Supplements intervention trials

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. 

Intervention trials confirmed this protective role of lycopene on prostate cancer risk. Three primary intervention studies evaluated the effect of lycopene supplementation on prostate cancer risk or on certain risk markers such as prostate-specific antigen (PSA) plasma concentration or oxidative alterations of leucocyte DNA. - All showed increases of plasma and prostate lycopene levels after diet supplementation with lycopene and inverse correlations between tumor incidence and risk biomarkers. 

However, intervention trials investigating the effects of P-carotene and lycopene supplementation on CVD have not reported convincing results (Table 3.1.3). Among the seven studies reviewed herein, four primary prevention trials, namely the Multicenter Skin Cancer Prevention Study, the Beta Carotene and Retinol Efficacy Trial, the ATBC cancer prevention study, " and the Physicians Health Study have shown no association between a supplementation of P-carotene and risk of death from CVD or fatal and non-fatal MI. 

In a 20-week multicenter intervention trial with lutein in healthy human subjects, no changes were noted in hematological or biochemical parameters after continuous daily lutein doses of 15 mg (0.25 mg/kg body weight, assuming a body weight of 60 kg). A relatively large number of human studies have examined correlations between macular degeneration and dietary intake of lutein or zeaxanthin, intakes via dietary supplements, and serum concentrations. 

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). 

While the high proportion of the mineral calcium in dairy products has been hypothesized as the factor contributing to favorable metabolic outcomes (Zemel, 2001), several studies have identified more favorable health outcomes in intervention trials whereby calcium is administered in the form of dairy products in contrast to supplementation (Zemel, 2004, 2008). It may be that the calcium phosphate found in dairy products exerts a more significant weight loss effect as opposed to the calcium citrate or calcium carbonate utilized in supplements (Lorenzen et al., 2006). 

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. 

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). 

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. 

Methotrexate is an antagonist of folic acid and is used for treating neoplastic diseases and non-neoplastic diseases such as rheumatoid arthritis and psoriasis. As methotrexate reduces the activity of dihydrofolate reductase, supplementation with folic acid and especially with folinic acid could reduce the beneficial effects of methotrexate. This assumption has been supported by the results of an intervention study (40). Patients with rheumatoid arthritis treated with methotrexate (15 g/week) had an increase in symptoms. An open intervention trial of folinic acid 45 mg/week also showed an increase in arthritis symptoms (41). However, other trials showed no effects of this sort, and administration of folic acid or folinic acid is important in preventing methotrexate-induced blood dyscrasias. 

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. 

Initial reports of deficiencies of essential fatty acids among children with attention-deficit hyperactivity disorder and dyslexia raised the promise of potential nondrug treatments. Convincing treatment data from interventional trials has not yet been reported. (Stevens et al. (1995) found that 53 subjects with attention-deficit hyperactivity disorder had significantly lower concentrations of AA, EPA. and DHA in plasma polar phospholipids when compared to 43 control subjects. (Stordy 1995) has described decreased rod function comparing 10 young dyslexics to 10 controls. In an open trial, supplementation... 

Yu SY, Zhu YJ, Li WG, et al. 1991. A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China. Biol Trace Elem Res 29(3) 289-294. 

Human Intervention Trials In several human intervention trials, significant cancer-preventive effects of supplemental selenium have already been demonstrated, and several other studies are pres-... 

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