Effects of a High Protein Food Supplement on Physical Activity, Motor Performance and Health Related Quality of Life of HIV Infected Botswana Children on Anti-Retroviral Therapy (ART).

OBJECTIVE: Despite existing evidence about the benefits of nutrition, physical activity (PA) and sport to the overall health and wellbeing of children, knowledge gaps remain on this relationship in children living with chronic conditions like HIV/AIDS. Such knowledge should inform context specific programs that could enhance the quality of life of children. The purpose of this study was to examine the effects of integrating a nutrition intervention (culturally tailored food supplement) into antiretroviral therapy (ART) on psychosocial outcomes and physical activity among HIV-positive children in Botswana. METHOD: 201 HIV-positive children (6-15 years; M = 9.44, SD = 2.40) were recruited and randomly assigned (stratified by age and gender) to two groups. The intervention group (n = 97) received a high protein (bean-sorghum plus micronutrients) food supplement, while the control group (n = 104) received a sorghum plus micronutrients supplement. Participants were followed over 12 months. Anthropometric measures, PA, motor performance, and health related quality of life (HRQL) were collected at baseline, 6 and 12 months. RESULTS: Mixed repeated-measures ANOVA revealed a significant time effect of the food supplement on target variables except body fat percentage, speed, and school functioning. Time × treatment interaction was found for physical functioning, psychosocial functioning and total quality of life score. Scores on physical functioning and total of quality life in the intervention group significantly increased from baseline to 6 months compared with the control group (p = 0.015). CONCLUSION: A combination of ART and nutritional intervention had a positive effect on physical functioning and total quality of life of HIV-positive children in this study. There were also improvements to physical activity and motor performance tests over time. More research is needed on long term effects of nutrition and PA interventions on HRQL in children living with HIV.

Efficacy of a low-dose ferric-EDTA in reducing iron deficiency anaemia among underfive children living in malaria-holoendemic district of Mvomero, Tanzania.

Iron deficiency anaemia is a public health problem in Tanzania especially among children under the age of five years. In malaria holoendemic areas, control of anaemia by supplementation with iron has been reported to increase serious adverse events. The World Health Organization recommends that, programs to control anaemia in such areas should go concurrently with malaria control programmes. The objectives of the study were to: (i) to determine if a supplement providing 2.5 mg of iron as ferric EDTA and 2.5 mg of iron as ferrous lactate (low dose) is as effective in correcting anaemia as a supplement providing the standard 10 mg of iron as ferrous lactate (high dose); and ii) determine if iron supplementation increased the risk of malaria. This study was carried out in Mvomero District of east-central Tanzania. Two groups (69 and 70 subjects per treatment) of moderately anaemic children (7.0-9.1 g of Hb/dl), received one of the two micronutrient supplements differing only in iron content for a period of 60 days. Results showed that, the average haemoglobin (Hb) concentration improved from 8.30 ± 0.60 g/dl to 11.08 ± 1.25 g/dl. The average weight-for-age for all children increased from 16.0 to 20.6% while their weight-for-height increased from 4.0 to 13.3%. The incidence of asymptomatic and symptomatic malaria ranged from 10.0 to 10.4% at all time points with no apparent increase in malaria severity due to iron supplementation. Overall, there was a significant reduction in anaemia during the 60 day supplementation period. This study demonstrated that, micronutrient supplements containing low-dose ferric-EDTA is just as effective as the high dose iron in reducing anaemia and can be safely utilized in malaria holoendemic areas to control iron deficiency anaemia. It is recommended that, a large study should be conducted to affirm the effectiveness of the low-dose ferric-EDTA in controlling iron deficiency anaemia among underfive children.

Diet-relevant phytochemical intake affects the cardiac AhR and nrf2 transcriptome and reduces heart failure in hypertensive rats.

Intake of phytochemical-rich diets is inversely related to hypertension. Phytochemicals alter in vitro aryl hydrocarbon receptor (AhR) and NF-E2 related factor (nrf2) transcription factor activity and related genes pertinent to antioxidant defense. However, it is unknown if these molecular effects occur in the heart with dietary intake of physiologically relevant phytochemicals and if this correlates with reduced hypertension-associated heart failure. This extended feeding study used whole grapes as a model of a phytochemical-rich food and hypertensive heart failure-prone rats to assess mechanisms of effect. Grape intake reduced cardiac hypertrophy and fibrosis and improved diastolic function. At the development of diastolic dysfunction, hypertensive rats show reduced AhR activity, reduced expression of AhR-regulated genes, reduced glutathione and reduced activity of glutathione-regulating proteins. However, grape intake significantly increased cardiac AhR and nrf2 activity, Phase I/II gene transcripts and protein activity related to antioxidant defense. Heart failure is the leading cause of morbidity and mortality in the aged and the intake of phytochemicals from fruits and vegetables decreases with age. Concentrated antioxidant nutrient trials have failed to affect heart failure. However, this study demonstrates that diet-relevant intake of non-nutrient phytochemicals significantly reduces heart failure progression. Therefore, this study suggests that higher intake of phytochemical-containing foods may achieve cardiac benefits that isolated antioxidant supplements may not. In summary, intake of diet-relevant phytochemicals altered the cardiac antioxidant transcriptome, antioxidant defense, oxidative damage and fibrosis. Regular phytochemical intake may therefore increase cardiac resistance to cardiac pathology instigated by prolonged hypertension.

Microarray Analyses of Genes Differentially Expressed by Diet (Black Beans and Soy Flour) during Azoxymethane-Induced Colon Carcinogenesis in Rats.

We previously demonstrated that black bean (BB) and soy flour (SF)-based diets inhibit azoxymethane (AOM)-induced colon cancer. The objective of this study was to identify genes altered by carcinogen treatment in normal-appearing colonic mucosa and those attenuated by bean feeding. Ninety-five male F344 rats were fed control (AIN) diets upon arrival. At 4 and 5 weeks, rats were injected with AOM (15 mg/kg) or saline and one week later administered an AIN, BB-, or SF-based diet. Rats were sacrificed after 31 weeks, and microarrays were conducted on RNA isolated from the distal colonic mucosa. AOM treatment induced a number of genes involved in immunity, including several MHC II-associated antigens and innate defense genes (RatNP-3, Lyz2, Pla2g2a). BB- and SF-fed rats exhibited a higher expression of genes involved in energy metabolism and water and sodium absorption and lower expression of innate (RatNP-3, Pla2g2a, Tlr4, Dmbt1) and cell cycle-associated (Cdc2, Ccnb1, Top2a) genes. Genes involved in the extracellular matrix (Col1a1, Fn1) and innate immunity (RatNP-3, Pla2g2a) were induced by AOM in all diets, but to a lower extent in bean-fed animals. This profile suggests beans inhibit colon carcinogenesis by modulating cellular kinetics and reducing inflammation, potentially by preserving mucosal barrier function.

Whole grape intake impacts cardiac peroxisome proliferator-activated receptor and nuclear factor kappaB activity and cytokine expression in rats with diastolic dysfunction.

Prolonged hypertension is the leading cause of heart failure. Failing hearts show reduced peroxisome proliferator-activating receptor (PPAR) activity and enhanced nuclear factor kappaB (NF-kappaB) activity, which together modify cardiac inflammation and fibrosis. In vitro studies suggest that phytochemicals alter PPAR and NF-kappaB activity, but the capabilities of a phytochemical-rich diet are less understood. Grapes contain an array of commonly consumed dietary phytochemicals. In Dahl salt-sensitive hypertensive rats, we showed previously that dietary provision of whole table grape powder (3% weight:weight) for 18 weeks reduced blood pressure, cardiac hypertrophy, and diastolic dysfunction. The hypothesis tested here is that, in this model, phytochemical provision from whole grape powder impacts cardiac PPAR and NF-kappaB activity and their related gene transcripts. Grape-fed rats had enhanced PPAR-alpha and PPAR-gamma DNA binding activity but reduced NF-kappaB DNA binding activity. RT-PCR revealed that grape-fed rats showed upregulated mRNA for PPAR-alpha, PPAR-gamma coactivator-1alpha, PPAR-gamma, and the cytosolic NF-kappaB inhibitor, inhibitor-kappaBalpha. By contrast, grape-fed rats showed downregulated mRNA for tumor necrosis factor-alpha and transforming growth factor-beta1. Finally, grape-fed rats showed significantly reduced cardiac tumor necrosis factor-alpha and transforming growth factor-beta protein expression, increased inhibitor-kappaBalpha expression, and reduced cardiac fibrosis. In the Dahl salt-sensitive rat, chronic intake of grapes altered cardiac transcripts related to PPAR and NF-kappaB that may be significant to the observed diet-associated cardioprotection.

Inflammation-associated serum and colon markers as indicators of dietary attenuation of colon carcinogenesis in ob/ob mice.

Although inflammatory cytokines and obesity-associated serum proteins have been reported as biomarkers of colorectal adenoma risk in humans, little is known of biomarkers of response to interventions that attenuate tumorigenesis. Dietary navy beans and their fractions attenuate colon carcinogenesis in carcinogen-induced genetically obese mice. We hypothesized that this attenuation would be associated with changes in inflammatory cytokines and obesity-related serum proteins that may serve as measures of efficacy. ob/ob mice (n = 160) were injected with the carcinogen azoxymethane (AOM) to induce colon cancer and randomly placed on one of four diets (control, whole navy bean, bean residue fraction, or bean extract fraction) for 26 to 28 wk. Serum was analyzed for 14 inflammation- or obesity-related proteins, and colon RNA was analyzed for expression of 84 inflammation-associated genes. Six of 14 serum proteins were increased [i.e., interleukin (IL)-4, IL-5, IL-6, IL-10, IFN gamma, granulocyte macrophage colony-stimulating factor] in hyperplastic/dysplastic stages of colon carcinogenesis. Bean-fed mice had significantly higher monocyte chemoattractant protein-1 and lower IL-6 levels in serum. In colon mucosa, 55 of 84 inflammation-associated genes differed between AOM-induced and noninduced mice. Of the 55 AOM-induced genes, 5 were counteracted by bean diets, including IL-6 whose increase in expression levels was attenuated by bean diets in AOM-induced mice. In summary, IL-6 emerged as a serum protein that was increased in hyperplastic/dysplastic stages of colon carcinogenesis, but attenuated with bean-based diet in serum and colon mucosa. Changes in a subset of inflammation-associated serum proteins and colon gene expression may serve as response indicators of dietary attenuation of colon carcinogenesis.

Chronic intake of a phytochemical-enriched diet reduces cardiac fibrosis and diastolic dysfunction caused by prolonged salt-sensitive hypertension.

Salt-sensitive hypertension is common in the aged population. Increased fruit and vegetable intake reduces hypertension, but its effect on eventual diastolic dysfunction is unknown. This relationship is tested in the Dahl Salt-Sensitive (Dahl-SS) rat model of salt-sensitive hypertension and diastolic dysfunction. Table grape powder contains phytochemicals that are relevant to human diets. For 18 weeks, male Dahl-SS rats were fed one of five diets: low salt (LS), a low salt + grape powder (LSG), high salt (HS), a high salt + grape powder (HSG), or high salt + vasodilator hydralazine (HSH). Compared to the HS diet, the HSG diet lowered blood pressure and improved cardiac function; reduced systemic inflammation; reduced cardiac hypertrophy, fibrosis, and oxidative damage; and increased cardiac glutathione. The HSH diet similarly reduced blood pressure but did not reduce cardiac pathogenesis. The LSG diet reduced cardiac oxidative damage and increased cardiac glutathione. In conclusion, physiologically relevant phytochemical intake reduced salt-sensitive hypertension and diastolic dysfunction.

Dietary cooked navy beans and their fractions attenuate colon carcinogenesis in azoxymethane-induced ob/ob mice.

Based on the protective effects of cooked dry bean consumption in a human intervention study, we evaluated which fraction of cooked dry beans is responsible for its cancer-preventive effects. Cooked navy beans (whole beans), the insoluble fraction (bean residue) or soluble fraction of the 60% (vol:vol) ethanol extract of cooked navy beans (bean extract), or a modified AIN-93G diet (16.6% fat including 12.9% lard) as control diet were fed to 160 male obese ob/ob mice after 2 azoxymethane injections. In comparison to control-fed mice, dysplasia, adenomas, or adenocarcinomas were detected in fewer mice on either bean fraction diet (percent reduction from control: whole beans 54%, P=0.10; bean residue 81%, P=0.003; bean extract 91%, P=0.007), and any type of colon lesions, including focal hyperplasia, were found in fewer mice on each of the 3 bean diets percent reduction from control: whole bean 56%, P=0.04; bean residue 67%, P=0.01; bean extract 87%, P=0.0003. These results suggest that both the soluble and the insoluble fraction of the extract contribute to the cancer-protective effect of cooked navy beans.

Ackee (Blighia sapida) hypoglycin A toxicity: dose response assessment in laboratory rats.

Hypoglycin A, the toxin found in the ackee fruit, has been reported in the literature as the causative agent in incidences of acute toxicity termed Jamaican vomiting sickness or toxic hypoglycemic syndrome. Hypoglycin A toxicity in this study was determined by feeding male and female Sprague-Dawley rats a control diet and ackee diets that contained 4-3840 ppm of hypoglycin. The fixed dose method was used to quantify the acute toxic dose of hypoglycin A and was determined by feeding a diet consisting of the lowest hypoglycin A concentration; this was increased to the next highest dose after 24h until toxicity was observed. The maximum tolerated dose (MTD) of hypoglycin A was determined by feeding rats the ackee and control diets over a 30-day period. The acute toxic dose for male and female rats was 231.19+/-62.5 5mg hypoglycinA/kgBW and 215.99+/-63.33 mg hypoglycinA/kgBW, respectively. This was considerably greater than the dose of 100 mg hypoglycin/kgBW reported in a previous study when aqueous hypoglycin was administered orally. The MTD of hypoglycin A in both male and female rats was 1.50+/-0.07 mg hypoglycinA/kgBW/day. These findings suggest that the form in which hypoglycin in ackee is administered could affect the toxicological properties it exhibits. Therefore, for the purpose of a hazard assessment, it may be best administered within the matrix of the fruit, which is the form that humans consume it.

Docosahexaenoic acid attenuates mycotoxin-induced immunoglobulin a nephropathy, interleukin-6 transcription, and mitogen-activated protein kinase phosphorylation in mice.

The purpose of this investigation was to evaluate the dose-dependent effects of docosahexaenoic acid (DHA) on deoxynivalenol (DON)-induced IgA nephropathy in mice and their relation to proinflammatory gene expression and mitogen-activated protein kinase (MAPK) activation. Consumption of a modified AIN-93G diet containing 1, 5, and 30 g/kg DHA resulted in dose-dependent increases of DHA in liver phospholipids with concomitant decreases in arachidonic acid compared with control diets. DHA dose dependently inhibited increases in serum IgA and IgA immune complexes (IC) as well as IgA deposition in the kidney in DON-fed mice; the 30 g/kg DHA diet had the earliest detectable effects and maximal efficacy. Both splenic interleukin-6 (IL-6) mRNA and heterogeneous nuclear RNA (hnRNA), an indicator of IL-6 transcription, were significantly reduced in DON-fed mice that consumed 5 and 30 g/kg DHA; a similar reduction was observed for cyclooxygenase (COX-2) mRNA. In a subsequent study, acute DON exposure (25 mg/kg body weight) induced splenic IL-6 mRNA and hnRNA as well as COX-2 mRNA in mice fed the control diet, whereas induction of both RNA species was significantly inhibited in mice fed 30 g/kg DHA. These latter inhibitory effects corresponded to a reduction in DON-induced phosphorylation of p38, extracellular-signal related kinase 1/2, and c-Jun N-terminal kinase 1/2 MAPKs in the spleen. Taken together, the results indicate that DHA dose-dependently inhibited DON-induced IgA dysregulation and nephropathy, and that impairment of MAPK activation and expression of COX-2 and IL-6 are potential critical upstream mechanisms.

Docosahexaenoic acid and eicosapentaenoic acid, but not alpha-linolenic acid, suppress deoxynivalenol-induced experimental IgA nephropathy in mice.

Diets enriched in the (n-3) PUFAs, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and their precursor alpha-linolenic acid (ALA), were evaluated for efficacy in ameliorating the development of IgA nephropathy (IgAN) induced in mice by the mycotoxin deoxynivalenol (DON). The effects of DON were compared in mice that were fed for 18 wk with AIN-93G diets containing 1) 10 g/kg corn oil plus 60 g/kg oleic acid (control); 2) 10 g/kg corn oil plus 35 g/kg oleic acid and 25 g/kg DHA-enriched fish oil (DHA); 3) 10 g/kg corn oil plus 33 g/kg oleic acid and 27 g/kg EPA-enriched fish oil (EPA); and 4) 10 g/kg corn oil plus 37 g/kg oleic acid and 23 g/kg DHA + EPA (1:1) enriched fish oil (DHA + EPA). The DHA, EPA and DHA + EPA diets attenuated induction by dietary DON (10 mg/kg) of serum IgA and IgA immune complexes, kidney mesangial IgA deposition, and ex vivo IgA secretion by spleen cells. Consumption of the DHA + EPA diet for 8 wk significantly abrogated the DON-induced gene expression of interleukin (IL)-6, a requisite cytokine for DON-induced IgA nephropathy, in spleen and Peyer's patches. Finally, incorporation of ALA-containing flaxseed oil up to 60 g/kg in the AIN-93G diet did not affect DON-induced IgA dysregulation in mice. Taken together, both DHA and EPA, but not ALA, ameliorated the early stages of IgAN, and these effects might be related to a reduced capacity for IL-6 production.

Dietary soy isoflavones and estrone protect ovariectomized ERalphaKO and wild-type mice from carcinogen-induced colon cancer.

Consumption of soy foods has been weakly associated with reduced colon cancer risk. Colon cancer risk is influenced by estrogen exposure, although the mechanism through which this occurs is not defined. Conversion of estradiol (E2) to estrone (E1) may be protective in the colon. We hypothesized that dietary phytoestrogens, or E1, would reduce colon tumorigenesis via an estrogen receptor (ER)-dependent mechanism. Ovariectomized ERalphaKO or wild-type (WT) female mice were fed diets containing casein (Casein), soy protein without isoflavones (Soy-IF), soy protein + genistein (Soy+Gen), soy protein + NovaSoy (Soy+NSoy) or soy protein + estrone (Soy+E1) from weaning. Colon tumors were induced with azoxymethane. Tumor incidence was affected by diet but not genotype. Colon tumor incidence was lower in ERalphaKO and WT mice fed the Soy+E1 diet compared with those fed the casein or Soy-IF diets. Mice fed Soy+NSoy had a lower tumor incidence than mice fed casein, but not Soy-IF. Genistein did not affect tumor incidence. Soy protein, independently of phytoestrogens or E1, significantly reduced relative colon weight, tumor burden and multiplicity. Relative colon weight was lower (P=0.008) in mice fed Soy+E1 than in the other soy-fed groups. Tumor incidence in this group was lower than in the casein and soy-IF-fed groups and tended to be lower than in the others (P=0.020). Hence, soy protein and NSoy protect mice from colon cancer, and E1 further reduces colon tumorigenesis in mice, independently of ERalpha.