Chronic Creatine Supplementation Alters Depression-like Behavior in Rodents in a Sex-Dependent Manner

Impairments in bioenergetic function, cellular resiliency, and structural plasticity are associated with the pathogenesis of mood disorders. Preliminary evidence suggests that creatine, an ergogenic compound known to promote cell survival and influence the production and usage of energy in the brain, can improve mood in treatment-resistant patients. This study examined the effects of chronic creatine supplementation using the forced swim test (FST), an animal model selectively sensitive to antidepressants with clinical efficacy in human beings. Thirty male (experiment 1) and 36 female (experiment 2) Sprague–Dawley rats were maintained on either chow alone or chow blended with either 2% w/w creatine monohydrate or 4% w/w creatine monohydrate for 5 weeks before the FST. Open field exploration and wire suspension tests were used to rule out general psychostimulant effects. Male rats maintained on 4% creatine displayed increased immobility in the FST as compared with controls with no differences by diet in the open field test, whereas female rats maintained on 4% creatine displayed decreased immobility in the FST and less anxiety in the open field test compared with controls. Open field and wire suspension tests confirmed that creatine supplementation did not produce differences in physical ability or motor function. The present findings suggest that creatine supplementation alters depression-like behavior in the FST in a sex-dependent manner in rodents, with female rats displaying an antidepressant-like response. Although the mechanisms of action are unclear, sex differences in creatine metabolism and the hormonal milieu are likely involved

The Role of Alliums and Their Sulfur and Selenium Constituents in Cancer Prevention

Garlic and its sulfur and selenium-containing components are widely known for their cancer preventive activities primarily in preclinical in vitro and in vivo model systems. Most of our common foods including garlic contain very low levels of selenium compounds relative to those of sulfur. Humans consume a substantial portion of their dietary sulfur and selenium in organic forms. Selenium-enriched foods such as garlic, broccoli and wheat are more effective chemopreventive agents than the corresponding regular dietary items. Naturally occurring and synthetic organoselenium compounds are superior cancer chemopreventive agents compared to their corresponding sulfur analogs. Mechanistic studies demonstrate that sulfur and selenium compounds are capable of cell growth inhibition, cell cycle arrest, induction of apoptosis, alterations of phase I and phase II enzyme activities, and histone deacetylase (HDAC) inhibition. The fact that organosulfur and organoselenium compounds can target multiple pathways suggests that these agents can be used directly as chemopreventive and/or therapeutic agents or in combination with other medicinal compounds. The effect of these agents on the aforementioned parameters varies depending on the dose and form (structure) and whether cells are normal or transformed. Whether the protective effects observed in animals and in cell cultures can be applicable to humans remain to be determined. Thus, studies using genomic, proteomic, and metabolomic techniques in well designed small-scale clinical trials are needed to unequivocally evaluate the potential of allium vegetable constituents on biomarkers of risk for specific cancers prior to entering into long-term expensive phase III clinical chemoprevention trials