Many studies have looked at the possibility that specific dietary components or nutrients are associated with increases or decreases in cancer risk. Studies of cancer cells in the laboratory and of animal models have sometimes provided evidence that isolated compounds may be carcinogenic (or have anticancer activity).

But with few exceptions, studies of human populations have not yet shown definitively that any dietary component causes or protects against cancer. Sometimes the results of epidemiologic studies that compare the diets of people with and without cancer have indicated that people with and without cancer differ in their intake of a particular dietary component.

However, these results show only that the dietary component is associated with a change in cancer risk, not that the dietary component is responsible for, or causes, the change in risk. For example, study participants with and without cancer could differ in other ways besides their diet, and it is possible that some other difference accounts for the difference in cancer.

When evidence emerges from an epidemiologic study that a dietary component is associated with a reduced risk of cancer, a randomized trial may be done to test this possibility. Random assignment to dietary groups ensures that any differences between people who have high and low intakes of a nutrient are due to the nutrient itself rather than to other undetected differences. (For ethical reasons, randomized studies are not generally done when evidence emerges that a dietary component may be associated with an increased risk of cancer.)

Scientists have studied many additives, nutrients, and other dietary components for possible associations with cancer risk. These include:

• Acrylamide
  Acrylamide is a chemical found in tobacco smoke and some foods. It can be produced when certain vegetables, such as potatoes, are heated to high temperatures. Studies in animal models have found that acrylamide exposure increases the risk for several types of cancer. However, there is no consistent evidence that dietary acrylamide exposure is associated with the risk of any type of cancer in humans.
• Alcohol
  Although red wine has been suspected of reducing cancer risk, there is no scientific evidence for such an association. Also, alcohol is a known cause of cancer. Heavy or regular alcohol consumption increases the risk of developing cancers of the oral cavity (excluding the lips), pharynx (throat), larynx (voice box), esophagus, liver, breast, colon, and rectum. The risk of developing cancer increases with the amount of alcohol a person drinks.
• Antioxidants
  Antioxidants are chemicals that block the activity of other chemicals, known as free radicals, that may damage cells. Laboratory and animal research has shown that exogenous antioxidants can help prevent the free radical damage associated with the development of cancer, but research in humans has not demonstrated convincingly that taking antioxidant supplements can help reduce the risk of developing or dying from cancer. Some studies have even shown an increased risk of some cancers.
• Artificial sweeteners
  Many studies have been conducted on the safety of the six FDA-approved artificial sweeteners (saccharin, aspartame, acesulfame potassium, sucralose, neotame, and advantame). In laboratory animal studies, these sweeteners have generally not been found to cause cancer or other adverse health effects. Most studies of the association between artificial sweetener intake and cancer in humans have also shown no increase in risk, although one large cohort study found a slight increase in cancer risk among users of several sweeteners.
• Charred meat
  Certain chemicals, called HCAs and PAHs, are formed when muscle meat, including beef, pork, fish, and poultry, is cooked using high-temperature methods. Exposure to high levels of HCAs and PAHs can cause cancer in animals; however, whether such exposure causes cancer in humans is unclear.
• Cruciferous vegetables
  Cruciferous vegetables contain chemicals known as glucosinolates, which break down into several compounds that are being studied for possible anticancer effects. Some of these compounds have shown anticancer effects in cells and animals, but the results of studies with humans have been less clear.
• Fluoride
  Fluoride in water helps to prevent and can even reverse tooth decay. Many studies, in both humans and animals, have shown no association between fluoridated water and cancer risk.
• Tea
  Tea contains polyphenol compounds, particularly catechins, which are antioxidants. Results of epidemiologic studies examining the association between tea consumption and cancer risk have been inconclusive. Few clinical trials of tea consumption and cancer prevention have been conducted and their results have also been inconclusive.
• Vitamin D
  Vitamin D helps the body use calcium and phosphorus to make strong bones and teeth. Possible associations of blood levels or intakes of vitamin D with cancer have been studied in both observational studies and randomized trials. Observational studies have provided some evidence that people with higher blood levels of vitamin D might have lower risks of colorectal cancer and of overall cancer mortality. Most randomized trials have not found an association between vitamin D supplement use and cancer risk or mortality.

What is acrylamide?

Acrylamide is a chemical used primarily to make substances called polyacrylamide and acrylamide copolymers. Polyacrylamide and acrylamide copolymers are used in many industrial processes, such as the production of paper, dyes, and plastics, and in the treatment of drinking water and wastewater, including sewage. They are also found in consumer products, such as caulking, food packaging, and some adhesives.

Acrylamide is also found in some foods. It can be produced when vegetables that contain the amino acid asparagine, such as potatoes, are heated to high temperatures in the presence of certain sugars. It is also a component of tobacco smoke.

How are people exposed to acrylamide?

Food and cigarette smoke are the major sources of acrylamide exposure for people in the general population.

The major food sources of acrylamide are French fries and potato chips; crackers, bread, and cookies; breakfast cereals; canned black olives; prune juice; and coffee.

Acrylamide levels in food vary widely depending on the manufacturer, the cooking time, and the method and temperature of the cooking process. Decreasing cooking time to avoid heavy crisping or browning, blanching potatoes before frying, not storing potatoes in a refrigerator, and post-drying (drying in a hot air oven after frying) have been shown to decrease the acrylamide content of some foods.

People are exposed to substantially more acrylamide from tobacco smoke than from food. People who smoke have three to five times higher levels of acrylamide exposure markers in their blood than do non-smokers. Exposure from other sources is likely to be significantly less than that from food or smoking, but scientists do not yet have a complete understanding of all sources of exposure. Regulations are in place to limit exposure in workplaces where acrylamide may be present, such as industrial settings that use polyacrylamide and acrylamide copolymers.

Is there an association between acrylamide and cancer?

Studies in rodent models have found that acrylamide exposure increases the risk for several types of cancer. In the body, acrylamide is converted to a compound called glycidamide, which causes mutations in and damage to DNA. However, a large number of epidemiologic studies (both case-control and cohort studies) in humans have found no consistent evidence that dietary acrylamide exposure is associated with the risk of any type of cancer. One reason for the inconsistent findings from human studies may be the difficulty in determining a person’s acrylamide intake based on their reported diet.

The National Toxicology Program’s Report on Carcinogens considers acrylamide to be reasonably anticipated to be a human carcinogen, based on studies in laboratory animals given acrylamide in drinking water. However, toxicology studies have shown that humans and rodents not only absorb acrylamide at different rates, they metabolize it differently as well.

Studies of workplace exposure have shown that high levels of occupational acrylamide exposure (which occurs through inhalation) cause neurological damage, for example, among workers using acrylamide polymers to clarify water in coal preparation plants. However, studies of occupational exposure have not suggested increased risks of cancer.

Are acrylamide levels regulated?

The U.S. Environmental Protection Agency (EPA) regulates acrylamide in drinking water. The EPA established an acceptable level of acrylamide exposure, set low enough to account for any uncertainty in the data relating acrylamide to cancer and neurotoxic effects. The U.S. Food and Drug Administration regulates the amount of residual acrylamide in a variety of materials that contact food, but there are currently no guidelines governing the presence of acrylamide in food itself.

What research is needed to better understand whether acrylamide is associated with cancer in people?

Additional epidemiologic studies in which acrylamide adduct or metabolite levels are serially measured in the same individuals over time (longitudinal cohorts) are needed to help determine whether dietary acrylamide intakes are associated with increased cancer risks in people. It is also important to determine how acrylamide is formed during the cooking process and whether acrylamide is present in foods other than those already tested. This information will enable researchers to make more accurate and comprehensive estimates of dietary exposure. Biospecimen collections in cohort studieswill provide an opportunity to examine biomarkers of exposure to acrylamide and its metabolites in relation to the subsequent risk of cancer.

Drinking alcohol can increase your risk of cancer of the mouth, throat, esophagus, larynx (voice box), liver, and breast. The more you drink, the higher your risk. The risk of cancer is much higher for those who drink alcohol and also use tobacco.

Doctors advise people who drink to do so in moderate amounts. The federal government’s Dietary Guidelines for Americans defines moderate alcohol drinking as up to one drink per day for women and up to two drinks per day for men.

It has been suggested that certain substances in red wine, such as resveratrol, have anticancer properties. However, there is no evidence that drinking red wine reduces the risk of cancer.

What are free radicals, and do they play a role in cancer development?

Free radicals are highly reactive chemicals that have the potential to harm cells. They are created when an atom or a molecule (a chemical that has two or more atoms) either gains or loses an electron (a small negatively charged particle found in atoms). Free radicals are formed naturally in the body and play an important role in many normal cellular processes. At high concentrations, however, free radicals can be hazardous to the body and damage all major components of cells, including DNA, proteins, and cell membranes. The damage to cells caused by free radicals, especially the damage to DNA, may play a role in the development of cancer and other health conditions.

Abnormally high concentrations of free radicals in the body can be caused by exposure to ionizing radiation and other environmental toxins. When ionizing radiation hits an atom or a molecule in a cell, an electron may be lost, leading to the formation of a free radical. The production of abnormally high levels of free radicals is the mechanism by which ionizing radiation kills cells. Moreover, some environmental toxins, such as cigarette smoke, some metals, and high-oxygen atmospheres, may contain large amounts of free radicals or stimulate the body’s cells to produce more free radicals.

Free radicals that contain the element oxygen are the most common type of free radicals produced in living tissue. Another name for them is “reactive oxygen species,” or “ROS”.

What are antioxidants?

Antioxidants are chemicals that interact with and neutralize free radicals, thus preventing them from causing damage. Antioxidants are also known as “free radical scavengers.”

The body makes some of the antioxidants that it uses to neutralize free radicals. These antioxidants are called endogenous antioxidants. However, the body relies on external (exogenous) sources, primarily the diet, to obtain the rest of the antioxidants it needs. These exogenous antioxidants are commonly called dietary antioxidants. Fruits, vegetables, and grains are rich sources of dietary antioxidants. Some dietary antioxidants are also available as dietary supplements.

Examples of dietary antioxidants include beta-carotene, lycopene, and vitamins A, C, and E (alpha-tocopherol). The mineral element selenium is often thought to be a dietary antioxidant, but the antioxidant effects of selenium are most likely due to the antioxidant activity of proteins that have this element as an essential component (i.e., selenium-containing proteins), and not to selenium itself.

Can antioxidant supplements help prevent cancer?

In laboratory and animal studies, the presence of increased levels of exogenous antioxidants has been shown to prevent the types of free radical damage that have been associated with cancer development. Therefore, researchers have investigated whether taking dietary antioxidant supplements can help lower the risk of developing or dying from cancer in humans.

Many observational studies, including case–control studies and cohort studies, have been conducted to investigate whether the use of dietary antioxidant supplements is associated with reduced risks of cancer in humans. Overall, these studies have yielded mixed results. Because observational studies cannot adequately control for biases that might influence study outcomes, the results of any individual observational study must be viewed with caution.

It is possible that the lack of benefit in clinical studies can be explained by differences in the effects of the tested antioxidants when they are consumed as purified chemicals as opposed to when they are consumed in foods, which contain complex mixtures of antioxidants, vitamins, and minerals . Therefore, acquiring a more complete understanding of the antioxidant content of individual foods, how the various antioxidants and other substances in foods interact with one another, and factors that influence the uptake and distribution of food-derived antioxidants in the body are active areas of ongoing cancer prevention research.

Should people already diagnosed with cancer take antioxidant supplements?

Several randomized controlled trials, some including only small numbers of patients, have investigated whether taking antioxidant supplements during cancer treatment alters the effectiveness or reduces the toxicity of specific therapies. Although these trials had mixed results, some found that people who took antioxidant supplements during cancer therapy had worse outcomes, especially if they were smokers.

In some preclinical studies, antioxidants have been found to promote tumor growth and metastasis in tumor-bearing mice and to increase the ability of circulating tumor cells to metastasize. Until more is known about the effects of antioxidant supplements in cancer patients, these supplements should be used with caution. Cancer patients should inform their doctors about their use of any dietary supplement.

What is calcium?

Calcium is an essential dietary mineral commonly found in milk, yogurt, cheese, and dark green vegetables. It also is found in certain grains, legumes (including peas, beans, lentils, and peanuts), and nuts.

Calcium is a major component of bones and teeth. It also is required for the clotting of blood to stop bleeding and for normal functioning of the nerves, muscles, and heart.

How much calcium is needed for good health?

Calcium is an important part of a healthy diet; however, the recommended intake differs according to age. As can be seen in the following table, the highest recommended intake is for children and adolescents between the ages of 9 and 18, when bones are growing rapidly.

For adults (including women who are pregnant or breastfeeding) and for children age 1 or older, the safe upper limit of calcium intake is 2.5 grams (or 2500 mg) per day.

Too much calcium in the diet and from dietary supplements can lead to unwanted side effects.

The U.S. Department of Agriculture’s 1994–1996 Continuing Survey of Food Intakes by Individuals showed that the average daily calcium intakes in the United States for males and females over age 9 were 925 mg and 657 mg, respectively, or less than the recommended intake.

How much calcium is in foods and calcium supplements?

Calcium is found in many foods. Foods high in calcium include dairy products, dark green vegetables, some soy products, fish, nuts, and legumes. The following table shows how much calcium is contained in some common foods.

Packaged foods are required to have a Nutrition Facts label (3). On foods that contain calcium, this label lists how much calcium there is in each serving of the packaged food. However, the Nutrition Facts labels on packaged foods do not list the calcium content in mg. They only provide the Percent Daily Value (%DV), which is the amount one serving of a food item contributes to the total amount of calcium you need each day. The %DV for calcium is based on a recommended Daily Value of 1000 mg per day. Therefore, a food with 20%DV or more contributes a fair amount of a person’s daily total, whereas a food with 5%DV or less contributes only a little. As an example, 1 cup of milk provides 300 mg of calcium and 30%DV.

Calcium supplements most often contain either calcium carbonate or calcium citrate, which are calcium salts. Sometimes, they contain both compounds. Calcium carbonate and calcium citrate have different amounts of elemental calcium, which is the actual amount of usable calcium in a supplement. Specifically, calcium carbonate has about 40 percent elemental calcium, meaning that 500 mg of calcium carbonate actually contains 200 mg of elemental calcium or 20%DV. In contrast, calcium citrate has approximately 21 percent elemental calcium. Therefore, nearly twice as much calcium citrate is needed to obtain the equivalent amount of elemental calcium as in calcium carbonate. Calcium supplements may also contain other calcium salts, but the body may not be able to use the calcium in these compounds. As with food labels, you should look at the Nutrition Facts label on a supplement to determine how much calcium it contains.

Is it safe to take calcium supplements?

For most people, it is safe to eat foods containing calcium and to take calcium supplements that together do not exceed the tolerable upper intake level of 2.5 grams of calcium per day. This upper level for daily calcium intake in adults is the highest level that likely will not pose risks of unwanted side effects in the general population. The upper level of 2.5 grams a day is an average recommendation for all healthy people who are older than a year, regardless of gender.

Consuming too much calcium—in excess of 5 grams a day, or 3 grams a day in people with existing kidney problems—can lead to several harmful side effects. Most of these side effects result from people taking too many calcium supplements. Rare harmful side effects from excess calcium include kidney stones, hypercalcemia (too much calcium in the blood), and kidney failure. In addition, excessive consumption of milk (which is high in calcium) and some types of antacids, especially antacids containing calcium carbonate or sodium bicarbonate (baking soda), over a long period of time can cause milk-alkali syndrome, a condition that can also lead to calcium deposits in the kidneys and other tissues and to kidney failure.

Is there evidence that calcium may help reduce the risk of colorectal cancer?

The results of epidemiologic studies regarding the relationship between calcium intake and colorectal cancer risk have not always been consistent.

In the American Cancer Society’s Cancer Prevention Study II Nutrition Cohort, the diet, medical history, and lifestyle of more than 120,000 men and women were analyzed. Men and women who had the highest intakes of calcium through both their diet and supplement use had a modestly reduced risk of colorectal cancer compared with those who had the lowest calcium intakes. However, the benefit from calcium appeared to plateau, or level off, at an intake of approximately 1200 mg per day. When calcium from the diet was analyzed by itself, no reduction in colorectal cancer risk was found. However, the use of calcium supplements in any amount was associated with reduced risk. This association was strongest (a 31 percent reduction in risk) for people who took calcium supplements of 500 mg per day or more.

A stronger relationship between calcium intake and colorectal cancer risk was found when participants of the Nurses’ Health Study and the Health Professionals Follow-up Study were combined in an analysis that included more than 135,000 men and women. Individuals who had a calcium intake of more than 700 mg per day had a 35 percent to 45 percent reduced risk of cancer of the distal (lower) part of the colon than those who had a calcium intake of 500 mg or less per day. No association was found between calcium intake and risk of cancer of the proximal (middle and upper) part of the colon. Another large study of Finnish men showed a similar relationship between higher calcium intake and reduced risk of colorectal cancer. This study, however, did not evaluate proximal and distal colorectal cancers separately.

In a study that included more than 61,000 Swedish women, colorectal cancer risk was approximately 28 percent lower among individuals who had the highest calcium intakes (approximately 800–1000 mg per day) compared with those with the lowest calcium intakes (approximately 400–500 mg per day). Data from this study also suggested that the benefit associated with calcium was limited to the distal colon. In a study that involved more than 34,000 postmenopausal Iowa women, high intakes of calcium (approximately 1280 mg per day or more) compared with lower calcium intakes (approximately 800 mg per day or less) from both the diet and supplements were associated with a 41 percent reduction in risk of rectal cancer. Reduced risks of rectal cancer were also observed for dietary calcium alone and supplemental calcium alone, but these associations were not statistically significant.

In an analysis involving more than 293,000 men and 198,000 women in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, high intakes of total calcium, dietary calcium, and supplemental calcium were associated with an approximately 20 percent lower risk of colorectal cancer among men and an approximately 30 percent lower risk of colorectal cancer among women.

Findings from two large randomized, placebo-controlled clinical trials, the Calcium PolypPrevention Study and the European Cancer Prevention Organisation InterventionStudy showed that daily supplementation with 1200 to 2000 mg elemental calcium was associated with a reduced risk of recurrence of colorectal polyps known as adenomas in both men and women. Adenomas are thought to be the precursors of most colorectal cancers. In these trials, individuals who previously had one or more large adenomas removed during colonoscopy were randomly assigned to receive calcium supplementation or a placebo, and the rates of polyp recurrence and other factors were compared between the groups.

The Calcium Polyp Prevention Study involved 930 participants who were randomly assigned to receive 3 grams of calcium carbonate (1200 mg elemental calcium) daily for 4 years or a placebo and then receive follow-up colonoscopies approximately 9 months later and again 3 years after that. Compared with those in the placebo group, the individuals assigned to take calcium had about a 20 percent lower risk of adenoma recurrence.

The European Cancer Prevention Organisation Intervention Study involved 665 participants who were randomly assigned to one of three treatment groups: 2 grams of elemental calcium daily (from calcium gluconolactate and calcium carbonate), 3 grams of fiber supplementation daily, or a placebo. The results showed that calcium supplementation was associated with a modest reduction in the risk of adenoma recurrence, but this finding was not statistically significant.

The results of another clinical trial conducted as part of the Women’s Health Initiative showed that supplementation with 1000 mg elemental calcium (from calcium carbonate) per day for an average duration of 7 years was not associated with a reduced risk of colorectal cancer. The calcium supplements in this trial also contained vitamin D (400 international units [IU]). During the trial, 128 cases of invasive colorectal cancer were diagnosed in the supplementation group and 126 cases were diagnosed in the placebo group.

In 2007, the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) published the most authoritative review of existing evidence relating food, nutrition, and physical activity to cancer risk. The report concluded that calcium probably has a protective effect against colorectal cancer.

Is there evidence that calcium can help reduce the risk of other cancers?

The results of some studies suggest that a high calcium intake may decrease the risk of one or more types of cancer, whereas other studies suggest that a high calcium intake may actually increase the risk of prostate cancer.

In a randomized trial that included nearly 1,200 healthy, postmenopausal Nebraska women, individuals were randomly assigned to receive daily calcium supplementation alone (300–600 mg elemental calcium), calcium supplementation (300–600 mg elemental calcium) combined with vitamin D supplementation (1000 IU), or a placebo for 4 years. The incidence of all cancers combined was approximately 60 percent lower for women who took the calcium plus vitamin D supplements compared with women who took the placebo. A lower risk of all cancers combined was also observed for women who took calcium supplements alone, but this finding was not statistically significant. The numbers of individual types of cancer diagnosed during this study were too low to be able to draw reliable conclusions about cancer-specific protective effects.

The results of some but not all studies suggest that a high intake of calcium may increase the risk of prostate cancer. For example, the European Prospective Investigation into Cancer and Nutrition analyzed the intakes of animal foods (meat, poultry, fish, dairy products, etc.), protein, and calcium in relation to prostate cancer risk among more than 142,000 men and found that a high intake of protein or calcium from dairy products was associated with an increased risk of prostate cancer (19). Calcium from nondairy sources, however, was not associated with increased risk. In addition, a prospective analysis of dairy product and calcium intakes among more than 29,000 men participating in the National Cancer Institute’s (NCI) Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial showed increased risks for prostate cancer associated with high dietary intakes of calcium and dairy products, particularly low-fat dairy products. Calcium from supplements was not associated with increased prostate cancer risk. In contrast, results from the NIH-AARP Diet and Health Study showed no increased risk of prostate cancer associated with total calcium, dietary calcium, or supplemental calcium intakes.

Other studies have suggested that intakes of low-fat milk, lactose, and calcium from dairy products may reduce the risk of ovarian cancer, but this risk reduction has not been found in all studies.

An analysis from the Nurses’ Health Study that included more than 3,000 women found that higher calcium intakes (more than 800 mg per day) from dairy products—particularly low-fat or nonfat milk, yogurt, and cheese—compared with lower calcium intakes (200 mg or less per day) from dairy products was associated with a reduced risk of breast cancer among premenopausal but not postmenopausal women. Calcium from nondairy sources was not associated with a reduction in risk. Another analysis that involved more than 30,000 women in the Women’s Health Study found a reduced risk of breast cancer associated with higher (1366 mg per day or more) versus lower (less than 617 mg per day) total intakes of calcium among premenopausal but not postmenopausal women. In this study, higher versus lower calcium intakes from the diet, from supplements, and from total dairy products were not associated with reduced risk.

How might calcium help prevent cancer?

Although the exact mechanism by which calcium may help reduce the risk of colorectal cancer is unclear, researchers know that, at the biochemical level, calcium binds to bileacids and fatty acids in the gastrointestinal tract to form insoluble complexes known as calcium soaps. This reduces the ability of the acids (or their metabolites) to damage cells in the lining of the colon and stimulate cell proliferation to repair the damage. Calcium may also act directly to reduce cell proliferation in the lining of the colon or cause proliferatingcolon cells to undergo differentiation, which, in turn, leads to a reduction in cell proliferation. Calcium also may improve signaling within cells and cause cancer cells to differentiate and/or die.

How does the body absorb calcium from foods and supplements?

Calcium is absorbed passively (no cellular energy required) in the intestines by diffusing through the spaces between cells. It is also absorbed actively (cellular energy required) through intestinal cells by binding to a transport protein known as calbindin. The production of calbindin is dependent on vitamin D.

Does NCI recommend the use of calcium supplements to prevent colorectal cancer?

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

Note: The information in this fact sheet is not to be used as the basis for making health claims about calcium-containing products.

What are heterocyclic amines and polycyclic aromatic hydrocarbons, and how are they formed in cooked meats?

Heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) are chemicals formed when muscle meat, including beef, pork, fish, or poultry, is cooked using high-temperature methods, such as pan frying or grilling directly over an open flame (1). In laboratory experiments, HCAs and PAHs have been found to be mutagenic—that is, they cause changes in DNA that may increase the risk of cancer.

HCAs are formed when amino acids (the building blocks of proteins), sugars, and creatine or creatinine (substances found in muscle) react at high temperatures. PAHs are formed when fat and juices from meat grilled directly over a heated surface or open fire drip onto the surface or fire, causing flames and smoke. The smoke contains PAHs that then adhere to the surface of the meat. PAHs can also be formed during other food preparation processes, such as smoking of meats.

HCAs are not found in significant amounts in foods other than meat cooked at high temperatures. PAHs can be found in other smoked foods, as well as in cigarette smoke and car exhaust fumes.

What factors influence the formation of HCA and PAH in cooked meats?

The formation of HCAs and PAHs varies by meat type, cooking method, and “doneness” level (rare, medium, or well done). Whatever the type of meat, however, meats cooked at high temperatures, especially above 300 ºF (as in grilling or pan frying), or that are cooked for a long time tend to form more HCAs. For example, well-done, grilled, or barbecued chicken and steak all have high concentrations of HCAs. Cooking methods that expose meat to smoke contribute to PAH formation.

HCAs and PAHs become capable of damaging DNA only after they are metabolized by specific enzymes in the body, a process called “bioactivation.” Studies have found that the activity of these enzymes, which can differ among people, may be relevant to the cancer risks associated with exposure to these compounds.

What evidence is there that HCAs and PAHs in cooked meats may increase cancer risk?

Studies have shown that exposure to HCAs and PAHs can cause cancer in animal models. In many experiments, rodents fed a diet supplemented with HCAs developed tumors of the breast, colon, liver, skin, lung, prostate, and other organs. Rodents fed PAHs also developed cancers, including leukemia and tumors of the gastrointestinal tract and lungs. However, the doses of HCAs and PAHs used in these studies were very high—equivalent to thousands of times the doses that a person would consume in a normal diet.

Population studies have not established a definitive link between HCA and PAH exposure from cooked meats and cancer in humans. One difficulty with conducting such studies is that it can be difficult to determine the exact level of HCA and/or PAH exposure a person gets from cooked meats. Although dietary questionnaires can provide good estimates, they may not capture all the detail about cooking techniques that is necessary to determine HCA and PAH exposure levels. In addition, individual variation in the activity of enzymes that metabolize HCAs and PAHs may result in exposure differences, even among people who ingest (take in) the same amount of these compounds. Also, people may have been exposed to PAHs from other environmental sources, not just food.

Numerous epidemiologic studies have used detailed questionnaires to examine participants’ meat consumption and cooking methods. Researchers found that high consumption of well-done, fried, or barbecued meats was associated with increased risks of colorectal, pancreatic, and prostate cancer. However, other studies have found no association with risks of colorectal or prostate cancer.

In 2015, an independent panel of experts convened by the International Agency for Research on Cancer (IARC) determined consumption of red meat to be “probably carcinogenic to humans” (Group 2A), based largely on data from the epidemiologic studies and on the strong evidence from mechanistic studies. However, IARC did not conclude that HCAs and PAHs were associated with cancer incidence.

Do guidelines exist for the consumption of food containing HCAs and PAHs?

Currently, no Federal guidelines address the consumption of foods containing HCAs and PAHs. The World Cancer Research Fund/American Institute for Cancer Research issued a report in 2007 with dietary guidelines that recommended limiting the consumption of red and processed (including smoked) meats; however, no recommendations were provided for HCA and PAH levels in meat.

Are there ways to reduce HCA and PAH formation in cooked meats?

Even though no specific guidelines for HCA/PAH consumption exist, concerned individuals can reduce their exposure by using several cooking methods:

• Avoiding direct exposure of meat to an open flame or a hot metal surface and avoiding prolonged cooking times (especially at high temperatures) can help reduce HCA and PAH formation.
• Using a microwave oven to cook meat prior to exposure to high temperatures can also substantially reduce HCA formation by reducing the time that meat must be in contact with high heat to finish cooking.
• Continuously turning meat over on a high heat source can substantially reduce HCA formation compared with just leaving the meat on the heat source without flipping it often.
• Removing charred portions of meat and refraining from using gravy made from meat drippings can also reduce HCA and PAH exposure.

What are cruciferous vegetables?

Cruciferous vegetables are part of the Brassica genus of plants. They include the following vegetables, among others:

Why are cancer researchers studying cruciferous vegetables?

Cruciferous vegetables are rich in nutrients, including several carotenoids (beta-carotene, lutein, zeaxanthin); vitamins C, E, and K; folate; and minerals. They also are a good fiber source.

In addition, cruciferous vegetables contain a group of substances known as glucosinolates, which are sulfur-containing chemicals. These chemicals are responsible for the pungent aroma and bitter flavor of cruciferous vegetables.

During food preparation, chewing, and digestion, the glucosinolates in cruciferous vegetables are broken down to form biologically active compounds such as indoles, nitriles, thiocyanates, and isothiocyanates. Indole-3-carbinol (an indole) and sulforaphane (an isothiocyanate) have been most frequently examined for their anticancer effects.

Indoles and isothiocyanates have been found to inhibit the development of cancer in several organs in rats and mice, including the bladder, breast, colon, liver, lung, and stomach. Studies in animals and experiments with cells grown in the laboratory have identified several potential ways in which these compounds may help prevent cancer:

• They help protect cells from DNA damage.
• They help inactivate carcinogens.
• They have antiviral and antibacterial effects.
• They have anti-inflammatory effects.
• They induce cell death (apoptosis).
• They inhibit tumor blood vessel formation (angiogenesis) and tumor cell migration (needed for metastasis).

Studies in humans, however, have shown mixed results.

Is there evidence that cruciferous vegetables can help reduce cancer risk in people?

Researchers have investigated possible associations between intake of cruciferous vegetables and the risk of cancer. The evidence has been reviewed by various experts. Key studies regarding four common forms of cancer are described briefly below.

• Prostate cancer: Cohort studies in the Netherlands, United States, and Europe have examined a wide range of daily cruciferous vegetable intakes and found little or no association with prostate cancer risk. However, some case-control studies have found that people who ate greater amounts of cruciferous vegetables had a lower risk of prostate cancer.
• Colorectal cancer: Cohort studies in the United States and the Netherlands have generally found no association between cruciferous vegetable intake and colorectal cancer risk. The exception is one study in the Netherlands—the Netherlands Cohort Study on Diet and Cancer—in which women (but not men) who had a high intake of cruciferous vegetables had a reduced risk of colon (but not rectal) cancer.
• Lung cancer: Cohort studies in Europe, the Netherlands, and the United States have had varying results. Most studies have reported little association, but one U.S. analysis—using data from the Nurses’ Health Study and the Health Professionals’ Follow-up Study—showed that women who ate more than 5 servings of cruciferous vegetables per week had a lower risk of lung cancer.
• Breast cancer: One case-control study found that women who ate greater amounts of cruciferous vegetables had a lower risk of breast cancer. A meta-analysis of studies conducted in the United States, Canada, Sweden, and the Netherlands found no association between cruciferous vegetable intake and breast cancer risk. An additional cohort study of women in the United States similarly showed only a weak association with breast cancer risk.

A few studies have shown that the bioactive components of cruciferous vegetables can have beneficial effects on biomarkers of cancer-related processes in people. For example, one study found that indole-3-carbinol was more effective than placebo in reducing the growth of abnormal cells on the surface of the cervix.

In addition, several case-control studies have shown that specific forms of the gene that encodes glutathione S-transferase, which is the enzyme that metabolizes and helps eliminate isothiocyanates from the body, may influence the association between cruciferous vegetable intake and human lung and colorectal cancer risk.

Are cruciferous vegetables part of a healthy diet?

The federal government’s Dietary Guidelines for Americans 2010 recommend consuming a variety of vegetables each day. Different vegetables are rich in different nutrients.

Vegetables are categorized into five subgroups: dark-green, red and orange, beans and peas (legumes), starchy, and other vegetables. Cruciferous vegetables fall into the “dark-green vegetables” category and the “other vegetables” category.

Higher consumption of vegetables in general may protect against some diseases, including some types of cancer. However, when researchers try to distinguish cruciferous vegetables from other foods in the diet, it can be challenging to get clear results because study participants may have trouble remembering precisely what they ate. Also, people who eat cruciferous vegetables may be more likely than people who don’t to have other healthy behaviors that reduce disease risk. It is also possible that some people, because of their genetic background, metabolize dietary isothiocyanates differently. However, research has not yet revealed a specific group of people who, because of their genetics, benefit more than other people from eating cruciferous vegetables.

What is fluoride, and where is it found?

Fluoride is the name given to a group of compounds that are composed of the naturally occurring element fluorine and one or more other elements. Fluorides are present naturally in water and soil at varying levels.

In the 1940s, scientists discovered that people who lived where drinking water supplies had naturally occurring fluoride levels of approximately 1 part fluoride per million parts water or greater (>1.0 ppm) had fewer dental caries (cavities) than people who lived where fluoride levels in drinking water were lower. Many more recent studies have supported this finding.

It was subsequently found that fluoride can prevent and even reverse tooth decay by inhibiting bacteria that produce acid in the mouth and by enhancing remineralization, the process through which tooth enamel is “rebuilt" after it begins to decay.

In addition to building up in teeth, ingested fluoride accumulates in bones.

What is water fluoridation?

Water fluoridation is the process of adding fluoride to the water supply so the level reaches approximately 0.7 ppm, or 0.7 milligrams of fluoride per liter of water; this is the optimal level for preventing tooth decay.

When did water fluoridation begin in the United States?

In 1945, Grand Rapids, Michigan, adjusted the fluoride content of its water supply to 1.0 ppm and thus became the first city to implement community water fluoridation. By 2008, more than 72 percent of the U.S. population served by public water systems had access to fluoridated water.

The Centers for Disease Control and Prevention (CDC) considers fluoridation of water one of the greatest achievements in public health in the 20th century.

Can fluoridated water cause cancer?

A possible relationship between fluoridated water and cancer risk has been debated for years. The debate resurfaced in 1990 when a study by the National Toxicology Program, part of the National Institute of Environmental Health Sciences, showed an increased number of osteosarcomas (bone tumors) in male rats given water high in fluoride for 2 years. However, other studies in humans and in animals have not shown an association between fluoridated water and cancer.

In a February 1991 Public Health Service (PHS) report, the agency said it found no evidence of an association between fluoride and cancer in humans. The report, based on a review of more than 50 human epidemiologic (population) studies produced over the past 40 years, concluded that optimal fluoridation of drinking water “does not pose a detectable cancer risk to humans” as evidenced by extensive human epidemiologic data reported to date.

In one of the studies reviewed for the PHS report, scientists at NCI evaluated the relationship between the fluoridation of drinking water and the number of deaths due to cancer in the United States during a 36-year period, and the relationship between water fluoridation and number of new cases of cancer during a 15-year period. After examining more than 2.2 million cancer death records and 125,000 cancer case records in counties using fluoridated water, the researchers found no indication of increased cancer risk associated with fluoridated drinking water.

In 1993, the Subcommittee on Health Effects of Ingested Fluoride of the National Research Council, part of the National Academy of Sciences, conducted an extensive literature review concerning the association between fluoridated drinking water and increased cancer risk. The review included data from more than 50 human epidemiologic studies and six animal studies. The Subcommittee concluded that none of the data demonstrated an association between fluoridated drinking water and cancer. A 1999 report by the CDC supported these findings. The CDC report concluded that studies to date have produced “no credible evidence” of an association between fluoridated drinking water and an increased risk for cancer. Subsequent interview studies of patients with osteosarcoma and their parents produced conflicting results, but with none showing clear evidence of a causal relationship between fluoride intake and risk of this tumor.

In 2011, researchers examined the possible relationship between fluoride exposure and osteosarcoma in a new way: they measured fluoride concentration in samples of normal bone that were adjacent to a person’s tumor. Because fluoride naturally accumulates in bone, this method provides a more accurate measure of cumulative fluoride exposure than relying on the memory of study participants or municipal water treatment records. The analysis showed no difference in bone fluoride levels between people with osteosarcoma and people in a control group who had other malignant bone tumors.

More recent population-based studies using cancer registry data found no evidence of an association between fluoride in drinking water and the risk of osteosarcoma or Ewing sarcoma.

What is vitamin D?

Vitamin D is the name given to a group of fat-soluble prohormones (substances that usually have little hormonal activity by themselves but that the body can turn into hormones). Vitamin D helps the body use calcium and phosphorus to make strong bones and teeth. Skin exposed to sunshine can make vitamin D, and vitamin D can also be obtained from certain foods. Vitamin D deficiency can cause a weakening of the bones that is called rickets in children and osteomalacia in adults.

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 skin is exposed to ultraviolet radiation in sunlight. Both forms are converted to 25-hydroxyvitamin D in the liver. 25-Hydroxyvitamin D then travels through the blood to the kidneys, where it is further modified to 1,25-dihydroxyvitamin D, or calcitriol, the active form of vitamin D in the body. The most accurate method of evaluating a person’s vitamin D status is to measure the level of 25-hydroxyvitamin D in the blood.

Most people get at least some of the vitamin D they need through sunlight exposure. Dietary sources include a few foods that naturally contain vitamin D, such as fatty fish, fish liver oil, and eggs. However, most dietary vitamin D comes from foods fortified with vitamin D, such as milk, juices, and breakfast cereals. Vitamin D can also be obtained through dietary supplements.

The Institute of Medicine (IOM) of the National Academies has developed the following recommended daily intakes of vitamin D, assuming minimal sun exposure:

• For those between 1 and 70 years of age, including women who are pregnant or lactating, the recommended dietary allowance (RDA) is 15 micrograms (μg) per day. Because 1 μg is equal to 40 International Units (IU), this RDA can also be expressed as 600 IU per day.
• For those 71 years or older, the RDA is 20 μg per day (800 IU per day).
• For infants, the IOM could not determine an RDA due to a lack of data. However, the IOM set an Adequate Intake level of 10 μg per day (400 IU per day), which should provide sufficient vitamin D.

Although the average dietary intakes of vitamin D in the United States are below guideline levels, data from the National Health and Nutrition Examination Survey revealed that more than 80 percent of Americans had adequate vitamin D levels in their blood.

Even though most people are unlikely to have high vitamin D intakes, it is important to remember that excessive intake of any nutrient, including vitamin D, can cause toxic effects. Too much vitamin D can be harmful because it increases calcium levels, which can lead to calcinosis (the deposit of calcium salts in soft tissues, such as the kidneys, heart, or lungs) and hypercalcemia (high blood levels of calcium). The safe upper intake level of vitamin D for adults and children older than 8 years of age is 100 μg per day (4000 IU per day). Toxicity from too much vitamin D is more likely to occur from high intakes of dietary supplements than from high intakes of foods that contain vitamin D. Excessive sun exposure does not cause vitamin D toxicity. However, the IOM states that people should not try to increase vitamin D production by increasing their exposure to sunlight because this will also increase their risk of skin cancer.

Why are cancer researchers studying a possible connection between vitamin D and cancer risk?

Early epidemiologic research showed that incidence and death rates for certain cancers were lower among individuals living in southern latitudes, where levels of sunlight exposure are relatively high, than among those living at northern latitudes. Because exposure to ultraviolet light from sunlight leads to the production of vitamin D, researchers hypothesized that variation in vitamin D levels might account for this association. However, additional research based on stronger study designs is required to determine whether higher vitamin D levels are related to lower cancer incidence or death rates.

Experimental evidence has also suggested a possible association between vitamin D and cancer risk. In studies of cancer cells and of tumors in mice, vitamin D has been found to have several activities that might slow or prevent the development of cancer, including promoting cellular differentiation, decreasing cancer cell growth, stimulating cell death (apoptosis), and reducing tumor blood vessel formation (angiogenesis).

What is the evidence that vitamin D can help reduce the risk of cancer in people?

A number of epidemiologic studies have investigated whether people with higher vitamin D intakes or higher blood levels of vitamin D have lower risks of specific cancers. The results of these studies have been inconsistent, possibly because of the challenges in carrying out such studies. For example, dietary studies do not account for vitamin D made in the skin from sunlight exposure, and the level of vitamin D measured in the blood at a single point in time (as in most studies) may not reflect a person’s true vitamin D status. Also, it is possible that people with higher vitamin D intakes or blood levels are more likely to have other healthy behaviors. It may be one of these other behaviors, rather than vitamin D intake, that influences cancer risk.

Several randomized trials of vitamin D intake have been carried out, but these were designed to assess bone health or other non-cancer outcomes. Although some of these trials have yielded information on cancer incidence and mortality, the results need to be confirmed by additional research because the trials were not designed to study cancer specifically.

The cancers for which the most human data are available are colorectal, breast, prostate, and pancreatic cancer. Numerous epidemiologic studies have shown that higher intake or blood levels of vitamin D are associated with a reduced risk of colorectal cancer. In contrast, the Women’s Health Initiative randomized trial found that healthy women who took vitamin D and calcium supplements for an average of 7 years did not have a reduced incidence of colorectal cancer. Some scientists have pointed out that the relatively low level of vitamin D supplementation (10 μg, or 400 IU, once a day), the ability of participants to take additional vitamin D on their own, and the short duration of participant follow-up in this trial might explain why no reduction in colorectal cancer risk was found. Evidence on the association between vitamin D and the risks of all other malignancies studied is inconclusive.

How is vitamin D being studied now in clinical cancer research?

Taken together, the available data are not comprehensive enough to establish whether taking vitamin D can prevent cancer. To fully understand the effects of vitamin D on cancer and other health outcomes, new randomized trials need to be conducted. However, the appropriate dose of vitamin D to use in such trials is still not clear. Other remaining questions include when to start taking vitamin D, and for how long, to potentially see a benefit.

To begin addressing these issues, researchers are conducting two phase I trials to determine what dose of vitamin D may be useful for chemoprevention of prostate, colorectal, and lung cancers. In addition, larger randomized trials have been initiated to examine the potential role of vitamin D in the prevention of cancer. The Vitamin D/Calcium Polyp Prevention Study, which has finished recruiting approximately 2,200 participants, is testing whether vitamin D supplements, given alone or with calcium, can prevent the development of colorectal adenomas (precancerous growths) in patients who previously had an adenoma removed. The study’s estimated completion date is December 2017. The Vitamin D and Omega-3 Trial (VITAL) will examine whether vitamin D supplements can prevent the development of a variety of cancer types in healthy older men and women. The organizers of VITAL expect to recruit 20,000 participants and complete the trial by June 2016.

Researchers are also beginning to study vitamin D analogs--chemicals with structures similar to that of vitamin D--which may have the anticancer activity of vitamin D but not its ability to increase calcium levels.