Niacin deficiency causes pellagra, the symptoms of which include dermatitis, diarrhoea and dementia. Investigating the mechanism underlying these phenotypes has been challenging due to the lack of an appropriate animal model. Here, we report a mouse model of pellagra-related nausea induced by feeding mice a low-niacin diet and administering isoniazid (INH), which is thought to induce pellagra. Mice fed a normal or low-niacin diet received INH (0·3 or 1·0 mg/mg per animal, twice daily, 5 d), and nausea was evaluated based on pica behaviour, which considered the rodent equivalent of the emetic reflex. Furthermore, the effect of therapeutic niacin administration on nausea was evaluated in this model. Urinary and hepatic metabolite levels were analysed by LC coupled with MS. INH-induced pica was observed in mice fed a low-niacin diet but not in those fed a normal diet. Levels of urinary metabolites, such as 1-methyl-2-pyridone-5-carboxamide, kynurenic acid and xanthurenic acid, were significantly reduced in the mice treated with INH compared with those that did not receive INH. Furthermore, niacin supplementation prevented pica and restored the levels of some metabolites in this mouse model. Our findings suggest that INH-related nausea is pellagra-like. We also believe that our newly established method for quantifying pica is a useful tool for investigating the mechanisms of pellagra-related nausea.

Due to the incorporation of niacin into the coenzymes NAD and NADP, niacin is of great importance for the metabolism of man and animals. Apart from niacin in feed and endogenous formation, microbial niacin synthesis in the rumen is an important source for dairy cows. But the amount synthesised seems to differ greatly, which might be influenced by the ration fed. Many studies revealed a positive impact of a niacin supplementation on rumen protozoa, but microbial protein synthesis or volatile fatty acid production in the rumen showed inconsistent reactions to supplemental niacin. The amount of niacin reaching the duodenum is usually higher when niacin is fed. However, not the whole quantity supplemented reaches the duodenum, indicating degradation or absorption before the duodenal cannula. Furthermore, supplementation of niacin did not always lead to a higher niacin concentration in blood. Effects on other blood parameters have been inconsistent, but might be more obvious when cows are in a tense metabolic situation, for example, ketosis or if high amounts are infused post-ruminally, since ruminal degradation appears to be substantial. The same is valid for milk parameters. In the few studies where blood niacin and milk parameters have been investigated, enhanced niacin concentrations in blood did not necessarily affect milk production or composition. These results are discussed in the present review, gaps of knowledge of niacin's mode of action on the metabolism of dairy cows are identified and directions for future research are suggested.

It is becoming increasingly evident that (a) risk for developmental and degenerative disease increases with more DNA damage, which in turn is dependent on nutritional status, and (b) the optimal concentration of micronutrients for prevention of genome damage is also dependent on genetic polymorphisms that alter the function of genes involved directly or indirectly in the uptake and metabolism of micronutrients required for DNA repair and DNA replication. The development of dietary patterns, functional foods and supplements that are designed to improve genome-health maintenance in individuals with specific genetic backgrounds may provide an important contribution to an optimum health strategy based on the diagnosis and individualised nutritional prevention of genome damage, i.e. genome health clinics. The present review summarises some of the recent knowledge relating to micronutrients that are associated with chromosomal stability and provides some initial insights into the likely nutritional factors that may be expected to have an impact on the maintenance of telomeres. It is evident that developing effective strategies for defining nutrient doses and combinations or ‘nutriomes’ for genome-health maintenance at the individual level is essential for further progress in this research field.

The guinea-pig was previously reported as being sensitive to a niacin-deficient (ND), high-protein diet, suggesting that it is a suitable model for the low tryptophan to NAD+ conversion observed in human subjects. However, these studies were based on growth rates and mortality. The objective of the present study was to determine whether guinea-pigs are suitable for ND studies based on measurements of blood and bone marrow NAD+. Using a 20 % casein diet, ND decreased blood NAD+ after 4 weeks, but this parameter returned to normal after 9 weeks of feeding, while bone marrow was decreased by 35 % at this time point. Using a 15 % casein diet, 7 weeks of ND caused 44 and 42 % decreases in blood and bone marrow NAD+. Using a 10 % casein diet, ND decreased NAD+ by 32 % in blood and 62 % in bone marrow at 7 weeks. Growth rates were directly related to the dietary tryptophan content, with the lowest growth rates seen with the 10 % casein diet. Changes in guinea-pig NAD+ are comparable with the rat model at similar levels of dietary tryptophan, while mortality rates were dramatically higher in the guinea-pig model. The present study concludes that mortality in ND guinea-pigs is not indicative of poor tryptophan conversion, but is due to environmental stresses in guinea-pigs that are not observed with rats. We conclude that guinea-pigs are not suitable for research on niacin deficiency and they present challenges for any study requiring purified diets and wire-bottomed cages.

The purpose of this study was to determine the effect of altering substrate availability on metabolism and performance during intense cycling. Seven highly trained men ingested a random order of three isoenergetic meals 90 min before cycling at 80 % maximal oxygen uptake (VO2max) for 20 min (about 310 W), followed by a 600 kJ time trial lasting about 30 min. Meals consisted of either 1·2 g saturated fat/kg body mass (BM) with 3500 U heparin intravenously (HIFAT) to elevate circulating plasma free fatty acid (FA) concentration, 2·5 g carbohydrate/kg BM (CHO) to elevate plasma glucose and insulin concentrations or 2·5 g carbohydrate+20 mg nicotinic acid/kg BM (NA) to suppress lipolysis and reduce free FA concentration. HIFAT elevated free FA concentration (HIFAT 1·3 (SEM 0·2), CHO 0·2 (sem 0·1), NA 0·1 (sem 0·1) mm; P<0·001), lowered the RER (HIFAT 0·94 (sem 0·01), CHO 0·97 (sem 0·01), NA 0·98 (sem 0·01); P<0·01) and increased the rate of fat oxidation (HIFAT 24 (sem 3), CHO 12 (sem 2), NA 8 (sem 3) μmol/kg per min; P<0·01) during the 20 min ride. Marked differences in fat availability and fuel utilisation, however, had little effect on performance in the subsequent time trial (HIFAT 320 (sem 16), CHO 324 (sem 15), NA 315 (sem 13) W). We conclude: (1) increased fat availability during intense cycling increases the rate of fat oxidation; but (2) the reduction in the rate of carbohydrate oxidation in the presence of high circulating plasma free FA is unlikely to enhance intense exercise performance lasting about 1 h; (3) substrate selection during intense (about 80 % VO2max) exercise is dominated by carbohydrate oxidation.

Semi-purified diets were used to determine the nicotinic acid requirement of the gilthead seabream, Sparus aurata. Vitamin losses during food manufacture were minimal resulting in dietary levels which were close to the declared content. Dietary nicotinic acid contents of 52·21 mg/kg and below resulted in sub-optimum growth, reduced food efficiency and poor values for apparent net protein utilization. Diets containing less than 28·67 mg/kg gave a low proportion of carcass lipid concomitant with an elevation in the relative content of carcass moisture. Although gross deficiency symptoms were not observed, a reduced hepatosomatic index and a slightly lower plasma glucose concentration were detected amongst the fish given diets supplemented with nicotinic acid at the level of 25 mg/kg or less. Based upon the results of broken line analysis and data derived by modelling the weight gain of the fish, the nicotinic acid requirement of Sparus aurata fingerlings lies between 63 and 83 mg/kg of diet or 1·57 to 2·07 µg/kg body weight per day.