Postweaning carnitine supplementation of iron-deficient rats

Severe iron deficiency in the suckling and weanling rat is associated with lipid accumulation in serum and liver, impaired ketogenesis in the suckling pup and low levels of carnitine in some tissues. Carnitine has been effective in reducing high triacylglycerol levels in humans and rats. This study examined tissue triacylglycerol concentrations of iron-deficient rats supplemented with carnitine or iron. Iron-adequate (C) and iron-deficient (D) pups were weaned to diets containing 38 ppm Fe (c) or 6 ppm Fe (d) with or without 0.2% DL-carnitine (Carn) resulting in six experimental treatments: CcCarn, DdCarn, Cc, Cd, Dc, Dd. Males received the diets for 2 wk and female littermates for 4. After 2 and 4 wk, carnitine supplementation significantly increased carnitine content in liver, heart and skeletal muscle by 30-60% in rats from control and Fe-deficient dams. Carnitine treatment significantly lowered the triacylglycerol level in liver of 49-d-old Fe-deficient females, but did not affect other tissues at either time point compared to other dietary treatments. Fe supplementation did not increase carnitine content in tissues, but did reduce triacylglycerol levels in liver by 4 wk and in skeletal muscle at both time points. Possible mechanisms by which iron and carnitine may lower lipids are discussed.     

Attenuation of ethanol metabolism by supplementary carnitine in rats

The purpose of this study was to examine the effect of supplementary D,L-carnitine on blood-ethanol levels and ascertain if the effect was a result of altered absorption or metabolism of ethanol. Mature male Sprague-Dawley rats were fed Purina Rat Chow as such or supplemented with various levels of D,L-carnitine. First it was established that supplementing carnitine at 1% (w/w) level produced steady state concentrations of carnitine in blood after 3 days of feeding. When a single dose of ethanol was given orally after 5 days of carnitine supplementation, the blood levels of ethanol remained significantly elevated for 2-8 hours in the carnitine supplemented animals. Time course of blood-ethanol concentrations revealed that carnitine did not affect the rates of ethanol absorption and therefore, the effect must be due to the attenuation of ethanol clearance from the blood.     

Dose-dependent lipotropic effect of carnitine in chronic alcoholic rats

The objective of this study was to determine if the lipotropic effect of supplementary DL-carnitine was dose dependent. Male Sprague-Dawley rats were fed for 45 d a liquid ethanol diet in which 36% of the total energy was derived from ethanol. The ethanol diet, containing 1.27 g L-carnitine per g of the diet, was fed as such or was supplemented with 0.1%, 0.4%, 0.8%, 1.2%, or 1.6% (wt/wt) DL-carnitine. Results showed a definite inverse relationship between the concentrations of lipids and those of carnitine fractions in both plasma and liver. The concentrations of total lipids and triglycerides were significantly lower with increasing levels of supplementary carnitine, whereas those of carnitine fractions were significantly higher than in controls up to 0.8% supplemental carnitine. The changes in the plasma and hepatic concentrations of various classes of lipid and carnitine were inversely related and were found to be progressive up to 0.8% DL-carnitine supplementation. Therefore, it was concluded that the lipotropic effect of dietary carnitine is dose dependent, and that the optimal supplementary level is 0.8% DL-carnitine.     

Effect of food restriction on tissue carnitine concentration in rats

The effect of feeding different amounts of a standard laboratory pellet diet on tissue carnitine concentration was studied in four groups of rats. Group I was fed ad libitum, whereas food intake was restricted to 25, 20, and 15g protein/kg body weight/day in group II, III, and IV, respectively. The intake of food, protein, energy and carnitine was constant and adjusted to actual body weight in groups 2-4. Six weeks food restriction had no effect on muscle carnitine. Restricted diet caused lowered concentrations of carnitine in serum (group I, fed ad libitum, total 95.0 +/- 13.8, free 80.2 +/- 2.7; group II total 78.4 +/- 8.4, free 56.9 +/- 4.7; group III total 81.7 +/- 8.8, free 66.0 +/- 8.8; and group IV total 73.8 +/- 8.7, free 59.5 +/- 7.6 mumol/l) and urinary carnitine excretion (group I, total 7.1 +/- 3.3, free 6.3 +/- 3.1; group II, total 2.5 +/- 0.7, free 2.2 +/- 0.7; group III, total 1.9 +/- 0.8, free 1.6 +/- 0.8; and group IV, total 1.3 +/- 0.4 free 1.1 +/- 0.3 mumol/day). In contrast, the liver carnitine tended to increase when dietary intake was reduced (group I total 1.1 +/- 0.1, free 1.0 +/- 0.1; group II total 1.5 +/- 0.2, free 1.4 +/- 0.2; group III total 1.3 +/- 0.1, free 1.1 +/- 0.1; and group IV total 1.5 +/- 0.2, free 1.4 +/- 0.2 mumol/g dry wt). The highest liver carnitine concentrations were observed during the lowest dietary intake when also the serum and urine carnitine were lowest. We conclude that the amount of food intake has a direct impact on carnitine concentrations in the liver, serum, and urine while muscle carnitine concentration remains relatively stable despite wide variations in food intake.     

Vitamin C depletion is associated with alterations in blood histamine and plasma free carnitine in adults.

The purpose of this study was to determine whether carnitine metabolism or histamine degradation would be useful parameters for investigating the optimal requirement for vitamin C.

Twenty-two non-scorbutic subjects with subnormal vitamin C status (plasma vitamin C < 28 mumol/L) were placed on a metabolic diet low in vitamin C for 3 weeks and repleted with graded doses of vitamin C: 10, 30 and 60 mg vitamin C daily (group 1) or 10,125 and 250 mg vitamin C daily (group 2) for weeks 1, 2 and 3, respectively. Fasting blood samples were collected weekly and analyzed for plasma vitamin C, plasma free carnitine and blood histamine.

Group 1 subjects remained in a subnormal vitamin C state throughout the 3-week study, and blood histamine and plasma free carnitine were not impacted by the experimental treatment. Plasma vitamin C in group 2 subjects rose significantly during the study, and these subjects finished the study with an ample vitamin C status indicative of vitamin C intakes above the recommended dietary allowance. Both blood histamine and plasma free carnitine were inversely related to vitamin C status in group 2 subjects.

These data indicate that blood histamine and plasma free carnitine are altered in individuals with subnormal, non-scorbutic vitamin C status and provide evidence that metabolic changes independent of collagen metabolism occur prior to the manifestation of scurvy. Thus utilizing scurvy as an end-point to determine vitamin C requirements may not provide adequate vitamin C to promote optimal health and well-being.     

Exercise training and supplementation with carnitine and antioxidants increases carnitine stores, triglyceride utilization, and endurance in exercising rats

This study evaluated the effects of supplementation of carnitine and antioxidants on lipids, carnitine concentrations, and exercise endurance time in both trained and untrained rats as compared to non-supplemented rats. Thirty-two male SD rats, age 7 wk were divided into four groups according to exercise training and modified AIN-76 diets: NTNS (non-trained non-supplemented), NTS (non-trained supplemented), LTNS (long-trained non-supplemented) and LTS (long-trained supplemented). The trained rats were run on a treadmill for 60 min per day (10(0) incline, 20 m/min for 8 wk). Carnitine (0.5%/diet) and vitamin E (0.5 mg/g b.w.) were supplemented in rat diets and vitamin C (0.5 mg/g b.w.) and melatonin (1 microg/g b.w.) were administered into the stomachs of the rats. LTNS and LTS rats had significantly lower serum total lipid, triglyceride, total cholesterol and liver triglycerides, but had higher serum HDL-cholesterol. There were no changes in exercise endurance time by supplementation in untrained animals, however endurance times were longer in LTS animals than in LTNS. The supplementation and training tended to increase carnitine palmitoyltransferase (CPT-I) activities, although the differences were not statistically significant. Likewise, CPT-I mRNA levels were higher in both supplemented and exercise trained rats. These results suggest that supplementation of carnitine and antioxidants may improve lipid profiles and exercise ability in exercise-trained rats.     

Necessity of carnitine supplementation in semistarved rats fed a high-fat diet.

We investigated the effects of carnitine supplementation on lipid metabolism in semistarved rats. The semistarved rats were fed a high-fat diet and half the normal energy intake for 2 wk. Carnitine was supplied daily at a dose of 250 mg/kg of body weight. The results showed that the concentration of plasma free carnitine increased significantly in semistarved and carnitine-supplemented rats compared with normal and semistarved rats. The activities of muscle carnitine palmitoyltransferase I and preheparin plasma lipoprotein lipase also were significantly increased in semistarved and carnitine-supplemented rats. The plasma triacylglycerol secretion rate was restored to normal by carnitine supplementation in semistarved rats. Urinary excretion of ketone bodies was reduced significantly after carnitine supplementation. We concluded that supplementation of carnitine can significantly increase the concentration of plasma free carnitine and improve lipid metabolism in semistarved rats fed a high-fat diet.     

Dietary carnitine intake and carnitine status in endurance-trained males

Background: Carnitine is an integral component of fatty acid transfer into the mitochondria, and also buffers excess intramitochondrial acyl‐CoA. It has previously been suggested that athletes may be at risk of low carnitine status and could therefore benefit from carnitine supplementation. Objective: To report the habitual dietary carnitine intakes of endurance‐trained adult males, and to determine whether they are at risk of carnitine insufficiency by measuring plasma and urinary carnitine concentrations. Methods: Fourteen non‐vegetarian endurance‐trained males completed a seven‐day weighed food record and exercise logs to determine habitual dietary carnitine intake. Resting venous blood samples and 24‐hour urine collections were used to determine plasma carnitine concentration and urinary carnitine excretion. Results: The mean dietary carnitine intake was 64 (range 21–110) mg/day. Mean ± SD resting plasma total carnitine was 44 ± 7 µmol/L and acyl : free carnitine ratio was 0.28 ± 0.11, which were within normal ranges. Urinary carnitine excretion was 437 ± 236 µmol/day. There was no correlation between dietary carnitine intake or dietary macro‐ and micronutrients and plasma carnitine or urinary carnitine excretion. Conclusion: The results of the present study indicate there is no evidence that endurance‐trained males consuming a mixed diet are at risk of carnitine insufficiency.     

Experimental sodium depletion and salt taste in normal human volunteers

To examine the sensory effects of extreme sodium depletion in humans, 10 normal volunteers were fed a very-low-sodium diet and were treated with diuretics for 10 d. Urine samples were collected and blood was drawn for hormone analyses. Taste tests included threshold and intensity judgments of salt (NaCl) and sucrose and preferences for salt and sucrose in foods. Subjects also rated the pleasantness of 29 foods listed on a questionnaire. Substantial sodium depletion was induced in all subjects. Salt thresholds decreased in a majority of the subjects whereas preference judgments for salt in foods tended to be greater during the depletion period. The changes in pleasantness of the 29 foods revealed that saltier foods were substantially more attractive during the depletion period than during the pre- and postdepletion periods. These data indicate that experimental sodium depletion in humans is followed by moderate sensory changes and an increased preference for salty foods.     

Distribution of carnitine and acylcarnitine in small intestine of carnitine-supplemented and fasted rats

Distribution of carnitine and acylcarnitine in lumen flush and tissue of the small intestine was examined in four groups of male Sprague-Dawley rats fed either a nonpurified diet (groups 1, 2) or the same supplemented with 1% DL-carnitine (groups 3, 4). One group of animals under each dietary regimen (groups 2, 4) was fasted for 24 h prior to killing. Carnitine and acylcarnitines were present in higher concentrations in tissue of the small intestine than in the lumen flush. Even though the diets contained only traces of acid-soluble acylcarnitine, it was present in high concentrations both in tissue of the small intestine and lumen flush. Proximal segments of small intestine tended to concentrate carnitine and acylcarnitines under all conditions of treatment. Carnitine supplementation increased the amounts of carnitines in tissue; however, there was only a minor alteration in the pattern of distribution of carnitine and acylcarnitines.     

半饥饿状态下高脂喂养对大鼠肉毒碱及脂类代谢的影响

目的探讨高脂饲料喂养半饥饿状态下大鼠肉碱及脂肪代谢的变化.方法用限食的方法造成半饥饿大鼠模型,观察给予普通饲料的半饥饿对照组与给予高脂饲料的实验组血浆肉碱浓度、附睾脂肪垫重量,肝游离氨基酸和脂肪含量,血中甘油三酯、游离脂肪酸以及游离氨基酸浓度等指标的变化.结果给予高脂饲料的实验组动物血浆游离肉碱浓度显著低于正常组和实验前水平(P＜0.05);肝脂肪含量、血游离脂肪酸浓度均显著高于半饥饿对照组(P＜0.05);两组半饥饿动物血和肝脏中大部分游离氨基酸浓度显著低于正常组,半饥饿对照组其浓度降低更显著,同时合成肉碱的赖氨酸和蛋氨酸浓度也显著降低.结论高脂饲料喂养半饥饿状态下,游离肉碱浓度降低,脂类代谢负担加重,提示在高脂半饥饿状态下需补充外源性肉碱.     

Distribution of endogenous and exogenous carnitine in rats with sepsis and acute liver failure

The distribution of carnitine was investigated in male Wistar rats with sepsis or acute liver failure. Sepsis was produced by cecal ligation and puncture, while acute liver failure was induced by intraperitoneal injection of carbon tetrachloride. Then 14C-carnitine or L-carnitine was injected intravenously. In healthy control rats and rats with sepsis, both 14C-radioactivity and carnitine were increased in the liver and kidneys. When the carnitine fractions were investigated, it was found that free carnitine and short-chain acylcarnitine were increased. In the rats with acute liver failure, 14C-radioactivity decreased in the liver, but carnitine increased, with free carnitine and short-chain acylcarnitine levels rising. These findings suggested that exogenous free carnitine accumulated directly in the organs with carnitine deficiency in rats with sepsis and acute liver failure. In addition, there was differential regulation of the fractions of both exogenous and endogenous carnitine (free carnitine, short-chain acylcarnitine, and long-chain acylcarnitine). Furthermore, the distribution of exogenous carnitine differed between sepsis and acute liver failure.