Use of ketogenic diets in the treatment of central nervous system diseases: a systematic review.

BACKGROUND: Studies have consistently shown that patients with epilepsy could benefit from ketogenic diets (KDs). Recent evidence suggests that KD could be used in the treatment of central nervous system (CNS) diseases. The aim of this systematic review was to investigate the use and efficacy of KD, modified Atkins diet (MAD) and medium-chain triglyceride (MCT) diet in infants, children, adolescents, and adults with CNS diseases. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Main databases, i.e. EMBASE, PubMed and PsycINFO, were searched on 4 December 2019. Only randomized clinical trials (RCTs) were included and only if they reported KD, MCT or MAD interventions on patients with CNS diseases. RESULTS: Twenty-four publications were eligible for inclusion (n = 1221). Twenty-one publications concerned epilepsy, two concerned Alzheimer's disease (AD), and one concerned Parkinson's disease (PD). All studies regarding epilepsy reported of seizure reduction compared to baseline. MCT did not significantly change regional cerebral blood flow (rCBF) in patients with AD, but MAD significantly improved memory at 6 weeks (p = .03). KD significantly improved motor and nonmotor functions in patients with PD at 8 weeks (p < .001). There was a trend towards fewer adverse effects in MAD compared to KD. CONCLUSION: In conclusion, various forms of KDs seem tolerable and effective as part of the treatment for epilepsy, AD and PD, although more investigation concerning the mechanism, efficacy and adverse events is necessary.

Effects of ketogenic diet and ketone monoester supplement on acute alcohol withdrawal symptoms in male mice.

RATIONALE: After alcohol ingestion, the brain partly switches from consumption of glucose to consumption of the alcohol metabolite acetate. In heavy drinkers, the switch persists after abrupt abstinence, leading to the hypothesis that the resting brain may be "starved" when acetate levels suddenly drop during abstinence, despite normal blood glucose, contributing to withdrawal symptoms. We hypothesized that ketone bodies, like acetate, could act as alternative fuels in the brain and alleviate withdrawal symptoms. OBJECTIVES: We previously reported that a ketogenic diet during alcohol exposure reduced acute withdrawal symptoms in rats. Here, our goals were to test whether (1) we could reproduce our findings, in mice and with longer alcohol exposure; (2) ketone bodies alone are sufficient to reduce withdrawal symptoms (clarifying mechanism); (3) introduction of ketogenic diets at abstinence (a clinically more practical implementation) would also be effective. METHODS: Male C57BL/6NTac mice had intermittent alcohol exposure for 3 weeks using liquid diet. Somatic alcohol withdrawal symptoms were measured as handling-induced convulsions; anxiety-like behavior was measured using the light-dark transition test. We tested a ketogenic diet, and a ketone monoester supplement with a regular carbohydrate-containing diet. RESULTS: The regular diet with ketone monoester was sufficient to reduce handling-induced convulsions and anxiety-like behaviors in early withdrawal. Only the ketone monoester reduced handling-induced convulsions when given during abstinence, consistent with faster elevation of blood ketones, relative to ketogenic diet. CONCLUSIONS: These findings support the potential utility of therapeutic ketosis as an adjunctive treatment in early detoxification in alcohol-dependent patients seeking to become abstinent. TRIAL REGISTRATION: clinicaltrials.gov NCT03878225, NCT03255031.

Varicocele Is Associated with Impaired Semen Quality and Reproductive Hormone Levels: A Study of 7035 Healthy Young Men from Six European Countries.

BACKGROUND: Present knowledge on the impact of varicoceles on testicular function is largely based on studies of subfertile and infertile men, making it difficult to extrapolate the impact of varicocele on the general population. OBJECTIVE: To describe associations between varicocele and testicular function assessed by semen analysis and reproductive hormones in men from the general population. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional multicentre study of 7035 young men, median age 19 yr, from the general population in six European countries (Denmark, Finland, Germany, Estonia, Latvia, and Lithuania) were investigated from 1996 to 2010. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We analysed results from physical examination, conventional semen variables, and serum reproductive hormones using multivariable regression analyses. RESULTS AND LIMITATIONS: A total of 1102 (15.7%) had grade 1-3 varicocele. Increasing varicocele grade was associated with poorer semen quality, even in grade 1 varicocele. In grade 3 varicocele, sperm concentration was less than half of that in men with no varicocele. Presence of varicocele was also associated with higher serum levels of follicle-stimulating hormone, lower inhibin B, and higher levels of luteinising hormone; testosterone and free testosterone were not significantly different between men with and without varicocele. This study cannot draw a conclusion on the progressiveness of varicocele or the effect of treatment. CONCLUSIONS: We demonstrated an adverse effect of increasing grade of varicocele on testicular function in men not selected due to fertility status. PATIENT SUMMARY: The presence and increasing grade of varicocele is adversely associated with semen quality and reproductive hormone levels in young men from the general population.