Circulatory and Urinary B-Vitamin Responses to Multivitamin Supplement Ingestion Differ between Older and Younger Adults.

Multivitamin and mineral (MVM) supplements are frequently used amongst older populations to improve adequacy of micronutrients, including B-vitamins, but evidence for improved health outcomes are limited and deficiencies remain prevalent. Although this may indicate poor efficacy of supplements, this could also suggest the possibility for altered B-vitamin bioavailability and metabolism in older people. This open-label, single-arm acute parallel study, conducted at the Liggins Institute Clinical Research Unit in Auckland, compared circulatory and urinary B-vitamer responses to MVM supplementation in older (70.1 ± 2.7 y, n = 10 male, n = 10 female) compared to younger (24.2 ± 2.8 y, n = 10 male, n = 10 female) participants for 4 h after the ingestion of a single dose of a commercial MVM supplement and standardized breakfast. Older adults had a lower area under the curve (AUC) of postprandial plasma pyridoxine (p = 0.02) and pyridoxal-5'phosphate (p = 0.03) forms of vitamin B6 but greater 4-pyridoxic acid AUC (p = 0.009). Urinary pyridoxine and pyridoxal excretion were higher in younger females than in older females (time × age × sex interaction, p < 0.05). Older adults had a greater AUC increase in plasma thiamine (p = 0.01), riboflavin (p = 0.009), and pantothenic acid (p = 0.027). In older adults, there was decreased plasma responsiveness of the ingested (pyridoxine) and active (pyridoxal-5'phosphate) forms of vitamin B6, which indicated a previously undescribed alteration in either absorption or subsequent metabolic interconversion. While these findings cannot determine whether acute B6 responsiveness is adequate, this difference may have potential implications for B6 function in older adults. Although this may imply higher B vitamin substrate requirements for older people, further work is required to understand the implications of postprandial differences in availability.

Riboflavin laurate nanosuspensions as an intramuscular injection for long-term riboflavin supplementation.

The aim of this study was to prepare riboflavin laurate (RFL) nanosuspensions as an intramuscular injection for long-term riboflavin supplementation. Stable RFL nanosuspensions were obtained by injecting RFL/poloxamer solution in N,N-dimethyl formamide into a trehalose solution. Long soft nanostructures initially appeared and then tube-like rigid nanostructures were obtained after removal of solvents according to the transmission electron microscopic images. The nanosuspensions had narrow size distribution and the mean size was about 300 nm. Molecular self-assembly of RFL may drive the formation of nanostructures. RFL formed a monolayer at the air/water interface and poloxamer 188 could insert into the monolayer. The nanosuspensions were intramuscularly injected into rats to provide long-term riboflavin supplementation for more than 30 days in light of body weight, food intake, and urinary riboflavin. The nanosuspensions were also used to resist the riboflavin deficiency induced by methotrexate chemotherapy. RFL nanosuspensions are a promising nanomedicine for long-term riboflavin supplementation.

Different variations of tissue B-group vitamin concentrations in short- and long-term starved rats.

Prolonged starvation changes energy metabolism; therefore, the metabolic response to starvation is divided into three phases according to changes in glucose, lipid and protein utilisation. B-group vitamins are involved in energy metabolism via metabolism of carbohydrates, fatty acids and amino acids. To determine how changes in energy metabolism alter B-group vitamin concentrations during starvation, we measured the concentration of eight kinds of B-group vitamins daily in rat blood, urine and in nine tissues including cerebrum, heart, lung, stomach, kidney, liver, spleen, testis and skeletal muscle during 8 d of starvation. Vitamin B1, vitamin B6, pantothenic acid, folate and biotin concentrations in the blood reduced after 6 or 8 d of starvation, and other vitamins did not change. Urinary excretion was decreased during starvation for all B-group vitamins except pantothenic acid and biotin. Less variation in B-group vitamin concentrations was found in the cerebrum and spleen. Concentrations of vitamin B1, vitamin B6, nicotinamide and pantothenic acid increased in the liver. The skeletal muscle and stomach showed reduced concentrations of five vitamins including vitamin B1, vitamin B2, vitamin B6, pantothenic acid and folate. Concentrations of two or three vitamins decreased in the kidney, testis and heart, and these changes showed different patterns in each tissue and for each vitamin. The concentration of pantothenic acid rapidly decreased in the heart, stomach, kidney and testis, whereas concentrations of nicotinamide were stable in all tissues except the liver. Different variations in B-group vitamin concentrations in the tissues of starved rats were found. The present findings will lead to a suitable supplementation of vitamins for the prevention of the re-feeding syndrome.

Development and characterization of a mouse with profound biotinidase deficiency: a biotin-responsive neurocutaneous disorder.

Biotinidase deficiency is the primary enzymatic defect in biotin-responsive, late-onset multiple carboxylase deficiency. Untreated children with profound biotinidase deficiency usually exhibit neurological symptoms including lethargy, hypotonia, seizures, developmental delay, sensorineural hearing loss and optic atrophy; and cutaneous symptoms including skin rash, conjunctivitis and alopecia. Although the clinical features of the disorder markedly improve or are prevented with biotin supplementation, some symptoms, once they occur, such as developmental delay, hearing loss and optic atrophy, are usually irreversible. To prevent development of symptoms, the disorder is screened for in the newborn period in essentially all states and in many countries. In order to better understand many aspects of the pathophysiology of the disorder, we have developed a transgenic biotinidase-deficient mouse. The mouse has a null mutation that results in no detectable serum biotinidase activity or cross-reacting material to antibody prepared against biotinidase. When fed a biotin-deficient diet these mice develop neurological and cutaneous symptoms, carboxylase deficiency, mild hyperammonemia, and exhibit increased urinary excretion of 3-hydroxyisovaleric acid and biotin and biotin metabolites. The clinical features are reversed with biotin supplementation. This biotinidase-deficient animal can be used to study systematically many aspects of the disorder and the role of biotinidase, biotin and biocytin in normal and in enzyme-deficient states.

Carnitine palmitoyltransferase 2 deficiency: the time-course of blood and urinary acylcarnitine levels during initial L-carnitine supplementation.

Carnitine palmitoyltransferase 2 (CPT2) deficiency is one of the most common mitochondrial beta-oxidation defects. A female patient with an infantile form of CPT2 deficiency first presented as having a Reye-like syndrome with hypoglycemic convulsions. Oral L-carnitine supplementation was administered since serum free carnitine level was very low (less than 10 micromol/L), indicating secondary carnitine deficiency. Her serum and urinary acylcarnitine profiles were analyzed successively to evaluate time-course effects of L-carnitine supplementation. After the first two days of L-carnitine supplementation, the serum level of free carnitine was elevated; however, the serum levels of acylcarnitines and the urinary excretion of both free carnitine and acylcarnitines remained low. A peak of the serum free carnitine level was detected on day 5, followed by a peak of acetylcarnitine on day 7, and peaks of long-chain acylcarnitines, such as C16, C18, C18:1 and C18:2 carnitines, on day 9. Thereafter free carnitine became predominant again. These peaks of the serum levels corresponded to urinary excretion peaks of free carnitine, acetylcarnitine, and medium-chain dicarboxylic carnitines, respectively. It took several days for oral L-carnitine administration to increase the serum carnitine levels, probably because the intracellular stores were depleted. Thereafter, the administration increased the excretion of abnormal acylcarnitines, some of which had accumulated within the tissues. The excretion of medium-chain dicarboxylic carnitines dramatically decreased on day 13, suggesting improvement of tissue acylcarnitine accumulation. These time-course changes in blood and urinary acylcarnitine levels after L-carnitine supplementation support the effectiveness of L-carnitine supplementation to CPT2-deficient patients.

Coffee consumption and circulating B-vitamins in healthy middle-aged men and women.

BACKGROUND: Coffee consumption has been associated with several risk factors for coronary heart disease, including increased cholesterol, increased blood pressure, and increased plasma total homocysteine (tHcy). tHcy is determined by several B-vitamins. However, reports about the association between coffee intake and B-vitamin status are few. METHODS: We measured plasma B-vitamins and tHcy in a cohort of 10,601 healthy, middle-aged Norwegian men and women. Information about lifestyle factors, including coffee consumption, smoking, alcohol use, height, and weight, was obtained by interview. RESULTS: Coffee consumption was dose-dependently associated with reduced plasma B-vitamin concentrations. Compared with coffee abstainers, individuals drinking >or=4 cups/day had 11.7% (P < 0.001), 14.1% (P < 0.001), and 5.5% (P = 0.01) lower plasma concentrations of folate, pyridoxal phosphate, and riboflavin, respectively, and the mean tHcy concentration was 6.8% (P < 0.001) higher. Quantile regression analysis showed essentially no difference in B-vitamin concentrations between coffee consumption categories at low vitamin concentrations but a progressive increase in the difference at higher concentrations. This pattern of differences (effect profile) was found independently of smoking status, alcohol intake, and sex. The decrease in folate explained approximately half of the increase in tHcy. CONCLUSIONS: Coffee consumption was associated with reduced circulating B-vitamin concentrations. The observed effect profiles indicated that coffee consumption preferentially affected the upper, but not the lower, part of the B-vitamin concentration distributions. We hypothesize that coffee consumption may increase the loss of surplus B-vitamins by excretion in urine.

Effect of B vitamins-fortified foods on primary school children in Beijing.

The objective of this study is to investigate the effect of B vitamins-fortified foods on primary school children. A controlled trial was conducted in 101 normal primary school children aged 9-11 years. They were randomly assigned to supplemental control group (S-control, n=36), riboflavin supplementation group (+riboflavin 0.625 mg/day, n=32), and B vitamin compound supplementation group (+riboflavin 0.625 mg/day, +thiamin 0.512 mg/day, +nicotinic acid 0.365 mg/day, +folic acid 0.13 mg/day, n=33) based on school classes. Urinary riboflavin excretion and erythrocyte glutathione reductase activity coefficient (EGRAC) along with erythrocyte transketolase activity (ETKA) were used to evaluate B vitamin levels in the children. AYP index, an index reflecting the brain performance ability, was chosen to assess the children's study abilities. Health education was carried out to help children and their parents adopt scientific dietary concepts. The urinary riboflavin excretion was higher in two supplementation groups (435.24 +/- 153.3 microg/g creatinine, 374.6 +/- 144.6 microg/g creatinine) than in S-control group (235.1 +/- 86.2 microg/g creatinine). Average values of EGRAC were lower in two supplementation groups (0.90 +/- 0.11, 0.80 +/- 0.10) than in S-control group (1.08 +/- 0.25). At the same time, the percentage of thiamine pyrophosphate (TPP%) decreased from 63.69 +/- 28.04 to 42.16 +/- 16.31 in B vitamin compound supplementation group. Meanwhile, AYP index increased at the end of the supplementation in two supplementation groups. B vitamins supplementation can significantly increase B vitamin level in children. Biochemical activities of riboflavin and thiamin can improve with the intake of fortified foods. The effect of B vitamin compound supplementation is better than that of single riboflavin supplementation when the effect of riboflavin's biofunction is considered. In addition, micronutrient supplementation appears to assist children's study abilities.

Weight loss favorably modifies anthropometrics and reverses the metabolic syndrome in premenopausal women.

OBJECTIVE: To determine the effects of a weight loss program, including dietary modifications, increased physical activity and dietary supplement (L-carnitine or placebo) on anthropometrics, leptin, insulin, the metabolic syndrome (MS) and insulin resistance in overweight /obese premenopausal women. METHODS: Participants consumed a hypocaloric diet; 30% protein, 30% fat and 40% carbohydrate in addition to increasing number of steps/day. Carnitine supplementation followed a randomized double blind protocol. Protocol lasted for 10 weeks. Seventy subjects (35 in the control and 35 in the carnitine group) completed the intervention. Anthropometrics, plasma insulin and leptin concentrations and body composition were measured. The number of subjects with the MetSyn and insulin resistance, were assessed at baseline and post-intervention. RESULTS: Because there were no significant differences between the carnitine and the placebo groups for all measured parameters, participants were grouped together for all analysis. Subjects decreased total energy (-26.6%, p < 0.01) and energy from carbohydrate (-17.3%, p < 0.01) and increased energy from protein by 67% (p < 0.01) and number of steps/day (42.6%, p < 0.01). Body weight (-4.6%, p < 0.001), body mass index (-4.5%, p < 0.01), waist circumference (-6.5%, p < 0.01), total fat mass (-1.7%, p < 0.01), trunk fat mass (-2.0%, p < 0.01), insulin (- 17.9%, p < 0.01) and leptin (-5.9%, p < 0.05) decreased after the intervention. Ten of 19 participants with insulin resistance became insulin sensitive and 7 of 8 participants with the MetSyn no longer had the syndrome after the intervention. CONCLUSION: Moderate increases in physical activity and a hypocaloric/high protein diet resulted in multiple beneficial effects on body anthropometrics and insulin sensitivity. Realistic dietary and physical activity goals must be the focus of intervention strategies for overweight and obese individuals.

Vitamin and mineral status in physically active men: effects of a high-potency supplement.

Changes in nutritional status during supplementation with a high-potency multivitamin-mineral supplement were examined in 22 physically active men randomly assigned to take a supplement (n = 11) or placebo (n = 11) for approximately 12 wk. Four-day dietary intakes, blood concentrations, and urinary excretions of selected vitamins and minerals were measured before, during (approximately 6 and 12 wk), and after supplementation. No changes were observed in blood concentrations of vitamins A and C and measures of zinc, magnesium, and calcium status; the supplement provided less than 300% of the recommended dietary allowance (RDA) of these nutrients. In contrast, blood concentrations of thiamin, riboflavin, vitamins B-6 and B-12, pantothenate, and biotin increased significantly (P less than 0.05) by 6 wk to values that were maintained until the end of the supplementation. These vitamins were provided in amounts that ranged from 396% (biotin) to 6250% (vitamin B-6) of the RDA. Urinary excretions of these vitamins also increased during supplementation and both blood and urine values returned to presupplementation concentrations at approximately 13.5 wk postsupplementation.

[Tissue thiamine, riboflavin and vitamin B6 in the aged rat. II. Effects of vitamin supplementation in the diet on the excretion of vitamins and its tissue levels]. / Thiamine, riboflavine et vitamine B6 tissulaires chez le rat agé. II. Influence d'une surcharge vitaminique administrée dans le régime sur l'excrétion des vitamines et sur leurs taux tissulaires.

Nine and twenty-one months old rats fed a balanced diet were given for 5 weeks an extra supplementation in thiamine, riboflavin and vitamin B6. Control animals were given the same diet but without vitamin extra supplementation. Fecal and urinary vitamin excretions were determined during this 5 weeks period. They were shown to be less important in older rats than in younger ones. Influence of aging and vitamin supplementation on the vitamin contents of organs and tissues were studied on these animals: previous results were confirmed [see LECLERC, Ann. nutrit, Aliment., 1976, 30, 10--25]. From these results and others published elsewhere, it is conclused that in older animals there could be an increased intestinal destruction of the above mentionned vitamin although changes in vitamin metabolism can be involved too.