Effects of Low Doses of L-Carnitine Tartrate and Lipid Multi-Particulate Formulated Creatine Monohydrate on Muscle Protein Synthesis in Myoblasts and Bioavailability in Humans and Rodents.

The primary objective of this study was to investigate the potential synergy between low doses of L-carnitine tartrate and creatine monohydrate to induce muscle protein synthesis and anabolic pathway activation in primary human myoblasts. In addition, the effects of Lipid multi-particulates (LMP) formulation on creatine stability and bioavailability were assessed in rodents and healthy human subjects. When used individually, L-carnitine tartrate at 50 µM and creatine monohydrate at 0.5 µM did not affect myoblast protein synthesis and signaling. However, when combined, they led to a significant increase in protein synthesis. Increased AKT and RPS6 phosphorylation were observed with 50 µM L-carnitine tartrate 5 µM creatine in combination in primary human myoblasts. When Wistar rats were administered creatine with LMP formulation at either 21 or 51 mg/kg, bioavailability was increased by 27% based on the increase in the area under the curve (AUC) at a 51 mg/kg dose compared to without LMP formulation. Tmax and Cmax were unchanged. Finally, in human subjects, a combination of LMP formulated L-carnitine at 500 mg (from L-carnitine tartrate) with LMP formulated creatine at 100, 200, or 500 mg revealed a significant and dose-dependent increase in plasma creatine concentrations. Serum total L-carnitine levels rose in a similar manner in the three combinations. These results suggest that a combination of low doses of L-carnitine tartrate and creatine monohydrate may lead to a significant and synergistic enhancement of muscle protein synthesis and activation of anabolic signaling. In addition, the LMP formulation of creatine improved its bioavailability. L-carnitine at 500 mg and LMP-formulated creatine at 200 or 500 mg may be useful for future clinical trials to evaluate the effects on muscle protein synthesis.

Comparison of protection and release behavior of different capsule polymer combinations based on L. acidophilus survivability and function and caffeine release.

Oral administration of active pharmaceutical ingredients, nutraceuticals, enzymes or probiotics requires an appropriate delivery system for optimal bioactivity and absorption. The harsh conditions during the gastrointestinal transit can degrade the administered products, hampering their efficacy. Enteric or delayed-release pharmaceutical formulations may help overcome these issues. In a Simulator of Human Intestinal Microbial Ecosystem model (SHIME) and using caffeine as a marker for release kinetics and L. acidophilus survivability as an indicator for protection, we compared the performance of ten capsule configurations, single or DUOCAP® combinations. The function of L. acidophilus and its impact on the gut microbiota was further tested in three selected capsule types, combinations of DRcaps® capsule in DRcaps® capsule (DR-in-DR) and DRcaps® capsule in Vcaps® capsule (DR-in-VC) and single Vcaps® Plus capsule under colonic conditions. We found that under stomach and small intestine conditions, DR-in-DR and DR-in-VC led to the best performance both under fed and fasted conditions based on the slow caffeine release and the highest L. acidophilus survivability. The Vcaps® Plus capsule however, led to the quickest caffeine and probiotic release. When DR-in-DR, DR-in-VC and single Vcaps® Plus capsules were tested through the whole gastrointestinal tract, including under colonic conditions, caffeine release was found to be slower in capsules containing DRcaps® capsules compared to the single Vcaps® capsules. In addition, colonic survival of L. acidophilus was significantly increased under fasted conditions in DR-in-DR or DR-in-VC formulation compared to Vcaps® Plus capsule. To assess the impact of these formulations on the microbial function, acetate, butyrate and propionate as well as ammonia were measured. L. acidophilus released from DR-in-DR or DR-in-VC induced a significant increase in butyrate and a decrease in ammonia, suggesting a proliferation of butyrate-producing bacteria and reduction in ammonia-producing bacteria. These data suggest that L. acidophilus included in DR-in-DR or DR-in-VC reaching the colon is viable and functional, potentially contributing to changes in colonic microbiota composition and diversity.

Bioavailability of a Capsaicin Lipid Multi-particulate Formulation in Rats.

BACKGROUND AND OBJECTIVE: Because of the stomach-burning sensation it induces, capsaicin has been used at relatively low doses as a nutritional supplement, which has limited its bioavailability. The objective of this study was to investigate the serum bioavailability of capsaicin supplementation with or without a lipid multi-particulate (LMP) formulation. METHODS: Thirty-five rats were divided into five groups and administered capsaicin at either 0.2 or 1 mg/kg with or without the LMP formulation. Capsaicin bioavailability was assessed based on the area under the concentation-time curve (AUC), the time to peak concentration (Tmax), and the peak serum concentration (Cmax). RESULTS: For each formulation, the capsaicin Cmax was reached at 90 min and decreased thereafter. Serum capsaicin concentrations were greater in rats administered the higher dose of capsaicin (1 mg/kg) in the LMP formulation at all measurement times (P  ≤ 0.05). The AUC showed a significant increase, about 20%, when capsaicin was administered in the LMP formulation at the high dose (P = 0.002). The Tmax for oral capsaicin was similar whether or not administration was via the LMP formulation (P = 0.163). However, the Cmax of capsaicin increased in a dose-dependent manner (P < 0.05). Although the LMP formulation of the high dose of capsaicin resulted in a numerically higher Cmax, it was not statistically significantly higher (P = 0.068). CONCLUSIONS: The present work demonstrated that administration of capsaicin via the LMP formulation significantly impacted the pharmacokinetic parameters and the serum bioavailability of orally administered 1 mg/kg capsaicin in rats. The bioavailability of capsaicin in humans may also be increased by using the LMP formulation.