxic levels of vitamin D. Vitamin D from foods is also unlikely to cause toxic effects unless large amounts of cod liver oil are used. Vitamin D toxicity is much more likely to occur as a result of taking too many supplements. Vitamin D toxicity has also been caused by foods that were incorrectly fortified (foods or milk that had accidentally been mixed with far more vitamin D than intended).

Laxatives, steroids, and anti-cholesterol drugs like cholestyramine (Questran, Locholest) and colestipol (Colestid) may lower the amount of vitamin D you can absorb. Vitamin D should be taken several hours before or after these drugs. Anti-seizure drugs and rifampin (an anti-tuberculosis drug) can lower your vitamin D levels. Too much vitamin D may raise calcium levels, which can cause abnormal heart rhythms if you are taking digoxin. People with low parathyroid function may have a higher risk of abnormally high calcium levels when taking vitamin D. This problem can be worsened by certain diuretics (water pills).

If you take vitamin D with calcium, note that calcium can keep certain drugs from being absorbed. Always talk with your doctor and pharmacist about all the herbs, supplements, and medicines you are taking. Relying on this type of treatment alone and avoiding or delaying conventional medical care for cancer may have serious health consequences.