Oral subchronic toxicity study and genetic toxicity evaluation of mitoquinone mesylate.

Mitochondrial dysfunction and excessive reactive oxygen species production contributes to the pathophysiology of aging. Coenzyme Q10 is thought to protect mitochondria from oxidative damage; thus, mitoquinone was developed as mitochondria-targeted analogue with similar antioxidant activity. Mitoquinone is the oxidized form of mitoquinol. Mitoquinone/mitoquinol mesylate has been proposed as a food ingredient. As part of the safety analysis, we performed genotoxicity assays and a 39-week toxicity study to determine overall toxicity potential. Mitoquinone mesylate showed no evidence of genotoxic potential in two in vitro assays, bacterial reverse mutation and human lymphocyte chromosome aberration, nor in the in vivo micronucleus test in rats. In the 39-week study in dogs, there were no findings observed, which were considered to represent adverse systemic toxicity; therefore, the high dose level (40 mg/kg/day) was considered the NOAEL. The principal findings in this study were fecal disturbances and vomiting. These findings were considered to be due to a local, possibly irritant effect of the test substance on the gastrointestinal tract and were not considered adverse as there were no impacts on clinical or histopathology. This highest dose exceeds the expected daily human intake more than 100-fold. Data from well-designed clinical trials actively collecting safety endpoints corroborate that 20 mg/day can be safely consumed and is not likely to result in significant gastrointestinal complaints. These results support the conclusion that the use of mitoquinone/mitoquinol mesylate as a food ingredient is safe.

Predictive capacity of COVID-19-related risk beliefs on weight management behaviors on a commercial weight loss program and speed of COVID-19 vaccination uptake: prospective cohort study.

BACKGROUND: Recent work has shown that obesity may be a risk factor for severe COVID-19. However, it is unclear to what extent individuals have heard or believe this risk factor information, and how these beliefs may predict their preventive behaviors (e.g., weight management behaviors or COVID-19 preventive behaviors). Previous work has primarily looked at overall risk likelihood perceptions (i.e., not about obesity as a risk factor) within general populations of varying weight and concentrated on COVID-19-related preventive behaviors. Therefore, this prospective cohort study explored whether beliefs about obesity as a risk factor and overall risk likelihood perceptions predicted weight management and COVID-19 preventive behaviors over the next 16 weeks in individuals with obesity or overweight. METHODS: Participants were 393 individuals in the US who joined a commercial weight management program in January, 2021. We leveraged the mobile program's automatic measurement of real-time engagement in weight management behaviors (e.g., steps taken), while surveys measured risk beliefs at baseline as well as when individuals received COVID-19 vaccination doses (asked monthly) over the next 16 weeks. Mixed effects models predicted engagement and weight loss each week for 16 weeks, while ordinal logistic regression models predicted the month that individuals got vaccinated against COVID-19. RESULTS: We found that belief in obesity as a risk factor at baseline significantly predicted greater engagement (e.g., steps taken, foods logged) in program-measured weight management behaviors over the next 16 weeks in models adjusted for baseline BMI, age, gender, and local vaccination rates (minimally adjusted) and in models additionally adjusted for demographic factors. Belief in obesity as a risk factor at baseline also significantly predicted speed of COVID-19 vaccination uptake in minimally adjusted models but not when demographic factors were taken into account. Exposure to obesity risk factor information at baseline predicted greater engagement over 16 weeks in minimally adjusted models. CONCLUSIONS: The results highlight the potential utility of effective education to increase individuals' belief in obesity risk factor information and ultimately promote engagement or faster vaccination. Future research should investigate to what extent the results generalize to other populations.

Goal language is associated with attrition and weight loss on a digital program: Observational study.

Behavioral weight loss reduces risk of weight-related health complications. Outcomes of behavioral weight loss programs include attrition and weight loss. There is reason to believe that individuals' written language on a weight management program may be associated with outcomes. Exploring associations between written language and these outcomes could potentially inform future efforts towards real-time automated identification of moments or individuals at high risk of suboptimal outcomes. Thus, in the first study of its kind, we explored whether individuals' written language in actual use of a program (i.e., outside of a controlled trial) is associated with attrition and weight loss. We examined two types of language: goal setting (i.e., language used in setting a goal at the start of the program) and goal striving (i.e., language used in conversations with a coach about the process of striving for goals) and whether they are associated with attrition and weight loss on a mobile weight management program. We used the most established automated text analysis program, Linguistic Inquiry Word Count (LIWC), to retrospectively analyze transcripts extracted from the program database. The strongest effects emerged for goal striving language. In striving for goals, psychologically distanced language was associated with more weight loss and less attrition, while psychologically immediate language was associated with less weight loss and higher attrition. Our results highlight the potential importance of distanced and immediate language in understanding outcomes like attrition and weight loss. These results, generated from real-world language, attrition, and weight loss (i.e., from individuals' natural usage of the program), have important implications for how future work can better understand outcomes, especially in real-world settings.

B vitamin polymorphisms and behavior: evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline.

The B vitamins folic acid, vitamin B12 and B6 are essential for neuronal function, and severe deficiencies have been linked to increased risk of neurodevelopmental disorders, psychiatric disease and dementia. Polymorphisms of genes involved in B vitamin absorption, metabolism and function, such as methylene tetrahydrofolate reductase (MTHFR), cystathionine ß synthase (CßS), transcobalamin 2 receptor (TCN2) and methionine synthase reductase (MTRR), have also been linked to increased incidence of psychiatric and cognitive disorders. However, the effects of these polymorphisms are often quite small and many studies failed to show any meaningful or consistent associations. This review discusses previous findings from clinical studies and highlights gaps in knowledge. Future studies assessing B vitamin-associated polymorphisms must take into account not just traditional demographics, but subjects' overall diet, relevant biomarkers of nutritional status and also analyze related genetic factors that may exacerbate behavioral effects or nutritional status.

Curcumin enhances neurogenesis and cognition in aged rats: implications for transcriptional interactions related to growth and synaptic plasticity.

BACKGROUND: Curcumin has been demonstrated to have many neuroprotective properties, including improvement of cognition in humans and neurogenesis in animals, yet the mechanism of such effects remains unclear. METHODOLOGY: We assessed behavioural performance and hippocampal cell proliferation in aged rats after 6- and 12-week curcumin-fortified diets. Curcumin enhanced non-spatial and spatial memory, as well as dentate gyrate cell proliferation as compared to control diet rats. We also investigated underlying mechanistic pathways that might link curcumin treatment to increased cognition and neurogenesis via exon array analysis of cortical and hippocampal mRNA transcription. The results revealed a transcriptional network interaction of genes involved in neurotransmission, neuronal development, signal transduction, and metabolism in response to the curcumin treatment. CONCLUSIONS: The results suggest a neurogenesis- and cognition-enhancing potential of prolonged curcumin treatment in aged rats, which may be due to its diverse effects on genes related to growth and plasticity.

Effect of hydrolysed egg protein on brain tryptophan availability.

Serotonin synthesis critically depends on plasma levels of tryptophan (TRP). Earlier studies have shown that for mood and cognitive benefits to occur, the ratio between TRP and other large neutral amino acids (LNAA) has to be increased by approximately 40 %. The present study investigated the dose-dependent effects of a TRP-rich hydrolysed protein (egg-protein hydrolysate, EPH) on the plasma TRP:LNAA. Moreover, it was investigated whether EPH could increase TRP:LNAA in the presence of 2 g of milk protein (MP). In a randomised double-blind crossover design, plasma amino acids were measured every 30 min for 3·5 h after ingestion of a drink containing either three different doses of 4, 8 and 12 g EPH containing 270, 560 or 800 mg of TRP, respectively, the combination of 4 g EPH and 2 g MP (74 mg TRP), or 4 g MP (148 mg TRP) in twenty healthy subjects with a mean age of 52 years. All three EPH doses caused significant increases of TRP:LNAA above 40 % at 30, 60 and 90 min after consumption in a dose-dependent manner. Compared with the 4 g EPH, the increase in TRP:LNAA in the 4 g EPH with 2 g MP condition was significantly lower at 60 min (63 v. 44 %, P < 0·001) and did not differ significantly at 90 min (58 v. 53 %, P>0·05). The present study showed that a low dose of 4 g EPH with even the addition of 2 g MP was sufficient to increase the ratio of TRP:LNAA above 40 %. Thus, EPH offers a viable ingredient to increase TRP availability.