1. What is vitamin D?

Vitamin D is technically not a vitamin. It is the name given to a group of fat-soluble prohormones (substances that are precursors to hormones that usually have little hormonal activity by themselves). Two major forms of vitamin D that are important to humans are vitamin D₂, or ergocalciferol, and vitamin D₃, or cholecalciferol. Vitamin D₂ is made naturally by plants, and vitamin D₃ is made naturally by the body when the skin is exposed to ultraviolet radiation (in particular, UVB radiation) in sunlight. Vitamin D₂ and vitamin D₃ can also be manufactured.

The active form of vitamin D in the body is 1,25-dihydroxyvitamin D, or calcitriol, which can be made from either vitamin D₂ or vitamin D₃. To make the active form, vitamin D₂ and vitamin D₃ are modified in the liver to produce 25-hydroxyvitamin D, which travels through the blood to the kidneys, where it is modified further to make 1,25-dihydroxyvitamin D.

Vitamin D is involved in a number of processes that are essential for good health, including the following:

• It helps improve muscle strength and immune function.
• It helps reduce inflammation.
• It promotes the absorption of calcium from the small intestine.
• It helps maintain adequate blood levels of the calcium and phosphate needed for bone formation, mineralization (incorporating minerals to increase strength and density), growth, and repair (1–3).

Most people get the vitamin D they need through sunlight exposure. It can also be obtained through the diet, but very few foods naturally contain vitamin D. These foods include fatty fish, fish liver oil, and eggs. Smaller amounts are found in meat and cheese. Most dietary vitamin D comes from fortified foods, such as milk, juices, yogurt, bread, and breakfast cereals. Vitamin D can also be obtained through dietary supplements. Fortified foods and dietary supplements usually contain either vitamin D₂ or vitamin D₃.

A person's vitamin D status is usually checked by measuring the level of 25-hydroxyvitamin D in their blood serum.

2. How much vitamin D is needed for health?

A serum level of 25-hydroxyvitamin D lower than 15 nanograms per milliliter (ng/mL)—equivalent to 37.5 nanomoles per liter (nmol/L)—is generally considered inadequate for a healthy person to maintain bone health and normal calcium metabolism (2). However, some experts say that this may be on the low side, and the 2005 Dietary Guidelines for Americans notes that the optimal level may be as high as 80 nmol/L. A serum level below 11 ng/mL (27.5 nmol/L) is consistent with vitamin D deficiency in infants, neonates, and young children (2). The Institute of Medicine of the National Academies has developed the following recommended daily intakes of vitamin D (on the assumption that vitamin D₃ is not being made in the skin through sun exposure) (1, 2):

Age	Recommended Minimum Vitamin D                 Intake (μg/day and IU/day)
Birth to 50 years	5 μg (=200 IU)
51–70 years	10 μg (=400 IU)
71+ years	15 μg (=600 IU)
Pregnancy	5 μg (=200 IU)
Lactation	5 μg (=200 IU)

μg = microgram; 1 μg = 40 International Units (IU)

The 2005 Dietary Guidelines for Americans recommends that older adults, people with dark skin, and people exposed to insufficient sunlight should consume extra vitamin D (25 µg, or 1,000 IU) from vitamin D-fortified foods and/or supplements.

People are more likely to not get enough vitamin D than to get too much. However, excessive intake of any nutrient, including vitamin D, can cause toxic effects (see Question 5). Excessive sun exposure does not cause vitamin D toxicity.

3. What are the health effects of vitamin D deficiency?

Vitamin D deficiency can impair normal bone metabolism, leading to the following conditions:

• Rickets (a condition in children marked by soft and deformed bones; it is caused by undermineralization of bone).
• Osteomalacia (adult rickets).
• Osteoporosis (weak and porous bones) (1, 2).


4. How much vitamin D is in fortified foods and supplements?

Fortification of foods with vitamin D in the United States is carefully regulated (4). Vitamin D fortification is allowed for milk and milk products, cereal flours and related products, margarine, and fruit juices and fruit juice drinks. Milk is usually fortified with 2.5 μg (100 IU) vitamin D per cup (4). Some yogurts are now fortified with vitamin D. Cheese, ice cream, and other dairy products made from milk are generally not fortified with vitamin D. To see if a food product has been fortified, check the food label.

The amount of vitamin D in multivitamins and other dietary supplements typically ranges from 10 μg (400 IU) to 50 μg (2,000 IU) (5).

5. Is it safe to take vitamin D supplements?

Vitamin D toxicity is more likely to occur from high intakes of dietary supplements than from high intakes of vitamin D-fortified foods. For most children and adults, the recommended upper limit of vitamin D intake from foods and supplements is 25 μg (1,000 IU) per day for those less than 1 year of age and 50 μg (2,000 IU) per day for older individuals (1, 2). The upper limit is the highest average daily intake level that is likely to pose no risk of adverse health effects to almost all individuals in the general population.

Excessive vitamin D intake is toxic because it increases calcium levels. Increased calcium levels can lead to calcinosis (the deposit of calcium salts in soft tissues of the body, such as the kidneys, heart, and lungs) and hypercalcemia (high blood levels of calcium). Symptoms of excessive vitamin D intake may include heart rhythm abnormalities; mental status changes, such as confusion; pain; conjunctivitis; anorexia; fever; chills; thirst; vomiting; and weight loss (1, 2, 4).

6. Is there a role for vitamin D in reducing cancer risk?

A large number of scientific studies of many types have provided evidence suggesting that vitamin D may have a role in cancer prevention. The first evidence came from epidemiologic studies known as geographic correlation studies. In these studies, an inverse relationship was found between sunlight exposure levels and the rates of incidence and death for certain cancers. Individuals living in southern latitudes were found to have lower rates of incidence and death for these cancers than those living at northern latitudes. Because sunlight/UV exposure is necessary for the production of vitamin D₃, researchers hypothesized that differences in vitamin D levels accounted for the observed relationships.

Evidence of a possible cancer-protective role for vitamin D was also found in laboratory studies of the effect of vitamin D treatment on cancer cells in culture. In these studies, vitamin D promoted the differentiation and death (apoptosis) of cancer cells, and it slowed their proliferation.

Randomized clinical trials designed to investigate the effects of vitamin D intake on bone health have also provided evidence that higher vitamin D intakes may reduce the risk of cancer. One study involved nearly 1,200 healthy postmenopausal women who took daily supplements of calcium and vitamin D (28 μg vitamin D, or 1,100 IU, a relatively large dose) or a placebo for 4 years. The women who took the supplements had a 60 percent lower overall incidence of cancer (6); however, the study did not include a vitamin D-only group. Moreover, the primary outcome of the study was fracture incidence; it was not designed to measure cancer incidence. This limits the ability to draw conclusions about the effect of vitamin D intake on cancer incidence.

A number of observational studies have been carried out to investigate the possibility that vitamin D reduces the risk of specific cancers, particularly colorectal cancer and breast cancer, but vitamin D's effects on prostate cancer and pancreatic cancer have also been examined. These studies have yielded inconsistent results, most likely because of the methodologic difficulties in conducting observational studies of dietary components (7). In these studies, information about dietary intakes is obtained from the participants through the use of food frequency questionnaires, diet records, or interviews in which the participants are asked to recall information about their dietary intakes. Information collected in this manner can be inaccurate. Other dietary components or energy balance may also modify vitamin D metabolism (8).

Measuring serum levels of 25-hydroxyvitamin D to determine vitamin D status avoids some of the limitations of assessing dietary intake. However, vitamin D levels in the blood can vary seasonally and with the laboratory technique used to measure them. These variations complicate the interpretation of studies that measure the concentration of vitamin D in serum at a single point in time.

Finally, it is difficult to separate the effects of vitamin D and calcium because of the complicated biological interactions between these micronutrients. To fully understand the effect of vitamin D on cancer and other health outcomes, new randomized trials will need to be carried out (9). However, the appropriate dose of vitamin D to use in such trials is still not clear (10).

7. Is there evidence that vitamin D can help reduce the risk of colorectal cancer?

Epidemiologic studies of the association between vitamin D and the risk of colorectal cancer have provided some indications that higher levels of intake are associated with a reduced risk. However, the data are inconsistent.

In the American Cancer Society's Cancer Prevention Study (CPS) II Nutrition Cohort, the diet, medical history, and lifestyle of more than 120,000 men and women were analyzed (11). Men who had the highest intakes of vitamin D through both their diet and supplement use (greater than 13 μg, or 525 IU, per day) had a slightly lower risk of colorectal cancer than men who had the lowest vitamin D intakes. However, this association was not observed among women.

In a pooled analysis of data from 10 cohort studies (including the CPS II cohort), individuals with the highest dietary vitamin D intakes had a slightly lower risk of colorectal cancer than those with the lowest intakes, but the reduction in risk was not statistically significant (12).

In the Women's Health Initiative randomized trial, healthy postmenopausal women took daily supplements that contained both calcium and 10 μg (400 IU) vitamin D or a placebo for an average of 7 years. Supplementation did not reduce the incidence of colorectal cancer (13). However, some scientists have raised the possibility that the relatively low level of vitamin D supplementation and the short duration of participant follow-up might account for the negative results.

At least one epidemiologic study has reported an association between vitamin D and reduced mortality from colorectal cancer. Among the 16,818 participants in the Third National Health and Nutrition Examination Survey, those with higher vitamin D blood levels (≥ 80 nmol/L) had a 72 percent lower risk of colorectal cancer death than those with lower vitamin D blood levels (< 50 nmol/L) (14).

Most colorectal cancers develop from pre-existing colorectal adenomas, and interventions that reduce the risk of adenoma development or recurrence are likely to reduce the risk of colorectal cancer. Several large studies have investigated the association of vitamin D intake or serum status with adenoma risk.

A cohort from the National Cancer Institute (NCI)-sponsored Polyp Prevention Trial (PPT) was evaluated for the association of vitamin D intake with recurrence of colorectal adenomas in individuals who previously had one or more adenomas removed during a qualifying colonoscopy (15). PPT was a multicenter randomized clinical trial to determine the effects of a diet high in fiber, fruits, and vegetables and low in fat on adenoma recurrence. The detailed dietary information obtained during the trial allowed the researchers to investigate the association between additional dietary factors and adenoma recurrence. Total vitamin D intake (that is, from dietary sources and supplements combined) was not associated with a reduced risk of adenoma recurrence (15). However, individuals who used any amount of vitamin D supplements had a lower risk of adenoma recurrence (15).

In another study, the vitamin D intakes of 3,000 people from several Veterans Affairs medical centers were examined to determine whether there was an association between intake and advanced colorectal neoplasia (an outcome that included high-risk adenomas as well as colon cancer) (16). Individuals with the highest vitamin D intakes (more than 16 μg, or 645 IU, per day) had a lower risk of developing advanced neoplasia than those with lower intakes (16).

A pooled analysis of data from these and a number of other observational studies found that higher circulating levels of vitamin D and higher vitamin D intakes were associated with lower risks of colorectal adenoma (17). Inverse associations were seen with both dietary and total vitamin D intake but not with supplemental vitamin D intake. However, the associations with dietary intake were not statistically significant.

Another large, NCI-sponsored randomized, placebo-controlled trial explored the effects of calcium supplementation and blood levels of vitamin D on adenoma recurrence (18). Calcium supplementation reduced the risk of adenoma recurrence only in individuals with vitamin D blood levels above 73 nmol/L. Among individuals with vitamin D levels at or below this level, calcium supplementation was not associated with a reduced risk (18).

8. Is there evidence that vitamin D can help reduce breast cancer risk?

As with colorectal cancer, epidemiologic studies of the association between vitamin D and breast cancer risk have had conflicting results. Although several studies have suggested an inverse association between vitamin D intake and the risk of breast cancer, others have shown no association or even a positive association (that is, individuals with higher intakes had higher risks). A meta-analysis of six studies that investigated the relationship between vitamin D intake and breast cancer risk found no association (19). However, most women in these studies had relatively low vitamin D intakes, and, when the analysis was restricted to women with the highest vitamin D intakes (>10 μg, or 400 IU, per day), their breast cancer risks were lower than those of women with the lowest intakes (typically < 1.25 μg, or 50 IU, per day) (19).

In the Women's Health Initiative randomized trial of calcium plus vitamin D supplementation, supplement use for an average of 7 years did not reduce the incidence of invasive breast cancer compared with placebo (20).

The association between blood levels of vitamin D and breast cancer risk was examined in a cohort of postmenopausal women who were enrolled in NCI's Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and from whom blood was drawn at study entry. During the subsequent follow-up period, 1,005 of these women developed breast cancer. When researchers compared the blood vitamin D levels of these women with those of 1,005 similar control women who did not develop breast cancer, they found no association between vitamin D status and risk of breast cancer (21).

9. Is there evidence that vitamin D can help reduce prostate cancer risk?

Some geographic correlation studies (see Question 6) have suggested that men exposed to higher levels of sunlight may have a lower risk of prostate cancer. Although some epidemiologic studies have suggested that higher vitamin D levels are associated with increased prostate cancer risk, most studies have not shown such an association.

In one relatively large study of men diagnosed 1 to 8 years after their blood was drawn, an increase in vitamin D blood levels was not associated with decreased risk of prostate cancer overall (20). Indeed, there was some evidence that men with higher vitamin D levels had an increased risk for aggressive disease (22).

In another study, the European Prospective Investigation into Cancer and Nutrition (EPIC), blood samples obtained at study entry were examined for 652 men who developed prostate cancer during follow-up and 752 matched control subjects (23). No association was observed between serum vitamin D levels and risk of prostate cancer, either overall or by cancer stage.

10. Is there evidence that vitamin D can help reduce pancreatic cancer risk?

Participants in the Health Professionals Follow-Up Study and the Nurses' Health Study (more than 120,000 total), who provided detailed information on their diet through questionnaires at study entry, were followed for 16 years for the incidence of pancreatic cancer, and 365 cases were identified. Compared with participants with the lowest vitamin D intakes, those with higher intakes had progressively lower risks of pancreatic cancer (24). In contrast, among Finnish male smokers participating in the Alpha-Tocopherol, Beta-Carotene (ATBC) study (25), higher serum levels of vitamin D were associated with an increased risk of pancreatic cancer.

In a study conducted among a large cohort of individuals aged 55 to 74 who were enrolled in the PLCO Screening Trial, vitamin D levels in blood samples obtained at study entry were compared among 184 individuals diagnosed with pancreatic cancer during nearly 12 years of follow-up and 368 matched cancer-free control subjects (26). No association between vitamin D level and pancreatic cancer incidence was observed.

11. What are the possible mechanisms by which vitamin D may modify cancer risk?

Mechanisms by which vitamin D may modify cancer risk are not fully understood. Laboratory studies have shown that vitamin D promotes cellular differentiation, decreases cancer cell growth, and stimulates apoptosis (27, 28).

Vitamin D acts on cells by binding to the vitamin D receptor (VDR). The VDR is a regulator of gene transcription that is found in the nucleus of cells. Vitamin D-bound VDR binds to the retinoid-X receptor (RXR), and the resulting complex activates the expression of specific genes. Among the many genes regulated by vitamin D are those that produce the proteins calbindin and TPRV6, both of which are involved in the absorption of calcium by intestinal cells (29). Another vitamin D-regulated gene is CYP3A4, whose protein product detoxifies the bile acid lithocholic acid (LCA). LCA is believed to damage the DNA of intestinal cells and may promote colon carcinogenesis. Stimulating the production of a detoxifying enzyme by vitamin D could explain a protective role for vitamin D against colon cancer (30).

Further insight into the mechanisms by which vitamin D might modify cancer risk could come from study of the vitamin D receptor itself. A large number of variant forms of the VDR gene have been identified, some of which are known to alter the structure or function of the VDR protein. Some of these variants have been linked to risk for certain cancers, including prostate, colorectal, breast, bladder, and melanoma (31). The association of VDR variants with cancer risk differs by cancer site and appears to be modified by environmental exposures, such as diet and sun exposure.
12. How can people get enough sunlight for vitamin D synthesis while minimizing the risk of skin cancer?

Although people obtain some vitamin D from dietary sources, most vitamin D is made in the body after the skin is exposed to sunlight. Despite the known and potential health benefits of vitamin D, increasing sun exposure increases the risk of skin cancer. In general, most experts believe that people should continue to use sun protection when UV levels are moderate or higher. Some researchers have suggested that brief daily exposure to UV will ensure adequate vitamin D production, but many variables (such as skin color, latitude, and season) can affect the production of vitamin D, and such recommendations have proven controversial. Other experts recommend vitamin D supplementation to avoid the problem of increasing skin cancer risk.

13. Does NCI recommend the use of vitamin D supplements to prevent colorectal or other cancers?

No. Although some evidence suggests that vitamin D may provide some protection against colorectal and possibly other cancers, the evidence of potential benefit is limited and inconsistent. Therefore, NCI does not recommend the use of vitamin D supplements to reduce the risk of colorectal or any other type of cancer.

Selected References

1. Otten JJ, Hellwig JP, Meyers LD. Vitamin D. In: Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: National Academies Press, 2006.
   
   
2. Institute of Medicine Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Vitamin D. In: Dietary Reference Intakes: For Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academies Press, 1997.
   
   
3. Holick MF. Evolution and function of vitamin D. Recent Results in Cancer Research 2003; 164:3–28.
   
   
4. Calvo MS, Whiting SJ, Barton CN. Vitamin D fortification in the United States and Canada: Current status and data needs. American Journal of Clinical Nutrition 2004; 80(6 Suppl):1710S–1716S.
   
   
5. Holick MF. Vitamin D deficiency. New England Journal of Medicine 2007; 357(3):266–281.
   
   
6. Lappe JM, Travers-Gustafson D, Davies KM, et al. Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial. American Journal of Clinical Nutrition 2007; 85(6):1586–1591.
   
   
7. Sempos CT, Liu K, Ernst ND. Food and nutrient exposures: What to consider when evaluating epidemiologic evidence. American Journal of Clinical Nutrition 1999; 69(6):1330S–1338S.
   


8. Kremer R, Campbell PP, Reinhardt T, Gilsanz V. Vitamin D status and its relationship to body fat, final height, and peak bone mass in young women. Journal of Clinical Endocrinology & Metabolism 2009; 94(1):67–73.
   
   
9. IARC Working Group on Vitamin D. Vitamin D and cancer: A report of the IARC Working Group on Vitamin D. IARC Working Group Reports. Lyon, France: International Agency for Research on Cancer, 2008.
   
   
10. Yetley EA, Brulé D, Cheney MC, et al. Dietary Reference Intakes for vitamin D: Justification for a review of the 1997 values. American Journal of Clinical Nutrition 2009; 89(3):719–727.
    
    
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14. Freedman DM, Looker AC, Chang SC, Graubard BI. Prospective study of serum vitamin D and cancer mortality in the United States. Journal of the National Cancer Institute 2007; 99(21):1594–1602.
    
    
15. Hartman TJ, Albert PS, Snyder K, et al. The association of calcium and vitamin D with risk of colorectal adenomas. Journal of Nutrition 2005; 135(2):252–259.
    
    
16. Lieberman DA, Prindiville S, Weiss DG, Willett W. Risk factors for advanced colonic neoplasia and hyperplastic polyps in asymptomatic individuals. Journal of the American Medical Association 2003; 290(22):2959–2967.
    
    
17. Wei MY, Garland CF, Gorham ED, et al. Vitamin D and prevention of colorectal adenoma: A meta-analysis. Cancer Epidemiology, Biomarkers, and Prevention 2008; 17(11):2958–2969.
    
    
18. Grau MV, Baron JA, Sandler RS, et al. Vitamin D, calcium supplementation, and colorectal adenomas: Results of a randomized trial. Journal of the National Cancer Institute 2003; 95(23):1765–1771.
    
    
19. Gissel T, Rejnmark L, Mosekilde L, Vestergaard P. Intake of vitamin D and risk of breast cancer--a meta-analysis. Journal of Steroid Biochemistry and Molecular Biology 2008; 111(3–5):195–199.
    
    
20. Chlebowski RT, Johnson KC, Kooperberg C, et al. Calcium plus vitamin D supplementation and the risk of breast cancer. Journal of the National Cancer Institute 2008; 100(22):1581–1591.
    
    
21. Freedman DM, Chang SC, Falk RT, et al. Serum levels of vitamin D metabolites and breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Epidemiology, Biomarkers, and Prevention 2008; 17(4):889–894.
    
    
22. Ahn J, Peters U, Albanes D, et al. Serum vitamin D concentration and prostate cancer risk: A nested case-control study. Journal of the National Cancer Institute 2008; 100(11):796–804.
    
    
23. Travis RC, Crowe FL, Allen NE, et al. Serum vitamin D and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). American Journal of Epidemiology 2009; 169(10):1223–1232.
    
    
24. Skinner HG, Michaud DS, Giovannucci E, et al. Vitamin D intake and the risk for pancreatic cancer in two cohort studies. Cancer Epidemiology, Biomarkers, and Prevention 2006; 15(9):1688–1695.
    
    
25. Stolzenberg-Solomon RZ, Vieth R, Azad A, et al. A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers. Cancer Research 2006; 66(20):10213–10219.
    
    
26. Stolzenberg-Solomon RZ, Hayes RB, Horst RL, et al. Serum vitamin D and risk of pancreatic cancer in the Prostate, Lung, Colorectal, and Ovarian Screening Trial. Cancer Research 2009; 69(4):1439–1447.
    
    
27. Moreno J, Krishnan AV, Feldman D. Molecular mechanisms mediating the antiproliferative effects of vitamin D in prostate cancer. Journal of Steroid Biochemistry and Molecular Biology 2005; 97(1–2):31–36.
    
    
28. Holt PR, Arber N, Halmos B, et al. Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D. Cancer Epidemiology, Biomarkers, and Prevention 2002; 11(1):113–119.
    
    
29. Christakos S, Dhawan P, Benn B, et al. Vitamin D: Molecular mechanism of action. Annals of the New York Academy of Sciences 2007; 1116:340–348.
    
    
30. Harris DM, Go VL. Vitamin D and colon carcinogenesis. Journal of Nutrition 2004; 134(12 Suppl):3463S–3471S.
    
    
31. Slattery ML. Vitamin D receptor gene (VDR) associations with cancer. Nutrition Reviews 2007; 65(8):S102–S104.

Related NCI materials and Web pages:

• National Cancer Institute Fact Sheet 5.34, Colorectal Cancer Research from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial: NCI Fact Sheet ¹
  (http://www.cancer.gov/cancertopics/factsheet/detection/plco-colorectal)
• PDQ® Prevention Summary for Health Professionals on Colorectal Cancer ²
  (http://www.cancer.gov/cancertopics/pdq/prevention/colorectal/HealthProfessional)
• Cancer Prevention Home Page ³
  (http://www.cancer.gov/cancertopics/prevention-genetics-causes/prevention)
• Colon and Rectal Cancer Home Page ⁴
  (http://www.cancer.gov/cancertopics/types/colon-and-rectal)
• Energy Balance: Weight and Obesity, Physical Activity, Diet Home Page ⁵
  (http://www.cancer.gov/cancertopics/energybalance)

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Glossary Terms

Not normal. An abnormal lesion or growth may be cancer, premalignant (likely to become cancer), or benign (not cancer).

The process of taking nutrients from the digestive system into the blood so they can be used in the body.

A tumor that is not cancer. It starts in gland-like cells of the epithelial tissue (thin layer of tissue that covers organs, glands, and other structures within the body).

A quickly growing cancer.

A process in which anything complex is separated into simple or less complex parts.

An abnormal loss of the appetite for food. Anorexia can be caused by cancer, AIDS, a mental disorder (i.e., anorexia nervosa), or other diseases.

A type of cell death in which a series of molecular steps in a cell leads to its death. This is the body’s normal way of getting rid of unneeded or abnormal cells. The process of apoptosis may be blocked in cancer cells. Also called programmed cell death.

A substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. The body can make vitamin A from beta carotene. Beta carotene is being studied in the prevention of some types of cancer. It is a type of antioxidant.

A fluid made by the liver and stored in the gallbladder. Bile is excreted into the small intestine, where it helps digest fat.

Pertaining to biology or to life and living things. In medicine, refers to a substance made from a living organism or its products. Biologicals may be used to prevent, diagnose, treat or relieve of symptoms of a disease. For example, antibodies, interleukins, and vaccines are biologicals. Biological also refers to parents and children who are related by blood.

The organ that stores urine.

A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.

Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.

The active form of vitamin D. Calcitriol is formed in the kidneys or made in the laboratory. It is used as a drug to increase calcium levels in the body in order to treat skeletal and tissue-related calcium deficiencies caused by kidney or thyroid disorders.

A mineral needed for healthy teeth, bones, and other body tissues. It is the most common mineral in the body. A deposit of calcium in body tissues, such as breast tissue, may be a sign of disease.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

The process by which normal cells are transformed into cancer cells.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

A nutrient that the body needs in small amounts to function and stay healthy. Cholecalciferol helps the body use calcium and phosphorus to make strong bones and teeth. It is fat-soluble (can dissolve in fats and oils) and is found in fatty fish, egg yolks, and dairy products. Skin exposed to sunshine can also make cholecalciferol. Not enough cholecalciferol can cause a bone disease called rickets. It is being studied in the prevention and treatment of some types of cancer. Also called vitamin D.

A group of individuals who share a common trait, such as birth year. In medicine, a cohort is a group that is part of a clinical trial or study and is observed over a period of time.

Cancer that forms in the tissues of the colon (the longest part of the large intestine). Most colon cancers are adenocarcinomas (cancers that begin in cells that make and release mucus and other fluids).

Examination of the inside of the colon using a colonoscope, inserted into the rectum. A colonoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue to be checked under a microscope for signs of disease.

Cancer that develops in the colon (the longest part of the large intestine) and/or the rectum (the last several inches of the large intestine before the anus).

In medicine, a health problem with certain characteristics or symptoms.

A mental state in which one is not thinking clearly.

A condition in which the conjunctiva (membranes lining the eyelids and covering the white part of the eye) become inflamed or infected. Also called pinkeye.

In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works.

In medicine, a shortage of a substance (such as a vitamin or mineral) needed by the body.

The process of identifying a disease, such as cancer, from its signs and symptoms.

The things a person eats and drinks.

A product that is added to the diet. A dietary supplement is taken by mouth, and usually contains one or more dietary ingredient (such as vitamin, mineral, herb, amino acid, and enzyme). Also called nutritional supplement.

In cancer, refers to how mature (developed) the cancer cells are in a tumor. Differentiated tumor cells resemble normal cells and tend to grow and spread at a slower rate than undifferentiated or poorly differentiated tumor cells, which lack the structure and function of normal cells and grow uncontrollably.

The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.

The amount of medicine taken, or radiation given, at one time.

In biology, the state at which the number of calories eaten equals the number of calories used. Energy balance is affected by physical activity, body size, amount of body fat and muscle, and genetics.

A protein that speeds up chemical reactions in the body.

An increase in body temperature above normal (98.6 degrees F), usually caused by disease.

In food, fiber is the part of fruits, vegetables, legumes, and whole grains that cannot be digested. The fiber in food may help prevent cancer. In the body, fiber refers to tissue made of long threadlike cells, such as muscle fiber or nerve fiber.

Monitoring a person's health over time after treatment. This includes keeping track of the health of people who participate in a clinical study or clinical trial for a period of time, both during the study and after the study ends.

The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.

One of many chemicals made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs. Some hormones can also be made in the laboratory.

Higher than normal levels of calcium in the blood. Some types of cancer increase the risk of hypercalcemia.

Production and action of cells that fight disease or infection.

The number of new cases of a disease diagnosed each year.

Redness, swelling, pain, and/or a feeling of heat in an area of the body. This is a protective reaction to injury, disease, or irritation of the tissues.

Having to do with the intestines.

Cancer that has spread from where it started in the breast into surrounding, healthy tissue. Most invasive breast cancers start in the ducts (tubes that carry milk from the lobules to the nipple). Invasive breast cancer can spread to other parts of the body through the blood and lymph systems. Also called infiltrating breast cancer.

A unit used to measure the activity of many vitamins, hormones, enzymes, and drugs. An IU is the amount of a substance that has a certain biological effect. For each substance there is an international agreement on the biological effect that is expected for 1 IU. Also called International Unit.

One of a pair of organs in the abdomen. Kidneys remove waste from the blood (as urine), produce erythropoietin (a substance that stimulates red blood cell production), and play a role in blood pressure regulation.

Research done in a laboratory. These studies may use test tubes or animals to find out if a drug, procedure, or treatment is likely to be useful. Laboratory studies take place before any testing is done in humans.

A large organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile.

One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.

Refers to the practices and procedures used for the prevention, treatment, or relief of symptoms of a diseases or abnormal conditions. This term may also refer to a legal drug used for the same purpose.

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

The total of all chemical changes that take place in a cell or an organism. These changes make energy and the materials needed for growth, reproduction, and maintaining health. They also help get rid of toxic substances.

One millionth of a gram.

A measure of volume in the metric system. One thousand milliliters equal one liter. Also called cc, cubic centimeter, and ml.

In medicine, a mineral is a nutrient that is needed in small amounts to keep the body healthy. Mineral nutrients include the elements calcium, magnesium, and iron.

The state of being mortal (destined to die). Mortality also refers to the death rate, or the number of deaths in a certain group of people in a certain period of time. Mortality may be reported for people who have a certain disease, live in one area of the country, or who are of a certain gender, age, or ethnic group.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

Abnormal and uncontrolled cell growth.

In biology, the structure in a cell that contains the chromosomes. The nucleus has a membrane around it, and is where RNA is made from the DNA in the chromosomes.

A health professional trained to care for people who are ill or disabled.

A chemical compound (such as protein, fat, carbohydrate, vitamin, or mineral) contained in foods. These compounds are used by the body to function and grow.

The taking in and use of food and other nourishing material by the body. Nutrition is a 3-part process. First, food or drink is consumed. Second, the body breaks down the food or drink into nutrients. Third, the nutrients travel through the bloodstream to different parts of the body where they are used as "fuel" and for many other purposes. To give the body proper nutrition, a person has to eat and drink enough of the foods that contain key nutrients.

A type of study in which individuals are observed or certain outcomes are measured. No attempt is made to affect the outcome (for example, no treatment is given).

A condition that is marked by a decrease in bone mass and density, causing bones to become fragile.

A specific result or effect that can be measured. Examples of outcomes include decreased pain, reduced tumor size, and improvement of disease.

Having to do with the ovaries, the female reproductive glands in which the ova (eggs) are formed. The ovaries are located in the pelvis, one on each side of the uterus.

A disease in which malignant (cancer) cells are found in the tissues of the pancreas. Also called exocrine cancer.

A form of phosphoric acid, which contains phosphorus. In the body, phosphates are found in the bones and teeth. Phosphates may be used to treat a high level of calcium in the blood. Adding or removing phosphate groups may affect the way proteins act in the body.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

Refers to a clinical study in which the control patients receive a placebo.

A growth that protrudes from a mucous membrane.

Having to do with the time after menopause. Menopause (“change of life”) is the time in a woman's life when menstrual periods stop permanently.

In medicine, action taken to decrease the chance of getting a disease or condition. For example, cancer prevention includes avoiding risk factors (such as smoking, obesity, lack of exercise, and radiation exposure) and increasing protective factors (such as getting regular physical activity, staying at a healthy weight, and having a healthy diet).

In medicine, a study or clinical trial in which participants are identified and then followed forward in time.

A gland in the male reproductive system. The prostate surrounds the part of the urethra (the tube that empties the bladder) just below the bladder, and produces a fluid that forms part of the semen.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell.

Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrent cancer.

Vitamin A or a vitamin A-like compound.

Checking for disease when there are no symptoms. Since screening may find diseases at an early stage, there may be a better chance of curing the disease. Examples of cancer screening tests are the mammogram (breast), colonoscopy (colon), Pap smear (cervix), and PSA blood level and digital rectal exam (prostate). Screening can also include checking for a person’s risk of developing an inherited disease by doing a genetic test.

The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed.

Cancer that forms in tissues of the skin. There are several types of skin cancer. Skin cancer that forms in melanocytes (skin cells that make pigment) is called melanoma. Skin cancer that forms in basal cells (small, round cells in the base of the outer layer of skin) is called basal cell carcinoma. Skin cancer that forms in squamous cells (flat cells that form the surface of the skin) is called squamous cell carcinoma. Skin cancer that forms in neuroendocrine cells (cells that release hormones in response to signals from the nervous system) is called neuroendocrine carcinoma of the skin. Most skin cancers form in older people on parts of the body exposed to the sun or in people who have weakened immune systems.

The part of the digestive tract that is located between the stomach and the large intestine.

Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body.

Able to be dissolved in a liquid.

The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

Adding nutrients to the diet.

An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.

Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects.

In biology, the process by which a cell makes an RNA copy of a sequence of DNA that is a gene.

Invisible rays that are part of the energy that comes from the sun. Ultraviolet radiation also comes from sun lamps and tanning beds. It can damage the skin and cause melanoma and other types of skin cancer. Ultraviolet radiation that reaches the Earth's surface is made up of two types of rays, called UVA and UVB rays. UVB rays are more likely than UVA rays to cause sunburn, but UVA rays pass deeper into the skin. Scientists have long thought that UVB radiation can cause melanoma and other types of skin cancer. They now think that UVA radiation also may add to skin damage that can lead to skin cancer and cause premature aging. For this reason, skin specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of ultraviolet radiation. Also called UV radiation.

A type of ultraviolet (UV) radiation. UV rays are invisible rays that are part of the energy that comes from the sun. UVB radiation causes sunburn, and scientists have long thought that it can cause melanoma and other types of skin cancer. Skin specialists recommend that people use sunscreens that reflect, absorb, or scatter ultraviolet radiation.

A nutrient that the body needs in small amounts to function and stay healthy. Sources of vitamins are plant and animal food products and dietary supplements. Some vitamins are made in the human body from food products. Vitamins are either fat-soluble (can dissolve in fats and oils) or water-soluble (can dissolve in water). Excess fat-soluble vitamins are stored in the body’s fatty tissue, but excess water-soluble vitamins are removed in the urine. Examples are vitamin A, vitamin C, and vitamin E.

A nutrient that the body needs in small amounts to function and stay healthy. Vitamin D helps the body use calcium and phosphorus to make strong bones and teeth. It is fat-soluble (can dissolve in fats and oils) and is found in fatty fish, egg yolks, and dairy products. Skin exposed to sunshine can also make vitamin D. Not enough vitamin D can cause a bone disease called rickets. It is being studied in the prevention and treatment of some types of cancer. Also called cholecalciferol.

To eject some or all of the contents of the stomach through the mouth.