MICRONUTRIENT SUPPLEMENTATION IN TUBERCULOSIS TREATMENT
Villamor E, Mugusi F, Urassa W, Bosch RJ, Saathoff E, Matsumoto K, Meydani SN, NS Fawzi WW. A trial of the effect of micronutrient supplementation on treatment outcome, T cell counts, morbidity, and mortality in adults with pulmonary tuberculosis. J Infect Dis. 2008;197:1499–1505.
Tuberculosis continues to be a significant public health issue worldwide and is frequently seen in populations with a high prevalence of HIV. Individuals with tuberculosis are often deficient in micronutrients such as vitamins A, C, and E, the B vitamins, and selenium. Historically, treatment of tuberculosis typically included nutritional support, but the focus turned away from nutrition to treat the disease with the advent of antibiotic therapy. The present study by Villamor et al. investigated the ability of micronutrient therapy to affect treatment of tuberculosis (TB) in individuals with or without HIV infection.
Participants were assigned to either a micronutrient-supplemented condition or placebo and were stratified by HIV status (HIV-positive, n = 471; HIV-negative, n = 416) within each intervention condition. Supplements contained megadoses of 5000 IU retinol, 20 mg vitamin B1, 20 mg vitamin B2, 25 mg vitamin B6, 100 mg niacin, 50 µg vitamin B12, 0.8 mg folic acid, 500 mg vitamin C, 200 mg vitamin E, and 100 µg selenium. High doses were chosen based on observations that individuals with HIV infection require higher intakes of micronutrients to achieve normal nutrient status. However, in the present study, baseline blood levels to determine nutrient status were not measured. Primary outcome measures included TB culture negativity after 1 month of treatment, mortality following at least 24 months of follow-up, and TB recurrence. All participants received standard anti-TB medications, but antiretroviral treatment was not available at the time of the study. Participants were followed for up to 48 months (median follow-up, 43 months). Mortality rates were not affected by micronutrient intake. Initiation of micronutrient supplementation was marginally associated (p = 0.08) with lower TB treatment failure at 1 month for all participants. Early recurrence between 1 and 8 months of treatment was significantly lower in individuals taking the supplement relative to those taking the placebo. This effect was stronger in HIV-positive individuals. Micronutrient supplementation was also associated with better immune function, as measured by CD4+ and CD3+ lymphocyte counts, with a stronger effect in HIV-negative individuals. Independent of HIV status, micronutrient supplementation significantly reduced the incidence of peripheral neuropathy seen with TB treatment. The authors conclude that micronutrient therapy may be a useful adjunct in the management of TB.
Comment: In an accompanying editorial, Benn et al. concur that micronutrient supplementation could be a powerful tool in the treatment of TB. However, different studies examining micronutrient supplements in TB management have found differing results, in part due to differing nutrients included in supplements. Importantly, the micronutrient supplement used by Villamor et al. contained neither zinc nor vitamin D. Zinc is important in immune response and in regaining lean muscle mass and body weight lost with TB or HIV infection. Vitamin D may be particularly effective in the treatment of TB, with inhibitory effects on the mycobacteria responsible for TB infection. Benn et al. call for standardized protocols, multicenter trials, and more rigorous examination of individual nutrients before a minimum therapeutic “package” of micronutrients can be widely recommended.
Benn CS, Friis H, Wejse C. Should micronutrient supplementation be integrated into the case management of tuberculosis? J Infect Dis. 2008;197:1487–1489.
LUTEIN/ZEAXANTHIN NOT PROTECTIVE IN EARLY AGE-RELATED MACULAR DEGENERATION
Cho E, Hankinson SE, Rosner B, Willett WC, Colditz GA. Prospective study of lutein/zeaxanthin intake and risk of age-related macular degeneration. Am J Clin Nutr. 2008;87:1837–1843.
Age-related macular degeneration (AMD) remains a leading cause of blindness in the elderly. Effective treatment for AMD remains elusive, and much emphasis is placed on prevention. The antioxidants lutein and zeaxanthin are concentrated in the macula and compose macular pigment; high macular density is associated with lower risk for AMD. Intake of lutein and zeaxanthin can increase macular pigment density, but the relationship between intake of lutein and zeaxanthin and incidence of AMD is less clear. The effects of lutein and zeaxanthin may be moderated by several factors, including smoking, body fatness, and intake of other antioxidants such as vitamins C and E. Each factor could affect the ability of lutein and zeaxanthin intakes to modify the development of AMD. Furthermore, AMD can be categorized into early AMD or neovascular AMD, and these different types of AMD may have different underlying foundations. Cho et al. prospectively examined dietary intakes and incidence of AMD in women (Nurses' Health Study; n = 71,494) and men (Health Professionals Follow-Up Study; n = 41,564) over the age of 50 years with no previous diagnosis of AMD.
Food intakes and AMD status were followed for up to 18 years. Data were stratified according to smoking status, BMI, and vitamin C and E intakes. Lutein and zeaxanthin intakes were not related to incidence of early AMD, and this effect was not modified by smoking status, BMI, or vitamin C and E intakes. Higher lutein and zeaxanthin intakes were weakly associated with reduced incidence of neovascular AMD, and this effect was stronger in those who never smoked. Taken together with previous research, the present data do not support a protective role of lutein and zeaxanthin in early AMD. The authors suggest, however, that the role of lutein and zeaxanthin in moderating neovascular AMD merits further attention.
DIETARY INTERVENTIONS TO LOWER HOMOCYSTEINE
Stea TH, Mansoor MA, Wandel M, Uglem S, Frølich W. Changes in predictors and status of homocysteine in young male adults after a dietary intervention with vegetables, fruits and bread. Eur J Nutr. 2008; June 2, doi: 10.1007/s00394-008-0714-y
High homocysteine is associated with increased risk of cardiovascular disease. Large controlled trials have successfully lowered homocysteine levels through the use of B-vitamin supplementation, but these trials have been mostly unsuccessful at reversing the risk for cardiovascular outcomes. Some studies show that diets rich in B vitamins can also effectively modify homocysteine levels, and that these diets may act synergistically to lower homocysteine. The study by Stea et al. examined the ability of dietary modification to reduce concentrations of homocysteine in young men.
A total of 750 men from the Norwegian Army and Norwegian National Guard were assigned to one of two diet conditions. Participants were fed all meals in the military mess hall. The intervention group was offered foods with an emphasis on fruits, green vegetables, reduced fat content, and breads. The control group was offered standard military mess hall fare. The participants chose their own foods and portions. The dietary intervention in the present study was intended to promote healthy lifestyle changes according to personal preferences, and was thus not strictly controlled. Intakes were measured using food diaries appropriate for Norwegian dietary patterns. Fasting blood samples were collected at baseline and after 5 months of dietary intervention. Plasma homocysteine levels were significantly decreased after 5 months on the intervention diets, and homocysteine levels remained the same in the control condition. Additionally, blood levels of B vitamin increased with the dietary intervention, although folate increased more in the control condition. One leading criticism of studies using homocysteine-lowering treatments is that the primary intervention comes relatively late in life, when the potential harm from chronically elevated homocysteine may have already been done. In the present study, the investigators used young men who already demonstrated somewhat elevated levels of homocysteine, and they were successful in lowering homocysteine through dietary modifications. These men were in compulsory military service, they regularly engaged in physical activity, and they were relatively healthy; as such, the ability to generalize the data from this study to the general population may be limited. However, it would be reasonable to propose that encouraging individuals to place a greater focus on whole-grain foods, fresh fruits, and green vegetables would have a positive impact on circulating homocysteine levels.
CALCIUM SUPPLEMENTATION AND FRACTURE RISK
Bischoff-Ferrari HA, Rees JR, Grau MV, Barry E, Gui J, Baron JA. Effect of calcium supplementation on fracture risk: a double-blind randomized controlled trial. Am J Clin Nutr. 2008;87:1945–1951.
Bone loss seen with aging is associated with increased risk for fracture. Fractures in the elderly can lead to loss of independence and are associated with mortality risk. Epidemiological studies suggest that calcium supplements, without vitamin D, may have positive effects on bone mass. The present study by Bischoff-Ferrari et al. was an opportunistic study using participants from the Calcium Polyp Prevention Study, a randomized 4-year trial examining the effects of calcium supplementation in the prevention of colorectal adenomas.
Participants had near-normal 25-OH-vitamin D levels, and had received either 1200 mg/d calcium carbonate (n = 464) or placebo (n = 466) for 4 years. Individuals were followed for a mean of 10.8 years. Primary outcomes were fractures (all-type) and minimal trauma fractures (resulting from a fall from standing height or lower). During the follow-up period, 100 participants reported at least one confirmed fracture (calcium = 46; placebo = 54). The numbers of minimal trauma fractures were significantly lower in the calcium condition relative to the placebo condition. This effect was not sustained beyond the time of supplementation, indicating that calcium must be taken consistently to confer positive effects on bone density and bone resorption.
BMI TO PREDICT RISK MAY BE LOWER IN CHINESE ADULTS THAN IN WESTERN POPULATIONS
Tuan NT, Adair LS, He K, Popkin BM. Optimal cutoff values for overweight: using body mass index to predict incidence of hypertension in 18- to 65-year-old Chinese adults. J Nutr. 2008;138:1377–1382.
Obesity is an emerging concern in China and other Asian countries where changes in diet and activity patterns related to economic development are occurring. Recent research indicates that Western BMI cutoffs for overweight (25 kg/m2) and obesity (30 kg/m2) may be too high for individuals of Asian descent. Asian individuals tend to have higher total body fat and higher levels of visceral fat at a particular BMI level than other races. The distribution of visceral fat, in particular, is a risk factor for type 2 diabetes, hypertension, and cardiovascular disease. Tuan et al. used data from the China Health and Nutrition Study (CHNS) to determine the optimal cutoff points for overweight as predictive of hypertension in Chinese adults.
CHNS data from survey years 2000 and 2004 were used. A total of 4492 participants with normal blood pressure in 2000 were included in the longitudinal sample. Blood pressure measurements were taken at the times of survey, and hypertension was defined as systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mm Hg. Cumulative incidence was determined by dividing new hypertension cases over the study period by the total at-risk population in 2000. Optimal BMI cutoffs were determined by computing and establishing the shortest distance on a sex-specific receiver operating characteristic (ROC) curve analysis. In both men and women, BMI was associated with increased risk for hypertension, with an optimal cutoff of 22.5 kg/m2 for men and 23.5 kg/m2 for women. Additionally, BMI cutoffs were slightly higher for older individuals, than young individuals. Using the standard Western BMI cutoff of 25 kg/m2 was less specific in predicting hypertension than the lower BMIs established by ROC analysis. The authors suggest that a lower cutoff of ∼23 kg/m2 be adopted as a definition of overweight in Chinese populations.