Intestinal permeability and oxidative stress in patients with alcoholic pellagra

BACKGROUND & AIMS: Increased intestinal permeability is one of the grastointestinal changes observed in alcoholic patients. However, there are no objective definitions as yet of how alcohol induces pathological changes in the various organs. The action of oxygen-free radicals during ethanol metabolism has been considered a determinant factor of these alterations. The present study was undertaken to determine the effect of niacin supplementation on intestinal permeability and oxidative stress in patients with alcoholic pellagra. METHODS: The study was divided into two phases: in Phase 1 we studied ten patients with pellagra before treatment with niacin, and in Phase 2 we studied the same patients after 27 days of treatment with niacin. Intestinal permeability was assessed by the (51)CrEDTA test and the antioxidant action of niacin supplementation was assessed by the determination of lipid peroxidation (plasma malondialdehyde, MDA), protein oxidation (plasma carbonyl group) and of the antioxidants plasma vitamin E and erythrocyte glutathione peroxidase. RESULTS: Comparison of intestinal permeability by the (51)CrEDTA test before and after niacin treatment showed a significant decrease in permeability from 4.29+/-1.92% to 1.90+/-1.19% (P<0.05). Assessment of oxidative stress showed a significant decrease (P<0.05) in lipid and protein peroxidation (MDA: 1.19+/-0.40-0.89+/-0.27 micromol/l; carbonyl groups: 2.22+/-0.36-1.84+/-0.40 nmol/mg protein). CONCLUSIONS: The results suggest that niacin and vitamin E deficiency in patients with pellagra could be important factors in increased intestinal permeability and decreased antioxidant conditions, recovering to normal values after treatment with niacin, associated to alcohol abstinence and a balanced diet.     

D-xylose absorption and jejunal morphology in African patients with pellagra (niacin tryptophan deficiency)

D-xylose absorption tests and jejunal morphology have been shown to be unaltered in 12 African patients with pellagra when compared with normal values for Zambian African adults; that result is contrary to two previous investigations in India and Egypt respectively. A significant inverse association has been shown, however, between D-xylose absorption and serum immunoglobulin IgG and IgA concentrations; that is consistent with previous studies and probably reflects malabsorption of xylose in the presence of systemic infections. It is concluded that pellagra per se does not alter intestinal structure or monosaccharide absorption.     

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.     

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.     

Low and deficient niacin status and pellagra are endemic in postwar Angola

BACKGROUND: Outbreaks of pellagra were documented during the civil war in Angola, but no contemporary data on the incidence of pellagra or the prevalence of niacin deficiency were available. OBJECTIVE: The objective was to investigate the incidence of pellagra and the prevalence of niacin deficiency in postwar Angola and their relation with dietary intake, poverty, and anthropometric status. DESIGN: Admissions data from 1999 to 2004 from the pellagra treatment clinic in Kuito, Angola, were analyzed. New patients admitted over 1 wk were examined, and urine and blood samples were collected. A multistage cluster population survey collected data on anthropometric measures, household dietary intakes, socioeconomic status, and clinical signs of pellagra for women and children. Urinary excretion of 1-methylnicotinamide, 1-methyl-2-pyridone-5-carboxymide, and creatinine was measured and hemoglobin concentrations were measured with a portable photometer. RESULTS: The incidence of clinical pellagra has not decreased since the end of the civil war in 2002. Low excretion of niacin metabolites was confirmed in 10 of 11 new clinic patients. Survey data were collected for 723 women aged 15-49 y and for 690 children aged 6-59 mo. Excretion of niacin metabolites was low in 29.4% of the women and 6.0% of the children, and the creatinine-adjusted concentrations were significantly lower in the women than in the children (P < 0.001, t test). In children, niacin status was positively correlated with the household consumption of peanuts (r = 0.374, P = 0.001) and eggs (r = 0.290, P = 0.012) but negatively correlated with socioeconomic status (r = -0.228, P = 0.037). CONCLUSIONS: The expected decrease in pellagra incidence after the end of the civil war has not occurred. The identification of niacin deficiency as a public health problem should refocus attention on this nutritional deficiency in Angola and other areas of Africa where maize is the staple.     

Interaction among niacin, vitamin B6 and zinc in rats receiving ethanol

The interaction of niacin, vitamin B6 and zinc was studied in Wistar rats. Seventy animals were submitted to a four-week depletion period during which they were fed a corn grits diet with no niacin, vitamin B6 or zinc added. These animals also received a 32% ethanol solution. Thirty additional rats were used as controls. After the period of depletion, the deficient animals were divided into five subgroups of 10 animals each. Each group received either the deficient diet, the deficient diet plus niacin, the deficient diet plus vitamin B6, the deficient diet plus zinc, or the control diet for the following two weeks. Five rats from each group were killed weekly after 24-hour urine collection. N'methylnicotinamide (N'MN), N'methyl-2-pyridone-5-carboxamide (2 PYR) and 4-pyridoxic acid (4 PYR) were measured in urine by HPLC. Niacin repletion increased the excretion of niacin metabolites, N'MN and 2 PYR (p less than 0.01), in relation to deficient animals. Niacin and vitamin B6 metabolites increased with vitamin B6 repletion (p less than 0.01). Repletion with zinc alone was followed by an increase in urinary excretion of N'MN (p less than 0.05), 2 PYR (p less than 0.01) and 4 PYR (p less than 0.01). When the deficient rats were fed the control diet containing the three nutrients, all three metabolites increased (p less than 0.01). The main conclusion is that zinc repletion per se caused activation of niacin metabolism, increasing the excretion of niacin metabolites. This emphasizes the role of zinc in the function of these vitamins.     

Tryptophan deficiency and picolinic acid: effect on zinc metabolism and clinical manifestations of pellagra

In five experiments, rats were fed tryptophan (Tryp)-deficient diets with 6-12 micrograms/g zinc (Zn) and, in one experiment, a Zn-deficient diet to test the effect on clinical manifestations, plasma and bone Zn, and ability of picolinic acid (PA) or extra (12 micrograms/g) Zn to compensate. Tryp deficiency caused classical manifestations of pellagra although niacin intake was in excess of normal requirements. At marginal Zn intakes, oral PA caused a significant increase of plasma Zn and, compared with Tryp-adequate controls, Tryp deficiency resulted in lower plasma Zn and plasma:bone Zn ratios. Extra Zn (total 24 micrograms/g) was ineffective. Subcutaneous PA showed a tendency to lower plasma Zn. PA had no effect on clinical manifestations. We conclude that a Tryp metabolite other than nicotinic acid is necessary in the prevention of pellagra. Our hypothesis links this finding with the observed Tryp and PA effect on Zn metabolism.     

The effect of alcoholic beverages on iron and zinc metabolism in the rat

1. Male Wistar rats (approximately 200 g) were given distilled water and a semi-synthetic control diet for 6 d. On day 7, 37 kBq 65Zn were administered intramuscularly and the rats were given distilled water, beer, cider, red wine, whisky or ethanol as their only source of fluid. The wine, whisky and ethanol were diluted so that each of the beverages contained a similar ethanol concentration (approximately 30 g/l). Food and fluid intake, growth rate and whole-body 65Zn were measured regularly over 11 d, after which animals were killed and blood haemoglobin (Hb) concentration, liver iron stores and the Zn concentration in testes determined. 2. There were no differences in body-weight gain or food intake between groups but fluid intake for the beer group was considerably higher than that for the other groups. 3. There was a significant effect of the type of alcoholic beverage consumed on whole-body 65Zn retention. Rats given whisky had a smaller daily loss of 65Zn than those given water, beer or cider. The ethanol group also showed a lower rate of 65Zn loss compared with the water group. The observed changes in whole-body 65Zn retention could be explained by an adverse influence of ethanol on Zn absorption from the diet. 4. Blood Hb and testes Zn concentration were similar in all groups but the type of liquid consumed influenced liver Fe levels. The cider group had the lowest liver Fe values and the ethanol group the highest values. 5. It is apparent from the present study that ethanol and alcoholic beverages affect Zn and Fe metabolism, but that the effects of ethanol are moderated by other components of the alcoholic beverages.     

不同态锌在动物体内代谢的比较

锌是动物体内必需微量元素之一，具有重要的生理功能。实验用葡萄糖酸锌、硫酸锌、氯化锌和醋酸锌４种状态锌各１０－６ｇ，给小白鼠饮水，结果表明，肝脏、肾脏、眼球中锌含量均以葡萄糖酸锌组最高，其次为硫酸锌组，再次为氯化锌和醋酸锌，１０－６ｇ锌对小白鼠有轻度毒性作用。     

Effect of lead and niacin on growth and serotonin metabolism in chicks

Interactions of lead and niacin were studied in growing broiler chicks fed one of four experimental diets from day-old to 3 wk of age. The diets were a low niacin basal diet (LN), the basal diet supplemented with 40 mg of niacin/kg (control), the basal diet supplemented with 2000 mg lead/kg, as lead acetate (LN + Pb) and the basal diet supplemented with both niacin and lead (control + Pb). Growth and feed efficiency were reduced significantly by lead. The lead-associated growth depression was less severe in chicks fed the low niacin diet as indicated by a significant lead X niacin interaction. The relative weights of two brain regions (telencephalon and diencephalon) and the adrenal glands were greater in lead-treated chicks than in their nonlead-treated counterparts. Plasma and telencephalon tryptophan were lower in lead-treated chicks than in nonlead-treated chicks. Diencephalon tryptophan was lower in chicks fed the LN diet than in chicks fed the control diet. Brain serotonin was lower and 5-hydroxyindoleacetic acid was higher in both brain regions of lead-treated chicks than in nonlead-treated chicks. The data indicate that tryptophan and serotonin metabolism were altered by lead treatment, whereas niacin was without effect. The interaction of lead and niacin on growth does not appear to be related to alterations of serotonin metabolism in the central nervous system.     

Zinc supplementation alters thyroid hormone metabolism in disabled patients with zinc deficiency.

We examined zinc (Zn) status in relation to thyroid function in disabled persons, because the association between Zn deficiency and thyroid function remains controversial.

After measuring serum free 3,5,3′-triiodothyronine (T3) and free thyroxine (T4) in 134 persons, TSH-releasing hormone (TRH) injection test and estimation of Zn status were conducted in persons with low free T3.

Thirteen had low levels of serum free T3 and normal T4. Patients with elevated levels of serum 3,3′,5′-triiodothyronine (rT3) showed an enhanced reaction of serum thyrotropin (TSH) after TRH injection. Nine of 13 patients had mild to moderate Zn deficiency evaluated by body Zn clearance and increased urinary Zn excretion. After oral supplementation of Zn sulphate (4-10 mg/kg body weight) for 12 months, levels of serum free T3 and T3 normalized, serum rT3 decreased, and the TRH-induced TSH reaction normalized. Serum selenium concentration (Type 1 T4 deionidase contains selenium in the rat) was unchanged by Zn supplementation.

Zn may play a role in thyroid hormone metabolism in low T3 patients and may in part contribute to conversion of T4 to T3 in humans.