Plasma and muscle carnitine in experimental uremia

The effect of uremia and dietary protein intake on carnitine levels in skeletal muscle and plasma of rats was evaluated. Male Sprague-Dawley rats weighing 160–180 g were made chronically uremic by partial ligation of left renal artery and contralateral nephrectomy. Rats were fed diets containing 8% or 18% casein ad libitum for 8 weeks and sham-operated pair-fed animals were used as controls. At the end of the experiment, all animals were fasted overnight and decapitated. Skeletal muscle and plasma were assayed for free, total acid-soluble and long-chain acylcarnitines. The concentration of total carnitines in skeletal muscle were similar in uremic and control rats fed either 8% or 18% casein diet. However, the muscle long chain acylcarnitines were higher in rats fed the 18% casein diet than those fed the 8% casein diet. Diets (8% or 18% casein) had no effect on the plasma carnitine level, although uremic rats had lower levels than the controls. This study has shown that kidney dysfunction may affect the plasma carnitines level but not the total skeletal muscle carnitines concentration.     

Muscle and plasma carnitine levels and urinary carnitine excretion in multiply injured patients on total parenteral nutrition

Carnitine is necessary for the transport of long-chain fatty acids across the mitochondrial membrane. Thirteen severely injured patients on total parenteral nutrition were studied during days 2-8 post injury. Initially plasma and skeletal muscle carnitine values were within the range earlier found for normal subjects, whereas the urinary carnitine excretion was markedly increased. On day 4 there was a simultaneous decrease in the carnitine concentration in plasma (alpha < 0.01) and urine (alpha < 0.05) as well as in skeletal muscle tissue (alpha < 0.05 using only the values that could be paired i.e. from eight subjects), whereas no difference was found between day 2 and 8. One explanation of this pattern might be that a redistribution of carnitine occurs to other organs not measured, for example the liver. In skeletal muscle tissue, statistically significant positive correlations were found between the carnitine level and ATP (alpha < 0.01) and phosphocreatine (alpha < 0.02) as well as between carnitine and glycogen (alpha < 0.05).     

Consumption of a high β-glucan barley flour improves glucose control and fatty liver and increases muscle acylcarnitines in the Zucker diabetic fatty rat

Purpose

The soluble fiber β-glucan, a natural component of barley, has been shown to lower the postprandial glucose response and is thought to improve insulin resistance.

Methods

This study examined the effect of chronic consumption of the high β-glucan barley flour on glucose control, liver lipids and markers of muscle fatty acid oxidation in the Zucker diabetic fatty (ZDF) rat. Two groups of ZDF rats were fed diets containing either 6 % β-glucan in the form of barley flour or cellulose as a control for 6 weeks. A group of Zucker lean rats served as a negative control.

Results

The barley flour group had an increased small intestinal contents viscosity compared to the obese control group. After 6 weeks, the barley flour group had reduced glycated hemoglobin, lower relative kidney weights and a reduced area under the curve during a glucose tolerance test, indicating improved glucose control. Fasting plasma adiponectin levels increased in the barley flour group and were not different than the lean control group. ZDF rats on the barley flour diet had lower relative epididymal fat pad weights than the obese control and a greater food efficiency ratio. The barley flour group also had reduced liver weights and a decreased concentration of liver lipids. The barley flour group had significantly higher concentrations of muscle acylcarnitines, a metabolite generated during fatty acid oxidation.

Conclusion

These results show that chronic consumption of β-glucans can improve glucose control and decrease fatty liver in a model of diabetes with obesity.     

Plasma and red blood cell carnitine and carnitine esters during L-carnitine therapy in hemodialysis patients

Plasma and red blood cell (RBC) carnitine and acylcarnitines were determined in 20 hemodialysis (HD) patients during three different L-carnitine dosages (1, 5, and 15 mg/kg body wt), each for 3 mo. Before L-carnitine treatment, free carnitine was significantly lowered in plasma but elevated in RBCs compared with healthy subjects. Short-chain acylcarnitines were elevated in plasma and normal in RBCs. HD therapy decreased plasma free and acylcarnitines markedly but did not influence RBC values. Low-dose L-carnitine treatment normalized both plasma- and RBC-free carnitine. Dosages of 5 and 15 mg/kg body wt increased plasma and intracellular carnitine and carnitine esters impressively. Plasma and RBC carnitine fractions remained elevated even after a 6-wk washout period. Low-dose L-carnitine treatment is sufficient to correct disturbed plasma and RBC carnitine and carnitine esters of HD patients. Elevated RBC carnitine esters decreased very slowly, suggesting low RBC carnitine turnover. Carnitine overdosage should be prevented in those patients who benefit from carnitine therapy.     

Effect on LDL-cholesterol of a large dose of a dietary supplement with plant extracts in subjects with untreated moderate hypercholesterolaemia: a randomised, double-blind, placebo-controlled study

Purpose

To determine the effect of 4 weeks of supplementation, then, withdrawal of a dietary supplement (DS) containing red yeast rice extract, policosanol and artichoke leaf extract at twice the recommended daily dose (6 tablets, 6-TAB) compared to the usual dose (3-TAB) or to a placebo (PLA), on blood lipid profiles and safety biomarkers.

Methods

Forty-five healthy subjects (15 per group), with untreated hypercholesterolaemia, were included in this randomised, double-blind, placebo-controlled clinical trial.

Results

After 4 weeks of supplementation, LDL-C was significantly lower in 6-TAB (?0.21 g/l; 95 % CI ?0.38 to ?0.03 g/l; p = 0.0217) and 3-TAB (?0.25 g/l; 95 % CI ?0.42 to ?0.07 g/l; p = 0.0071) compared to PLA, although no difference in LDL-cholesterol was observed between the two groups, while no effect was seen on triacylglycerol and HDL-cholesterol. Four weeks after the end of supplementation, no difference in LDL-C was seen between the PLA group and the DS-treated groups. The muscle breakdown biomarkers, as well as biomarkers of liver and renal function, were altered by neither dose of the DS. Acute application of the DS on permeabilised skeletal muscle fibres of rats did not induce deleterious effects on mitochondrial function.

Conclusions

Supplementation with twice the recommended dose of the DS was effective in reducing LDL-cholesterol and appeared safe, but according to the present results, no additional benefit could be achieved compared to the recommended dose.     

Enhanced sensitivity of skeletal muscle growth in offspring of mice long-term selected for high body mass in response to a maternal high-protein/low-carbohydrate diet during lactation

Aim

To investigate the effects of a high-protein/low-carbohydrate diet fed to mice of different genotypes during pregnancy and/or lactation on offspring skeletal muscle growth and metabolism.

Methods

Pregnant mice from strains selected for high body mass (DU6) or endurance running performance (DUhLB) and from an unselected control strain (DUK) were fed iso-energetic diets containing 20 % (C) or 40 % protein and low carbohydrate (HP) from mating to weaning at day 21 of age. At birth, offspring were cross-fostered resulting in different exposure to maternal prenatal-preweaning diets (C–C, HP–C, C–HP, HP–HP). Rectus femoris muscle of male mice (n = 291) was examined at day 23, 44, 181 and 396 of age for cellular growth and metabolism.

Results

At day 23 of age, body and muscle growth was retarded by 30–40 % (P < 0.0001) in response to the C–HP and HP–HP, but not to the HP–C diet, due to reduced fibre size (P < 0.0001) but not fibre number. DNA was highly reduced in DU6, less in DUhLB, but not in DUK muscle (strain × diet; P < 0.0001). Despite some compensation, muscle growth was still impaired (P < 0.001) in adulthood (day 44; day 181), but at senescence only in DU6 mice (strain × diet; P < 0.05). Only at weaning, isocitrate and lactate dehydrogenase activities were increased or decreased (P < 0.0001), respectively, without influence on fibre type composition.

Conclusion

A high-protein/low-carbohydrate diet fed to dams during lactation, but not during pregnancy, retards skeletal muscle growth in offspring with greater response of a heavy, obese compared with a physically fit and a control genotype and causes a transient shift towards oxidative versus glycolytic muscle metabolism.     

Supplementation with tocotrienol-rich fraction alters the plasma levels of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor from young and old individuals

Purpose

Tocotrienol possess beneficial effects not exhibited by tocopherol. In vitro studies using animal models have suggested that these effects are caused via modulation of gene and protein expression. However, human supplementation studies using tocotrienol-rich isomers are limited. This study aims to identify plasma proteins that changed in expression following tocotrienol-rich fraction (TRF) supplementation within two different age groups.

Methods

Subjects were divided into two age groups—32 ± 2 (young) and 52 ± 2 (old) years old. Four subjects from each group were assigned with TRF (78 % tocotrienol and 22 % tocopherol, 150 mg/day) or placebo capsules for 6 months. Fasting plasma were obtained at 0, 3, and 6 months. Plasma tocopherol and tocotrienol levels were determined. Plasma proteome was resolved by 2DE, and differentially expressed proteins identified by MS. The expressions of three proteins were validated by Western blotting.

Results

Six months of TRF supplementation significantly increased plasma levels of tocopherols and tocotrienols. Proteins identified as being differentially expressed were related to cholesterol homeostasis, acute-phase response, protease inhibitor, and immune response. The expressions of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor were validated. The old groups showed more proteins changing in expression.

Conclusions

TRF appears to not only affect plasma levels of tocopherols and tocotrienols, but also the levels of plasma proteins. The identity of these proteins may provide insights into how TRF exerts its beneficial effects. They may also be potentially developed into biomarkers for the study of the effects and effectiveness of TRF supplementation.     

Effect of intermittent glutamine supplementation on skeletal muscle is not long-lasting in very old rats

Background and objective

Muscle is the major site for glutamine synthesis via glutamine synthetase (GS). This enzyme is increased 1.5–2 fold in 25–27-mo rats and may be a consequence of aging-induced stress. This stimulation is similar to the induction observed following a catabolic state such as glucocorticoid treatment (6 to 24 months). Although oral glutamine supply regulates the plasma glutamine level, nothing is known if this supplementation is interrupted before the experiment.

Design

Adult (8-mo) and very old (27-mo) female rats were exposed to intermittent glutamine supplementation for 50 % of their age lifetime. Treated rats received glutamine added to their drinking water and control rats water alone but the effect of glutamine supplementation was only studied 15 days after the last supplementation.

Results

Glutamine pretreatment discontinued 15 days before the experiment increased plasma glutamine to ～ 0.6 mM, a normal value in very old rats. However, it failed to decrease the up-regulated GS activity in skeletal muscle from very old rats.

Conclusion

Our results suggest that long-term treatment with glutamine started before advanced age but discontinued 15 days before rat sacrifice is effective in increasing plasma glutamine to recover basal adult value and in maintaining plasma glutamine in very old rats, but has no long-lasting effect on the GS activity of skeletal muscle with advanced age.     

Erythritol reduces small intestinal glucose absorption,increases muscle glucose uptake,improves glucose metabolic enzymes activities and increases expression of Glut-4 and IRS-1 in type 2 diabetic rats

Purpose

Studies have reported that erythritol, a low or non-glycemic sugar alcohol possesses anti-hyperglycemic and anti-diabetic potentials but the underlying mode of actions is not clear. This study investigated the underlying mode of actions behind the anti-hyperglycemic and anti-diabetic potentials of erythritol using different experimental models (experiment 1, 2 and 3).

Methods

Experiment 1 examined the effects of increasing concentrations (2.5–20%) of erythritol on glucose absorption and uptake in isolated rat jejunum and psoas muscle, respectively. Experiments 2 and 3 examined the effects of a single oral dose of erythritol (1 g/kg bw) on intestinal glucose absorption, gastric emptying and postprandial blood glucose increase, glucose tolerance, serum insulin level, muscle/liver hexokinase and liver glucose-6 phosphatase activities, liver and muscle glycogen contents and mRNA and protein expression of muscle Glut-4 and IRS-1 in normal and type 2 diabetic animals.

Results

Experiment 1 revealed that erythritol dose dependently enhanced muscle glucose ex vivo. Experiment 2 demonstrated that erythritol feeding delayed gastric emptying and reduced small intestinal glucose absorption as well as postprandial blood glucose rise, especially in diabetic animals. Experiment 3 showed that erythritol feeding improved glucose tolerance, muscle/liver hexokinase and liver glucose-6 phosphatase activities, glycogen storage and also modulated expression of muscle Glut-4 and IRS-1 in diabetic animals.

Conclusion

Data suggest that erythritol may exert anti-hyperglycemic effects not only via reducing small intestinal glucose absorption, but also by increasing muscle glucose uptake, improving glucose metabolic enzymes activity and modulating muscle Glut-4 and IRS-1 mRNA and protein expression. Hence, erythritol may be a useful dietary supplement for managing hyperglycemia, particularly for T2D.

     

Dietary carnitine intake related to skeletal muscle and plasma carnitine concentrations in adult men and women

The purpose of this investigation was to determine if there was any relationship between dietary carnitine intake and the concentrations of carnitine in skeletal muscle and blood plasma in healthy adult men and women. Subjects (14 men, 14 women, fasted 8 h) reported to the Biodynamics Laboratory where they completed a 24-h diet recall questionnaire. Resting muscle biopsy (vastus lateralis) and blood plasma samples were taken and assayed for free, short-chain, and long-chain acyl carnitine concentrations. Dietary carnitine intake was estimated from data on concentrations in food. There was no significant relationship between either protein or carnitine intake with skeletal muscle carnitine concentrations. There was a significant relationship between both dietary carnitine (r = 0.50) and protein (r = 0.48) intake with blood plasma total acid soluble carnitine concentrations (p less than 0.01) in all subjects.     

Dietary supplementation of herring roe and milt enhances hepatic fatty acid catabolism in female mice transgenic for hTNFα

Purpose

The beneficial effects of a seafood-rich diet are highly documented and can be attributed to both n-3 polyunsaturated fatty acids and other less studied nutritional components including protein and antioxidants. The aim of the work was to investigate whether an under-utilized seafood source, eggs (roe) and sperm (milt) from herring (Clupea harengus), can affect lipid metabolism and inflammation in a mouse model transgenic for human tumor necrosis factor alpha (hTNFα).

Methods

A high-fat control diet (25% total fats, 20% protein, w/w) or high-fat diets supplemented with herring roe (3.7% fat, 15% protein, w/w), or milt (1.3% fat, 15% protein) were administered to female C57BL/6 hTNFα mice. After 2?weeks, hepatic enzyme activity, gene expression, lipid and fatty acid composition, fatty acid composition of epididymal adipose tissue, and plasma lipid and cytokine levels were determined.

Results

Animals fed herring roe and milt displayed an increased hepatic fatty acid β-oxidation and reduced fatty acid synthase activity. However, while plasma TAG was reduced, hepatic TAG and plasma and hepatic cholesterol levels were increased by the herring diets. Both herring diets led to a substantial shift in the n-6:n-3 ratio in both liver and ovarian white adipose tissue. The herring diets also increased plasma carnitine and reduced the carnitine precursor trimethyllysine. Plasma short-chained acylcarnitine esters were significantly increased, which may reflect an increased β-oxidation of long-chained fatty acids. In addition, the diets tended to reduce the plasma levels of pro-inflammatory cytokines.

Conclusion

Herring roe or milt diets enhanced lipid catabolism and influenced the chronic inflammatory state in hTNFα-transgenic mice.     

Protective effects of garlic extract on cardiac function,heart rate variability,and cardiac mitochondria in obese insulin-resistant rats

Purpose

Garlic has been shown to exhibit antioxidant effects and cardioprotective properties. However, the effects of garlic extract on the heart in insulin resistance induced by long-term high-fat-diet consumption are not well defined. Therefore, we sought to determine the effects of garlic extract in the obese insulin-resistant rats.

Methods

Male Wistar rats (180–200 g) were divided into two groups: normal-diet or high-fat-diet (n = 24/group) fed for 12 weeks. Rats in each groups were divided into three subgroups (n = 8 each): vehicle or garlic extract (250 or 500 mg/kg/day, respectively) treated for 28 days. At the end of the treatment, the metabolic parameters, heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined.

Results

Rats that received a high-fat-diet for 12 weeks had increased body weight, visceral fat, plasma insulin levels, total cholesterol, oxidative stress levels, depressed HRV, and cardiac mitochondrial dysfunction. Garlic extract at both concentrations significantly decreased the plasma insulin, total cholesterol, homeostasis model assessment index, and oxidative stress levels. Furthermore, garlic extract at both doses restored the HRV, cardiac function, and cardiac mitochondrial function.

Conclusion

We concluded that garlic extract at both concentrations exerted cardioprotective effects against cardiac dysfunction and mitochondrial dysfunction in obese insulin-resistant rats.     

Skeletal muscle mass abnormalities are associated with survival rates of institutionalized elderly nursing home residents

Background

Knowledge about the changes in skeletal muscle mass in nursing home residents is very limited. We hypothesized that such patients have different types of skeletal muscle mass abnormalities that may affect mortality rates. Therefore, the objective of this study was to evaluate the prevalence and extent of skeletal muscle mass decline, its different clinical phenotypes (sarcopenia, wasting/atrophy and cachexia) and the mortality rates associated with these abnormalities.

Methods

A retrospective chart-review study comprising 109 institutionalized nursing home residents. Body mass index, body fat mass, fat free mass, skeletal muscle mass and survival rates were assessed.

Results

Skeletal muscle mass abnormalities were found among 73 out of 109 (67.0%) patients and were more prevalent in males compared with females (97.8% and 43.8%, respectively, p<0.001). Most of these patients had muscle wasting/atrophy (51.4%) or sarcopenia (40.3%), and 9.7% suffered from cachexia. One third of the patients with abnorrmal skeletal muscle mass showed a moderate decline of skeletal muscle mass (34.7%) while the remainder (65.3%) had very low levels of skeletal muscle mass. Each group was characterized by typical medical conditions associated with skeletal muscle mass abnormality. A Kaplan-Meier survival plot of mortality showed only lower one-year survival rates in the group with sarcopenia (60%) and muscle atrophy or cachexia (53%), compared with elderly participants with a normal skeletal muscle mass (73%), (p<0.0001). There were no significant differences in 1-year mortality rates between patients with abnormal skeletal muscle mass (whether sarcopenia, cachexia or wasting).

Conclusion

About two thirds of nursing home patients show skeletal muscle mass abnormalities, most within the range of very low skeletal muscle mass rather than moderately low skeletal muscle mass, that are associated with shorter survival rates, compared with normal skeletal muscle mass patients.     

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.     

Psychosocial work conditions, perceived stress, perceived muscular tension, and neck/shoulder symptoms among medical secretaries

Purpose

Unfavorable psychosocial working conditions are hypothesized to lead to perceived stress, which, in turn, can be related to an increased risk of development of neck/shoulder symptoms through increased and sustained muscle activation. The aim of the present study was to test this hypothesized process model among medical secretaries, a female-dominated profession characterized by a high amount of visual display unit use and a high prevalence of neck/shoulder symptoms.

Methods

In this cross-sectional study, a questionnaire survey was conducted among medical secretaries (n = 200). The proposed process model was tested using a path model framework.

Results

The results indicate that high work demands were related to high perceived stress, which in turn was related to a high perceived muscle tension and neck/shoulder symptoms. Low influence at work was not related to perceived stress, but was directly related to a high perceived muscle tension.

Conclusions

In general, these cross-sectional results lend tentative support for the hypothesis that adverse psychosocial work conditions (high work demands) may contribute to the development of neck/shoulder symptoms through the mechanism of stress-induced sustained muscular activation. This process model needs to be further tested in longitudinal studies.     

Krill oil versus fish oil in modulation of inflammation and lipid metabolism in mice transgenic for TNF-α

Purpose

Biological effects of marine oils, fish oil (FO) and krill oil (KO), are mostly attributed to the high content of n-3 polyunsaturated fatty acids (n-3 PUFAs), predominantly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The study was aimed to investigate the influence of FO and KO on lipid homeostasis and inflammation in an animal model of persistent low-grade exposure to human tumor necrosis factor α (hTNF-α) and to evaluate whether these effects depend on the structural forms of EPA and DHA [triacylglycerols (TAG) vs. phospholipids].

Methods

Male C57BL/6 hTNF-α mice were fed for 6 weeks a high-fat control diet (24.50 % total fats, w/w) or high-fat diets containing either FO or KO at similar doses of n-3 PUFAs (EPA: 5.23 vs. 5.39 wt%, DHA: 2.82 vs. 2.36 wt% of total fatty acids).

Results

We found that KO, containing bioactive n-3 PUFAs in the form of phospholipids, was capable of modulating lipid metabolism by lowering plasma levels of TAG and cholesterol and stimulating the mitochondrial and peroxisomal fatty acid β-oxidation, as well as improving the overall carnitine turnover. Though the administration of FO was not as effective as KO in the lowering of plasma TAG, FO significantly improved the levels of all cholesterol classes in plasma. Except from the increase in the levels of IL-17 in FO-fed mice and a trend to decrease in MCP-1 levels in KO-fed animals, the levels of pro-inflammatory cytokines were not substantially different between treatment groups.

Conclusion

Our findings demonstrate that FO and KO are comparable dietary sources of n-3 PUFAs. However, when quantitatively similar doses of n-3 PUFAs are administered, KO seems to have a greater potential to promote lipid catabolism. The effect of dietary oils on the levels of inflammatory markers in hTNF-α transgenic mice fed a high-fat diet needs further investigations.     

Contribution of creatine to protein homeostasis in athletes after endurance and sprint running

Purpose

Few studies have focused on the metabolic changes induced by creatine supplementation. This study investigated the effects of creatine supplementation on plasma and urinary metabolite changes of athletes after endurance and sprint running.

Methods

Twelve male athletes (20.3 ± 1.4 y) performed two identical (65–70 % maximum heart rate reserved) 60 min running exercises (endurance trial) before and after creatine supplementation (12 g creatine monohydrate/day for 15 days), followed by a 5-day washout period. Subsequently, they performed two identical 100 m sprint running exercises (power trial) before and after 15 days of creatine supplementation in accordance with the supplementary protocol of the endurance trial. Body composition measurements were performed during the entire study. Plasma samples were examined for the concentrations of glucose, lactate, branched-chain amino acids (BCAAs), free-tryptophan (f-TRP), glutamine, alanine, hypoxanthine, and uric acid. Urinary samples were examined for the concentrations of hydroxyproline, 3-methylhistidine, urea nitrogen, and creatinine.

Results

Creatine supplementation significantly increased body weights of the athletes of endurance trial. Plasma lactate concentration and ratio of f-TRP/BCAAs after recovery from endurance running were significantly decreased with creatine supplementation. Plasma purine metabolites (the sum of hypoxanthine and uric acid), glutamine, urinary 3-methylhistidine, and urea nitrogen concentrations tended to decrease before running in trials with creatine supplements. After running, urinary hydroxyproline concentration significantly increased in the power trial with creatine supplements.

Conclusions

The findings suggest that creatine supplementation tended to decrease muscle glycogen and protein degradation, especially after endurance exercise. However, creatine supplementation might induce collagen proteolysis in athletes after sprint running.     

The effect of carnitine supplemented total parenteral nutrition on lipid, energy and nitrogen metabolism in severely ill patients

To analyse the effects of L-carnitine supplemented TPN on lipid, energy and nitrogen metabolism, 16 severely injured patients were studied during the first 8 days after trauma. An L-carnitine solution (3g = 18.6mmol) was added to the fat emulsion and infused over 16h in a blind randomised fashion to half of the patients. Plasma triglyceride, free fatty acid and 3-OH-butyrate concentrations increased during the fat infusion, and fell to pre-infusion concentrations within 24h. There were no differences in plasma levels before, during or after infusion between the groups. ATP and phosphocreatine in muscle tissue were not influenced by carnitine supplementation. Glycogen, however, remained unchanged in the carnitine group and fell in the non-carnitine group. A cumulative N-balance measured from day 2 to day 8 was equally negative in both groups. Plasma carnitine levels were significantly higher in the supplemented group from day 3. The mean daily urinary carnitine excretion was increased 15-fold in the supplemented group. Muscle carnitine, however, remained unchanged in both groups and did not differ between them. The present results do not demonstrate any beneficial effects of parenterally administered L-carnitine on lipid, energy or nitrogen metabolism except for maintaining normal muscle glycogen levels in critically ill patients receiving TPN during the early phase after trauma.     

High-dose thiamine supplementation improves glucose tolerance in hyperglycemic individuals: a randomized, double-blind cross-over trial

Purpose

To assess the effect of high-dose oral thiamine supplements on glucose tolerance in patients with impaired glucose metabolism.

Methods

Twelve hyperglycemic subjects (10 cases of impaired glucose tolerance and 2 new cases of type 2 diabetes) completed this randomized, double-blind trial, where all participants received both placebo and thiamine capsules (3 × 100 mg/day) for 6 weeks in a cross-over manner. The main endpoint was changes in 2-h plasma glucose. Fasting plasma glucose and insulin, 2-h plasma insulin, the hemostatic model assessment of insulin resistance (HOMA-IR), renal function measurement and thiamin status were also evaluated at the commencement and completion of each treatment period.

Results

Thiamine supplementation resulted in significant decrease in 2-h plasma glucose relative to baseline (8.78 ± 2.20 vs. 9.89 ± 2.50 mmol/l, p = 0.004), with no significant change in the placebo arm. Fasting plasma glucose and insulin, and HOMA-IR increased significantly from baseline after 6 weeks in the placebo arm (p = 0.003, p = 0.04 and p = 0.02, respectively). These variables did not change with thiamine supplementation. There were no significant changes in 2-h plasma insulin or renal function marker, within or between arms.

Conclusion/interpretation

Supplementation with high-dose thiamine may prevent deterioration in fasting glucose and insulin, and improve glucose tolerance in patients with hyperglycemia. High-dose thiamine supplementation may prevent or slow the progression of hyperglycemia toward diabetes mellitus in individuals with impaired glucose regulation.