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).

Vitamin E
The need to supplement is perhaps most obvious in the case of vitamin-E (alpha-tocopherol). Alpha-tocopherol is a fat-soluble antioxidant which protects our cells against free radical attacks (23,24). It is particularly important in protecting against peroxidation of low-density lipoproteins (LDLs) and thereby preventing atherosclerosis and cardiovascular disease (23,24,25,26,27,28).

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).

Recommended Daily Allowances
The evidence is indeed overwhelming and growing daily that supplementation with antioxidants can help prevent the development of most degenerative diseases. So what are the RDAs (Recommended Daily Allowances) for antioxidants? Surprisingly enough, there are none! Beta-carotene, selenium, and coenzyme Q10 have no RDAs although the National Academy of Sciences has stated that a daily selenium intake of 50-200 micrograms is safe and adequate (61). Two of the most powerful antioxidants, ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E), are also vitamins and as vitamins they have RDAs of 60 mg/day and 12-15 IU/day respectively.

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.

REFERENCES

1. Halliwell, Barry. Free radicals and antioxidants: a personal view. Nutrition Reviews, Vol. 52, No. 8, August 1994, pp. 253-65
2. Halliwell, Barry. Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? The Lancet, Vol. 344, September 10, 1994, pp. 721-24
3. Jenner, P. Oxidative damage in neurodegenerative disease. The Lancet, Vol. 344, September 17, 1994, pp. 796-98
4. Grisham, Matthew B. Oxidants and free radicals in inflammatory bowel disease. The Lancet, Vol. 344, September 24, 1994, pp. 859-61
5. Stadtman, Earl R. Protein oxidation and aging. Science, Vol. 257, August 28, 1992, pp. 1220-24
6. Pearce, Fred. Mounting evidence ties asthma to car fumes. New Scientist, October 1, 1994, p. 4
7. Hatch, Gary E. Asthma, inhaled oxidants, and dietary antioxidants. American Journal of Clinical Nutrition, Vol. 61, No. 3, March 1995, pp. 625S- 30S
8. Danielson, Christa, et al. Hip fractures anf fluoridation in Utah's elderly population. Journal of the American Medical Association, Vol. 268, No. 6, August 12, 1992, pp. 746-48
9. Is aluminium a dementing ion? The Lancet, Vol. 339, March 21, 1992, pp. 713-14
10. Gault, M. Henry. Would decreased aluminum ingestion reduce the incidence of Alzheimer's disease? Canadian Medical Association Journal, Vol. 147, No. 6, September 15, 1992, pp. 845-46
11. Diplock, Anthony T. Antioxidant nutrients and disease prevention: an overview. American Journal of Clinical Nutrition, Vol. 53, 1991, pp. 189S-93S
12. Malvy, D.J., et al. Serum beta-carotene and antioxidant micronutrients in childen with cancer. International Journal of Epidemiology, Vol. 22, No. 5, October 1993, pp. 761-71
13. Kardinaal, A.F.M., et al. Antioxidants in adipose tissue and risk of myocardial infarction: the EURAMIC study. The Lancet, Vol. 342, December 4, 1993, pp. 1379-84
14. Block, Gladys. The data support a role for antioxidants in reducing cancer risk. Nutrition Reviews, Vol. 50, No. 7, July 1992, pp. 207-13
15. Block, Gladys. Micronutrients and cancer: time for action? Journal of the National Cancer Institute, Vol. 85, No. 11, June 2, 1993, pp. 846-47
16. Frei, Balz. Reactive oxygen species and antioxidant vitamins: mechansims of action. The American Journal of Medicine, Vol. 97, Suppl. 3A, September 26, 1994, pp. 5S-13S
17. Gershoff, Stanley N. Vitamin C (ascorbic acid): new roles, new requirements? Nutrition Reviews, Vol. 51, No. 11, November 1993, pp. 313-26
18. Block, G. Epidemiologic evidence regarding vitamin C and cancer. American Journal of Clinical Nutrition, Vol. 54 (6 suppl.), December 1991, pp. 1310S- 14S
19. Johnston, Carol S. Vitamin C elevates red blood cell glutathione in healthy adults. American Journal of Clinical Nutrition, Vol. 58, 1993, pp. 103-5
20. Bradley, David. An orange a day helps to keep sperm OK. New Scientist, March 14, 1992, pp. 20
21. Hankinson, Susan E., et al. Nutrient intake and cataract extraction in women: a prospective study. British Medical Journal, Vol. 305, August 8, 1992, pp. 335-39
22. Herbert, Victor. Viewpoint - Does mega-C do more good than harm, or more harm than good? Nutrition Today, January/February 1993, p. 28-32
23. Halliwell, Barry. Oxidation of low-density lipoproteins: questions of initiation, propagation, and the effect of antioxidants. American Journal of Clinical Nutrition, Vol. 61, No. 3, March 1995, pp. 670S-77S
24. Packer, L. Protective role of vitamin E in biological systems. American Journal of Clinical Nutrition, Vol. 53, 1991, pp. 1050S-55S
25. Steinberg, Daniel, et al. Beyond cholesterol. The New England Journal of Medicine, Vol. 320, 1989, pp. 915-24
26. Sevanian, Alex and McLeod, L.L. Cholesterol auto-oxidation in phospholipid membrane bilayers. Lipids, Vol. 22, 1987, pp. 627-36
27. Hoffman, Richard M. and Garewal, Harinder S. Antioxidants and the prevention of coronary heart disease. Archives of Internal Medicine, Vol. 155, February 13, 1995, pp. 241-46
28. Meydani, Mohsen. Vitamin E. The Lancet, Vol. 345, January 21, 1995, pp. 170-75
29. Rimm, Eric B., et al. Vitamin E consumption and the risk of coronary heart disease in men. The New England Journal of Medicine, Vol. 328, No. 20, May 20, 1993, pp. 1450-55
30. Stampfer, Meir J., et al. Vitamin E consumption and the risk of coronary disease in women. The New England Journal of Medicine, Vol. 328, No. 20, May 20, 1993, pp. 1444-49
31. Smigel, Kara. Vitamin E moves on stage in cancer prevention studies. Journal of the National Cancer Institute, Vol. 84, No. 13, July 1, 1992, pp. 996-7
32. Paolisso, Giuseppe, et al. Pharmacologic doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetic patients. American Journal of Clinical Nutrition, Vol. 57, 1993, pp. 650-6
33. Meydani, M., et al. Effect of long-term vitamin E supplementation on lipid peroxidation and immune responses of young and old subjects. FASEB Journal, Vol. 7, 1993, pp. A415
34. Meydani, S.N., et al. Effect of vitamin E supplementation on immune responsiveness of the aged. Annals of the New York Academy of Science, Vol. 570, 1989, pp. 283-90
35. Haeger, K. Long-term treatment of intermittent claudication with vitamin E. American Journal of Clinical Nutrition, Vol. 27, 1974, pp. 1179-81
36. Livingstone, P.D. and Jones, C. Treatment of intermittent claudication with vitamin E. The Lancet, Vol. 2, 1958, pp. 602-04
37. Williams, H.T.G., et al. Alpha tocopherol in the treatment of intermittent claudication. Surg. Gynecol. Obstet., Vol. 132, 1971, pp. 662-66
38. Robertson, J.M., et al. Vitamin E intake and risk of cataracts in humans. Annals of the New York Academy of Science, Vol. 570, 1989, pp. 372-82
39. Olson, Patrick E., et al. Oral vitamin E for refractory hand dermatitis. The Lancet, Vol. 343, March 12, 1994, pp. 672-73
40. Bendich, A. and Machlin, L.J. Safety of oral intake of vitamin E. American Journal of Clinical Nutrition, Vol. 48, 1988, pp. 612-19
41. Meydani, S.N., et al. Assessment of the safety of high-dose, short-term supplementation with vitamin E in healthy older adults. American Journal of Clinical Nutrition, Vol. 60, November 1994, pp. 704-09
42. Umegaki, Keizo, et al. Beta-carotene prevents x-ray induction of micronuclei in human lymphocytes. American Journal of Clinical Nutrition, Vol. 59, No. 2, February 1994, pp. 409-12
43. Ferraroni, M. et al. Selected micronutrient intake and the risk of colorectal cancer. British Journal of Cancer, Vol. 70, December 1994, pp. 1150-55
44. Jain, Meera, et al. Premorbid diet and the prognosis of women with breast cancer. Journal of the National Cancer Institute, Vol. 86, No. 18, September 21, 1994, pp. 1390-97
45. Garewal, Harinder, et al. Oral cancer prevention: the case for carotenoids and anti-oxidant nutrients. Preventive Medicine, Vol. 22, September 1993, pp. 701-11
46. Fuller, Cindy J., et al. Effect of beta-carotene supplementation on photosupression of delayed-type hypersensitivity in normal young men. American Journal of Clinical Nutrition, Vol. 56, 1992, pp. 684-90
47. Stahelin, Hannes B., et al. Beta-carotene and cancer prevention: the Basel Study. American Journal of Clinical Nutrition, Vol. 53, 1991, pp. 265S-69S
48. Stahelin, H.B., et al. Plasma antioxidant vitamins and subsequent cancer mortality in the 12-year follow-up of the prospective Basel Study. American Journal of Epidemiology, Vol. 133, No. 8, April 15, 1991, pp. 766-75
49. Jacques, Paul F. and Chylack, Leo T. Epidemiologic evidence of a role for the antioxidant vitamins and carotenoids in cataract prevention. American Journal of Clinical Nutrition, Vol. 53, 1991, pp. 352S-55S
50. Knekt, Paul, et al. Serum antioxidant vitamins and risk of cataract. British Medical Journal, Vol. 305, December 5, 1992, pp. 1392-94
51. Morris, Dexter L., et al. Serum carotenoids and coronary heart disease. Journal of the American Medical Association, Vol. 272, No. 18, November 9, 1994, pp. 1439-41
52. Street, Debra A., et al. Serum antioxidants and myocardial infarction. Circulation, Vol. 90, No. 3, September 1994, pp. 1154-61
53. Mayne, Susan Taylor, et al. Dietary beta carotene and lung cancer risk in U.S. nonsmokers. Journal of the National Cancer Institute, Vol. 86, No. 1, January 5, 1994, pp. 33-38
54. Gaziano, J.M., et al. Beta-carotene therapy for chronic stable angina. Circulation, Vol. 82, Suppl. 3, 1990, p. 201
55. Gaziano, J.M., et al. Dietary antioxidants and cardiovascular disease. Annals of the New York Academy of Science, Vol. 669, 1992, pp. 249-59
56. Prince, Martin R. and Frisoli, Joan K. Beta-carotene accumulation in serum and skin. American Journal of Clinical Nutrition, Vol. 57, March 1993, pp. 175-81
57. Solomons, N.W. and Bulux, J. Plant sources of provitamin A and human nutriture. Nutrition Reviews, Vol. 51, No. 7, July 1993, pp. 199-204
58. Spallholz, J.E. On the nature of selenium toxicity and carcinostatic activity. Free Radical Biology and Medicine, Vol. 17, No. 1, July 1994, pp. 45-64
59. Brtkova, A. Biological effects of selenium. Bratislavske Lekarske Listy, Vol. 93, No. 12, December 1992, pp. 629-32
60. Goyer, Robert A. Nutrition and metal toxicity. American Journal of Clinical Nutrition, Vol. 61, No. 3, March 1995, pp. 646S-650S
61. Oldfield, J.E. Some implications of selenium for human health. Nutrition Today, July/August 1991, pp. 6-11
62. Clark, L.C., et al. Selenium in forage crops and cancer mortality in U.S. counties. Archives of Environmental Health, Vol. 46, No. 1, Jan/Feb. 1991, pp. 37-42
63. Thomson, Christine D., et al. Long-term supplementation with selenate and selenomethionine: selenium and glutathione peroxidase in blood components of New Zealand women. British Journal of Nutrition, Vol. 69, March 1993, pp. 577- 88
64. Blot, William J., et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. Journal of the National Cancer Institute, Vol. 85, No. 18, September 15, 1993, pp. 1483-91
65. Blot, William J., et al. Lung cancer and vitamin supplementation. The New England Journal of Medicine, Vol. 331, No. 9, September 1, 1994, p. 614
66. Han, Jui. Highlights of the cancer chemoprevention studies in China. Preventive Medicine, Vol. 22, September 1993, pp. 712-22
67. Frei, Balz, et al. Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc. Natl. Acad. Sci. USA, Medical Sciences, Vol. 87, June 1990, pp. 4879-83
68. Stocker, Roland, et al. Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha- tocopherol. Proc. Natl. Acad. Sci. USA, Medical Sciences, Vol. 88, March 1991, pp. 1646-50
69. Hanaki, Yoshihiro, et al. Ratio of low-density lipoprotein cholesterol to ubiquinone as a coronary risk factor. The New England Journal of Medicine, Vol. 325, No. 11, September 12, 1991, pp. 814-15
70. Mohr, D., et al. Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation. Biochimica et Biophysica Acta, Vol. 1126, No. 3, June 26, 1992, pp. 247-54
71. Kamikawa, T., et al. Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris. American Journal of Cardiology, Vol. 56, 1985, p. 247
72. Mortensen, S.A., et al. Long-term coenzyme Q10 therapy: a major advance in the management of resistant myocardial failure. Drug Exp. Clin. Res. (8), 1985, p. 581
73. Langsjoen, P.H., et al. Effective treatment with coenzyme Q10 of patients with chronic myocardial disease. Drug Exp. Clin. Res. (8), 1985, p. 577
74. Langsjoen, P.H., et al. Response of patients in classes III and IV of cardiomyopathy to therpay in a blind and crossover trial with coenzyme Q10. Proc. Natl. Acad. Sci. USA, Vol. 82, 1985, p. 4240
75. Yamagami, T., et al. Effect of coenzyme Q10 on essential hypertension: a double-blind controlled study, in Folkers, K. and Yamamura, Y. (eds): Biomedical and Clinical Aspects of Coenzyme Q, Vol. 5, Elsevier Sci. Publ. B.V., Amsterdam, 1986, pp. 337-43
76. Tanaka, J., et al. Coenzyme Q10: the prophylactic effect on low cardiac output following cardiac valve replacement. Ann. Thorac. Surg. Vol. 33, No. 2, 1982, p. 145
77. Sunamori, M., et al. Clinical application of coenzyme Q to coronary artery bypass graft surgery, in Folkers, K. and Yamamura, Y. (eds): Biomedical and Clinical Aspects of Coenzyme Q, Vol. 4, Elsevier Sci. Publ. B.V., Amsterdam, 1984, pp. 333-42
78. Oda, T., et al. Stress echocardiography for pediatric patients with symptomatic mitral valve prolapse. Jpn. Circ. J. Vol. 47, 1983, p. 1335
79. Oda, T. and Hamamoto, K. Effect of coenzyme Q10 on the stress-induced decrease in cardiac performance in pediatric patients with mitral valve prolapse. Jpn. Circ. J. Vol. 48, 1984, p. 1387
80. Oda, T. Coenzyme Q10 therapy on the cardiac dysfunction in patients with mitral valve prolapse - dose vs. effect and dose vs. serum level of coenzyme Q10, in Folkers, K. and Yamamura, Y. (eds): Biomedical and Clinical Aspects of Coenzyme Q, Vol. 5, Elsevier Sci. Publ. B.V., Amsterdam, 1986, pp. 269-80
81. Greenberg, Steven and Frishman, William H. Co-enzyme Q10: a new drug for cardiovascular disease. Journal of Clinical Pharmacology, Vol. 30, 1990, pp. 596-608
82. Horwitt, M.K. Status of human requirement for vitamin E. American Journal of Clinical Nutrition, Vol. 27, October 1974, pp. 1182-93
83. Horwitt, Max K. Data supporting supplementation of humans with vitamin E. Journal of Nutrition, Vol. 121, 1991, pp. 424-29
84. Voelker, Rebecca. Recommendations for antioxidants: how much evidence is enough? Journal of the American Medical Association, Vol. 271, No. 15, April 20, 1994, pp. 1148-49