Urinary N-methylnicotinamide and ß-aminoisobutyric acid predict catch-up growth in undernourished Brazilian children.

Enteric infections, enteropathy and undernutrition in early childhood are preventable risk factors for child deaths, impaired neurodevelopment, and later life metabolic diseases. However, the mechanisms linking these exposures and outcomes remain to be elucidated, as do biomarkers for identifying children at risk. By examining the urinary metabolic phenotypes of nourished and undernourished children participating in a case-control study in Semi-Arid Brazil, we identified key differences with potential relevance to mechanisms, biomarkers and outcomes. Undernutrition was found to perturb several biochemical pathways, including choline and tryptophan metabolism, while also increasing the proteolytic activity of the gut microbiome. Furthermore, a metabolic adaptation was observed in the undernourished children to reduce energy expenditure, reflected by increased N-methylnicotinamide and reduced ß-aminoisobutyric acid excretion. Interestingly, accelerated catch-up growth was observed in those undernourished children displaying a more robust metabolic adaptation several months earlier. Hence, urinary N-methylnicotinamide and ß-aminoisobutyric acid represent promising biomarkers for predicting short-term growth outcomes in undernourished children and for identifying children destined for further growth shortfalls. These findings have important implications for understanding contributors to long-term sequelae of early undernutrition, including cognitive, growth, and metabolic functions.

Niacin nutritional status in HIV type 1-positive children: preliminary data.

OBJECTIVE: HIV infection induces a state of pellagra in cell culture models. This study compared the nutritional status and the 24-hour urine excretion of N-methylnicotinamide between HIV-positive children and HIV-negative children who were or were not born of mothers with HIV-1 infection. PATIENTS AND METHODS: Forty patients were included in the study: HIV-positive children (group 1; n = 20), HIV-negative children born to infected mothers (group 2; n = 10), and HIV-negative control children (group 3; n = 10). Usual dietary intake was assessed by a semiquantitative food-frequency questionnaire. Weight and height were assessed and compared with the reference data of the U.S. National Center for Health Statistics/Centers for Disease Control and Prevention. For the estimation of fat-free mass and total body water, bioelectrical impedance technique was used. N-methylnicotinamide was measured by a modified method of high-performance liquid chromatography. RESULTS: Groups were matched in relation to age, sex, percentage of malnutrition, anthropometric measures, and body composition. Daily niacin intake did not differ statistically across groups (group 1 = 18.0 +/- 11.4 mg/day; group 2 = 18.9 +/- 8.0 mg/day; group 3 = 14.2 +/- 5.2 mg/day), nor did intake of tryptophan, vitamin B6, and zinc. The values of urinary niacin per gram of creatinine were similar and adequate across the groups (group 1 = 4.68 [0.75-14.9]; group 2 = 3.74 [1.13-5.69]; group 3 = 3.85 [1.80-8.19]). CONCLUSIONS: HIV-positive children excreted the same amount of N-methylnicotinamide in urine as did the control children. These findings may be attributed to similarities in nutritional status, adequate intestinal absorption (no children experienced diarrhea) and stable clinical condition.

Effect of standard nicotinamide in the prevention of type 1 diabetes in first degree relatives of persons with type 1 diabetes.

BACKGROUND: Nicotinamide has been used with success to prevent type 1 diabetes in animal models and humans. This vitamin B3 derivative has attracting effects on beta-cell protection and regeneration. AIM/HYPOTHESIS: To evaluate the effect of standard nicotinamide administration on type 1 diabetes prevention in first degree relatives of persons with type 1 diabetes as well as on the concentrations of islet-cell-related autoantibodies, insulin secretion and peripheral sensitivity. SUBJECTS AND METHODS: A randomized double-blind placebo controlled intervention trial was conducted in 40 first degree relatives of type 1 diabetic patients. Persistence of ICA ( >or= 10 JDF units) was among inclusion criteria. Participants were randomly allocated oral standard nicotinamide (1.2 g/m2) or placebo for 5 years. Groups were also stratified by age. Islet associated antibodies, fasting blood glucose, fasting plasma insulin concentrations, OGTT, IVGTT and HLA-DR genotyping were performed in all participants. The main criterion to stop treatment was type 1 diabetes development as defined by WHO. RESULTS: Type 1 diabetes development frequencies were similar between the treatment groups. ICA frequencies at the end of the study, first phase insulin release, and insulin sensitivity did not differ between groups as well. None of the participants suffered from any adverse events described for nicotinamide. CONCLUSIONS: Type 1 diabetes prevention trial using standard nicotinamide is feasible but fails to prevent or delay the disease onset at the dose we used.

Niacin metabolite excretion in alcoholic pellagra and AIDS patients with and without diarrhea.

OBJECTIVE: Malnourished patients with the acquired immunodeficiency syndrome (AIDS) can develop pellagra-like manifestations such as dermatitis, diarrhea, and dementia; therefore, we tested the hypothesis that patients with AIDS and diarrhea would have niacin depletion. This study compared 24-h urine excretion of N1-methyl-nicotinamide (N1MN) among patients with pellagra and patients with AIDS who did and did not have diarrhea. METHODS: Three groups were studied: G1 (patients with AIDS and diarrhea, n = 5); G2 (patients with AIDS and no diarrhea, n = 7), and G3 (patients with alcoholic pellagra and without the human immunodeficiency virus, n = 8). Diarrhea was defined as the production of at least three liquid stools per day over 3 to 5 d. Studies included mucosal intestinal biopsy, malabsorption tests, detection of parasites in stool, and serum albumin measurements. Semiquantitative food-frequency questionnaire, anthropometry, and daily urinary N1MN excretion were also determined. Groups were matched in relation to age, sex, presence of parasites in stool, and intestinal absorption results. RESULTS: G1 had normal intestinal examination by light microscopy and no parasites in stools. G2 group showed lower levels of serum albumin (2.6 +/- 0.3 g/dL) when compared with G1 (3.4 +/- 0.3 g/dL) and G3 (3.1 +/- 0.7 g/dL). Except for patients with pellagra, groups met their energy requirements. Patients in G3 (0.013, 0.01-0.081 mg/dL) and G1 (0.062, 0.001-0.33 mg/dL) excreted smaller amounts of N1MN in urine than did those in G2 (0.63, 0.02-2.9 mg/dL). CONCLUSIONS: Patients with AIDS and diarrhea excreted less N1MN in urine than did those without diarrhea. These patients may have an impaired niacin nutritional status, possibly associated with increased metabolic needs.

Lipid peroxidation in nicotinamide-deficient and nicotinamide-supplemented rats.

Supplementation or deficiency of nicotinamide in rats may interfere with the oxidative balance, with excess leading to greater lipid peroxidation, measured by TBARS, and deficiency causing a greater consumption of antioxidants such as vitamin E and glutathione. Urinary N-methylnicotinamide excretion was much more marked in the supplemented group, whereas the difference between deficient and control animals was nonsignificant.

Transporte jejunal eletrogênico da glicose em ratos com deficiência de niacina / Jejunal electrogenic transport of glucose in rats with niacin deficiency

A absorçäo jejunal eletrogênica ativa da glicose foi estudada pelo método da perfusäo intestinal "in vivo", infundido-se soluçöes de glicose com concentraçäo crescente (2,5;5,0; 10,0; 20,0; 50,0 e 100,0 mM/L) em 15 cm de jejuno isolado de 12 ratos com deficiência de niacina. Os resultados dos animais carentes foram comparados com os de 12 animais que ingeriram dieta controle na mesma quantidade ingerida pelo seu par carente. A diferença de potencial transmural média em cada concentraçäo infundida de glicose foi estatisticamente menor nos animais carentes, em relaçäo aos controles. Além disso, nos ratos carentes, o Km foi maior (16,1 x 12,7), enquanto que Pdmax foi menor que o dos controles (12,5 x 19,4), respectivamente, demonstrando a ocorrência da depleçäo do transporte ativo eletrogênico da glicose, na carência de niacina. Uma possível explicaçäo para este achado seria a depleçäo das fontes de energia intra-enterocitária

[Jejunal electrogenic transport of glucose in rats with niacin deficiency]. / Transporte jejunal eletrogênico da glicose em ratos com deficiência de niacina.

The active electrogenic absorption of glucose was studied in 12 niacin deficient rats using a method for measuring changes in transmural potential difference across jejunal mucosa. The glucose was infused in 6 different concentrations (2.5; 5.0; 10.0; 20.0; 50.0 and 100.0 mM/L) at a constant rate of 1.7 ml per minute. The apparent kinetic parameters (Km and Pdmax) of active electrogenic transport were obtained graphically from curves of glucose transfer potentials. The results were compared with that obtained in a control group. The curve of glucose transfer potential in niacin deficient group was significantly lower than that of the control group. The apparent Km of niacin deficient group was greater than in the control group (16.1 x 12.7 mM/L). Furthermore, the Pdmax of the deficient group was lower than that of the control group (12.5 x 19.4 mV). The results showed that in niacin deficiency occurs a decreasing of the active electrogenic glucose absorption. One of the possible interpretation of the differences in the kinetic characteristics of electrogenic glucose transport would be a depleted energy supplement for the active transport in the enterocyte of the niacin deficient rats.

Plasma amino acid patterns in alcoholic pellagra patients.

Plasma amino acid concentrations in 33 male alcoholic patients with pellagra (age 20-68 years) were compared with those in 17 healthy male subjects (age 20-45 years). Pellagra diagnosis was made on the basis of the typical clinical skin picture, and low urinary excretion of N'methylnicotinamide and N'methyl-2-pyridone-5-carboxamide (reduced by 70 and 80%, respectively, compared with controls). There were significant differences in body mass index, creatinine/high index and serum albumin between the two groups, indicating that besides pellagra the alcoholic patients had some degree of malnutrition. Of 17 plasma amino acids measured, the following had significantly lower concentrations in the pellagrins: tryptophan (3.65 vs 5.93 mumol/dl, pellagrin vs control), isoleucine (6.31 vs 11.13), leucine (11.54 vs 24.19), lysine (16.25 vs 34.47), methionine (2.61 vs 4.22), phenylalanine (5.71 vs 9.23), threonine (13.29 vs 26.81), valine (17.60 vs 41.06), alanine (42.54 vs 70.87), arginine (5.87 vs 10.09), tyrosine (5.57 vs 9.30). Glutamic acid was significantly higher in the pellagrins (18.45 vs 9.49). There was no difference between the groups of aspartic acid, glycine, histidine, proline and serine concentrations. It is concluded that pellagra is an important factor influencing the amino acid profiles in these patients. This finding should be taken into account when using plasma amino acid levels to assess the clinical status of the pellagrin.

Interaction of niacin and zinc metabolism in patients with alcoholic pellagra.

The effect of zinc supplementation on the metabolism of tryptophan conversion to niacin was studied in 14 alcoholic patients with pellagra and in 7 male control subjects aged 21-45 y. The pellagrins received chemically defined diets based on crystalline amino acids through an enteral tube for 7 d. Patients were divided into two groups (A and B), both receiving a diet from which tryptophan, Zn, and niacin were excluded. Patients in group B, however, received 220 mg Zn sulfate orally. Upon admission the pellagra patients had low plasma Zn levels and low urinary excretion values of N'methylnicotinamide (N'MN) and N'methyl-2-pyridone-5-carboxamide (2-PYR) in relation to the control subjects (p less than 0.01). During the experimental period there was an increase in plasma Zn levels (p less than 0.005) and in urinary N'MN (p less than 0.05) and 2-PYR (p less than 0.05) excretion in the patients receiving Zn supplementation (group B). These results suggest that Zn interacts with niacin metabolism in alcoholic patients with pellagra through a probable mediation by vitamin B-6.