INFANT FEEDING AND VISUAL DEVELOPMENT
Rudnicka AR, Owen CG, Richards M, Wadsworth MEJ, and Strachan DP. Effect of breastfeeding and sociodemographic factors on visual outcome in childhood and adolescence. Am J Clin Nutr. 2008;87:1392–1399.
Reduced vision in childhood is predominantly attributed to myopia. The prevalence of myopia varies across geographical regions and is reported to be increasing among children in industrialized areas leading to the supposition that environmental factors have an important role in the ontogeny of myopia. Some research indicates myopia incidence is reduced in individuals who were initially breastfed relative to formula-fed individuals. One proposed factor in this relationship is the presence of long-chain PUFA in breast milk, whereas long-chain PUFAs are not universally found in infant formula. Rudnicka et al. analyzed data collected in three British birth cohorts from 1946, 1958, and 1970.
Analysis of vision outcomes for this study was limited to the period birth–16 years. Feeding status (breastfed vs. formula), socioeconomic status, maternal age, parental education, and birth order were included in the analysis. In British individuals born between 1946 and 1970, there was no association between myopia and feeding status in those initially breastfed for at least 1 month prior to the age of 2 years and those who were initially formula fed. Rates of breastfeeding decreased over successive cohorts, but rates of myopia did not appreciably increase. Environmental factors including increasing maternal age, birth order (with first-born at higher risk), and level of parental education were positively associated with risk of developing myopia.
Comment: Although the authors conclude that breastfeeding in infancy does not influence vision at later ages, there are caveats to be addressed. First, breastfeeding was dichotomized into “yes” or “no” categories without gathering information on duration of breastfeeding. Second, reduced vision in this study was limited to myopia without considering other problems such as astigmatism or hyperopia. Dr. Heird suggests that while the study has limitations, it does highlight the importance of environmental and socioeconomic factors in visual development and outcome in children.
Editorial Comment: Heird WC. Infant feeding and vision. Am J Clin Nutr. 2008;87:1120.
ORAL CALCITRIOL IMPROVES SURVIVAL IN CHRONIC KIDNEY DISEASE
Shoben AB, Rudser KD, de Boer IH, Young B, and Kestenbaum B. Association of oral calcitriol with improved survival in nondialyzed CKD. J Am Soc Nephrol. 2008;doi:10.1681/ASN.2007111164.
The kidney plays an important role in converting 25-OH vitamin D to calcitriol, the active form of vitamin D. Chronic kidney disease (CKD) is associated with perturbations in vitamin D metabolism, and calcium, phosphorus, and parathyroid hormone (PTH) levels. Intravenous vitamin D supplementation improves survival in long-term hemodialysis patients. In the present study, Shoben et al. compare the effects of oral calcitriol use with mortality and eventual long-term dialysis in CKD patients.
Calcitriol users with stage 3 or 4 CKD (n = 429) were paired with control CKD patients not taking calcitriol (n = 989). Participants were followed for up to 3.5 years (median follow-up 1.9 years) and primary outcome measures included mortality and dialysis dependence. Mortality rates were lower in the calcitriol group relative to controls, including groups categorized by age, diabetes status, eGFR, and baseline PTH levels. Additionally, calcitriol use was associated with lower combined risk for death or dialysis, although risk for initiation of dialysis alone was not reduced. The present study suggests that oral use of the bioactive form of vitamin D may be beneficial for long-term survival in patients with impaired kidney function.
LONG-CHAIN PUFA AND IMMUNE MEASURES IN CHILDREN
Mazurak VC, Lien V, Field CJ, Goruk SD, Pramuk K, and Clandinin MI. Long-chain polyunsaturated fat supplementation in children with low docosahexaenoic acid intakes alters immune phenotypes compared with placebo. J Ped Gastroenter Nutr. 2008;46:570–579.
Essential fatty acids are important in brain development and infant growth. Deficits in n-3 and n-6 long-chain PUFA are associated with impaired mental ability and visual acuity. Deficits of long-chain PUFA are also implicated in reduced immune function and affect lymphocyte activation and proliferation, release of cytokines, and cell phenotypes. In children with low docosahexaenoic acid (DHA) intakes, supplementation with n-3 long-chain PUFA may improve immune function. Mazurak et al. identified 37 children between the ages of 5 and 7 years with DHA intakes below 78 mg/d. Children were randomized into the supplementation condition (20–30 mg/d arachidonic acid [AA] and 14–21 mg/d DHA) or placebo condition; supplements were provided in powder form and were reconstituted in water prior to consumption.
Children were given supplements for 7 months. At the end of the supplementation period, children were exposed to various compounds to elicit peripheral immune factors, including cytokine production, T cells, and B cells. Proportions of T cells, B cells, and macrophages were not influenced by PUFA supplementation in children with low DHA intakes. PUFA supplementation altered the phenotype of mononuclear cells with fewer CD8 cells expressing CD25 and CD80 after exposure to mitogens, suggesting a reduced reaction to immune response-provoking compounds. Although the sample size in this study was relatively small, the results suggest that children at risk for immune-related conditions who show deficiency in n-3 long-chain PUFA may benefit from PUFA supplementation.
FOLIC ACID AND B-VITAMIN SUPPLEMENTATION AND CARDIOVASCULAR EVENTS IN HIGH-RISK WOMEN
Albert CM, Cook NR, Gaziano JM, Zaharris E, MacFadyen J, Danielson E, Buring JE, and Manson JE. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease. JAMA. 2008;299:2027–2036.
Elevated levels of homocysteine are associated with increased risk for cardiovascular disease (CVD), and several large trials have attempted to reduce the risk of CVD by lowering homocysteine levels in a number of populations. The metabolism of homocysteine into methionine is driven by folate and vitamin B12, and the eventual conversion of homocysteine to cysteine is mediated by vitamin B6. Most research trials use a combination of folic acid, vitamin B6, and vitamin B12 to effectively reduce circulating levels of homocysteine. Albert et al. report on the effects of 7 years of treatment using a combination of folic acid (2.5 mg), vitamin B12 (1 mg), and vitamin B6 (50 mg) on homocysteine-lowering and cardiovascular events in the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS). Other arms of this study included treatment with antioxidant vitamins, but these data are described elsewhere.
Participants at high risk for CVD or with a history of CVD were randomly assigned to receive either the combination B vitamin pill (n = 2721) or placebo (n = 2721). Primary outcome measures included cardiovascular morbidity and cardiovascular mortality. Baseline and follow-up blood measures were determined in a smaller sample of participants for homocysteine and folate levels. Homocysteine levels were significantly lower in the group given a combination pill of folic acid, vitamin B6 and vitamin B12 after 7 years of treatment. Treatment with the combination pill did not offset the risk of cardiovascular morbidity or mortality in high-risk women.
Comment: Dr. Lonn called for attention to several key factors to consider in research using vitamin supplementation to lower homocysteine levels and reduce cardiovascular risk. One widely discussed limitation in many ongoing trials using folic acid supplements is the fact that flour and cereal grains in the United States have been fortified with folic acid, ostensibly to offset the risk of neural tube defects. In the years since fortification, there has been a decrease in homocysteine levels, and this reduction could mask any additional benefits conferred by vitamin supplements. Although epidemiological studies provide strong support for homocysteine as an associated risk factor for cardiovascular disease, several large trials have yet to convincingly demonstrate reduced risk for cardiovascular disease in the presence of homocysteine-lowering treatment. At present, there is little evidence to support the use of B vitamin treatment for the prevention of cardiovascular events.
Editorial Comment: Lonn E. Homocysteine-lowering B vitamin therapy in cardiovascular prevention – Wrong again? JAMA. 2008;299:2086–2087.
MEDITERRANEAN DIET AND INFLAMMATORY MARKERS
Salas-Salvado J, Garcia-Arellano A, Estruch R, et al. Components of the Mediterranean-type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease. Eur J Clin Nutr. 2008;62:651–659.
Following a Mediterranean-style diet is associated with reduced risk for cardiovascular disease and risk of mortality. One proposed mechanism for this reduction is the high levels of inflammation-modulating nutrients found in the traditional Mediterranean diet, including olive oil, nuts, fruits and vegetables, and legumes. In addition to maximizing intake of anti-inflammatory nutrients, the traditional Mediterranean diet is also relatively low in foods thought to promote inflammation including meats, processed foods, and dairy. In the present study, Salas-Salvado et al. aimed to identify the specific components of a Mediterranean-style diet that contribute improvements in inflammatory markers that are predictors of cardiovascular disease.
Participants (n = 772; 56% women) from the PREDIMED trial were selected for the study if they met one of two criteria: present diagnosis of type-2 diabetes and three or more coronary heart disease risk factors, which included current smoking, hypertension, BMI >25, and dyslipidemia. Participants were excluded if they had a history of CVD. Food intake was measured using a food frequency questionnaire that was then scored for adherence to a Mediterranean-style diet. Serum inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were compared with intakes of specific nutrients in the diet. Individuals with high overall adherence to a Mediterranean-style diet did not show significantly reduced concentrations of inflammatory markers. Participants who ate more fruits and cereals had lower concentrations of IL-6. Participants consuming the highest levels of nuts and virgin olive oil showed the lowest concentrations of IL-6, VCAM-1, ICAM-1, and CRP. These data suggest that, in those following a Mediterranean-style pattern of eating, the consumption of nuts and virgin olive oil can have positive effects on the inflammatory profile in people at high risk for coronary heart disease.
VARIANTS NEAR MC4R: ASSOCIATION WITH OBESITY
Loos RJF, Lindgren CM, Li S, et al. Common variants near MC4R are associated with fat mass, weight, and risk of obesity. Nature Genetics. 2008;doi:10.1038/ng.140.
New advances in high-throughput single-nucleotide polymorphisms (SNPs) chips and the availability of genome-wide associated (GWA) data allows for relatively rapid methods to identify and associate gene variants with specific traits. Recent work using GWA data identified the FTO gene as the first locus with a direct impact on the predisposition to obesity on a population-wide scale. FTO, however, contributes a relatively small effect (∼1%) to the genetics of obesity, and other genetic variants with a role in obesity are actively pursued. Using GWA data from 16,876 Europeans phenotyped for adult BMI, Loos et al. mapped variants with strong associations with BMI.
FTO variants had the strongest association with BMI, but two independent signals (rs17782313 and rs17700633) closely localized to the melanocortin-4 receptor (MC4R) region were also associated with BMI. Data from a further 60,352 samples in European adults and 5988 British children revealed that rs17782313 is significantly associated with body weight, fat mass, and BMI from the age of 7 years and upwards. Mutations of MC4R are a leading cause of severe childhood-onset obesity, and the present data suggest that genetic variations in close proximity to MC4R are important in population-wide fat mass and body weight. Variants near MC4R and FTO appear to have additive effects on BMI, with the incidence of overweight being higher in individuals homozygous for both