Vitamins intervention trials

It has been proposed that the development of the complications of diabetes mellitus may be linked to oxidative stress and therefore might be attenuated by antioxidants such as vitamin E. Furthermore, it is discussed that glucose-induced vascular dysfunction in diabetes can be reduced by vitamin E treatment due to the inactivation of PKC. Cardiovascular complications are among the leading causes of death in diabetics. In addition, a postulated protective effect of vitamin E (antioxidants) on fasting plasma glucose in type 2 diabetic patients is also mentioned but could not be confirmed in a recently published triple-blind, placebo-controlled clinical trial [3]. To our knowledge, up to now no clinical intervention trials have tested directly whether vitamin E can ameliorate the complication of diabetes. 

More recently, large human intervention trials were undertaken with P-carotene alone, or in combination with non-dietary amounts of vitamin E. These trials were undertaken because of promising animal studies that suggested that these antioxidants could offer chemo-preventive action against oxidative stress. The results, which are summarised in Table 11.1, were disappointing. Although the study population in two of the studies (ATBC and CARET)... 

Many epidemiological studies have analyzed the correlations between different carotenoids and the various forms of cancer and a lot of conclusions converge toward protective effects of carotenoids. Many studies were carried out with (i-carotene. The SUVIMAX study, a primary intervention trial of the health effects of antioxidant vitamins and minerals, revealed that a supplementation of p-carotene (6 mg/day) was inversely correlated with total cancer risk. Intervention studies investigating the association between carotenoids and different types of cancers and cardiovascular diseases are reported in Table 3.1.2 and Table 3.1.3. 

Epidemiological studies in Europe reveal an inverse relationship between plasma vitamin E levels and the incidence of ischaemic heart disease (Gey and Puska 1989), and the risk of angina pectoris appears to increase with low plasma levels of vitamins E, A and C (Rie-mersma et al., 1991). These interesting observations require further population-based controlled intervention trials with specific supplements of antioxidant vitamins (Gey etal., 1991). 

IboleJF etal. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004 291 (5) 565-575. 

Li JY Taylor PR, Li B, et al. Nutrition intervention trial in Linxian, China multiple vitamin/mineral supplementation, cancer incidence, and disease specific mortality among adults with esophageal displasia. J Natl Cancer Inst 1993 85 1492-1498. 

Pryor, W.A. 2000. Vitamin E and heart disease Basic science to clinical intervention trials. Free Radio. Biol. Med. 28, 141—164. 

Bll. Blot, W. J., Li, J. Y., Taylor, P. R., Guo, W., Dawsey, S., et al., Nutrition intervention trials in Linxian, China. Supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J. Natl. Cancer Inst. 85, 1483-1492 (1993). 

There is an association between the rare inborn recessive condition of homocystinemia and arterial and venous thrombosis, and observational data link coronary heart disease, stroke, and venous thromboembolism with increasing plasma homocysteine (Wald et al. 2002, 2004). This led to trials of foUc acid and pyridoxine supplementation to lower homocysteine levels (Hankey 2002 Hankey and Eikelboom 2005). Results from such trials have so far been disappointing the Vitamin Intervention for Stroke Prevention Study (VISP) and the Norwegian Vitamin Trial (NORVIT) (Toole et al. 2004 Bonaa et al. 2006) trials showed no treatment effect on recurrent stroke, coronary events or deaths. Preliminary results from the Study of Vitamins to Prevent Stroke (VITATOPS) trial have shown no evidence of reduced levels of iirflammation, endothelial dysfunction, or the hypercoagulability postulated to be increased by elevated homocysteine levels in patients with previous TIA or stroke treated with foUc acid, vitamin B12 and vitamin Bs... 

Nevertheless, at least six randomized, double-blind, placebo-controlled, intervention trials have assessed the effect of vitamin or micronutrient supplements on AMD risk. The consensus from these and other trials seems to suggest a positive response of the retina as well as improved visual performance from vitamin and mineral supplementation such as the AREDS formulation (see above). Specifically, the AREDS results should be interpreted as understanding that the formulation was effective in slowing the risk of progression of AMD in persons 55 years of age and older who had some macular changes consistent with early age-related maculopathy. More recently, substantiation of these results was reported on a primarily white population as part of the Rotterdam Study. An above-median intake of beta-carotene, vitamin C, vitamin E, and zinc was associated with a 35% reduced risk of AMD. Still other clinical research has demonstrated shortterm beneficial effects in small populations for lutein and a combination of lutein and antioxidants in AMD. 

Abdeljaber MH, Monto AS, Tilden RL, Schork MA, Tarwotjo I. The impact of vitamin A supplementation on morbidity a randomized community intervention trial. Am J Pubhc Health 1991 81(12) 1654-6. 

Oxidative DNA Damage in vivo Intervention Trials Supplementing Vitamin C, Vitamin E, or P-Carotene... 

Several small intervention trials have used indices of colorectal epithelial cell proliferation as intermediate endpoints. Supplementation with 3g/d of vitamin C for at least 18 months resulted in a significantly decreased proliferation index in rectal epithehal cells compared with placebo in patients with FAP " " In another small trial, supplementation with 750mg/d of vitamin C or 9mg/d of p-carotene but not 160mg/d of vitamin E for one month decreased cell proliferation in colonic crypts of adenoma patients compared with the baseline. However, supplementation of colorectal adenoma or colorectal cancer patients with 30mg/d of p-carotene for 3 months decreased indices of colonic cell proliferation when compared with a placebo. A stndy of colon cancer patients randomized to receive a combination of lOOOmg/d of vitamin C, 70mg/d of a-tocopherol, 30,000 lU/d of vitamin A, and 2000mg/d of calcinm or placebo for 6 months... 

Numerous controlled supplementation trials have failed to demonstrate that vitamin C, vitamin E, or p-carotene decrease in vivo oxidative DNA damage in humans (Table 21.1). Yet, the findings of prospective cohort studies and controlled intervention trials suggest that these compounds may be beneficial in preventing specific types of cancer and in specific populations (Table 21.2). 

---