Vitamin D supplementation and its influence on muscle strength and mobility in community-dwelling older persons: a systematic review and meta-analysis.

BACKGROUND: It has been suggested that vitamin D status or supplementation is important for maintaining or improving muscle strength and mobility in older adults. The study results, however, do not provide consistent results. We therefore aimed to summarise the available evidence systematically, including only studies conducted in community-dwelling older persons. METHODS: A systematic search of the literature was performed in April of 2016. The systematic review includes studies that used vitamin D with or without calcium supplementation as the exposure variable and various measurements of muscle strength and mobility. The meta-analysis was limited to studies using hand grip strength (HGS) and timed-up-and-go test as the outcome variables. RESULTS: A total of 15 studies out of 2408 articles from the literature search were included in the systematic review, providing 2866 participants above the age of 65 years. In the majority of studies, no improvement in muscle strength and mobility was observed after administration of vitamin D with or without calcium supplements. In the meta-analysis, we observed a nonsignificant change in HGS [+0.2 kg (95% confidence interval = -0.25 to 0.7 kg; seven studies)] and a small, significant increase in the timed-up-and-go test [0.3 s (95% confidence interval = 0.1 to 0.5 s; five studies)] after vitamin D supplementation. The meta-analyses showed a high degree of heterogeneity between the studies. CONCLUSIONS: In conclusion, we observed no improvement in muscle strength after the administration of vitamin D with or without calcium supplements. We did find a small but significant deterioration of mobility. However, this is based on a limited number of studies and participants.

Effects of duodenal switch alone or in combination with sleeve gastrectomy on body weight and lipid metabolism in rats.

BACKGROUND: A combined procedure of sleeve gastrectomy and duodenal switch (SG+DS) has been applied to the treatment of super obesity. The aim of the present study was to test whether duodenal switch alone (DS) leads to similar weight loss and changes in lipid metabolism as SG+DS. METHODS: Male Sprague-Dawley rats underwent sham surgery (Sham, N=7), duodenal switch alone (DS, N=5) or sleeve gastrectomy followed by duodenal switch (SG+DS, N=5). Body weight, feed and water intakes, and ambulatory activity were recorded 2 months post surgery. Tissue and faecal lipids, faecal bile acids, plasma cytokines and lipid metabolism-related gene expression in adipose tissue and liver were analysed. RESULTS: Daily energy intake, relative feed uptake, ambulatory activity and body weight reduction were similar between DS and SG+DS rats. The hepatic triacylglycerol content was higher and faecal secretion of triacylglycerol was lower after SG+DS compared to DS (P<0.05). Faecal bile acid secretion was higher in SG+DS than in DS rats (P<0.05) despite similar hepatic CYP7A1mRNA level. Plasma levels of proinflammatory cytokines interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-12, granulocyte-macrophage colony stimulating factor and tumour necrosis factor alpha were higher in SG+DS than in DS rats (P<0.05). CONCLUSIONS: Although DS and SG+DS had similar efficacy in terms of body weight loss, SG+DS resulted in a poorer regulation of lipid metabolism than DS.

Dietary supplementation of tetradecylthioacetic acid increases feed intake but reduces body weight gain and adipose depot sizes in rats fed on high-fat diets.

AIM: The pan-peroxisome proliferator-activated receptor (PPAR) ligand and fatty acid analogue tetradecylthioacetic acid (TTA) may reduce plasma lipids and enhance hepatic lipid metabolism, as well as reduce adipose tissue sizes in rats fed on high-fat diets. This study further explores the effects of TTA on weight gain, feed intake and adipose tissue functions in rats that are fed a high-fat diet for 7 weeks. METHODS: The effects on feed intake and body weight during 7 weeks' dietary supplement with TTA ( approximately 200 mg/kg bw) were studied in male Wistar rats fed on a lard-based diet containing approximately 40% energy from fat. Adipose tissue mass, body composition and expression of relevant genes in fat depots and liver were measured at the end of the feeding. RESULTS: Despite higher feed intake during the final 2 weeks of the study, rats fed on TTA gained less body weight than lard-fed rats and had markedly decreased subcutaneous, epididymal, perirenal and mesenteric adipose depots. The effects of TTA feeding with reduced body weight gain and energy efficiency (weight gain/feed intake) started between day 10 and 13. Body contents of fat, protein and water were reduced after feeding lard plus TTA, with a stronger decrease in fat relative to protein. Plasma lipids, including Non-Esterified Fatty Acids (NEFA), were significantly reduced, whereas fatty acid beta-oxidation in liver and heart was enhanced in lard plus TTA-fed rats. Hepatic UCP3 was expressed ectopically both at protein and mRNA level (>1900-fold), whereas Ucp1 mRNA was increased approximately 30-fold in epididymal and approximately 90-fold in mesenteric fat after lard plus TTA feeding. CONCLUSION: Our data support the hypothesis that TTA feeding may increase hepatic fatty acid beta-oxidation, and thereby reduce the size of adipose tissues. The functional importance of ectopic hepatic UCP3 is unknown, but might be associated with enhanced energy expenditure and thus the reduced feed efficiency.

Tetradecylthioacetic acid attenuates dyslipidaemia in male patients with type 2 diabetes mellitus, possibly by dual PPAR-alpha/delta activation and increased mitochondrial fatty acid oxidation.

AIM: We previously demonstrated that a modified fatty acid, tetradecylthioacetic acid (TTA), improves transport and utilization of lipids and increases mitochondrial fatty acid oxidation in animal and cell studies. We conducted an exploratory study of safety and effects of this novel drug in patients with type 2 diabetes mellitus and investigated the mechanism of action in human cell lines. METHODS: Sixteen male patients with type 2 diabetes mellitus received 1 g TTA daily for 28 days in an open-labelled study, with measurement of parameters of lipid metabolism, glucose metabolism and safety (ClinicalTrials.gov NCT00605787). The mechanism of action was further investigated in a human liver cell line (HepG2) and in cultured human skeletal muscle cells (myotubes). RESULTS: Mean LDL cholesterol level declined from 4.2 to 3.7 mmol/l (p < 0.001), accompanied by increased levels of the HDL apolipoproteins A1 and A2, and a decline in LDL/HDL ratio from 4.00 to 3.66 (p = 0.008). Total fatty acid levels declined, especially the fraction of the polyunsaturated n-3 fatty acids docosahexaenoic acid (-13%, p = 0.002) and eicosapentaenoic acid (-10%, p = 0.07). Glucose metabolism was not altered and the drug was well tolerated. In cultured liver cells, TTA acted as a pan-PPAR agonist with predominant PPAR-alpha and PPAR-delta activation at low TTA concentrations. In myotubes, TTA and a PPAR-delta agonist, but not the PPAR-alpha or PPAR-gamma agonists, increased the fatty acid oxidation. CONCLUSIONS: We demonstrate for the first time that TTA attenuates dyslipidaemia in patients with type 2 diabetes mellitus. These effects may occur through mechanisms involving PPAR-alpha and PPAR-delta activation, resulting in increased mitochondrial fatty acid oxidation.

The metabolic syndrome and the hepatic fatty acid drainage hypothesis.

Much data indicates that lowering of plasma triglyceride levels by hypolipidemic agents is caused by a shift in the liver metabolism towards activation of peroxisome proliferator activated receptor (PPAR)alpha-regulated fatty acid catabolism in mitochondria. Feeding rats with lipid lowering agents leads to hypolipidemia, possibly by increased channeling of fatty acids to mitochondrial fatty acid oxidation at the expense of triglyceride synthesis. Our hypothesis is that increased hepatic fatty acid oxidation and ketogenesis drain fatty acids from blood and extrahepatic tissues and that this contributes significantly to the beneficial effects on fat mass accumulation and improved peripheral insulin sensitivity. To investigate this theory we employ modified fatty acids that change the plasma profile from atherogenic to cardioprotective. One of these novel agents, tetradecylthioacetic acid (TTA), is of particular interest due to its beneficial effects on lipid transport and utilization. These hypolipidemic effects are associated with increased fatty acid oxidation and altered energy state parameters of the liver. Experiments in PPAR alpha-null mice have demonstrated that the effects hypolipidemic of TTA cannot be explained by altered PPAR alpha regulation alone. TTA also activates the other PPARs (e.g., PPAR delta) and this might compensate for deficiency of PPAR alpha. Altogether, TTA-mediated clearance of blood triglycerides may result from a lowered level of apo C-III, with a subsequently induction of hepatic lipoprotein lipase activity and (re)uptake of fatty acids from very low density lipoprotein (VLDL). This is associated with an increased hepatic capacity for fatty acid oxidation, causing drainage of fatty acids from the blood stream. This can ultimately be linked to hypolipidemia, anti-adiposity, and improved insulin sensitivity.