Since 1970, this quarterly Journal for health professionals has published the best of nutritional research and clinical trials. New articles describing orthomolecular approaches to health management and treatment of disease are accompanied by lively editorials, book reviews, letters and reports.

The Journal of Orthomolecular Medicine has led the way for a quarter century in presenting, far in advance of other medical journals, new health concerns and treatments including: Candidiasis; Mercury Amalgam Toxicity; Niacin Therapy for Schizophrenia and Coronary Disease; Chronic Fatigue Syndrome; Vitamin C and Cancer; Allergies and Behavioral Disorders; Drug and Alcohol Abuse; Tissue and Mineral Analysis; and Orthomolecular Treatment for AIDS and Cardiovascular Disease.

Priscilla Slagle, M.D. is in the private practice of Nutritional /Functional Medicine & Psychiatry in Palm Springs & Encino, California.She is the author of The Way Up site which contains a great deal of information on nutritional medicine. She has helped thousands overcome the effects of stress, low moods, depression, & a variety of chronic symptoms & diseases and is one of the foremost experts on the prevention & treatment of mental and physical conditions by the use of amino acids. Dr. Slagle evaluates & treats numerous illnesses from a holistic perspective and is the author of "The Way Up From Down," a book on natural treatments for depression.

This not-for-profit public interest site looks at the food and supplement side of the heart health. Created by Eddy Vos, this site offers a comprehensive archive of medical and nutritional research without any commercial funding and provides the basic orthomolecular information necessary to improve your cardiovascular health.

A great many links to orthomolecular papers, sites and other information by a leading practitioner in the field

A major internet jumpsite to complementary and alternative medicine sites.

A good collection of complementary medicine related links covering basic nutrition facts, vitamins and aternative cancer therapies

News about orthomolecular medicine in the Dutch language, updated every day.

Dr. Huggins website is devoted to providing information and education to the public about dental materials (such as mercury, dental amalgam, nickel, and root canals) and practices that may be connected to health issues. Hugnet also discusses some of the emerging techniques being utilized to ensure safer dentistry.

The literature on clinical and scientific research into alternative medicine treatments is widely scattered, as is background information on alternative medicine systems and approaches. This database is a compilation of established sources in the USA, Europe and Asia. The listing is hyperlinked to existing Web sites where available, or to brief information on the resource, such as: how to obtain further details; type of literature covered; size of the holding or mode of access.

A large complementary medicine site which includes the Journal of Orthomolecular Medicine's archives as well as other journals, professional organizations, libraries, and bookstores.

The worlds largest searchable database of internet nutrition resources. Contains journal listings, food and nutrient databases, education resources, alternative medicine information and many other items.

A medical site which offers everything from searchable medical libraries to medical yellow pages and physician consultations. A good starting point for health care consumers.

This page is a jumpstation for sources of information on alternative, complementary, and integrative therapies for the public.

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Center for the Improvement of Human Functioning

The recommendations below are meant for generally healthy individuals interested in optimum health and preventing chronic diseases such as cardiovascular diseases (heart disease and stroke), diabetes, cancer, and osteoporosis. More detailed information regarding deficiencies of and requirements for specific nutrients is available in the Linus Pauling Institute'sMicronutrient Information Center.

Healthy Eating

• Eat at least five servings (2½ cups) of fruits and vegetables daily, but don't include potatoes in your tally. In fact, the latest Dietary Guidelines for Americans recommend that a person who consumes 2,000 calories a day should aim for nine daily servings of fruits and vegetables (the equivalent of 2½ cups of vegetables and 2 cups of fruit). More on fruits and vegetables
• To increase your omega-3 fatty acid intake, eat fish twice weekly and eat foods rich in alpha-linolenic acid, such as walnuts, flaxseeds, and flaxseed and canola oil. More on omega-3 fatty acids
• Use oils rich in unsaturated fats, such as soy, corn, safflower, and olive oil.
• Reduce your intake of saturated and hydrogenated (trans) fat, such as butter, cheese, animal fat, stick margarine, and vegetable shortening.
• Reduce your intake of potatoes, white flour, and white rice by substituting whole grain products, such as whole wheat flour and pasta, whole grain breads and cereals, and brown rice. More on whole grains
• Avoid foods and drinks that are high in sugar and low in nutrients, such as soft drinks, sugar-coated breakfast cereals, and candy.
• Limit your intake of overcooked or charred meat, and eat meat or fish with ample portions of vegetables.

Healthy Lifestyle

• Aim for a healthy weight. Becoming overweight (BMI of 25-29.5) or obese (BMI of 30 or more) increases the risk of many chronic diseases. Calculate your BMI. Having too much abdominal fat (waist circumference greater than 40 inches for men and greater than 35 inches for women) also increases disease risk. If you are at risk of obesity-associated diseases (see table), even a relatively small weight loss (10% of your current weight) can help lower your risk.
• Accumulate a minimum of 30 minutes of moderate-intensity exercise most days of the week. Most people can realize additional health benefits by increasing the duration of moderate-intensity exercise to an average of 60 minutes daily or by engaging in more vigorous physical activity. Examples of activities and their intensity levels. To improve muscular strength and balance and minimize bone loss, include strength-building activities, such as weight lifting, at least twice a week.
• If you smoke, make every effort to quit. Even if you have smoked many years, quitting will result in dramatically decreased risk of chronic diseases. Smoking cessation resources
• Moderate alcohol consumption is associated with reduced risk of cardiovascular diseases, but increased risk of some cancers. If you drink alcohol, limit your consumption to one alcoholic drink per day for women and two for men. Avoid alcohol if you have a personal or family history of breast or colon cancer or alcoholism. More on alcohol

Supplements

• Multivitamins:

  Take a multivitamin supplement with 100% of the Daily Value (DV) for most vitamins and essential minerals, keeping the following suggestions in mind: More on multivitamins
  • Iron: In general, men and postmenopausal women should take a multivitamin without iron. More on iron
  • Vitamin A: Look for a multivitamin containing no more than 2,500 IU of vitamin A, or, if unavailable, a multivitamin containing 5,000 IU of vitamin A, of which at least 50% comes from beta-carotene. More on vitamin A

• Vitamin C:

  Aim for a daily intake of at least 400 mg. Multivitamins usually provide 60 mg of vitamin C, and five servings of fruits and vegetables about 200 mg. More on vitamin C

• Vitamin D:

  The Linus Pauling Institute recommends that generally healthy adults take 2,000 IU (50 mcg) of supplemental vitamin D daily. Most multivitamins contain 400 IU of vitamin D, and single ingredient vitamin D supplements are available for additional supplementation.More on vitamin D

• Vitamin E:

  Take an extra supplement of 200 IU of natural source alpha-tocopherol (d-alpha-tocopherol) daily with a meal. More on vitamin E

• Calcium:

  No multivitamin supplement contains 100% of the DV for calcium. If your total daily calcium intake doesn't add up to 1,000 mg add an extra calcium supplement (with a meal) to make up the difference.More on calcium

* More on the difference between Dr. Linus Pauling's recommendation and the Linus Pauling Institute's recommendation for vitamin C intake

Vitamin C

Vitamin C, also known as ascorbic acid, is a water-soluble vitamin. Unlike most mammals and other animals, humans do not have the ability to make their own vitamin C. Therefore, we must obtain vitamin C through our diet.

Function

Vitamin C is required for the synthesis of collagen, an important structural component of blood vessels, tendons, ligaments, and bone. Vitamin C also plays an important role in the synthesis of the neurotransmitter, norepinephrine. Neurotransmitters are critical to brain function and are known to affect mood. In addition, vitamin C is required for the synthesis ofcarnitine, a small molecule that is essential for the transport of fat into cellular organelles called mitochondria, where the fat is converted to energy(1). Research also suggests that vitamin C is involved in the metabolism of cholesterol to bile acids, which may have implications for blood cholesterol levels and the incidence of gallstones (2).

Vitamin C is also a highly effective antioxidant. Even in small amounts vitamin C can protect indispensable molecules in the body, such as proteins, lipids (fats), carbohydrates, and nucleic acids (DNA and RNA), from damage by free radicals and reactive oxygen species that can be generated during normal metabolism as well as through exposure to toxins and pollutants (e.g., cigarette smoke). Vitamin C may also be able to regenerate other antioxidants such as vitamin E (1). One recent study of cigarette smokers found that vitamin C regenerated vitamin E from its oxidized form (3).

Deficiency

Scurvy

Severe vitamin C deficiency has been known for many centuries as the potentially fatal disease, scurvy. By the late 1700s the British navy was aware that scurvy could be cured by eating oranges or lemons, even though vitamin C would not be isolated until the early 1930s. Symptoms of scurvy include bleeding and bruising easily, hair and tooth loss, and joint pain and swelling. Such symptoms appear to be related to the weakening of blood vessels, connective tissue, and bone, which all contain collagen. Early symptoms of scurvy like fatigue may result from diminished levels of carnitine, which is needed to derive energy from fat, or from decreased synthesis of theneurotransmitter norepinephrine (see Function). Scurvy is rare in developed countries because it can be prevented by as little as 10 mg of vitamin C daily(4). However, cases have occurred in children and the elderly on very restricted diets (5, 6).

The Recommended Dietary Allowance (RDA)

In the U.S., the recommended dietary allowance (RDA) for vitamin C was revised in 2000 upward from the previous recommendation of 60 mg daily for men and women. The RDA continues to be based primarily on the prevention of deficiency disease, rather than the prevention of chronic disease and the promotion of optimum health. The recommended intake for smokers is 35 mg/day higher than for nonsmokers, because smokers are under increasedoxidative stress from the toxins in cigarette smoke and generally have lower blood levels of vitamin C (7).

Disease Prevention

The amount of vitamin C required to prevent chronic disease appears to be more than that required for prevention of scurvy. Much of the information regarding vitamin C and the prevention of chronic disease is based onprospective studies, in which vitamin C intake is assessed in large numbers of people who are followed over time to determine whether they develop specific chronic diseases.

Cardiovascular Diseases

Coronary Heart Disease

Until recently, the results of most prospective studies indicated that low or deficient intakes of vitamin C were associated with an increased risk ofcardiovascular diseases, and that modest dietary intakes of about 100 mg/day were sufficient for maximal reduction of cardiovascular disease risk among nonsmoking men and women (1). A recent meta-analysis of 14 cohort studies concluded that dietary vitamin C intake, but not supplemental vitamin C intake, was inversely related to coronary heart disease (CHD) risk (8). Thus, some studies did not find significant reductions in CHD risk among vitamin C supplement users in well-nourished populations (9-11). One notable exception was the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study (12). This study found that the risk of death from cardiovascular diseases was 42% lower in men and 25% lower in women who consumed more than 50 mg/day of dietary vitamin C and regularly took vitamin C supplements, corresponding to a total vitamin C intake of about 300 mg/day (13). Results from the Nurses’ Health Study (NHS), based on the follow-up of more than 85,000 women over 16 years, also suggested that higher vitamin C intakes may be cardioprotective (14). In this study, vitamin C intake of more than 359 mg/day from diet plus supplements or supplement use itself was associated with a 27-28% reduction in CHD risk. However, in those women who did not take vitamin C supplements, dietary vitamin C intake was not significantly associated with CHD risk. Hence, both the NHANES I Epidemiologic Follow-up Study (12, 13)and NHS (14) do not support the conclusions of the above meta-analysis (8). Another pooled analysis of nine prospective cohort studies, including more than 290,000 adults who were free of CHD at baseline and followed for an average of ten years, found that those who took more than 700 mg/day of supplemental vitamin C had a 25% lower risk of CHD than those who did not take vitamin C supplements (15). Additionally, a randomized, double-blind,placebo-controlled trial in more than 14,000 older men participating in the Physicians’ Health Study II found that vitamin C supplementation (500 mg/day) for an average of eight years had no significant effect on major cardiovascular events, total myocardial infarction, or cardiovascular mortality(16). However, this study had several limitations (17); see the Linus Pauling Institute’s response to this study. Data from pharmacokinetic studies of vitamin C at the National Institutes of Health (NIH) indicate that plasma and circulating cells—and thus, presumably, total body pool—in healthy, young subjects became fully saturated with vitamin C at a dose of about 400 mg/day (18). Therefore, the results of the pooled analysis of prospective cohort studies as well as individual, large prospective studies, such as the NHANES I Epidemiologic Follow-up Study (12, 13) and NHS (14), together with pharmacokinetic data of vitamin C in humans (18), suggest that maximal reduction of CHD risk may require vitamin C intakes of 400 mg/day or more(19).

Stroke

With respect to vitamin C and cerebrovascular disease, a prospective studythat followed more than 2,000 residents of a rural Japanese community for 20 years found that the risk of stroke in those with the highest serum levels of vitamin C was 29% lower than in those with the lowest serum levels of vitamin C (20). Additionally, the risk of stroke in those who consumed vegetables 6-7 days of the week was 54% lower than in those who consumed vegetables 0-2 days of the week. In this population, serum levels of vitamin C were highly correlated with fruit and vegetable intake. Therefore, as in many studies of vitamin C intake and chronic disease risk, it is difficult to separate the effects of vitamin C on stroke risk from the effects of other components of fruits and vegetables, emphasizing the benefits of a diet rich in fruits and vegetables in reducing stroke risk. Hence, plasma vitamin C levels may be a good biomarker for fruit and vegetable intake and other lifestyle factors that contribute to a reduced risk of stroke. A recent 10-year prospective study in 20,649 adults found that those in the top quartile of plasma vitamin C concentrations had a 42% lower risk of stroke compared to those in the lowest quartile (21). A randomized, double-blind, placebo-controlled trial in more than 14,000 older men participating in the Physicians’ Health Study II found that vitamin C supplementation (500 mg/day) for an average of eight years had no significant effect on stroke death, ischemic stroke, or hemorrhagic stroke (16). However, this study had numerous limitations that make it difficult to draw conclusions for the general population(17); see the Linus Pauling Institute’s response to this study.

Cancer

A large number of studies have shown that increased consumption of fresh fruits and vegetables is associated with a reduced risk for most types ofcancer (22). Such studies were the basis for dietary guidelines endorsed by the U.S. Department of Agriculture and the National Cancer Institute, which recommended at least five servings of fruits and vegetables per day. U.S. government organizations currently recommend eating a variety of fruits and vegetables daily; the recommended serving number depends on total caloric intake, which is governed by age, gender, body composition, and physical activity level (23). A number of case-control studies have investigated the role of vitamin C in cancer prevention.  Most have shown that higher intakes of vitamin C are associated with decreased incidence of cancers of the mouth, throat and vocal chords, esophagus, stomach, colon-rectum, and lung. Because the possibility of bias is greater in case-control studies, prospective cohort studies are generally given more weight when evaluating the effect of nutrient intake on disease. In general, prospective studies in which the lowest intake group consumed more than 86 mg of vitamin C daily have not found differences in cancer risk, while studies finding significant cancer risk reductions found them in people consuming at least 80 to 110 mg of vitamin C daily (1).

A prospective study that followed 870 men over a period of 25 years found that those who consumed more than 83 mg of vitamin C daily had a striking, 64% reduction in lung cancer compared with those who consumed less than 63 mg per day (24). However, a pooled analysis of eight prospective studies concluded that dietary vitamin C was not related to lung cancer when the analysis was controlled for other dietary factors (25). Although most large prospective studies observed no association between breast cancer and vitamin C intake, two studies found dietary vitamin C intake to be inversely associated with breast cancer risk in certain subgroups. In the Nurses' Health Study, premenopausal women with a family history of breast cancer who consumed an average of 205 mg/day of vitamin C from foods had a 63% lower risk of breast cancer than those who consumed an average of 70 mg/day (26). In the Swedish Mammography Cohort, overweight women who consumed an average of 110 mg/day of vitamin C had a 39% lower risk of breast cancer compared to overweight women who consumed an average of 31 mg/day (27). A number of observational studies have found increased dietary vitamin C intake to be associated with decreased risk of stomach cancer, and laboratory experiments indicate that vitamin C inhibits the formation of carcinogenic compounds in the stomach (28, 29). Infection with the bacteria, Helicobacter pylori (H. pylori), is known to increase the risk of stomach cancer and also appears to lower the vitamin C content of stomach secretions. Although two intervention studies did not find a decrease in the occurrence of stomach cancer with vitamin C supplementation (7), more recent research suggests that vitamin C supplementation may be a useful addition to standard H. pylori eradication therapy in reducing the risk of gastric cancer (30, 31). Another intervention trial, a randomized, double-blind, placebo-controlled trial in more than 14,000 older men participating in the Physicians’ Health Study (PHS) II, reported vitamin C supplementation (500 mg/day) for an average of eight years had no significant effect on total cancer or site-specific cancers, including colorectal, lung, and prostate cancer(32). However, the PHS II had several limitations; see the Linus Pauling Institute’s response to the PHS II.

Cataracts

Cataracts are a leading cause of visual impairment throughout the world. In the U.S., cataract-related expenditures are estimated to exceed $3 billion annually (33). Cataracts occur more frequently and become more severe as people age. Decreased vitamin C levels in the lens of the eye have been associated with increased severity of cataracts in humans. Some, but not all, studies have observed increased dietary vitamin C intake (34, 35) and increased blood levels of vitamin C (36, 37) to be associated with decreased risk of cataracts. In general, those studies that have found a relationship suggest that vitamin C intake may have to be higher than 300 mg/day for a number of years before a protective effect can be detected (1). A 7-year controlled intervention trial in 4,629 men and women found that a daily antioxidant supplement containing 500 mg of vitamin C, 400 IU of vitamin E, and 15 mg of beta-carotene had no effect on the development and progression of age-related cataracts compared to a placebo (38). Therefore, the relationship between vitamin C intake and the development of cataracts requires further clarification before specific recommendations can be made.

Gout

Gout, a condition that afflicts more than 1% of U.S. adults, is characterized by abnormally high blood levels of uric acid (urate) (39). Urate crystals may form in joints, resulting in inflammation and pain, as well as in the kidneys and urinary tract, resulting in kidney stones. The tendency to develop elevated blood uric acid levels and gout is often inherited; however, dietary and lifestyle modification may be helpful in both the prevention and treatment of gout (40). In an observational study that included 1,387 men, higher intakes of vitamin C were associated with lower serum levels of uric acid (41). More recently, a prospective study that followed a cohort of 46,994 men for 20 years found that total daily vitamin C intake was inversely associated with risk of gout, with higher intakes being associated with greater risk reductions(42). The results of this study also indicate that supplemental vitamin C may be helpful in the prevention of gout (42). Interestingly, a randomized, double-blind, placebo-controlled trial in 184 adult nonsmokers reported that vitamin C supplementation (500 mg/day) for two months lowered serum concentrations of uric acid compared to placebo (43).

Lead toxicity

Although the use of lead paint and leaded gasoline has been discontinued in the U.S., lead toxicity continues to be a significant health problem, especially in children living in urban areas. Abnormal growth and development have been observed in infants of women exposed to lead during pregnancy, while children who are chronically exposed to lead are more likely to develop learning disabilities, behavioral problems, and to have a low IQ. In adults, lead toxicity may result in kidney damage, high blood pressure, and anemia. In a study of 747 older men, blood lead levels were significantly higher in those who reported total dietary vitamin C intakes averaging less than 109 mg/day compared to those who reported higher vitamin C intakes (44). A much larger study of 19,578 people, including 4,214 children from six to 16 years of age, found higher serum vitamin C levels to be associated with significantly lower blood lead levels (45). A U.S. national survey of more than 10,000 adults found that blood lead levels were inversely related to serum vitamin C levels (46). An intervention trial that examined the effects of vitamin C supplementation on blood lead levels in 75 adult male smokers found that 1,000 mg/day of vitamin C resulted in significantly lower blood lead levels over a four-week treatment period compared to placebo (47). A lower dose of 200 mg/day did not significantly affect blood lead levels, despite the finding that serum vitamin C levels were not different than those in the group who took 1,000 mg/day. The mechanism for the relationship between vitamin C intake and blood lead levels is not known, although it has been postulated that vitamin C may inhibit intestinal absorption or enhance urinary excretion of lead.

Role in Immunity

Vitamin C affects several components of the human immune system; for example, vitamin C has been shown to stimulate both the production (48-52)and function (53, 54) of leukocytes (white blood cells), especially neutrophils,lymphocytes, and phagocytes. Specific measures of functions stimulated by vitamin C include cellular motility (54), chemotaxis (53, 54), and phagocytosis(53). Neutrophils, which attack foreign bacteria and viruses, seem to be the primary cell type stimulated by vitamin C, but lymphocytes and other phagocytes are also affected (55). Additionally, several studies have shown that supplemental vitamin C increases serum levels of antibodies (56, 57)and C1q complement proteins (58-60) in guinea pigs, which—like humans—cannot synthesize vitamin C and hence depend on dietary vitamin C. However, some studies have reported no beneficial changes in leukocyte production or function with vitamin C treatment (61-64). Vitamin C may also protect the integrity of immune cells. Neutrophils, mononuclear phagocytes, and lymphocytes accumulate vitamin C to high concentrations, which can protect these cell types from oxidative damage (52, 65, 66). In response to invading microorganisms, phagocytic leukocytes release non-specific toxins, such as superoxide radicals, hypochlorous acid (“bleach”), and peroxynitrite; these reactive oxygen species kill pathogens and, in the process, can damage the leukocytes themselves (67). Vitamin C, through its antioxidant functions, has been shown to protect leukocytes from such effects of autooxidation (68). Phagocytic leukocytes also produce and releasecytokines, including interferons, which have antiviral activity (69). Vitamin C has been shown to increase interferon levels in vitro (70).

It is widely thought by the general public that vitamin C boosts the function of the immune system, and accordingly, may protect against viral infections and perhaps other diseases. While some studies suggest the biological plausibility of vitamin C as an immune enhancer, human studies published to date are conflicting. Further, controlled clinical trials of appropriate statistical power would be necessary to determine if supplemental vitamin C boosts the immune system.

Disease Treatment

Cardiovascular Diseases

Vasodilation

The ability of blood vessels to relax or dilate (vasodilation) is compromised in individuals with atherosclerosis. Damage to the heart muscle caused by a heart attack and damage to the brain caused by a stroke are related, in part, to the inability of blood vessels to dilate enough to allow blood flow to the affected areas. The pain of angina pectoris is also related to insufficient dilation of the coronary arteries. Impaired vasodilation has been identified as an independent risk factor for cardiovascular disease (71). Many randomized,double-blind, placebo-controlled studies have shown that treatment with vitamin C consistently results in improved vasodilation in individuals with coronary heart disease as well as those with angina pectoris, congestive heart failure, diabetes, high cholesterol, and high blood pressure (1, 72-74). Improved vasodilation has been demonstrated at an oral dose of 500 mg of vitamin C daily (72).

Hypertension

Individuals with high blood pressure (hypertension) are at increased risk of developing cardiovascular diseases. Several, but not all, studies have demonstrated a blood pressure lowering effect of vitamin C supplementation(75). A small study in individuals with hypertension found that vitamin C supplementation with 500 mg/day for six weeks slightly decreased systolic blood pressure (1.8 mm Hg reduction) compared to a placebo (76). Another study in individuals with elevated blood pressure found that a daily supplement of 500 mg of vitamin C resulted in an average drop in systolic blood pressure of 9% after four weeks (77). It should be noted that those participants who were taking antihypertensive medications continued taking them throughout the four-week study. Because the findings regarding vitamin C and high blood pressure have not yet been replicated in larger studies, it is important for individuals with significantly elevated blood pressure to continue current therapy (medication, lifestyle changes, etc.) in consultation with their health care provider.

Cancer

Studies in the 1970s and 1980s conducted by Linus Pauling, Ewan Cameron, and colleagues suggested that very large doses of vitamin C (10 grams/day intravenously for ten days followed by at least 10 grams/day orally indefinitely) were helpful in increasing the survival time and improving the quality of life of terminal cancer patients (78). However, two randomized placebo-controlled studies conducted at the Mayo Clinic found no differences in outcome between terminal cancer patients receiving 10 grams/day of vitamin C orally or placebo (79, 80). There were significant methodological differences between the Mayo Clinic and Pauling's studies, and recently, researchers from the NIH suggested that the route of administration (intravenous versus oral) may have been the key to the discrepant results. Intravenous (IV) administration can result in much higher blood levels of vitamin C than oral administration, and vitamin C levels that are toxic to cancer cells in culture can be achieved in humans only with intravenous but not oral administration of vitamin C (81). Dr. Mark Levine and colleagues at NIH have investigated the anticancer mechanism responsible for vitamin C and reported that it involves production of hydrogen peroxide, which is selectively toxic to cancer cells (82-84). Thus, it appears reasonable to reevaluate the use of high-dose vitamin C as adjunctive cancer therapy.

Currently, there are no results from controlled clinical trials indicating that vitamin C would adversely affect the survival of cancer patients. Recently, two phase I clinical trials in patients with advanced cancer found that intravenous administration of vitamin C at doses up to 1.5 g/kg of body weight was well tolerated and safe in pre-screened patients (85, 86); other phase I trials are ongoing (87). Additionally, phase II clinical trials evaluating the efficacy of vitamin C in cancer treatment are currently under way (87). Some case reports have suggested that intravenous vitamin C may aid in cancer treatment (88, 89). However, vitamin C should not be used in place of therapy that has been demonstrated effective in the treatment of a particular type of cancer, for example, chemotherapy or radiation therapy. If an individual with cancer chooses to take vitamin supplements, it is important that the clinician coordinating his or her treatment is aware of the type and dose of each supplement. While research is under way to determine whether combinations of antioxidant vitamins might be beneficial as an adjunct to conventional cancer therapy, definitive conclusions are not yet possible (90). For more information about intravenous vitamin C and cancer, see the Linus Pauling Institute Spring/Summer 2006 Research Newsletter.

In a presentation at a meeting of the American Cancer Society, a scientist suggested that supplemental vitamin C might enhance the growth of cancer cells or protect them from cell-killing free radicals produced by radiation and some forms of chemotherapy. An article published in the Spring/Summer 2000 issue of the Linus Pauling Institute Newsletter, Is vitamin C harmful for cancer patients?, provides additional insight on this topic.

For information about the clinical use of high-dose intravenous vitamin C as an adjunct in cancer treatment, visit the University of Kansas Medical Center Program in Integrative Medicine Web site.

Diabetes Mellitus

Cardiovascular diseases (heart disease and stroke) are the leading cause of death in individuals with diabetes. Evidence that diabetes is a condition of increased oxidative stress led to the hypothesis that higher intakes ofantioxidant nutrients could help decrease cardiovascular disease risk in diabetic individuals. In support of this hypothesis, a 16-year study of 85,000 women, 2% of whom were diabetic, found that vitamin C supplement use (400 mg/day or more) was associated with significant reductions in the risk of fatal and nonfatal coronary heart disease in the entire cohort as well as in those with diabetes (14). In contrast, a 15-year study of postmenopausal women found that diabetic women who reported taking at least 300 mg/day of vitamin C from supplements when the study began were at significantly higher risk of death from coronary heart disease and stroke than those who did not take vitamin C supplements (91). Vitamin C supplement use was not associated with a significant increase in cardiovascular disease mortality in the cohort as a whole. Although a number of observational studies have found that higher dietary intakes of vitamin C are associated with lower cardiovascular disease risk, randomized controlled trials have not found antioxidant supplementation that included vitamin C to reduce the risk of cardiovascular disease in diabetic or other high-risk individuals (92, 93).

It is possible that genetic differences may influence the effect of vitamin C supplementation on cardiovascular disease. When the results of one randomized controlled trial were reanalyzed based on haptoglobin genotype, antioxidant therapy (1,000 mg/day of vitamin C + 800 IU/day of vitamin E) was associated with improvement of coronary atherosclerosis in diabetic women with two copies of the haptoglobin 1 gene but worsening of coronary atherosclerosis in those with two copies of the haptoglobin 2 gene (94). The significance of these findings is not entirely clear, but they suggest that there may be a subpopulation of people with diabetes who will benefit from antioxidant therapy, while others may not benefit or could actually be harmed.

Common cold

The work of Linus Pauling stimulated public interest in the use of large doses (greater than 1 gram/day, also sometimes called "mega-doses") of vitamin C to prevent the common cold (95). In the past 30 years, numerous placebo-controlled trials have examined the effect of vitamin C supplementation on the prevention and treatment of colds. A meta-analysis of 30 placebo-controlled prevention trials found that vitamin C supplementation in doses up to 2 grams/day did not decrease the incidence of colds (96). However, in a subgroup of marathon runners, skiers, and soldiers training in the Arctic, doses ranging from 250 mg/day to 1 gram/day decreased the incidence of colds by 50%. Overall, the preventive use of vitamin C supplementation reduced the duration of colds by about 8% in adults and 14% in children. Most of the prevention trials used a dose of 1 gram/day. When treatment was started at the onset of symptoms, vitamin C supplementation did not shorten the duration of colds in seven placebo-controlled trials at doses ranging from 1-4 grams/day. Additionally, the same authors completed a meta-analysis of the 15 trials that assessed the effect of vitamin C on cold severity; no consistent evidence that vitamin C was beneficial in ameliorating cold symptoms was found in this analysis. Thus, the overall conclusion of this meta-analysis was that vitamin C is ineffective as a prophylactic against the common cold, but individuals under stress, such as those exposed to strenuous physical exercise or cold weather, may experience some therapeutic benefit (96). More recently, a randomized, double-blind (but not placebo-controlled) study reported that those who took 500 mg/day of supplemental vitamin C had a 66% lower risk for contracting three or more colds in a five-year period compared to those who took 50 mg/day of supplemental vitamin C (97). The authors of this study did not find any significant differences in the two groups when analyzing data regarding cold severity or duration. However, the doses used in this study were smaller than those used in most of the previous studies.

Some authors have asserted that the studies included in the above mentioned meta-analysis (96) utilized daily doses of vitamin C that would be too low to observe a therapeutic benefit (98, 99). Additionally, results of a recent pharmacokinetic study suggest that dividing the daily dose and administering it several times throughout the day, thereby increasing dose frequency, would better sustain plasma ascorbate levels (81). Large-scale, controlled clinical trials using pharmacological doses of vitamin C are necessary to determine whether or not higher doses of vitamin C have any therapeutic value in preventing or treating the common cold. For a more detailed discussion on vitamin C and the common cold, see the Linus Pauling Institute's Spring/Summer 2006 Research Newsletter.

Vitamin C (L-ascorbic acid) is available in many forms, but there is little scientific evidence that any one form is better absorbed or more effective than another. Most experimental and clinical research uses ascorbic acid or sodium ascorbate.

Natural vs. synthetic vitamin C

Natural and synthetic L-ascorbic acid are chemically identical and there are no known differences in their biological activities or bioavailabilities (101).

Mineral ascorbates

Mineral salts of ascorbic acid are buffered and, therefore, less acidic than ascorbic acid. Some people find them less irritating to the gastrointestinal tract than ascorbic acid. Sodium ascorbate and calcium ascorbate are the most common forms, although a number of other mineral ascorbates are available. Sodium ascorbate generally provides 131 mg of sodium per 1,000 mg of ascorbic acid, and pure calcium ascorbate provides 114 mg of calcium per 1,000 mg of ascorbic acid.

Vitamin C with bioflavonoids

Bioflavonoids are a class of water-soluble plant pigments that are often found in vitamin C-rich fruits and vegetables, especially citrus fruits. There is little evidence that the bioflavonoids in most commercial preparations increase the bioavailability or efficacy of vitamin C (102). Studies in cell culture indicate that a number of flavonoids inhibit the transport of vitamin C into cells (103-105), and supplementation of rats with quercetin and vitamin C decreased the intestinal absorption of vitamin C (103). More research is needed to determine the significance of these findings in humans.

Ascorbate and vitamin C metabolites

One supplement, Ester-C^® contains mainly calcium ascorbate, but also contains small amounts of the vitamin C metabolites dehydroascorbate (oxidized ascorbic acid), calcium threonate, and trace levels of xylonate and lyxonate. Although the metabolites are supposed to increase the bioavailability of vitamin C, the only published study in humans addressing this issue found no difference between Ester-C^® and commercially available ascorbic acid tablets with respect to the absorption and urinary excretion of vitamin C (102). Ester-C^® should not be confused with ascorbyl palmitate, which is also marketed as "vitamin C ester" (see below).

Ascorbyl palmitate

Ascorbyl palmitate is actually a vitamin C ester (i.e., vitamin C that has been esterified to a fatty acid). In this case, vitamin C is esterified to the saturated fatty acid, palmitic acid, resulting in a fat-soluble form of vitamin C. Ascorbyl palmitate has been added to a number of skin creams due to interest in its antioxidant properties as well as its importance in collagen synthesis (106). Although ascorbyl palmitate is also available as an oral supplement, it is likely that most of it is hydrolyzed (broken apart) to ascorbic acid and palmitic acid in the digestive tract before it is absorbed (107). Ascorbyl palmitate is also marketed as "vitamin C ester," which should not be confused with Ester-C^®(see above).

For a more detailed review of scientific research on the bioavailability of different forms of vitamin C, see The Bioavailability of Different Forms of Vitamin C.

Toxicity

A number of possible problems with very large doses of vitamin C have been suggested, mainly based on in vitro experiments or isolated case reports, including genetic mutations, birth defects, cancer, atherosclerosis, kidney stones, "rebound scurvy," increased oxidative stress, excess iron absorption, vitamin B₁₂ deficiency, and erosion of dental enamel. However, none of these alleged adverse health effects have been confirmed, and there is no reliable scientific evidence that large amounts of vitamin C (up to 10 grams/day in adults) are toxic or detrimental to health. The concerns of kidney stone formation with vitamin C supplementation are discussed below. With the latest RDA published in 2000, a tolerable upper intake level (UL) for vitamin C was set for the first time. A UL of 2 grams (2,000 milligrams) daily was recommended in order to prevent most adults from experiencing diarrhea andgastrointestinal disturbances (7). Such symptoms are not generally serious, especially if they resolve with temporary discontinuation or reduction of high-dose vitamin C supplementation. For a more thorough discussion of the Linus Pauling Institute's response to the UL for vitamin C, see the article, The New Recommendations for Dietary Antioxidants: A Response and Position Statement by the Linus Pauling Institute, in the Spring/Summer 2000 Newsletter. A more detailed discussion of vitamin C and the risk of kidney stones can be found below and in the article, What About Vitamin C and Kidney Stones?, in the Fall/Winter 1999 Newsletter.

*Source of intake should be from foods or formula only.

Does vitamin C promote oxidative damage under physiological conditions?Vitamin C is known to function as a highly effective antioxidant in living organisms. However, in test tube experiments, vitamin C can interact with some free metal ions to produce potentially damaging free radicals. Although free metal ions are not generally found under physiological conditions, the idea that high doses of vitamin C might be able to promote oxidative damage in vivo has received a great deal of attention. Widespread publicity has been given to a few studies suggesting a pro-oxidant effect of vitamin C (108, 109), but these studies turned out to be either flawed or of no physiological relevance. A comprehensive review of the literature found no credible scientific evidence that supplemental vitamin C promotes oxidative damage under physiological conditions or in humans (110). Studies that report a pro-oxidant effect for vitamin C should be evaluated carefully to determine whether the study system was physiologically relevant and to rule out the possibility of methodological and design flaws.

For example, a study in the June 15, 2001 issue of the journal Sciencereported that lipid hydroperoxides (rancid fat molecules) can react with vitamin C to form products that could potentially harm DNA, although the reaction of these products with DNA was not demonstrated in this study(108). To find out why the Linus Pauling Institute considers the study's conclusions unwarranted, see Vitamin C doesn't cause cancer! in the Linus Pauling Institute Newsletter.

Kidney Stones

Because oxalate is a metabolite of vitamin C, there is some concern that high vitamin C intake could increase the risk of oxalate kidney stones. Some (111-113), but not all (114-116), studies have reported that supplemental vitamin C increases urinary oxalate levels. Whether any increase in oxalate levels would translate to an elevation in risk for kidney stones has been examined in epidemiological studies. Two large prospective studies, one following 45,251 men for six years and the other following 85,557 women for 14 years, reported that consumption of ≥1,500 mg of vitamin C daily did not increase the risk of kidney stone formation compared to those consuming <250 mg daily. However, a more recent prospective study that followed 45,619 men for 14 years found that those who consumed ≥1,000 mg/day of vitamin C had a 41% higher risk of kidney stones compared to men consuming <90 mg of vitamin C daily—the current recommended dietary allowance (see RDA;(117)). In this study, low intakes (90-249 mg/day) of vitamin C (primarily from the diet) were also associated with a significantly elevated risk. Supplemental vitamin C intake was only weakly associated with increased risk of kidney stones in this study (117). Despite conflicting results, it may be prudent for individuals predisposed to oxalate kidney stone formation to avoid high-dose vitamin C supplementation.

Drug Interactions

A number of drugs are known to lower vitamin C levels, requiring an increase in its intake. Estrogen-containing contraceptives (birth control pills) are known to lower vitamin C levels in plasma and white blood cells. Aspirin can lower vitamin C levels if taken frequently. For example, taking two aspirin tablets every six hours for a week has been reported to lower vitamin C levels in white blood cells by 50%, primarily by increasing urinary excretion of vitamin C (118).

There is some evidence, though controversial, that vitamin C interacts with anticoagulant medications (blood thinners) like warfarin (Coumadin). Large doses of vitamin C may block the action of warfarin, requiring an increase in dose to maintain its effectiveness. Individuals on anticoagulants should limit their vitamin C intake to 1 gram/day and have their prothrombin time monitored by the clinician following their anticoagulant therapy. Because high doses of vitamin C have also been found to interfere with the interpretation of certain laboratory tests (e.g., serum bilirubin, serum creatinine, and the guaiac assay for occult blood), it is important to inform one's health care provider of any recent supplement use (119).

Antioxidant Supplements and HMG-CoA Reductase Inhibitors (Statins)

A 3-year randomized controlled trial in 160 patients with documented coronary heart disease (CHD) and low HDL levels found that a combination of simvastatin (Zocor) and niacin increased HDL₂ levels, inhibited the progression of coronary artery stenosis (narrowing), and decreased the frequency of cardiovascular events, such as myocardial infarction (heart attack) and stroke (120). Surprisingly, when an antioxidant combination (1,000 mg vitamin C, 800 IU alpha-tocopherol, 100 mcg selenium, and 25 mg beta-carotene daily) was taken with the simvastatin-niacin combination, the protective effects were diminished. Since the antioxidants were taken together in this trial, the individual contribution of vitamin C cannot be determined. In contrast, a much larger randomized controlled trial in more than 20,000 men and women with CHD or diabetes found that simvastatin and an antioxidant combination (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) did not diminish the cardioprotective effects of simvastatin therapy over a 5-year period (121). These contradictory findings indicate that further research is needed on potential interactions between antioxidant supplements and cholesterol-lowering drugs, such as HMG-CoA reductase inhibitors (statins).

For healthy men and women, the Linus Pauling Institute recommends a vitamin C intake of at least 400 mg daily—the amount that has been found to fully saturate plasma and circulating cells with vitamin C in young, healthy nonsmokers (18). Consuming at least five servings (2½ cups) of fruits and vegetables daily provides about 200 mg of vitamin C. Most multivitamin supplements provide 60 mg of vitamin C. To make sure you meet the Institute’s recommendation, supplemental vitamin C in two separate 250-mg doses taken in the morning and evening is recommended.

Older adults (65 years and older)

Although it is not yet known with certainty whether older adults have higher requirements for vitamin C than younger people, some older populations have been found to have vitamin C intakes considerably below the RDA of 75 and 90 mg/day for women and men, respectively. A vitamin C intake of at least 400 mg daily may be particularly important for older adults who are at higher risk for chronic diseases. In addition, a meta-analysis of 36 publications examining the relationship between vitamin C intake and plasma concentrations of vitamin C concluded that older adults (age 60-96 years) have considerably lower plasma levels of vitamin C following a certain intake of vitamin C compared with younger individuals (age 15-65 years) (122), suggesting that older adults may have higher vitamin C requirements. Studies conducted at the National Institutes of Health indicated that plasma and circulating cells in healthy, young subjects attain maximal concentrations of vitamin C at a dose of about 400 mg/day—a dose much higher than the current RDA. Pharmacokinetic studies in older adults have not yet been conducted, but evidence suggests that the efficiency of one of the molecular mechanisms for the cellular uptake of vitamin C declines with age (123). Because maximizing blood levels of vitamin C may be important in protection against oxidative damage to cells and biological molecules, a vitamin C intake of at least 400 mg daily is particularly important for older adults who are at higher risk for chronic diseases caused, in part, by oxidative damage, such as heart disease, stroke, certain cancers, and cataract.

For more information on the difference between Dr Linus Pauling's recommendation and the Linus Pauling Institute's recommendation for vitamin C intake, select the highlighted text.

References

Written in January 2006 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in November 2009 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed in November 2009 by:
Balz Frei, Ph.D.
Director and Endowed Chair, Linus Pauling Institute
Professor, Dept. of Biochemistry and Biophysics
Oregon State University

Copyright 2000-2010  Linus Pauling Institute

Disease Index

Select a disease or health condition for a list of related articles.

Nutrient Index

Articles on the following nutrients, phytochemicals, foods and beverages are available in the Linus Pauling Institute's Micronutrient Information Center:

Relevant Links

U.S. Government Sites

• Cancer.gov Cancer Information
  (Current information about cancer from the National Cancer Institute)
• Dietary Guidelines for Americans 2005
  Dietary guidelines published jointly every 5 years by the Department of Health and Human Services (HHS) and the Department of Agriculture (USDA).
• Dietary Supplements
  U.S. Food and Drug Administration (FDA) Center for Food Safety and Applied Nutrition
  (Information and warnings about dietary supplements from the FDA)
• Food and Nutrition Board of the Institute of Medicine
  (Includes tables of Dietary Reference Intakes for Vitamins, Minerals, and Macronutrients)
• Food and Nutrition Information Center
  (Food and nutrition information and resources from the U.S. Department of Agriculture)
• Healthfinder
  (A guide to health information from the U.S. Department of Health and Human Services)
• MEDLINE plus
  (Health information from the National Library of Medicine)
• National Center for Complementary and Alternative Medicine
  (Information for consumers and practitioners on complementary and alternative therapies)
• National Heart, Lung, and Blood Institute Health Information
  (Information regarding cardiovascular, lung, and blood diseases, and sleep disorders)
• National Institute of Aging Health Information
  (Information and resources regarding aging, Alzheimer's disease, and related disorders)
• National Institute of Diabetes & Digestive & Kidney Disease Health Information 
  (Health information on diabetes, digestive diseases, endocrine (hormonal) and metabolic diseases, hematologic (blood) diseases, kidney diseases, and nutrition)
• National Library of Medicine Pub Med
  (A search engine for the MEDLINE database)
• Office of Dietary Supplements at the National Institutes of Health (NIH) 
  (Information and resources regarding dietary supplements, including
  the IBIDS dietary supplements database)
• Osteoporosis and Related Bone Diseases National Resource Center
  (NIH resource center for osteoporosis and other bone disease such as
  Paget's disease, osteogenesis imperfects, and hyperparathyroidism)
• USDA Nutrient Data Laboratory 
  (Includes a search engine for the nutritional composition of over 7,000 foods)

Dietary Reference Intakes (DRI) and Recommended Dietary Allowances (RDA)
(Full text versions of the recent reports by the Food and Nutrition Board of the Institute of Medicine on recommended intakes of specific nutrients)

• Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride 
  (1997)
• Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline
  (1998)
• Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids
  (2000)
• Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
  (2001)
• Dietary Reference Intakes for Energy, Carbohydrates, Fiber, Fat, Protein and Amino Acids (Macronutrients)
  (2002)
• Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate
  (2004)
  

Other Health Related Links

• American Cancer Society
  (Information and resources on preventing, treating, and coping with cancers)
• American Diabetes Association
  (Information and resources for consumers and health professionals on many aspects of diabetes)
• American Heart Association
  (Information and resources for consumers and health professionals on prevention and treatment of cardiovascular diseases including heart attack and stroke)
• National Osteoporosis Foundation
  (Information and resources for consumers and health professionals on osteoporosis)
• Infoaging.org
  (Current research on healthy aging provided by the American Federation for Aging Research)

Micronutrients for Older Adults

Listed below are vitamin and mineral dietary intake recommendations for individuals over the age of 50 years. For each micronutrient, the Food and Nutrition Board of the Institute of Medicine establishes a recommended dietary allowance (RDA) or adequate intake (AI). Generally, the Linus Pauling Institute supports the recommendations of the Food and Nutrition Board, but any discrepancies in dietary recommendations are listed in the rightmost column of the table. Additionally, more information on the Linus Pauling Institute recommendation for a specific micronutrient can be found by clicking on the name of the micronutrient of interest.

LINUS PAULING INSTITUTE RECOMMENDATIONS

Vitamins

Biotin:
Presently, there is no indication that older adults have an increased requirement for biotin. If dietary biotin intake is not sufficient, a daily multivitamin/multimineral supplement will generally provide an intake of at least 30 mcg of biotin/day.

Folic acid:
The Linus Pauling Institute recommends that adults take a 400 mcg supplement of folic acid daily, in addition to folate and folic acid consumed in the diet. A daily multivitamin-mineral supplement, containing 100% of the Daily Value (DV) for folic acid provides 400 mcg of folic acid. Even with a larger than average intake of folic acid from fortified foods, it is unlikely that an individual's daily folic acid intake would regularly exceed the tolerable upper intake level of 1,000 mcg/day established by the Food and Nutrition Board. The recommendation for 400 mcg/day of supplemental folic acid as part of a daily multivitamin-multimineral supplement, in addition to a folate-rich diet, is especially important for older adults because blood homocysteine levels tend to increase with age.

Niacin:
Dietary surveys indicate that 15% to 25% of older adults do not consume enough niacin in their diets to meet the RDA (16 mg NE/day for men and 14 mg NE/day for women), and that dietary intake of niacin decreases between the ages of 60 and 90 years. Thus, it is advisable for older adults to supplement their dietary intake with a multivitamin/multimineral supplement, which will generally provide at least 20 mg of niacin daily.

Pantothenic acid:
Presently, there is little evidence that older adults differ in their intake or requirement for pantothenic acid. Most multivitamin/multimineral supplements provide at least 5 mg/day of pantothenic acid. The Linus Pauling Institute supports the recommendation by the Food and Nutrition Board of 5 mg/day of pantothenic acid for older adults. A varied diet should provide enough pantothenic acid for most people. Following the Linus Pauling Institute recommendation to take a daily multivitamin-mineral supplement, containing 100% of the Daily Value (DV), will ensure an intake of at least 5 mg/day of pantothenic acid.

Riboflavin:
Some experts in nutrition and aging feel that the RDA (1.3 mg/day for men and 1.1 mg/day for women) leaves little margin for error in people over 50 years of age (1, 2). A study of independently living people between 65 and 90 years of age found that almost 25% consumed less than the recommended riboflavin intake, and 10% had biochemical evidence of deficiency (3). Additionally, epidemiological studies of cataract prevalence indicate that riboflavin intakes of 1.6 to 2.2 mg/day may reduce the risk of developing age-related cataracts. Individuals whose diets may not supply adequate riboflavin, especially those over 50, should consider taking a multivitamin/multimineral supplement, which generally provides at least 1.7 mg of riboflavin/day.

Thiamin:
Presently, there is no evidence that the requirement for thiamin is increased in older adults, but some studies have found inadequate dietary intake and thiamin insufficiency to be more common in elderly populations (2). Thus, it would be prudent for older adults to take a multivitamin/multimineral supplement, which will generally provide at least 1.5 mg of thiamin/day.

Vitamin A:
Currently, there is little evidence that the requirement for vitamin A in older adults differs from that of younger adults. Additionally, because intestinal absorption of vitamin A may increase with age (2), vitamin A toxicity may occur at lower doses in older adults than in younger adults. Following the Linus Pauling Institute's recommendation to take a multivitamin/multimineral supplement daily could supply as much as 5,000 IU/day of retinol, the amount that has been associated with adverse effects on bone health in older adults. For this reason, we recommend taking a multivitamin/multimineral supplement that provides no more than 2,500 IU of vitamin A or a supplement that provides 5,000 IU of vitamin A, of which at least 50% comes from beta-carotene (see example supplement label). High potency vitamin A supplements should not be used without medical supervision due to the risk of toxicity.

Vitamin B₆:
Metabolic studies have indicated that the requirement for vitamin B₆ in older adults is approximately 2.0 mg daily (4); this requirement could be even higher if the effect of marginally deficient vitamin B₆ intakes on immune function and homocysteine levels are clarified. Despite evidence that the requirement for vitamin B₆ may be slightly higher in older adults, several surveys have found that over half of individuals over age 60 consume less than the current RDA (1.7 mg/day for men and 1.5 mg/day for women). For these reasons, the Linus Pauling Institute recommends that older adults take a multivitamin/multimineral supplement, which generally provides at least 2.0 mg of vitamin B₆ daily.

Vitamin B₁₂:
Because vitamin B₁₂ malabsorption and vitamin B₁₂ deficiency are more common in older adults, some respected nutritionists recommend that adults older than 50 years take 100 to 400 mcg/day of supplemental vitamin B₁₂, an amount provided by a number of vitamin B-complex supplements.

Vitamin C:
Older adults may have higher requirements for vitamin C than younger people. A meta-analysis of 36 publications examining the relationship between vitamin C intake and plasma concentrations of vitamin C concluded that older adults (age 60-96 years) have lower plasma levels following a certain intake of vitamin C compared with younger individuals (age 15-65 years) (5), suggesting that older adults may indeed have higher vitamin C requirements. Moreover, some older populations have been found to have vitamin C intakes considerably below the RDA of 75 mg/day and 90 mg/day for women and men, respectively. Studies conducted at the National Institutes of Health indicate that plasma and circulating cells in healthy, young subjects attain maximal concentrations of vitamin C at a dose of about 400 mg/day-a dose much higher than the current RDA. Pharmacokinetic studies in older adults have not yet been conducted, but evidence suggests that the efficiency of one of the molecular mechanisms for the cellular uptake of vitamin C declines with age (6). Because maximizing blood levels of vitamin C may be important in protection against oxidative damage to cells and biological molecules, a vitamin C intake of at least 400 mg daily is particularly important for older adults who are at higher risk for chronic diseases caused, in part, by oxidative damage, such as heart disease, stroke, or cataract. Consuming at least five servings (2½ cups) of fruits and vegetables daily may provide about 200 mg of vitamin C. Most multivitamin supplements provide 60 mg of vitamin C.

Vitamin D:
The Linus Pauling Institute recommends that generally healthy adults take 2,000 IU (50 mcg) of supplemental vitamin D daily. Most multivitamins contain 400 IU of vitamin D, and single ingredient vitamin D supplements are available for additional supplementation. Sun exposure, diet, skin color, and obesity have variable, substantial impact on body vitamin D levels. To adjust for individual differences and ensure adequate body vitamin D status, the Linus Pauling Institute recommends aiming for a serum 25-hydroxyvitamin D level of at least 80 nmol/L (32 ng/mL). Numerous observational studies have found that serum 25-hydroxyvitamin D levels of 80 nmol/L (32 ng/mL) and above are associated with reduced risk of bone fractures, several cancers, multiple sclerosis, and type 1 (insulin-dependent) diabetes. Daily supplementation with 2,000 IU (50 mcg) of vitamin D is especially important for older adults because aging is associated with a reduced capacity to synthesize vitamin D in the skin upon sun exposure.

Vitamin E:
Scientists at the Linus Pauling Institute feel there exists credible evidence that taking a supplement of 200 IU of natural-source d-α-tocopherol (RRR-α-tocopherol) daily with a meal may help protect adults from chronic diseases like heart disease, stroke, neurodegenerative diseases, and some types of cancer. This recommendation is also appropriate for older adults. The amount of α-tocopherol required for such beneficial effects appears to be much greater than that which could be achieved through diet alone. Because supplements containing 200 IU of d-α-tocopherol are often as expensive as supplements containing 400 IU of d-α-tocopherol, a less expensive alternative may be to take 400 IU of d-α-tocopherol every other day. It is important thatα-tocopherol supplements be taken with a meal containing some fat.

Vitamin K:
Older adults are at increased risk of osteoporosis and hip fracture. Because adequate intake of vitamin K is essential in maintaining bone health, the Linus Pauling Institute recommends that adults take a multivitamin-mineral supplement and consume at least 1 cup of dark green leafy vegetables daily. Although the AI for vitamin K was recently increased, it is not clear if it will be enough to optimize the gamma-carboxylation of vitamin K-dependent proteins in bone (see Osteoporosis section of the article on vitamin K). Multivitamins generally contain 10 to 25 mcg of vitamin K, whereas vitamin K or "bone" supplements may contain 100 to 120 mcg of vitamin K. To consume the amount of vitamin K associated with a decreased risk of hip fracture in the Framingham Heart Study (about 250 mcg/day) (7), an individual would need to eat a little more than 1/2 cup of chopped broccoli or a large salad of mixed greens every day. In addition to taking a multivitamin-mineral supplement and eating at least 1 cup of dark green leafy vegetables daily, replacing dietary saturated fats (e.g., butter and cheese) with monounsaturated fats (e.g., olive and canola oils) will increase dietary vitamin K intake and may also decrease the risk of cardiovascular diseases.

Minerals

Calcium:
To minimize bone loss, older men and postmenopausal women should consume a total (diet plus supplements) of 1,200 mg/day of calcium. No multivitamin/multimineral supplement contains the AI for calcium (1,000-1,200 mg/day) because the resulting pill would be too large to swallow. Taking a multivitamin/multimineral supplement containing at least 10 mcg (400 IU)/day of vitamin D₃ will help to ensure adequate calcium absorption.

Chromium:
Although the requirement for chromium is not known to be higher for older adults, one study found that chromium concentrations in hair, sweat, and urine decreased with age (8). Following the Linus Pauling Institute recommendation to take a multivitamin/multimineral supplement containing 100% of the daily values (DV) of most nutrients should provide sufficient chromium for most older adults.

Because impaired glucose tolerance and type 2 diabetes are associated with potentially serious health problems, individuals considering high-dose chromium supplementation to treat either condition should do so in collaboration with a qualified health care provider.

Copper:
Aging has not been associated with significant changes in the requirement for copper (9); thus, the Linus Pauling Institute recommendation for copper intake in older adults is the same as younger adults. The RDA for copper (900 mcg/day for all adults) is sufficient to prevent deficiency, but the lack of clear indicators of copper nutritional status in humans makes it difficult to determine the level of copper intake most likely to promote optimum health or prevent chronic disease. A varied diet should provide enough copper for most people. For those who are concerned that their diet may not provide adequate copper, a multivitamin/multimineral supplement will generally provide at least the RDA for copper.

Fluoride:
The safety and public health benefits of optimally fluoridated water for prevention of tooth decay in people of all ages have been well-established. The Linus Pauling Institute supports the recommendations of the American Dental Association and the Centers for Disease Control and Prevention, which include optimally fluoridated water as well as the use of fluoride toothpaste, fluoride mouthrinse, fluoride varnish, and when necessary, fluoride supplementation. Due to the risk of fluorosis, any fluoride supplementation should be prescribed and closely monitored by a dentist or physician.

Iodine:
The RDA for iodine (150 mcg/day for men and women) is sufficient to ensure normal thyroid function. There is presently no evidence that iodine intakes higher than the RDA are beneficial. Most people in the U.S. consume more than sufficient iodine in their diets, making supplementation unnecessary.

Iron:
A study in an elderly population found that high iron stores were much more common than iron deficiency (10). Thus, older adults should not generally take nutritional supplements containing iron unless they have been diagnosed with iron deficiency. Moreover, it is extremely important to determine the underlying cause of the iron deficiency, rather than simply treating it with iron supplements.

Magnesium:
Older adults are less likely than younger adults to consume enough magnesium to meet their needs and should therefore take care to eat magnesium-rich foods in addition to taking a multivitamin-mineral supplement daily. Because older adults are more likely to have impaired kidney function, they should avoid taking more than 350 mg/day of supplemental magnesium without medical consultation (see Safety section of the article on magnesium).

Manganese:
The requirement for manganese is not known to be higher for older adults compared to younger adults. However, liver disease is more common in older adults and may increase the risk of manganese toxicity by decreasing the elimination of manganese from the body (see Toxicity section of the article on manganese). Manganese supplementation beyond 100% of the Daily Value (DV=2 mg/day) is not recommended.

Molybdenum:
Because aging has not been associated with significant changes in the requirement for molybdenum (11), the Linus Pauling Institute recommendation for older adults is the same as that for younger adults. Specifically, the RDA for molybdenum, 45 mcg/day for adults of all ages, is sufficient to prevent deficiency. Although the intake of molybdenum most likely to promote optimum health is not known, there is presently no evidence that intakes higher than the RDA are beneficial. Most people in the U.S. consume more than sufficient molybdenum in their diets, making supplementation unnecessary. Following the Linus Pauling Institute's general recommendation to take a multivitamin-mineral supplement that contains 100% of the daily values (DV) for most nutrients is likely to provide 75 mcg/day of molybdenum because the DV for molybdenum has not been revised to reflect the most recent RDA. Although the amount of molybdenum presently found in most multivitamin-mineral supplements is higher than the RDA, it is well below the tolerable upper intake level (UL) of 2,000 mcg/day and should be safe for adults.

Phosphorus:
At present, there is no evidence that the phosphorus requirements of older adults differ from that of younger adults (700 mg/day). Although few multivitamin/multimineral supplements contain more than 15% of the current RDA for phosphorus, a varied diet should easily provide adequate phosphorus for most people.

Potassium:
A diet supplying at least 4.7 grams/day of potassium is appropriate for healthy older adults because such diets are associated with decreased risk of stroke, hypertension, osteoporosis, and kidney stones. This recommendation does not apply to individuals who have been advised to limit potassium consumption by a health care professional (see Safety section of the article on potassium).

Selenium:
Aging has not been associated with significant changes in the requirement for selenium. The Linus Pauling Institute supports the recommendation of the Food and Nutrition Board, which is 55 mcg of selenium/day for adults of all ages. Although the amount of selenium in multivitamin/multimineral supplements varies considerably, multivitamin-mineral supplements rarely provide more than the Daily Value (DV) of 70 mcg. The average American diet is estimated to provide about 100 mcg/day of selenium (12, 13). Thus, eating a varied diet and taking a daily multivitamin supplement should provide sufficient selenium for most adults in the U.S.

Sodium:
There is consistent evidence that diets relatively low in salt (5.8 grams/day or less) and high in potassium (at least 4.7 grams/day) are associated with decreased risk of high blood pressure and the associated risks of cardiovascular and kidney diseases. Diets low in sodium and rich in potassium are likely to be of particular benefit for older individuals, who are at increased risk of high blood pressure. Moreover, the Dietary Approaches to Stop Hypertension (DASH) trial demonstrated that a diet emphasizing fruits, vegetables, whole grains, nuts, and low-fat dairy products substantially lowered blood pressure, an effect that was enhanced by reducing salt intake to 5.8 grams/day or less. For more information on the DASH diet, see the article on sodium. The Linus Pauling Institute recommends a diet that is rich in fruits and vegetables (at least 5 servings/day) and limits processed foods that are high in salt. Sensitivity to the blood pressure-raising effects of salt increases with age; therefore, consuming diets that are low in salt and high in potassium may especially benefit older adults.

Diets rich in potassium (at least 4.7 grams/day) and low in salt (5.8 grams/day or less) are likely to be of particular benefit for older adults, who are at increased risk of high blood pressure along with its associated risks of cardiovascular and kidney diseases. Since sensitivity to the blood pressure-raising effects of salt increases with age, consuming diets that are low in salt and high in potassium may especially benefit older adults.

Zinc:
Although the requirement for zinc is not known to be higher for older adults, their average zinc intake tends to be considerably less than the RDA. A reduced capacity to absorb zinc, increased likelihood of disease states that alter zinc utilization, and increased use of drugs that increase zinc excretion may contribute to an increased risk of mild zinc deficiency in older adults. Because the consequences of mild zinc deficiency, such as impaired immune system function, are particularly relevant to the health of older adults, they should pay particular attention to maintaining adequate zinc intake.

Other Nutrients

L-carnitine:
Age-related declines in mitochondrial function and increases in mitochondrialoxidant production are thought to be important contributors to the adverse effects of aging. Tissue L-carnitine levels have been found to decline with age in humans and animals (14). One study found that feeding aged rats acetyl-L-carnitine (ALCAR) reversed the age-related declines in tissue L-carnitine levels and also reversed a number of age-related changes in liver mitochondrial function; however, high doses of ALCAR increased liver mitochondrial oxidant production (15). More recently, two studies found that supplementing aged rats with either ALCAR or alpha-lipoic acid, a mitochondrial cofactor and antioxidant, improved mitochondrial energy metabolism, decreased oxidative stress, and improved memory (16, 17). Interestingly, co-supplementation of ALCAR and alpha-lipoic acid resulted in even greater improvements than either compound administered alone. Likewise, several studies have reported that supplementing rats with both L-carnitine and alpha-lipoic acid blunts the age-related increases in reactive oxygen species (ROS), lipid peroxidation, protein carbonylation, and DNAstrand breaks in a variety of tissues (heart, skeletal muscle, brain). Improvements in mitochondrial enzyme and respiratory chain activities were also observed (18-26). While these findings are very exciting, it is important to realize that these studies used relatively high doses (100 to 300 mg/kg body weight/day) of the compounds and only for a short time (one month). It is not yet known whether taking relatively high doses of these two naturally occurring substances will benefit rats in the long-term or will have similar effects in humans. Clinical trials in humans are planned, but it will be several years before the results are available. If you choose to take carnitine supplements, the Linus Pauling Institute recommends acetyl-L-carnitine at a daily dose of 500 to 1,000 mg.

Choline:
Little is known regarding the amount of dietary choline most likely to promote optimum health or prevent chronic disease in older adults. At present, there is no evidence to support a different intake of choline from that of younger adults (550 mg/day for men and 425 mg/day for women).

Coenzyme Q₁₀:
According to the free radical and mitochondrial theories of aging, oxidative damage of cell structures by reactive oxygen species (ROS) plays an important role in the functional declines that accompany aging (27). ROS are generated by mitochondria as a byproduct of ATP production. If not neutralized by antioxidants, ROS may damage mitochondria over time, causing them to function less efficiently and to generate more damaging ROS in a self-perpetuating cycle. Coenzyme Q₁₀ plays an important role in mitochondrial ATP synthesis and functions as an antioxidant in mitochondrial membranes. Moreover, tissue levels of coenzyme Q₁₀ have been reported to decline with age (28). One of the hallmarks of aging is a decline in energy metabolism in many tissues, especially liver, heart, and skeletal muscle. It has been proposed that age-associated declines in tissue coenzyme Q₁₀levels may play a role in this decline (26). In recent studies, lifelong dietary supplementation with coenzyme Q₁₀ did not increase the life spans of rats or mice (29, 30); however, one study showed that coenzyme Q₁₀supplementation attenuates the age-related increase in DNA damage (31). Presently, there is no scientific evidence that coenzyme Q₁₀ supplementation prolongs life or prevents age-related functional declines in humans.

Essential Fatty Acids:
Alpha-linolenic acid (ALA), an omega-3 fatty acid, and linoleic acid (LA), an omega-6 fatty acid, are considered essential fatty acids because they cannot be synthesized by humans. In 2002, the Food and Nutrition Board of the U.S.Institute of Medicine established adequate intake (AI) levels for omega-6 and omega-3 fatty acids. Essential fatty acid recommendations for adults over the age of 50 are listed in the table below. For more information on ALA and LA, see the article on essential fatty acids.

International Recommendations
The European Commission recommends an omega-6 fatty acid intake of 4-8% of energy and an omega-3 fatty acid intake of 2 g/day of ALA and 200 mg/day of long-chain omega-3 fatty acids (EPA and DHA) (33). The World Health Organization recommends an omega-6 fatty acid intake of 5-8% of energy and an omega-3 fatty acid intake of 1-2% of energy (34). However, the Japan Society for Lipid Nutrition has recommended that LA intake be reduced to 3-4% of energy in Japanese people whose omega-3 fatty acid intakes average 2.6 g/day, including about 1 g/day of EPA + DHA (35).

American Heart Association Recommendation
The American Heart Association recommends that people without documented CHD eat a variety of fish (preferably oily) at least twice weekly, in addition to consuming oils and foods rich in ALA (36). People with documented CHD are advised to consume approximately 1 g/day of EPA + DHA preferably from oily fish, or to consider EPA + DHA supplements in consultation with a physician. Patients who need to lower serum triglycerides may take 2-4 g/day of EPA + DHA supplements under a physician's care.

Lipoic Acid:
Lipoic acid alone or in combination with other antioxidants or L-carnitine has been found to improve measures of memory in animal models of age-associated cognitive decline, including rats (16, 17), mice (37), and dogs (38). However, it is not clear whether oral lipoic acid supplementation can slow cognitive decline related to aging or other pathology in humans. An uncontrolled, open-label trial in nine patients with Alzheimer's disease and related dementias, who were also taking acetylcholinesterase inhibitors, reported that oral supplementation with 600 mg/day of racemic lipoic acid appeared to stabilize cognitive function over a one-year period (39). However, the significance of these findings is difficult to assess without a control group for comparison. A randomized controlled trial found that oral supplementation with 1,200 mg/day of racemic lipoic acid for ten weeks was of no benefit in treating HIV-associated cognitive impairment (40). Although studies in animals suggest that lipoic acid may be helpful in slowing age-related cognitive decline, randomized controlled trials are needed to determine whether lipoic acid supplementation is effective in preventing or slowing cognitive decline associated with age or neurodegenerative disease. If you choose to take lipoic acid supplements, the Linus Pauling Institute recommends a daily dose of 200-400 mg/day of racemic lipoic acid for generally healthy people.

Phytochemicals

Flavonoids:
The prevalence of several neurodegenerative disease increases with advanced age. Inflammation, oxidative stress, and transition metal accumulation appear to play a role in the pathology of several neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Because flavonoids have anti-inflammatory, antioxidant and metal-chelating properties, scientists are interested in the neuroprotective potential of flavonoid-rich diets or individual flavonoids. At present, the extent to which various dietary flavonoids and flavonoid metabolites cross the blood-brain barrier in humans is not known (41). Although flavonoid-rich diets and flavonoid administration have been found to prevent cognitive impairment associated with aging and inflammation in some animal studies (42-45),prospective cohort studies have not found consistent inverse associations between flavonoid intake and the risk of dementia or neurodegenerative disease in humans (46-50).

In a cohort of Japanese-American men followed for 25-30 years, flavonoid intake from tea during midlife was not associated with the risk of Alzheimer's or other types of dementia in late life (46). Surprisingly, higher intakes of isoflavone-rich tofu during midlife were associated with cognitive impairment and brain atrophy in late life (see the article on soy isoflavones) (47). A prospective study of Dutch adults found that total dietary flavonoid intake was not associated with the risk of developing Parkinson's disease (48) or Alzheimer's disease (49), except in current smokers whose risk of Alzheimer's disease decreased by 50% for every 12 mg increase in daily flavonoid intake. In contrast, a study of elderly French men and women found that those with the lowest flavonoid intakes had a risk of developing dementia over the next five years that was 50% higher than those with the highest intakes (50). More recently, a study in 1,640 elderly men and women found that those with higher dietary flavonoid intake (>13.6 mg/day) had better cognitive performance at baseline and experienced significantly less age-related cognitive decline over a 10-year period than those with a lower flavonoid intake (0-10.4 mg/day) (51). Additionally, a randomized, double-blind,placebo-controlled clinical trial in 202 postmenopausal women reported that daily supplementation with 25.6 g of soy protein (containing 99 mg of isoflavones) for one year did not improve cognitive function (52). However, a randomized, double-blind, placebo-controlled, cross-over trial in 77 postmenopausal women found that 6-month supplementation with 60 mg/day of isoflavones improved some measures of cognitive performance(53). Although scientists are interested in the potential of flavonoids to protect the aging brain, it is not yet clear how flavonoid consumption affects neurodegenerative disease risk in humans.

Resveratrol:
Caloric restriction is known to extend the lifespans of a number of species, including mammals (54). In yeast, caloric restriction stimulates the activity of an enzyme known as Sir2 (55). Providing resveratrol to yeast increased Sir2 activity in the absence of caloric restriction and extended the replicative lifespan of yeast by 70% (56). Resveratrol feeding also extended the lifespans of worms (C. elegans) and fruit flies (D. melanogaster) by a similar mechanism (55). Moreover, one study showed that resveratrol extended the lifespan of mice on a high-calorie diet (57), but effects in higher animals are not known. Although resveratrol increased the activity of the homologoushuman enzyme (Sirt1) in the test tube (56), it is not known whether resveratrol can extend the human lifespan. Moreover, the resveratrol concentrations required to increase human Sirt1 activity were considerably higher than concentrations that have been measured in human plasma after oral consumption.

The Linus Pauling Institute provides dietary and lifestyle recommendations for generally healthy individuals interested in optimum health and prevention of chronic diseases such as cardiovascular diseases (heart disease and stroke), diabetes, cancer, and osteoporosis. These recommendations are contained in the Linus Pauling Institute Prescription for Health.

Micronutrients and Phytochemicals Related to Cognitive Decline

Micronutrients and Phytochemicals Related to Neurodegenerative Diseases

Micronutrients and Phytochemicals Related to Cardiovascular Diseases

Micronutrients and Phytochemicals Related to Cancer

Micronutrients and Phytochemicals Related to Type 2 Diabetes Mellitus

Micronutrients and Phytochemicals Related to Osteoporosis

Micronutrients and Phytochemicals Related to Age-related Eye Disorders

Micronutrients Related to Rheumatoid Arthritis

References

Last updated 9/3/09   Copyright 2008-2010   Linus Pauling Institute

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The Linus Pauling Institute Micronutrient Information Center provides scientific information on health aspects of micronutrients and phytochemicals for the general public. The information is made available with the understanding that the author and publisher are not providing medical, psychological, or nutritional counseling services on this site. The information should not be used in place of a consultation with a competent health care or nutrition professional.

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