Antioxidants: The Case for Supplements

Oxidative Stress
Oxidative stress occurs when the quantity of free radicals the body has to cope with exceeds the availability of antioxidants (1). This concept is relatively new and is closely linked to the growing awareness that our environment is a potent source of disease. Air pollution has been linked to heart attacks, asthma, and other respiratory diseases (6,7). Cigarette smoke causes lung cancer, heart disease and a host of other diseases. Chemicals in our drinking water have been linked to cancer, hip fractures and Alzheimer's disease (8,9,10). Nitrites and other food additives have been linked to cancer. Excessive amounts of radiation can cause cancer and allergens in the air we breathe and the food we eat can cause a whole raft of diseases and even death. We are surrounded by toxic chemicals from drycleaning fluids to pesticides and many have been implicated in the development of cancer.

All these environmental stressors are man-made and have only been around for a very short time in evolutionary terms; not nearly long enough for us to adapt to them.

Our body is constantly coping with oxidative stress whether it has its origins in our digestive processes, our energy-producing processes or in the processes we use in killing off foreign invaders like bacteria and viruses. When we add environmental stressors the load can easily become excessive. It has been estimated that each cell in our body has to cope with something like 10,000 individual attacks by free radicals every day (5).

Fortunately, all living systems have developed defense mechanisms against oxidative stress - if they had not, they would no longer be around.

Antioxidants
Superoxide dismutase is the body's main defense and is especially effective in deactivating superoxide radicals. Another natural antioxidant which effectively scavenges free radicals is the selenium-containing antioxidant glutathione peroxidase.

Progressive researchers are now concluding that our natural antioxidants are no longer able to cope with the oxidative stress we are exposed to. They believe we need to sharply increase our intake of dietary antioxidants to help in the fight.

Antioxidants should preferably be obtained through whole, unpolluted food. However, more and more researchers are realizing that the average intake from the diet is far too low to provide significant help to the body in its fight against degenerative diseases. This and the fact that a clear link has been established between a low intake of antioxidants and heart disease and cancer makes it clear that we need to boost our antioxidant intake through supplementation (11,12,13,14,15).

Vitamin C
Numerous epidemiologic studies have found that vitamin-C or vitamin C-rich foods prevent cancer and heart disease and even asthma (7,14,16,17,18,19). Now evidence is accumulating that direct supplementation with vitamin C has many beneficial effects as well.

Researchers at the Arizona State University have found that supplementing with 500 mg/day of ascorbic acid for two weeks increased the glutathione concentration in the blood by 50 per cent (19). This is good news as glutathione is one of the body's most important natural antioxidants.

A team of scientists at the University of California have found that a minimum daily intake of 250 mg of vitamin C is required to protect human sperm against oxidative degradation (20). This is far higher than the actual mean daily intake which, in the United States, is about 70 mg/day or just enough to prevent scurvy (14,17).

Researchers at Harvard Medical School concluded from an eight-year study of 50,000 nurses that supplementing with vitamin C (250-500 mg/day) for ten years or longer significantly lowers the risk of cataract formation (21).

Vitamin C is generally safe even in large doses. However, people who are born with a gene that increases iron absorption should not supplement with more than 500 mg/day without consulting their health care professional (22).

Researchers at the Harvard Medical School have found that men and women who supplemented with more than 100 IU/day of vitamin E for at least two years lowered their risk of coronary disease by 37 to 40 per cent. This study was very comprehensive and involved more than 125,000 nurses and male health professionals. The study found that even the highest dietary intakes of vitamin E were far too low to afford any protection and that multivitamin pills also contain too little vitamin E to provide any protective effect (29,30).

Other researchers have found that supplementation with vitamin E for at least six months lowers the risk of developing oral cancer by 50 per cent (31). Italian scientists report that supplementation with 900 mg/day of synthetic vitamin E improves the glucose balance in diabetics (32). Daily supplementation with 400 IU/day of vitamin E has also been found to improve the immune response in both young and elderly people (33,34). Other studies have shown that vitamin E supplementation helps relieve intermittent claudication and cuts the risk of lung cancer in half (35,36,37). Supplementation with 400 IU/day of vitamin E and 600 mg/day of vitamin C has been found to lower the risk of cataract formation (38). Oral supplementation with 400 IU/day of vitamin E has even been reported to be beneficial in the treatment of dermatitis (39).

Vitamin E is safe in intakes as large as 3200 IU/day but medical advice should be obtained before starting a supplementation program by individuals who have a vitamin K deficiency, a tendency to prolonged bleeding or who are taking anticoagulants (40,41).

Beta-carotene
Beta-carotene is another fat-soluble antioxidant which is highly effective in protecting against free radical attacks. Japanese researchers have found that supplementation with 30 mg/day of beta-carotene protects against damage caused by x-ray irradiation (42). Italian scientists have found that beta-carotene protects against colon cancer and Canadian researchers have found a protective effect against breast cancer (43,44). Oral supplementation with beta-carotene has been found to reverse oral leukoplakia and to prevent suppression of the immune system (45,46). Several studies have found that people with a low level of beta-carotene in their blood have a higher risk of developing lung cancer, stomach cancer, coronary heart disease, and cataracts (47,48,49,50,51,52,53). Another study found that supplementing with beta- carotene (50 mg every second day) halves the risk of heart attack and heart disease (54,55).

Beta-carotene supplements are well absorbed, especially with a fatty meal and some recent research even concludes that beta-carotene from supplements is absorbed more efficiently by the body than is beta-carotene from carrots (56,57).

Selenium
The importance of selenium as a dietary antioxidant is becoming increasingly clear. Selenium is an important component of the body's natural antioxidant, glutathione peroxidase, and also plays an important role in combatting the toxic effects of mercury and cadmium (58,59,60). A low content of selenium in the blood has been linked to an increased risk of cancer and heart disease (59,61,62).

Supplementation with 200 micrograms/day of selenomethionine has been found to increase the level of glutathione peroxidase in the blood (63). A large trial in China found that supplementing with 50 micrograms/day of selenium (plus 15 mg beta-carotene and 30 mg vitamin E) lowered the risk of dying from stomach cancer by 21 per cent (64,65). Other Chinese researchers have found that supplementation with 200 micrograms per day of selenium significantly lowers the risk of developing liver cancer in a high risk population (66).

Coenzyme Q10
Some very recent research has shown that Ubiquinol-10, the reduced form of ubiquinone-10 (coenzyme Q10) is even more powerful than vitamin E and beta- carotene in protecting low-density lipoproteins (LDLs) against peroxidation (67,68,69,70). It is, unfortunately, only found in very low levels in LDLs, but its concentration can be significantly increased by supplementing with coenzyme Q10 (70). Japanese researchers have found that oral supplementation with coenzyme Q10 improves the exercise capacity of patients with angina pectoris (71). Oral supplementation has also been used with good success in patients suffering from congestive heart failure and essential hypertension (72,73,74,75). Research is ongoing to evaluate the benefits of ubiquinone supplementation prior to cardiac surgery and preliminary results are very promising (76,77). There is also some evidence that coenzyme Q10 is useful in the treatment of ventricular arrhythmias and mitral valve prolapse (78,79,80).

Coenzyme Q10 is relatively free of adverse effects in daily intakes as high as 300 mg/day (81). Most treatment protocols use between 30 and 100 mg daily (81).

However, to suggest that an RDA for a vitamin which acts as a catalyst without being consumed bears any relationship to the RDA for an antioxidant which is consumed in carrying out its function demonstrates a lack of understanding of basic chemistry. As a matter of fact, the way RDAs are determined leaves a lot to be desired. RDAs are based on two very erroneous assumptions: one, that the average American diet is healthy - which is hard to accept considering that three out of four of the people eating this diet die prematurely from either cancer or heart disease. The other assumption is that our vitamin requirements are the minimum amounts needed to avoid developing serious deficiency diseases such as scurvy, beriberi, and pellagra.

Just how illogical some RDAs are can be illustrated by reviewing the case of vitamin E. In 1968 the RDA for adults was set at 30 IU/day even though extensive dietary surveys showed that even the best American diet could only supply about 20 IU (15 mg). In 1974 the RDA was lowered to 15 IU/day for men and 12 IU/day for women to reflect this fact. Perhaps the crowning irony is that one of the key members of the panel who supported the reduction in the RDA for vitamin E in 1974 admitted in 1991 that he was himself taking 400 IU of vitamin E every second day "to decrease the undesirable products of lipid peroxidation in human tissues" (82,83).

The Case for Supplements
The tide is now turning and more and more researchers and even medical doctors are recommending daily supplementation with antioxidants. Dr. Gladys Block of the University of California points out that only 9 per cent of all Americans consume the recommended five or more servings a day of fresh fruits and vegetables. She and a group of progressive medical doctors recommend that people take antioxidants to reduce their risk of cancer (14,15). Recently a scientific advisory panel to the U.S. government sponsored Alliance for Aging Research advised all healthy adults to sharply increase their intake of selected antioxidants. They recommend a daily intake of 250-1000 mg of vitamin C, 100-400 IU of vitamin E, and 10-30 mg of beta-carotene (84). To put this in perspective, to get 1000 mg of vitamin C from the diet one would need to eat 14 oranges or 10 cups of cooked broccoli a day; to get 400 IU of vitamin E would require the consumption of 200 cups of brown rice or 80 cups of cooked spinach each and every day.