PART IV – Safety of Multivitamins and Antioxidants

Nutritional supplements have been widely used and highly valued by American consumers ever since vitamins were discovered and commercialized, beginning in the early decades of the 1900′s. According to recent national health survey, as many as 78 million Americans adults use multivitamins on a regular basis.

Multivitamin/mineral supplements are an effective means of delivering adequate amounts of most essential nutrients to help people achieve recommended intakes. The great majority of dietary supplements, including multivitamins, are safe for regular use. Despite widespread usage, there have been no specific published reports of toxicity or adverse effects associated with the use of multivitamins.

A series of well-publicized clinical trials conducted in diseased patients utilizing relatively high doses of single nutrients or combinations of nutrients (such as vitamin E and/or beta-carotene), have yielded disappointing results, and even suggested the presence of harm. However, those trials were conducted in patients with serious illnesses (ie. cancer or cardiovascular disease) who were on multiple medications or who were current heavy smokers. The results of these trials should be placed in context and are not applicable to the generally healthy population.

Advanced levels of antioxidants are a common thread among nearly every population that is less prone to premature chronic degenerative disease. The Japanese have high levels of fruit, vegetables, green tea and soy as part of their traditional diet. Vegetarians have lower levels of heart disease and cancer, compared to the typical mixed diet, likely in part due to higher intakes of antioxidants. While high levels of single nutrients and foods may pose a risk of danger and toxicity, there is no known unsafe intake level of total antioxidants in normally healthy individuals.

PART III – Health Benefits of antioxidants

Plentiful intakes of antioxidants have been associated with reduced risk of some chronic diseases, in the same way that generous intakes of fruits, vegetables and grains have been associated with similar health benefits.

Some examples of scientific evidence are the following:

Cancer

• People with high beta-carotene intakes have about one-third the cancer risk as people with low beta-carotene intakes. Peto R. Cancer Surveys 1983;2:327-340.
• People with higher intakes of vitamin C have about half the risk for many types of cancer, compared to people with low vitamin C intakes. Block G. Am J Clin Nutr 1991;53:270S-282S.
• People with low intakes of several antioxidants have more DNA damage than people with generous intakes. Ames BN. Metat Res 2001;475:7-20.
• People with the highest intakes of vitamin C, E, and beta-carotene have a significantly lower risk of lung cancer. Yong LC et al. Am J Epidemiol 1997;146:231-43.
• Men who took vitamin E supplements for 10 years or more had a 30% lower risk of bladder cancer. Michaud DS et al. Am J Epidemiol 2000;152:1145-53.
• There are over 66 studies showing cancer-prevention activity of green tea, black tea, and their constituents. These include cancer reduction in the skin, lung, oral cavity, esophagus, stomach, liver, pancreas, bladder, small intestine, colon and prostate. Lambert JD et al. Am J Clin Nutr

Heart Disease

• Elderly people who took dietary supplements of both vitamin C and vitamin E had a decreased risk of death from heart disease as well as overall mortality. Losonczy KG, Harris TB, Havlik RJ. Am J Clin Nutr 1996;64:190- 196.
• Men who took vitamin supplements had a 70% lower risk of dying from heart disease and a 50% lower risk of a heart attack. Meyer F, Bairati I, Dagenasis GR. Can J Cardiol 1996;12:930-934.
• In the Nurses’ Health Study involving over 87,000 women, there was a 41% reduction in risk of heart disease for those who took vitamin E for more than two years. Stampfer MJ, Hennekens CH, Manson JE, et al. New Engl J Med 1993;328:1444-1449.
• In the Nurses’ Health Study vitamin C supplements were also related to a lower risk of heart disease. Osganian SK et al. J Am Coll Cardiol 2003;42:246-52.
• In the Health Professionals Follow-Up Study involving almost 40,000 men, there was a 37% reduction in risk of heart disease in men who took vitamin E for more than two years. The average intake in the lowest risk group was 400 IU per day. Rimm EB, Stampfer MJ. Ascherio A, et al. New Engl J Med 1993;328:1450-1456.
• To date, 17 human group studies have been published on flavonoid intake and the risk of coronary artery disease and stroke. Positive studies have shown reduction in mortality risk of up to 65%. Arts ICW and Hollman PCH. Am J Clin Nutr 2005;81:317S-325S.
• The largest and longest study to date, done as part of the Harvard- based Nurses’ Health Study and Health Professionals Follow-up Study, included almost 110,000 men and women whose health and dietary habits were followed for 14 years. The higher the average daily intake of fruits and vegetables, the lower the chances of developing cardiovascular disease. Compared with those in the lowest category of fruit and vegetable intake (less than 1.5 servings a day), those who averaged 8 or more servings a day were 30% less likely to have had a heart attack or stroke. Joshipura KJ, et al. Ann Intern Med

Other Chronic diseases

• Several long-term studies have shown a reduced risk of cataracts in those who have taken vitamin C and/or Vitamin E for more than 10 years. Jacques PF et al. Arch Ophthalmol 2001;119:1009-19.
• The Age-Related Eye Disease Study (AREDS) at NIH found that daily supplementation with antioxidants, zinc, and copper delayed progression of age- related macular degeneration. AREDS report no. 8. Arch Ophthalmol 2001;119:1417-36.
• Research has shown a significant relationship between flavonoid intakes and the occurrence of asthma. Knekt P et al. Am J Clin Nutr 2002;76:560-8.
• Other research suggests antioxidants may help support lung function and protect the lungs from oxidative damage. Schunemann HJ et al. Am J Respir Crit Care Med 2001;163:1246-55.
• In a study on Alzheimer’s disease, high levels of vitamin E delayed progression of the disease. Sano M et al. N Engl J Med.

Essentials of
Health Summary

Did you take your
Essentials today?
Yes No

Plentiful intakes of antioxidants have been associated with reduced risk of some chronic diseases, in the same way that generous intakes of fruits, vegetables and grains have been associated with similar health benefits.

Some examples of scientific evidence are the following:

Cancer

• People with high beta-carotene intakes have about one-third the cancer risk as people with low beta-carotene intakes. Peto R. Cancer Surveys 1983;2:327-340.
• People with higher intakes of vitamin C have about half the risk for many types of cancer, compared to people with low vitamin C intakes. Block G. Am J Clin Nutr 1991;53:270S-282S.
• People with low intakes of several antioxidants have more DNA damage than people with generous intakes. Ames BN. Metat Res 2001;475:7-20.
• People with the highest intakes of vitamin C, E, and beta-carotene have a significantly lower risk of lung cancer. Yong LC et al. Am J Epidemiol 1997;146:231-43.
• Men who took vitamin E supplements for 10 years or more had a 30% lower risk of bladder cancer. Michaud DS et al. Am J Epidemiol 2000;152:1145-53.
• There are over 66 studies showing cancer-prevention activity of green tea, black tea, and their constituents. These include cancer reduction in the skin, lung, oral cavity, esophagus, stomach, liver, pancreas, bladder, small intestine, colon and prostate. Lambert JD et al. Am J Clin Nutr 05;81:284S- 291S.

Heart Disease

• Elderly people who took dietary supplements of both vitamin C and vitamin E had a decreased risk of death from heart disease as well as overall mortality. Losonczy KG, Harris TB, Havlik RJ. Am J Clin Nutr 1996;64:190- 196.
• Men who took vitamin supplements had a 70% lower risk of dying from heart disease and a 50% lower risk of a heart attack. Meyer F, Bairati I, Dagenasis GR. Can J Cardiol 1996;12:930-934.
• In the Nurses’ Health Study involving over 87,000 women, there was a 41% reduction in risk of heart disease for those who took vitamin E for more than two years. Stampfer MJ, Hennekens CH, Manson JE, et al. New Engl J Med 1993;328:1444-1449.
• In the Nurses’ Health Study vitamin C supplements were also related to a lower risk of heart disease. Osganian SK et al. J Am Coll Cardiol 2003;42:246-52.
• In the Health Professionals Follow-Up Study involving almost 40,000 men, there was a 37% reduction in risk of heart disease in men who took vitamin E for more than two years. The average intake in the lowest risk group was 400 IU per day. Rimm EB, Stampfer MJ. Ascherio A, et al. New Engl J Med 1993;328:1450-1456.
• To date, 17 human group studies have been published on flavonoid intake and the risk of coronary artery disease and stroke. Positive studies have shown reduction in mortality risk of up to 65%. Arts ICW and Hollman PCH. Am J Clin Nutr 2005;81:317S-325S.
• The largest and longest study to date, done as part of the Harvard- based Nurses’ Health Study and Health Professionals Follow-up Study, included almost 110,000 men and women whose health and dietary habits were followed for 14 years. The higher the average daily intake of fruits and vegetables, the lower the chances of developing cardiovascular disease. Compared with those in the lowest category of fruit and vegetable intake (less than 1.5 servings a day), those who averaged 8 or more servings a day were 30% less likely to have had a heart attack or stroke. Joshipura KJ, et al. Ann Intern Med 2001 Jun 19;134(12):1106-14.

Other Chronic diseases

• Several long-term studies have shown a reduced risk of cataracts in those who have taken vitamin C and/or Vitamin E for more than 10 years. Jacques PF et al. Arch Ophthalmol 2001;119:1009-19.
• The Age-Related Eye Disease Study (AREDS) at NIH found that daily supplementation with antioxidants, zinc, and copper delayed progression of age- related macular degeneration. AREDS report no. 8. Arch Ophthalmol 2001;119:1417-36.
• Research has shown a significant relationship between flavonoid intakes and the occurrence of asthma. Knekt P et al. Am J Clin Nutr 2002;76:560-8.
• Other research suggests antioxidants may help support lung function and protect the lungs from oxidative damage. Schunemann HJ et al. Am J Respir Crit Care Med 2001;163:1246-55.
• In a study on Alzheimer’s disease, high levels of vitamin E delayed progression of the disease. Sano M et al. N Engl J Med 1997;336:1216- 22.

 
]]> http://poweroftwo.wordpress.com/2009/06/17/antioxidants-function-sources-benefits-and-safety/feed/ 0 poweroftwo Bookmark and Share http://poweroftwo.wordpress.com/2009/06/11/antioxidants-function-sources-benefits-and-safety%e2%80%8f/ http://poweroftwo.wordpress.com/2009/06/11/antioxidants-function-sources-benefits-and-safety%e2%80%8f/#comments Thu, 11 Jun 2009 23:29:47 +0000 krasi1 http://poweroftwo.wordpress.com/?p=54 ]]> PART II – Sources and Dietary Intakes

Antioxidants can be vitamins, minerals, enzymes or plant derived nutrients called phytonutrients.

The major vitamin antioxidants are vitamin C, vitamin E, beta-carotene, while selenium is the major mineral antioxidant. Many researchers and nutritionists discuss and report on “antioxidants” as if these were the only sources of importance. A thorough examination of antioxidants and their importance to human health must include a much larger list of compounds that are present in healthy, varied diet. The following list is an example of the wide variety of phytonutrient antioxidants present in a healthy diet:

Phytochemical Food Source
Allyl Sulfides Onions, garlic, leeks, chives
Carotenoids (e.g. lycopene, lutein, zeaxanthin) Tomatoes, carrots, watermelon, kale, spinach
Curcumin Turmeric
Flavonoids (e.g. anthocyanadins, resveratrol, quercitin, catechins) Grapes, blueberries, strawberries, cherries, apples, grapefruit, cranberries, raspberries, blackberries
Glutathione Green leafy vegetables
Indoles Broccoli, cauliflower, cabbage, brussels sprouts, bok choy
Isoflavones Legumes (peas, soybeans)
Isothiocyanates (e.g. sulforaphane) Broccoli, cauliflower, cabbage, brussels sprouts, bok choy
Lignans Seeds (flax seeds, sunflower seeds)
Monoterpenes Citrus fruit peels, cherries, nuts
Phytic Acid Whole grains, legumes
Phenols, polyphenols, phenolic compounds (e.g. ellagic acid, ferrulic acid, tannins) Grapes, blueberries, strawberries, cherries, grapefruit, cranberries, raspberries, blackberries, tea
Saponins Beans, legumes

Recommendations by the National Cancer Institute, the U.S.D.A., other government agencies and nutrition experts are to eat a minimum of 5-13 servings of fruits and vegetables per day, depending on calorie needs. Based on these recommendations, a typical varied diet would provide approximately 200-600 mg of vitamin C and 10-20 mg (16,000-32,000 IU) of carotenoids.

Overall, polyphenols are the most abundant antioxidants in the diet. Their total dietary intake could be as high as 1 gram/day in a mixed, varied diet of fruits, vegetables, grains, and beverages.

Possible intakes of other phytonutrient antioxidants would be anthocyandins ” 2 oz black grapes 1,500 mg; proanthocyanidins ” 100-300 mg/d red wine; catechins ” 50 mg day ” tea (one cup brewed green tea ” 240-320 mg catechins), chocolate, apples, pears, grapes, red wine; isoflavones ” 50 mg/day from soy foods; chlorogenic acid ” as high as 800 mg/day coffee drinkers.

Although it may seem reasonable that a consistently healthy and varied diet could provide high doses of antioxidants, the average American gets a total of just three servings of fruits and vegetables a day. The latest dietary guidelines call for five to thirteen servings of fruits and vegetables a day, depending on one’s caloric intake. For a person who needs 2,000 calories a day to maintain weight and health, this translates into nine servings, or 4½ cups per day.

The 2001-2002 NHANES survey of dietary intakes shows that 93% of Americans fail to get even the Estimated Average Requirement (EAR) for vitamin E, let alone the RDA. More than half of adults fail to get even the average requirement for vitamin A. About one-third of non-smokers and two-thirds of smokers fall short on minimum vitamin C requirements.

If the governmental dietary recommendations are meant to be taken seriously, then it follows that it would be better for people to achieve recommended amounts of nutrients than to fall short. Obviously, since the average intake of 3 servings or less of fruits and vegetables fails to provide minimum levels of even basic vitamins, intakes of the numerous other antioxidants are sure to be well under optimal and beneficial levels.

It has been established that a good multivitamin can fill in gaps in missing vitamins, but availability of broad spectrum antioxidant supplements has lagged behind. Although there is much to be learned about the characteristics of the literally hundreds of dietary antioxidants, it seems reasonable that providing supplements of various antioxidant classes may fill in nutritional gaps and provide many of the benefits missing from the typical American diet.

Oxidation is a natural process that happens to all cells in nature, including the cells in your body. Antioxidants provide an important defense against the daily assault of free radicals on healthy cells. This Essentials of Health four-part series will review the function, benefits, sources, and safety of dietary antioxidants.

Free radicals are atoms or groups of atoms with an odd (unpaired) number of electrons and can be formed when oxygen interacts with certain molecules. Once formed these highly reactive radicals can start a chain reaction, like dominoes. Their chief danger comes from the damage they can do when they react with important cellular components such as DNA, or the cell membrane. Cells may function poorly or die if this occurs. To prevent free radical damage the body has a defense system of antioxidants.

Antioxidants are molecules that can safely interact with free radicals and terminate the chain reaction before vital tissues and cells are damaged. Although there are several enzyme systems within the body that scavenge free radicals, the principle micronutrient (vitamin/mineral) antioxidants are vitamin E, beta-carotene, vitamin C and selenium. The body cannot manufacture these micronutrients so they must be supplied in the diet. In addition, there are literally hundreds of plant derived nutrients (phytonutrients) that act as important antioxidants in the diet.

It is impossible to avoid damage by free radicals. Free radicals arise from sources both inside (endogenous) and outside (exogenous) our bodies. Oxidants that develop from processes within our bodies form as a result of normal breathing, metabolism, and inflammation. Exogenous free radicals form from environmental factors such as pollution, sunlight, strenuous exercise, X-rays, smoking and alcohol. Our antioxidant systems are not perfect, so as we age, cell parts damaged by oxidation accumulate.

 
]]> http://poweroftwo.wordpress.com/2009/06/04/antioxidants-function-benefits-sources-and-safety/feed/ 0 poweroftwo Bookmark and Share http://poweroftwo.wordpress.com/2009/06/03/antioxidants-block-prostate-cancer/ http://poweroftwo.wordpress.com/2009/06/03/antioxidants-block-prostate-cancer/#comments Wed, 03 Jun 2009 01:39:07 +0000 krasi1 http://poweroftwo.wordpress.com/?p=48 ]]>

In experimental mice that naturally develop prostate cancer, supplementing with antioxidants vitamin E, lycopene and selenium effectively blocks the development or progression of prostate cancer.

According to a study published in the journal Cancer Research, dietary antioxidants (vitamin E, selenium, and lycopene) inhibited prostate cancer development in a group of mice that naturally develop prostate cancer. The prostate cancer disease process in these mice is similar to the human process in many respects, providing a good research model for the natural history of human prostate cancer.

Treatment of animals with the antioxidants resulted in a 4-fold reduction in the incidence of prostate cancer compared with the untreated animals. Prostate cancer developed in 73.68% (14 of 19) and 100% (19 of 19) of the animals from the standard and high fat diet, respectively.

In contrast, tumors developed in only 10.53% (2 of 19) and 15.79% (3 of 19) of the animals in the standard and high fat diets supplemented with antioxidants.

These observations support results from a growing body of research indicating a significant protective benefit of antioxidants on the development of prostate cancer.

A new study, published in October’s American Journal of Public Health, concluded that since fortification was implemented folic acid intake has in fact increased, but not nearly enough to meet FDA goals and recommendations. Even with significant improvements and widespread fortification, only 39 percent of white women, 26 percent of black women, and 28 percent of Mexican American women attained the 400 microgram per day target for folate consumption. In addition, over half the subgroups showed a decrease in folic acid intake since fortification began in 1998.

The FDA recommends at least 400 micrograms of folate daily for nonpregnant women, and adult men, as well as children four and older. However, the daily recommendation for pregnant women increases to at least 800 micrograms per day. Despite the fact that recent surveys show that the majority of women know the importance of folic acid, daily folic acid supplementation appears to be critical since dietary intakes still fall well below recommendations.

The Mediterranean diet, rich in cereals, wine, fruits, nuts, legumes and whole grains, fish and olive oil, has been linked to lower incidence of heart disease, protection against some cancers, and a longer life. The diet’s main nutritional components include beta-carotene, vitamin C, tocopherols, polyphenols and essential minerals. A new study published on-line in the Archives of Neurology indicates that it is these antioxidants and polyphenols that appear to offer protection, not simply an improvement in heart health.

After adjusting the results for age, education, BMI, smoking status, and ethnicity, the researchers reported that people with the highest adherence to a model Mediterranean diet were associated with a 60 per cent lower risk of Alzheimer’s disease, compared to people with the lowest adherence to the diet.

When the researchers took into account general heart health, such as history of stroke, hypertension, heart disease, diabetes, and cholesterol, the associations for the high adherence group grew stronger, with an associated risk reduction of 68 per cent.

These results indicate that the protection gained by following a Mediterranean- type diet is not a result of the cardiovascular factors, and it may be more related to factors such as inflammation and oxidative stress. The researchers noted that the Mediterranean diet contains high levels of important antioxidants and polyphenols, and it could be the combination of these various dietary compounds that could partially explain the reduced risk of Alzheimer’s Disease.

The study follows another study by the same researchers, published earlier this year in the Annals of Neurology (Vol. 59, pp. 912 – 921), in which elderly individuals whose diet closely resembled the Mediterranean diet had a 40 per cent lower risk of Alzheimer’s than those who followed the diet the least. 

A new study published in the October 2005 issue of the American Journal of Clinical Nutrition indicates that a dosage of at least 800 mcg of folic acid is needed to maximally reduce plasma homocysteine concentrations. Increased blood homocysteine levels are considered to be a risk factor for cardiovascular disease.

This meta-analysis of 25 studies evaluated the effect of various doses of folic acid on plasma homocysteine. Doses of 800 micrograms provided a significantly greater reduction in plasma homocysteine compared to 400 micrograms. Supplementation with 800 micrograms folic acid per day was associated with a 23 percent reduction in homocysteine, compared to a 20 percent reduction associated with 400 micrograms. A dosage of 200 mcg was associated with a 13 percent reduction. Higher doses provided only a slightly greater benefit. The addition of vitamin B12 was associated with a synergistic benefit.

Although some fortified foods contribute to daily intake in the U.S., many multi-nutrient supplements provide just 400 mcg of folic acid.

American Journal of Clinical Nutrition, Vol. 82, No. 4, 806-812, October 2005