L-carnitine has an important role in the control of oxidative stress and lipid β-oxidation during in vitro culture and cryopreservation of ovarian follicles, oocytes and embryos. This substance balances the acetyl-CoA/CoA ratio, maintains glucose metabolism and increases energy production in mitochondria. It also plays a key role in reducing endoplasmic reticulum stress, by transferring palmitate to mitochondria or eliminating it to avoid toxicity. By eliminating reactive oxygen species, L-carnitine increases the percentages of mature oocytes with uniform mitochondrial distribution and improves embryo post-thaw cryotolerance. Therefore, L-carnitine controls lipid β-oxidation and oxidative stress during in vitro culture of ovarian follicles, oocyte maturation, embryonic development and cryopreservation.

It is inconclusive whether trimethylamine N-oxide (TMAO) and choline and related metabolites, namely trimethylamine (TMA), l-carnitine, betaine and dimethylglycine (DMG), are associated with non-alcoholic fatty liver disease (NAFLD). Our objective was to investigate these potential associations. Additionally, we sought to determine the mediating role of TMAO. In this 1:1 age- and sex-matched case–control study, a total of 150 pairs comprising NAFLD cases and healthy controls were identified. According to the fully adjusted model, after the highest tertile was compared with the lowest tertile, the plasma TMAO concentration (OR = 2·02 (95 % CI 1·04, 3·92); P trend = 0·003), l-carnitine concentration (OR = 1·79 (1·01, 3·17); P trend = 0·020) and DMG concentration (OR = 1·81 (1·00, 3·28); P trend = 0·014) were significantly positively associated with NAFLD incidence. However, a significantly negative association was found for plasma betaine (OR = 0. 50 (0·28, 0·88); P trend = 0·001). The restricted cubic splines model consistently indicated positive dose–response relationships between exposure to TMAO, l-carnitine, and DMG and NAFLD risk, with a negative association being observed for betaine. The corresponding AUC increased significantly from 0·685 (0·626, 0·745) in the traditional risk factor model to 0·769 (0·716, 0·822) when TMAO and its precursors were included (l-carnitine, betaine and choline) (P = 0·032). Mediation analyses revealed that 14·7 and 18·6 % of the excess NAFLD risk associated with l-carnitine and DMG, respectively, was mediated by TMAO (the P values for the mediating effects were 0·021 and 0·036, respectively). These results suggest that a higher concentration of TMAO is associated with increased NAFLD risk among Chinese adults and provide evidence of the possible mediating role of TMAO.

Dietary l-carnitine (LC) is a nutritional factor that reduces liver lipid content. However, whether dietary LC can improve lipid metabolism via simultaneous activation of mitochondrial fatty acid (FA) β-oxidation and suppression of endoplasmic reticulum (ER) stress is still unknown. Large yellow croaker were fed with a high-fat diet (HFD) supplemented with dietary LC at 0, 1·2 or 2·4 ‰ for 10 weeks. The results indicated that a HFD supplemented with LC reduced the liver total lipid and TAG content and improved serum lipid profiles. LC supplementation administered to this fish increased the liver antioxidant capacity by decreasing serum and liver malondialdehyde levels and enhancing the liver antioxidant capacity, which then relieved the liver damage. Dietary LC increased the ATP dynamic process and mitochondrial number, decreased mitochondrial DNA damage and enhanced the protein expression of mitochondrial β-oxidation, biogenesis and mitophagy. Furthermore, dietary LC supplementation increased the expression of genes and proteins related to peroxisomal β-oxidation and biogenesis. Interestingly, feeding fish with LC-enriched diets decreased the protein levels indicative of ER stress, such as glucose-regulated protein 78, p-eukaryotic translational initiation factor 2a and activating transcription factor 6. Dietary LC supplementation downregulated mRNA expression relative to FA synthesis, reduced liver lipid and relieved liver damage through regulating β-oxidation and biogenesis of mitochondria and peroxisomes, as well as the ER stress pathway in fish fed with HFD. The present study provides the first evidence that dietary LC can improve lipid metabolism via simultaneously promoting FA β-oxidation capability and suppressing the ER stress pathway in fish.

The present study was conducted to determine the effects of dietary terrestrial oils (TO) supplemented with l-carnitine on growth performance, biochemical and antioxidant response, lipid metabolism and inflammation in large yellow croaker (Larimichthys crocea). Three iso-nitrogenous and iso-lipidic experimental diets were formulated with FO (fish oil, the control group), 75 % TO (75 % FO was substituted by the oil mixture with equal amounts of soyabean oil, linseed oil and pork lard) and 75 % TOC (75 % TO supplemented with 800 mg/kg l-carnitine). Compared with the control group, feed efficiency ratio and specific growth rate were significantly increased in fish fed diets with 75 % TO and 75 % TOC. Hepatic lipid content, serum TAG level, LDL-cholesterol level and the mRNA expression of pro-inflammatory genes (tnfα and ifnγ) were significantly increased in fish fed the diet with 75 % TO compared with the control group. However, the supplementation of 800 mg/kg l-carnitine in the 75 % TO diet repressed hepatic lipid content, serum LDL-cholesterol level and the mRNA expression of tnfα and ifnγ in fish compared with fish fed the diet with 75 % TO. Total antioxidant capacity, the activity of superoxide dismutase, the mRNA expression of cpt-I and the activity of CPT-I were significantly increased in fish fed the diet with 75 % TOC compared with 75 % TO. In conclusion, these results suggested that the supplementation of 800 mg/kg l-carnitine in the diet with TO mixture could increase growth, antioxidant capacity and fatty acid oxidation and decrease the expression of inflammatory genes in large yellow croaker.

Genetic selection for increased sow prolificacy has resulted in decreased mean piglet birth weight. This study aimed to investigate the effect of l-carnitine (CAR) supplementation to sows during gestation and/or lactation on sow productivity, semitendinosus muscle (STM) maturity and lifetime growth in progeny. Sixty-four sows were randomly assigned to one of the four dietary treatments at breeding until weaning: CONTROL (0 mg CAR/d), GEST (125 mg CAR/d during gestation), LACT (250 mg CAR/d during lactation) and BOTH (125 mg CAR/d during gestation and 250 mg CAR/d during lactation). The total number of piglets born per litter was greater for sows supplemented with CAR during gestation (17·3 v. 15·8 (sem 0·52); P < 0·05). Piglet birth weight (total and live) was unaffected by sow treatment (P > 0·05). Total myofibre number (P = 0·08) and the expression level of selected myosin heavy chain genes in the STM (P < 0·05) were greater in piglets of sows supplemented with CAR during gestation. Pigs from sows supplemented with CAR during gestation had lighter carcasses at slaughter than pigs from non-supplemented sows during gestation (83·8 v. 86·7 (sem 0·86) kg; P < 0·05). In conclusion, CAR supplementation during gestation increased litter size at birth without compromising piglet birth weight. Results also showed that the STM of piglets born to sows supplemented with CAR during gestation was more developed at birth. However, carcass weight at slaughter was reduced in progeny of sows supplemented with CAR during gestation. The CAR supplementation strategy applied during gestation in this study could be utilised by commercial pork producers to increase sow litter size and improve offspring muscle development.

l-Carnitine is essential for mitochondrial β-oxidation and has been used as a lipid-lowering feed additive in humans and farmed animals. d-Carnitine is an optical isomer of l-carnitine and dl-carnitine has been widely used in animal feeds. However, the functional differences between l- and d-carnitine are difficult to study because of the endogenous l-carnitine background. In the present study, we developed a low-carnitine Nile tilapia model by treating fish with a carnitine synthesis inhibitor, and used this model to investigate the functional differences between l- and d-carnitine in nutrient metabolism in fish. l- or d-carnitine (0·4 g/kg diet) was fed to the low-carnitine tilapia for 6 weeks. l-Carnitine feeding increased the acyl-carnitine concentration from 3522 to 10 822 ng/g and alleviated the lipid deposition from 15·89 to 11·97 % in the liver of low-carnitine tilapia. However, as compared with l-carnitine group, d-carnitine feeding reduced the acyl-carnitine concentration from 10 822 to 5482 ng/g, and increased lipid deposition from 11·97 to 20·21 % and the mRNA expression of the genes involved in β-oxidation and detoxification in the liver. d-Carnitine feeding also induced hepatic inflammation, oxidative stress and apoptosis. A metabolomic investigation further showed that d-carnitine feeding increased glycolysis, protein metabolism and activity of the tricarboxylic acid cycle and oxidative phosphorylation. Thus, l-carnitine can be physiologically utilised in fish, whereas d-carnitine is metabolised as a xenobiotic and induces lipotoxicity. d-Carnitine-fed fish demonstrates increases in peroxisomal β-oxidation, glycolysis and amino acid degradation to maintain energy homeostasis. Therefore, d-carnitine is not recommended for use in farmed animals.

Sepsis is defined as the dysregulated host response to an infection resulting in life-threatening organ dysfunction. The metabolic demand from inefficiencies in anaerobic metabolism, mitochondrial and cellular dysfunction, increased cellular turnover, and free-radical damage result in the increased focus of micronutrients in sepsis as they play a pivotal role in these processes. In the present review, we will evaluate the potential role of micronutrients in sepsis, specifically, thiamine, l-carnitine, vitamin C, Se and vitamin D. Each micronutrient will be reviewed in a similar fashion, discussing its major role in normal physiology, suspected role in sepsis, use as a biomarker, discussion of the major basic science and human studies, and conclusion statement. Based on the current available data, we conclude that thiamine may be considered in all septic patients at risk for thiamine deficiency and l-carnitine and vitamin C to those in septic shock. Clinical trials are currently underway which may provide greater insight into the role of micronutrients in sepsis and validate standard utilisation.

L-carnitine (B-hydroxy-Y-N-trimethyl aminobutyrate) is a water-soluble product, found in animals, plants and microorganisms. Its synthesis takes place from two important amino acids, lysine and methionine. Essentially, L-carnitine has an intermediary role in metabolism. It promotes energy metabolism for cell and regulates co-enzyme A concentration in cystosol and mitochondria, which are important in glucose and lipid metabolism. L-carnitine was first isolated from the chicken embryo in a significant amount, but is absent in the egg. Under normal physiological conditions, the endogenously synthesised levels are sufficient for normal growth and functions. Its requirements are increased in stressful conditions and during metabolic and physiological higher demands, such as growth and laying periods. L-carnitine increases energy production, fat metabolism and improves immune status in birds, which is energy demanding. In this review, several aspects of the beneficial effects of dietary supplementation of L-carnitine on poultry health and production are briefly summarised.

The primary goal was to investigate the effects of l-carnitine on fuel efficiency, as an antioxidant, and for muscle recovery in Labrador retrievers. Dogs were split into two groups, with one group being supplemented with 250 mg/d of Carniking™ l-carnitine powder. Two experiments (Expt 1 and Expt 2) were performed over a 2-year period which included running programmes, activity monitoring, body composition scans and evaluation of recovery using biomarkers. Each experiment differed slightly in dog number and design: fifty-six v. forty dogs; one endurance and two sprint runs per week v. two endurance runs; and differing blood collection time points. All dogs were fed a low-carnitine diet in which a fixed amount was offered based on maintaining the minimum starting weight. Results from Expt 1 found that the carnitine dogs produced approximately 4000 more activity points per km compared with the control group during sprint (P = 0·052) and endurance runs (P = 0·0001). Male carnitine dogs produced half the creatine phosphokinase (CPK) following exercise compared with male control dogs (P = 0·05). Carnitine dogs had lower myoglobin at 6·69 ng/ml following intensive exercise compared with controls at 24·02 ng/ml (P = 0·0295). Total antioxidant capacity (TAC) and thiobarbituric acid reactive substance (TBARS) results were not considered significant. In Expt 2, body composition scans indicated that the carnitine group gained more total tissue mass while controls lost tissue mass (P = 0·0006) and also gained lean mass while the control group lost lean mass (P < 0·0001). Carnitine dogs had lower CPK secretion at 23·06 v. control at 28·37 mU/ml 24 h after post-run (P = 0·003). Myoglobin levels were lower in carnitine v. control dogs both 1 h post-run (P = 0·0157; 23·83 v. 37·91 ng/ml) and 24 h post-run (P = 0·0189; 6·25 v.13·5 ng/ml). TAC indicated more antioxidant activity in carnitine dogs at 0·16 mmv. control at 0·13 mm (P = 0·0496). TBARS were also significantly lower in carnitine dogs both pre-run (P = 0·0013; 15·36 v. 23·42 µm) and 1 h post-run (P = 0·056; 16·45 v. 20·65 µm). Supplementing l-carnitine in the form of Carniking™ had positive benefits in Labrador retrievers for activity intensity, body composition, muscle recovery and oxidative capacity.

The objective of this study was to investigate the effects of l-carnitine and/or maize distillers dried grains with solubles (DDGS) in diets of gestating and lactating sows on the intestinal barrier functions of their offspring. The experiment was designed as a 2×2 factorial with two dietary treatments (soyabean meal v. DDGS) and two l-carnitine levels (0 v. 100 mg/kg in gestating diets and 0 v. 200 mg/kg in lactating diets). Sows (Landrace×Large White) with an average parity of 4·2 with similar body weight were randomly assigned to four groups of thirty each. Dietary supplementation with l-carnitine increased the total superoxide dismutase activity but decreased the concentration of malondialdehyde of the jejunal mucosa in newborn piglets and weaning piglets on day 21. Dietary supplementation with l-carnitine decreased the concentrations of IL-1β, IL-12 and TNF-α in the jejunal mucosa of newborn piglets and decreased the concentrations of IL-6 and TNF-α in the jejunal mucosa of weaning piglets on day 21. There was an interaction between dietary treatment and l-carnitine on the bacterial numbers of total eubacteria in the digesta of caecum in weaning piglets on day 21. Bacterial numbers of total eubacteria in weaning piglets on day 21 were significantly increased by l-carnitine only in soyabean meal diet, but there was no significant effect of l-carnitine in DDGS-based diet. Dietary supplementation with l-carnitine increased the bacterial numbers of Lactobacillus spp. and bifidobacteria spp. in the digesta of caecum in weaning piglets on day 21. Dietary supplementation with l-carnitine in sows affected the expression of tight junction proteins (claudin 1, zonula occludens-1 (ZO-1) and occludin) in the jejunal mucosa of their offspring by increasing the expression of ZO-1 mRNA in the jejunal mucosa of newborn piglets, and by increasing the expression of ZO-1 and occludin mRNA in the jejunal mucosa of weaning piglets on day 21. In conclusion, dietary supplementation with l-carnitine in gestating and lactating sows had positive effects on intestinal barrier functions of newborn piglets and weaning piglets on day 21, but it did not have effects on intestinal barrier functions of growing–finishing pigs in the filial generation. There were no effects of dietary treatment of sows on intestinal barrier functions in their offspring.

This study was conducted to determine the effects of l-carnitine (LC), as an antioxidant, in preventing spermatozoa damage during the freezing–thawing process in both astheno- and normozoospermic human semen samples. Seventy semen samples (37 asthenozoospermic and 33 normozoospermic) were involved in this study. Cryopreservation medium supplemented with 1.0 g/l LC was mixed with semen at a ratio of 1:1 (v/v). Controls were cryopreserved with freezing medium only. Assessment of motility, viability (VIA), mitochondrial membrane potential (MMP) and DNA fragmentation index (DFI) were performed on aliquots of fresh semen, frozen–thawed control and frozen–thawed LC treated samples. Supplementation of the cryopreservation medium with LC induced a significant improvement in post-thaw sperm parameters in both the asthenozoospermic and normozoospermic semen samples, compared with those of the control, regarding sperm fast forward motility, forward motility, total motility and VIA. LC showed better protective effects towards asthenozoospermia for DFI (F = 115.85, P < 0.01) and VIA (F = 67.14, P < 0.01) than did normozoospermic semen samples. We conclude that supplementation with LC prior to the cryopreservation process reduced spermatozoa cryodamage in both asthenozoospermic and normozoospermic semen samples. LC had better protective effects for asthenozoospermic human semen samples. Future research should focus on the molecular mechanism for and the different protective effects of LC between asthenozoospermic and normozoospermic semen samples during cryopreservation.

The enhancement of fat oxidation during exercise is an aim for both recreational exercising individuals and endurance athletes. Nutritional status may explain a large part of the variation in maximal rates of fat oxidation during exercise. This review reveals novel insights into nutritional manipulation of substrate selection during exercise, explaining putative mechanisms of action and evaluating the current evidence. Lowering the glycaemic index of the pre-exercise meal can enhance lipid utilisation by up to 100 % through reduced insulin concentrations, although its application may be restricted to specific training sessions rather than competition. Chronic effects of dietary glycaemic index are less clear and warrant future study before firm recommendations can be made. A flurry of recent advances has overthrown the conventional view of l-carnitine supplementation, with skeletal muscle uptake possible under certain dietary conditions and providing a strategy to influence energy metabolism in an exercise intensity-dependent manner. Use of non-carbohydrate nutrients to stimulate muscle l-carnitine uptake may prove more beneficial for optimising lipid utilisation, but this requires more research. Studies investigating fish oil supplementation on fat oxidation during exercise are conflicting. In spite of some strong putative mechanisms, the only crossover trial showed no significant effect on lipid use during exercise. Ca may increase NEFA availability although it is not clear whether these effects occur. Ca and caffeine can increase NEFA availability under certain circumstances which could theoretically enhance fat oxidation, yet strong experimental evidence for this effect during exercise is lacking. Co-administration of nutrients to maximise their effectiveness needs further investigation.

L-carnitine has indispensable functions in intermediary metabolism and is received by endogenous synthesis and from exogenous sources. It plays an obligate role in fatty acid metabolism by directing fatty acids into the mitochondrial oxidative pathway through the action of specialised acyltransferases. In poultry production, L-carnitine has a multi functional purpose, which includes: growth promotion, strengthening the immune system, antioxidant effects and improving semen quality. The concentration of L-carnitine in animals varies widely across species, tissue type, and nutritional status of the animal. It has been suggested that the L-carnitine requirement may be increased under certain circumstances such as via higher performance, various stress conditions and where the diet is deficient in animal protein sources. The review of L-carnitine functions uniquely includes the main aspects of this consequential feed supplementary inclusion in poultry nutrition.

In recent years, l-carnitine has been used increasingly as a supplement in livestock animals. The present review gives an overview of the effects of dietary l-carnitine supplementation on the reproductive performance of sows. Results concerning the effect of l-carnitine supplementation during pregnancy on litter sizes are controversial. There are some studies reporting an increased number of piglets born alive per litter, while others could not find such an effect. In contrast, most studies performed show consistently that l-carnitine supplementation to a sow diet low in native carnitine during gestation increases piglet and litter weights at birth and enhances growth of litters during the suckling period. Biochemical mechanisms underlying the favourable effect of carnitine on intra-uterine growth have not been fully elucidated. There is, however, some evidence that carnitine influences the insulin-like growth factor-axis in sows and leads to greater placentae, which in turn improves intra-uterine nutrition, and stimulates oxidation of glucose in the fetuses. These effects may, at least in part, be responsible for higher birth weights of piglets. The stimulating effect of carnitine on growth of the litters might be due to an improved suckling behaviour of piglets born to l-carnitine-supplemented sows, causing the sows' milk production to rise. In conclusion, recent studies have clearly shown that dietary l-carnitine supplementation increases the reproductive performance of sows. These findings suggest that endogenous de novo synthesis of carnitine is insufficient to meet the metabolic requirement of sows during gestation.

It has been shown that l-carnitine supplementation of sows increases their milk production and the postnatal growth of the suckling piglets. To test the hypothesis that this effect is due to an improved suckling behaviour of the piglets, two experiments with sows were performed. Two groups of thirteen or ten sows each (in experiments 1 and 2, respectively) were fed diets with or without supplemental l-carnitine during pregnancy (125mg/d) and lactation (250mg/d). After birth, the litters of all sows were standardised to equal sizes of eleven and nine piglets per litter in experiments 1 and 2, respectively. In experiment 1, the piglets of l-carnitine-supplemented sows had a higher total suckling time per day on days 3, 6 and 9, and greater weight gains during the suckling period, than the piglets of control sows (P<0·05). In experiment 2, all litters were taken away from their mothers and switched to other sows. Half of the control sows and half of the l-carnitine-supplemented sows were given litters born to control sows, the other half of each group being given litters born to l-carnitine-supplemented sows. Piglets born to l-carnitine-supplemented sows had a higher total suckling time per day on day 3 and greater body weight gains during the first 14d compared with piglets born to control sows (P<0·05). This study shows that piglets born to sows supplemented with l-carnitine are able to suckle for longer, which enables them to obtain more milk and grow faster than piglets born to control sows.

The present study investigated the effect of l-carnitine supplementation during pregnancy (125 mg/d) and lactation (250 mg/d) on milk production, litter gains and back-fat thickness in sows fed a low-energy and low-protein diet during lactation. Sows supplemented with l-carnitine produced more milk on days 11 and 18 of lactation (+18 %; P<0·05) and had higher litter gains during suckling (+20 %; P<0·01) than control sows. Loss of body weight during lactation was similar in both groups, but sows supplemented with l-carnitine had a greater reduction of back-fat thickness (+45 %; P<0·05) during lactation than control sows. In conclusion, this study shows that l-carnitine increases milk production and litter gains in sows in a strongly negative energy and N balance, and enhances body fat mobilisation.

The composition of fourteen infant formulae and six follow-up milks with regard to their free amino acids (including taurine), free nucleotides, orotic acid, and free and total L-carnitine content was studied. The levels found were compared with the limits established in European legislation and with the composition of human and cows' milk samples. HPLC methodologies, optimized and validated for the matrices under study, were used, except for free and total L-carnitine contents that were quantified using a flow-injection manifold, also optimized and validated for the matrices under study. Global statistical treatment of the results by cluster analysis indicated similarities between the contents of the N compounds under study of infant formulae, follow-up milks and cows' milk and differences with regard to human milk composition. The principal component analysis showed that 60·2% of the variation in data was due to the first principal component, and the second component represented 23·8% of the total information. Nucleotide profiles, orotic acid, and free and total L-carnitine contents explain the main differences observed between human milk and the other milks studied (cows' milk, infant formulae and follow-up milks). Cows' milk is distinguished from infant formulae and follow-up milks mainly owing to the different uric acid contents and free amino acids profiles.

The usefulness of supplementary dietary L-CARNITINE AS AN IMMUNOMODULATOR TO INCREASE ANTIGEN-SPECIFIC ANTIBODY LEVELS WAS ANALYSED IN 2–6-WEEK-OLD BROILERS. THE CHICKENS RECEIVED COMMERCIAL FEEDS EITHER UNSUPPLEMENTED (STARTER FEED 17·8 MG CARNITINE/KG, FINISHER DIET 22·9 MG CARNITINE/KG) OR SUPPLEMENTED WITH l-carnitine (100 mg carnitine/kg added to feed). At 14 d of age, both groups were distributed in equal numbers and sex ratios over two environmentally controlled chambers where temperature (28°) was either reduced immediately to 20°, or gradually to 22° at 36 d of age. Antigen-specific immunoglobulin (Ig)M, IgG, IgA and total Ig responses were measured following two immunizations with bovine serum albumin (BSA). The typical BSA-specific IgM responses followed by IgG responses to the primary immunization were boosted by the secondary immunization. The kinetics of these responses were not altered by l-carnitine treatment. However, BSA-specific total Ig and IgG, but not IgM, responses were significantly increased by dietary l-carnitine supplementation, after both the primary and the secondary immunization. No significant influence of the sex of the chicks or the imposed environmental temperature on Ig responses was found. Temperature treatment and sex, but not l-carnitine supplementation, did significantly influence body-weight gain: cockerels were heavier than females and this became most evident in the second half of the rearing period. Further, lowering the temperature increased body weight. In conclusion, dietary l-carnitine supplementation appeared to be beneficial in enhancing specific humoral responses on vaccination.