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Patients with thalassemia are frequently deficient in key micronutrients. Attempts to correct these inadequacies through nutritional supplementation have been met with some success, although disparities between intake and circulating levels continue to be observed. This study employed a convenience sample of 41 well-nourished transfusion dependent patients with thalassemia to identify possible mechanisms behind nutritional deficiencies. Each subject completed a Block 2005© Food Frequency Questionnaire (FFQ), through which macro and micronutrient intake was quantified. Fasting blood was drawn to assess vitamins A, C, D, E, copper, selenium, zinc and hematologic parameters. Dietary intake was found to be inadequate compared to Institute of Medicine (IOM) recommendations for many of the fat-soluble vitamins, as well as calcium and zinc. Circulating deficiencies of vitamins C, D, copper, zinc and γ tocopherol were also present in over 20% of patients. Many individuals who consumed an adequate dietary intake had deficient levels of circulating nutrients, which suggest alternative etiologies of nutrient excretion or loss, in addition to higher micronutrient requirements. Liver iron concentration displayed a significant negative relationship with vitamins C (r=-0.62, p

Objective: The qualitative recommendation to ‘drink water instead of caloric beverages’ may facilitate pediatric obesity treatment by lowering total energy intake. The quantitative recommendation to ‘drink enough water to dilute urine’ might further facilitate weight loss by increasing fat oxidation via cell hydration-mediated changes in insulin. Methods: This 8 week randomized intervention tested whether both Qualitative-plus-Quantitative (QQ) drinking water recommendations result in more weight loss than the Qualitative recommendation alone (Q) in 25 children (9-12 y) with body mass index at or above the 85th percentile, given a reduced glycemic diet and usual physical activity. Random urine osmolality, saliva insulin, and body weight were assessed weekly. Mixed models explored if insulin mediated an effect of urine osmolality on weight loss. Results: In intention-to-treat analyses, QQ and Q participants did not differ significantly with respect to level of urine osmolality, saliva insulin, or weight loss. Only 4 out of 16 QQ participants complied with instruction to drink enough water to dilute urine, however. In completers analyses, the compliant QQ participants, who diluted urine osmolality from 910 ± 161 mmol/kg at baseline to below 500 mmol/kg over time (8 week mean ± SE: 450 ± 67 mmol/ kg), had significantly lower saliva insulin over time (8 week mean ± SE: 13 ± 8 pmol/l vs. 22 ± 4 pmol/l) and greater weight loss (mean ± SE: -3.3 ± 0.7kg vs. -2.0 ± 0.5 kg) than compliant Q participants (7 out of 9 participants) who maintained elevated urine osmolality over time (8- week mean ± SE: 888 ± 41 mmol/kg). Urine osmolality below 500 mmol/kg was significantly associated with weight loss. Change in saliva insulin partially explained the association. Conclusions: QQ recommendations may increase weight loss for those able to dilute urine. Work is warranted to pursue cell hydration effects of drinking water for pediatric obesity treatment.

Biomarkers of chronic cell hydration status are needed to determine whether chronic hyperosmotic stress increases chronic disease risk in population-representative samples. In vitro, cells adapt to chronic hyperosmotic stress by upregulating protein breakdown to counter the osmotic gradient with higher intracellular amino acid concentrations. If cells are subsequently exposed to hypo-osmotic conditions, the adaptation results in excess cell swelling and/or efflux of free amino acids. This study explored whether increased red blood cell (RBC) swelling and/or plasma or urine amino acid concentrations after hypo-osmotic challenge might be informative about relative chronic hyperosmotic stress in free-living men. Five healthy men (20–25 years) with baseline total water intake below 2 L/day participated in an 8-week clinical study: four 2-week periods in a U-shaped A-B-C-A design. Intake of drinking water was increased by +0.8 ± 0.3 L/day in period 2, and +1.5 ± 0.3 L/day in period 3, and returned to baseline intake (0.4 ± 0.2 L/day) in period 4. Each week, fasting blood and urine were collected after a 750 mL bolus of drinking water, following overnight water restriction. The periods of higher water intake were associated with significant decreases in RBC deformability (index of cell swelling), plasma histidine, urine arginine, and urine glutamic acid. After 4 weeks of higher water intake, four out of five participants had ½ maximal RBC deformability below 400 mmol/kg; plasma histidine below 100 μmol/L; and/or undetectable urine arginine and urine glutamic acid concentrations. Work is warranted to pursue RBC deformability and amino acid concentrations after hypo-osmotic challenge as possible biomarkers of chronic cell hydration.