Intervention trials

The Multiple Risk Eactor Intervention Trial Research Group, J. Med. 35, 1 (1985). 

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. 

Swanson K, Abdellatif M, Fye C, Reda D, Williams D, Harris C, Clegg D. Adverse event reporting and monitoring system for the Glucosamine/Chondroi-tin Arthritis Intervention Trial (GAIT). Clin Trials 2005 2 S49. 

An overall osteoprotective effect is associated with soy diets, the major active component being the isoflavones although the contribution (if any) of soy protein has to be clarified. The spine, rather than the femur, appears to be the most consistently protected bone site. The average daily intake in Japanese women is around 50 mg/day and appears to be sufficient to have a long-term protective effect on the spine. In non-Asian, postmenopausal women, the demonstrated effective dose is 80-90 mg/day. In future clinical studies, investigating the effect of isoflavones on bone metabolism, larger scale, randomized, controlled, intervention trials for longer time periods (1-3 years) will be necessary with a standardized source of soy protein/isoflavones and... 

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)... 

Table 11.1 Summary of human intervention trials with 3-carotene...

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. 

Data concerning gastric cancer are scarce. The prospective Netherlands Cohort Study found no correlation between lutein dietary intake and gastric cancer risk, whereas findings from the Physicians Health Study and the ATBC study reported no effect of P-carotene on gastric cancer incidence. Two case-control studies and three intervention trials (ATBC, CARET, and the Physicians Health Study ) showed no association of P-carotene, lycopene, lutein, zeaxanthin, and P-cryptoxanthin. 

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. 

Epidemiological studies and intervention trials with food and beverages rich in flavonoids are not conclusive although flavonoids were recognized to display numerous antioxidant, anti-inflammatory, anti-tumoral, and anti-microbial activities. The antioxidant capacity of flavonoids has been largely reported in numerous in vitro and ex vivo systems. Numerous reviews "" have been published on the antioxidant properties of flavonoids. Degenerative diseases are largely associated with oxidative mechanisms that may be counteracted by flavonoids. 

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). 

Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure myocardial infarction... 

Stamler, J., Caggaila, A. and Grandiits, G., Relation of body mass and alcohol, nutrient, fiber and caffeine intkae to blood preussre in the special intervention and usual care groups in the multiple risk factor intervention trial. Am J Clin Nutr 65(1), 338-365, 1997. 

On patients with cancer, the effects of green tea catechins, soy isoflavones and quercetin as chemoprotective/chemotherapeutic agents have also been studied. Although results have not been entirely satisfactory, a partial response has been achieved in some trials. For example, small decreases in plasma concentration of prostate-specific antigen were observed in prostate cancer patients who consumed soy isoflavones. Nevertheless, results in individuals with premalignant disease who consumed green tea polyphenols support their advancement into phase III clinical intervention trials aimed at the prevention of PIN, leukoplakia, or premalignant cervical disease (Thomasset and others 2006). 

Cummings SR, Black DM, Thompson DE, Applegate WB, Barret-Connor E, Musliner TA, Palermo L (1998) Alendronate reduces the risk of vertebral fractures in women witout pre-existing vertebral fractures results of the fracture intervention Trial. J Am Med Assoc 280 2077-2078... 

Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC et al. (2000) Fracture risk reduction with alendronate in women with osteoporosis the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab 85 4118-4124... 

This Directive establishes specific provisions regarding the conduct of clinical trials, including multi-centre trials, on human subjects involving medicinal products as defined in Article 1 of Directive 65/65/EEC, in particular relating to the implementation of good clinical practice. This Directive does not apply to non-interventional trials. 

MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure Metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet. Jun 12 1999 353(9169) 2001-2007. 

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