Mark Hudes

Oxidative stress and inflammation in iron‐overloaded patients with β‐thalassaemia or sickle cell disease

Blood transfusion therapy is life‐saving for patients with β‐thalassaemia and sickle cell disease (SCD), but often results in severe iron overload. This pilot study examined whether the biomarkers of tissue injury or inflammation differ in these two diseases. Plasma malondialdehyde (MDA) was significantly increased 1·8‐fold in thalassaemia relative to control patients. In contrast, MDA in SCD was not significantly different from controls. In multivariate analysis, the strongest predictors of elevated MDA were liver iron concentration (P < 0·001) and specific diagnosis (P = 0·019). A significant 2‐fold elevation of non‐transferrin bound iron (NTBI) was observed in thalassaemia relative to SCD. NTBI was not a significant predictor of high MDA in multivariate analysis. SCD patients showed a significant 2·2‐fold elevation of the inflammatory marker interleukin (IL)‐6 relative to controls, and a 3·6‐ and 1·7‐fold increase in IL‐5 and IL‐10 relative to thalassaemia. Although α‐tocopherol was significantly decreased by at least 32% in both thalassaemia and SCD, indicating ongoing oxidant stress and antioxidant consumption, γ‐tocopherol, a nitric oxide‐selective antioxidant, was increased 36% in SCD relative to thalassaemia. These results demonstrate that thalassaemia patients have increased MDA and circulating NTBI relative to SCD patients and lower levels of some cytokines and γ‐tocopherol. This supports the hypothesis that the biology of SCD may show increased inflammation and increased levels of protective antioxidants compared with thalassaemia.

An overview of evidence for a causal relationship between dietary availability of choline during development and cognitive function in offspring

This review is part of a series intended for non-specialists that will provide an overview of evidence for causal relationships between micronutrient deficiencies and brain function. Here, we review 34 studies in rodents linking the availability of choline during gestation and perinatal development to neurological function or performance of offspring in cognitive and behavioral tests. Experimental designs, major results, and statistical criteria are summarized in Tables 1-4. Based on our reading of the literature, the evidence suggests that choline supplementation during development results in improved performance of offspring in cognitive or behavioral tests, and in changes in a variety of neurological functional indicators: (1) enhanced performance was observed, particularly on more difficult tasks; (2) increases (choline supplementation) or decreases (choline deficiency) were observed in electrophysiological responsiveness and size of neurons in offspring; and (3) supplementation resulted in some protection against adverse effects of several neurotoxic agents (including alcohol) in offspring. Discussion topics include methodological issues, such as the importance of independent replication, causal criteria, and uncertainties in interpreting test results.

Usage patterns, health, and nutritional status of long-term multiple dietary supplement users: a cross-sectional study

BackgroundDietary supplement use in the United States is prevalent and represents an important source of nutrition. However, little is known about individuals who routinely consume multiple dietary supplements. This study describes the dietary supplement usage patterns, health, and nutritional status of long-term multiple dietary supplement users, and where possible makes comparisons to non-users and multivitamin/mineral supplement users.MethodsUsing a cross-sectional study design, information was obtained by online questionnaires and physical examination (fasting blood, blood pressure, body weight) from a convenience sample of long-term users of multiple dietary supplements manufactured by Shaklee Corporation (Multiple Supp users, n = 278). Data for non-users (No Supp users, n = 602) and multivitamin/mineral supplement users (Single Supp users, n = 176) were obtained from the National Health and Nutrition Examination Survey (NHANES) 2001–2002 and NHANES III 1988–1994. Logistic regression methods were used to estimate odds ratios with 95% confidence intervals.ResultsDietary supplements consumed on a daily basis by more than 50% of Multiple Supp users included a multivitamin/mineral, B-complex, vitamin C, carotenoids, vitamin E, calcium with vitamin D, omega-3 fatty acids, flavonoids, lecithin, alfalfa, coenzyme Q10 with resveratrol, glucosamine, and a herbal immune supplement. The majority of women also consumed gamma linolenic acid and a probiotic supplement, whereas men also consumed zinc, garlic, saw palmetto, and a soy protein supplement. Serum nutrient concentrations generally increased with increasing dietary supplement use. After adjustment for age, gender, income, education and body mass index, greater degree of supplement use was associated with more favorable concentrations of serum homocysteine, C-reactive protein, high-density lipoprotein cholesterol, and triglycerides, as well as lower risk of prevalent elevated blood pressure and diabetes.ConclusionThis group of long-term multiple dietary supplement users consumed a broad array of vitamin/mineral, herbal, and condition-specific dietary supplements on a daily basis. They were more likely to have optimal concentrations of chronic disease-related biomarkers, and less likely to have suboptimal blood nutrient concentrations, elevated blood pressure, and diabetes compared to non-users and multivitamin/mineral users. These findings should be confirmed by studying the dietary supplement usage patterns, health, and nutritional status of other groups of heavy users of dietary supplements.

Nutritional and health status of Tibetan children living at high altitudes

BACKGROUND Children living at high altitudes often have delayed growth, but whether growth retardation is related to altitude or to other factors is not known. METHODS A multicultural health care team assessed 2078 Tibetan children 0 to 84 months of age for anthropometric and clinical signs of malnutrition. The children lived in 11 counties, which contained more than 50 diverse urban and nonurban (nomadic, agricultural, or periurban) communities in the Tibet Autonomous Region of China. The height and weight of the children were compared with those of U.S. children. Height and weight were expressed as z scores (the number of standard deviations from the median of the age- and sex-specific reference group). RESULTS The mean z score for height fell from -0.5 to -1.6 in the first 12 months of life and generally ranged from -2.0 to -2.4 in older children. Overall, of 2078 children, 1067 (51 percent) had moderately or severely stunted growth, as defined by a z score of -2.0 or lower. Of the 1556 children 24 months of age or older, 871 (56 percent) had stunted growth, which was severe (z score, -3.0 or lower) in 380 (24 percent). Among the children in this age group, 787 of the 1313 nonurban children (60 percent) had stunting, as compared with 84 of the 243 urban children (35 percent). Stunting was associated with clinical conditions such as rickets, abdominal distention, hair depigmentation, and skin lesions and with a maternal history of hepatitis or goiter. Stunting was not associated with altitude, after adjustment for the type of community. CONCLUSIONS In Tibetan children, severe stunting due to malnutrition occurs early in life, and morbidity is high.

The effect of vitamins C and E on biomarkers of oxidative stress depends on baseline level

Oxidative stress is elevated in obesity, and may be a major mechanism for obesity-related diseases. Nonsmokers (n=396) were randomized to 1000 mg/day vitamin C, 800 IU/day vitamin E, or placebo, for 2 months. Treatment effect was examined in multiple regression analyses using an intention-to-treat approach. Vitamin C (P=0.001) and vitamin E (P=0.043) reduced plasma F2-isoprostanes. In the overall sample, changes from baseline were +6.8, -10.6, and -3.9% for placebo, vitamin C, and vitamin E groups, respectively. However, a significant interaction with baseline F2-isoprostane was found. When baseline F2-isoprostane was >50 microg/mL, vitamin C reduced F2-isoprostane by 22% (P=0.01). Vitamin E reduced it by 9.8% (P=0.46). Below that cut point, neither treatment produced further reductions. F2-isoprostane>50 microg/mL was strongly associated with obesity, and was present in 42% of the sample. Change in malondialdehyde concentration was minimal. These findings suggest a role for vitamin C in reducing lipid peroxidation. Future research on effects of vitamins C or E on plasma F2-isoprostane should limit participants to those with baseline levels >50 mug/mL. Further studies are needed to establish whether treatment with vitamins C or E in persons with concentrations above that cut point could slow the development of cardiovascular disease.

The California Childrenʼs 5 a Day- Power Play! Campaign: Evaluation of a Large-Scale Social Marketing Initiative

Fruit and vegetable consumption among Californias fourth and fifth graders appears to be lower than in adults, and there is little literature reporting large-scale interventions that increase consumption. A oneyear evaluation funded by the National Cancer Institute (NCI) and the Centers for Disease Control and Prevention (CDC) was conducted with 3,966 students in 49 schools located in three geographically distant school communities. One community conducted intervention activities in the schools (T1), one conducted activities in school and community channels (T2), and the third served as a control. Behavioral and attitudinal changes were based on one-day food diaries administered preintervention and postintervention. Consumption rose in T1 and T2% and 14%, respectively, while dropping 12% in the control group (p<.05, control different from T1 and T2. While behavioral changes can occur in the school environment, even larger changes can be made when the school interventions are accompanied by community-wide involvement.

Effect of keyboard keyswitch design on hand pain.

This randomized clinical trial evaluated the effects of keyboard keyswitch design on computer users with hand paresthesias. Twenty computer users were matched and randomly assigned to keyboard A (n = 10) or B (n = 10). The keyboards were of conventional layout and differed in keyswitch design. Various outcome measures were assessed during the 12 weeks of use. Subjects assigned keyboard A experienced a decrease in hand pain between weeks 6 and 12 when compared with keyboard B subjects (P = 0.05) and demonstrated an improvement in the Phalen test time (right hand, P = 0.006; left hand, P = 0.06). Keyboard assignment had no significant effect on change in hand function or median nerve latency. We conclude that use of keyboard A for 12 weeks led to a reduction in hand pain and an improved physical examination finding when compared with keyboard B. There was no corresponding improvement in hand function or median nerve latency.

Vitamin C treatment reduces elevated C-reactive protein

Plasma C-reactive protein (CRP) is an inflammatory biomarker that predicts cardiovascular disease. Lowering elevated CRP with statins has reduced the incidence of cardiovascular disease. We investigated whether vitamin C or E could reduce CRP. Healthy nonsmokers (N=396) were randomized to three groups, 1000 mg/day vitamin C, 800 IU/day vitamin E, or placebo, for 2 months. Median baseline CRP was low, 0.85 mg/L. No treatment effect was seen when all participants were included. However, a significant interaction was found, indicating that treatment effect depends on baseline CRP concentration. Among participants with CRP indicative of elevated cardiovascular risk (> or =1.0 mg/L), vitamin C reduced the median CRP by 25.3% vs placebo (p=0.02) (median reduction in the vitamin C group, 0.25 mg/L, 16.7%). These effects are similar to those of statins. The vitamin E effect was not significant. In summary, treatment with vitamin C but not vitamin E significantly reduced CRP among individuals with CRP > or =1.0 mg/L. Among the obese, 75% had CRP > or =1.0 mg/L. Research is needed to determine whether reducing this inflammatory biomarker with vitamin C could reduce diseases associated with obesity. But research on clinical benefits of antioxidants should limit participants to persons with elevations in the target biomarkers.

Intraindividual variability of plasma antioxidants, markers of oxidative stress, C-reactive protein, cotinine, and other biomarkers

Background: Within-person variability in biomarkers results in random error that can attenuate estimates of association. Little information on such variability is available for a number of nutrition-related biomarkers. Methods: Blood samples obtained 2 to 4 weeks apart were analyzed for tocopherols, carotenoids, ascorbate, lipids, cotinine, C-reactive protein, and oxidative stress. Subjects (n = 206 men and women, mean age 45.4 years) were either smokers or passively exposed to smoke. We calculated intraindividual and interindividual variability and the number of measurements required to reduce attenuation. Results: For most biomarkers, 2 measurements would be required to limit the attenuation of correlation coefficients to no lower than 90% of the true correlation. If only one measurement were obtained, observed correlations would be approximately 80–88% of true correlations. For regression coefficients, 3 or 4 measures would be required. Exceptions were ascorbic acid and malondialdehyde, for which a single measure resulted in little attenuation. Conclusions: For most serum markers, collection of 2 or more measurements per person is desirable to increase the ability to detect associations between biomarkers and health-related variables. If only one measure is possible, sample sizes should be planned to permit detection of associations that are likely to be observed, not the theoretical true associations. The results of this study, in which measurements were obtained 2 to 4 weeks apart, are relevant for epidemiologic research in which the exposure of interest is the subject’s baseline or current status. It is likely that within-person variability would be greater over a period of months or years.

Influence of Pre-adolescent Diet on Quantitative Ultrasound Measurements of the Calcaneus in Young Adult Women

Abstract: Nongenetic determinants of quantitative ultrasound (QUS) properties of the bone remain to be identified. The purpose of this study was to determine relationships between early adolescent diet and QUS bone measurements taken in young adulthood. Subjects were participants in the 10-year longitudinal National Heart, Lung, and Blood Institute Growth and Health Study (NGHS). QUS parameters measured at the calcaneus in a convenience subsample of 63 18- to 19-year-old black and white women were correlated with dietary data collected when the subjects were aged 9-11 years. We hypothesized that pre-adolescent intake of calcium, magnesium, vitamin C and protein, nutrients known to be associated with bone development, would be associated with QUS measurements in young women. Stepwise multiple regression analysis, controlling for race, height and weight, demonstrated that pre-adolescent intake of calcium and magnesium were positively related to QUS parameters (calcium with broadband ultrasound attenuation, and magnesium with speed of sound and bone velocity). Our findings suggest that pre-adolescent diet may be associated with bone properties as measured by ultrasound. Further investigations of this relationship may yield a deeper understanding of the impact of diet on skeletal development. The small size of the convenience sample used for the analysis precludes stronger inferences at this time.