The concept of "metabolic jet lag" in the pathophysiology of bipolar disorder: implications for research and clinical care.

Bipolar disorder (BD) is a potentially chronic mental disorder marked by recurrent depressive and manic episodes, circadian rhythm disruption, and changes in energetic metabolism. "Metabolic jet lag" refers to a state of shift in circadian patterns of energy homeostasis, affecting neuroendocrine, immune, and adipose tissue function, expressed through behavioral changes such as irregularities in sleep and appetite. Risk factors include genetic variation, mitochondrial dysfunction, lifestyle factors, poor gut microbiome health and abnormalities in hunger, satiety, and hedonistic function. Evidence suggests metabolic jet lag is a core component of BD pathophysiology, as individuals with BD frequently exhibit irregular eating rhythms and circadian desynchronization of their energetic metabolism, which is associated with unfavorable clinical outcomes. Although current diagnostic criteria lack any assessment of eating rhythms, technological advancements including mobile phone applications and ecological momentary assessment allow for the reliable tracking of biological rhythms. Overall, methodological refinement of metabolic jet lag assessment will increase knowledge in this field and stimulate the development of interventions targeting metabolic rhythms, such as time-restricted eating.

Effects of the ketogenic diet on cognition: a systematic review.

INTRODUCTION: Ketogenic diet (KD) therapy has been used as a dietary intervention in drug-resistant epilepsy for several years. Research currently suggests that KD therapy may carry neuroprotective and cognition enhancing effects for individuals with non-epileptic conditions as well as for healthy individuals. Therefore, KD may have potential as a non-invasive, nutritional treatment approach for difficult to manage conditions such as neurodegenerative illnesses or mood disorders. The aim of this review is to summarize the available evidence on ketogenic interventions and the resulting cognitive outcomes. MATERIALS AND METHODS: The paper was based on PRISMA 2020 guidelines. The search was conducted in June 2021 on the following databases: CENTRAL, PubMed, EMBASE, PsycInfo, Web of Science. The search yielded 2014 studies, of which 49 were included. RESULTS: There were 22 animal studies assessing murine models and 27 studies on humans. The primary indications in these studies were epileptic conditions, neurodegenerative disorders, cognitive impairment, and healthy populations. DISCUSSION: Administration of KD seems to confer cognitive-enhancing effects in areas such as working memory, reference memory and attention. Studies found that KD treatment in animals has the potential to alleviate age-related cognitive decline. Over 80% of the 27 human studies reported a favourable effect of intervention, and none reported a detrimental effect of KD. While these findings suggest that KD may improve the functioning of certain cognitive domains, definitive conclusions were limited by studies with small sample sizes, the absence of controls and randomization, and the lack of objective measures of cognition.

Maintenance of response to ketogenic diet therapy for drug-resistant epilepsy post diet discontinuation: A multi-centre case note review.

PURPOSE: There is limited research on the proportion of individuals with epilepsy who maintain response to ketogenic diet therapy (KDT) after discontinuing treatment. We aimed to determine the proportion of individuals who did / did not maintain response post KDT and explore factors that may influence the likelihood of maintaining response. METHODS: Retrospective data were collected from 97 individuals from 9 KDT centres. Individuals had achieved ≥50 % seizure reduction on KDT for at least 12 months, with seizure frequency data available at 3 months+ post diet. Outcome 1 was: recurrence of seizures or increase in seizure frequency post diet; outcome 2: recurrence of seizures, increase in seizure frequency or an additional anti-seizure treatment started post diet. RESULTS: 61/97 (62.9 %) individuals maintained response at latest follow-up (mean 2.5[2.0] years since stopping KDT). Approximately one third maintained response without further anti-seizure treatments. One quarter of individuals had an increase in frequency or recurrence of seizures within 6 months (95 %CI 4, 12) for outcome 1 and within 3 months (3, 6) for outcome 2. Individuals who did not achieve seizure freedom on diet were significantly more likely to have an increase in seizures or to require additional anti-seizure treatments post diet compared to those who were seizure-free on diet (hazard ratio 4.02, 95 %CI (1.46, 11.16) p < 0.01). CONCLUSION: Our findings should help guide clinical teams with the information they provide patients and their families regarding likelihood of long-term seizure response to KDT. Realistic costings for KDT services may need to be considered.

Effects of nutritional interventions on the severity of depressive and anxiety symptoms of women in the menopausal transition and menopause: a systematic review, meta-analysis, and meta-regression.

IMPORTANCE: Depression and anxiety may significantly affect women during the menopausal transition. In addition to traditional treatment strategies such as hormone therapy, antidepressants, and psychotherapy, nutritional interventions have been increasingly studied, but there is no consensus about their role in this patient population. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the effect of nutritional interventions on the severity of depressive (DS) and anxiety (AS) symptoms in women during the menopausal transition or menopausal years. EVIDENCE REVIEW: Electronic search using databases PubMed, Cochrane, and Embase to identify articles indexed until January 31, 2021, focusing on randomized placebo-controlled trials documenting the effect of diet, food supplements, and nutraceuticals on DS and AS. FINDINGS: Thirty-two studies were included (DS, n = 15; AS, n = 1; DS and AS combined, n = 16). We found two studies that demonstrated data combined with other interventions: one with lifestyle interventions (vitamin D plus lifestyle-based weight-loss program) and another with exercise (omega 3 plus exercise). The pooled effect size favored the intervention group over placebo for both DS and AS (DS: standardized mean difference, -0.35 [95% confidence interval, -0.68 to -0.03; P = 0.0351]; AS: standardized mean difference, -0.74 [95% CI, -1.37 to -0.11; P = 0.0229]). There was significant heterogeneity in the pooled results, which can be attributed to differences in assessment tools for depression and anxiety as well as the variety of nutritional interventions studied. The subgroup analysis showed a statistically significant effect of menopausal status (perimenopausal or menopausal) but not the type or duration of nutritional intervention. Older age was the only significant predictor of the effect size of nutritional interventions in the meta-regression. CONCLUSIONS AND RELEVANCE: Nutritional interventions are promising tools for the management of mood/anxiety symptoms in women during the menopausal transition and in postmenopausal years. Because of significant heterogeneity and risk of bias among studies, the actual effect of different approaches is still unclear.

Increase of Human Milk Fat Inducing Nutritional Ketosis in Exclusively Breastfed Infant, Brought About by Treating the Mother With Ketogenic Dietary Therapy.

INTRODUCTION: Medicalized Ketogenic Therapy is commonly used to treat refractory epilepsy. Patients have varying degrees of seizure or symptom relief, responding at individual levels of ketone production. Typically, initiating the therapy necessitates the discontinuation of breastfeeding. Our case study mother was keen to continue breastfeeding if possible. We were able to achieve this by placing the healthy mother on a ketogenic diet and altering the composition of the mother's own milk. MAIN LACTATION ISSUE: Pediatric Medicalized Ketogenic Therapy is delivered through a ketogenic diet consisting of up to 90% fat, measuring of ingredients to 0.1 g matching a food prescription of fat, protein, and carbohydrate. We placed the mother on a less stringent ketogenic diet achieving 61% fat and measured both infant and mother's blood sugar levels and ketones. The hypothesis was that changes would occur in the mother's own milk fat content, and/or ketones would be passed directly to the infant. If therapeutic levels of ketones were reached in the infant and a reduction in seizures observed, breastfeeding could continue. MANAGEMENT OVERVIEW: Over 3 months we achieved a calorific increase of the mother's mature milk by an additional 134%. The infant was successfully put into nutritional ketosis and visible seizures eliminated. CONCLUSION: Medicalized Ketogenic Therapy can be safely used to treat seizures of breastfeeding infants diagnosed with epilepsy, through management of the mother on a ketogenic diet. Significantly increasing the mature mothers own milk fat component could have implications for other areas, including faltering growth.

Is there a place for dietetic interventions in adult ADHD?

Current treatments for Attention-Deficit/Hyperactivity Disorder (ADHD) in adults are limited by lack of response and side effects in about one third of the individuals. Changes towards a healthier lifestyle could have a positive impact beyond the relief of specific symptoms. However, it is not clear if nutritional interventions influence mental health and cognition. The objective of this study was to summarize the available literature addressing the impact of different diets in ADHD. The most promising dietetic approaches in ADHD are diets considered to be healthy (Mediterranean-type; DASH) and the Few-Foods Diet for children. Studies should take into account the presence of multiple confounders, biases associated with difficulties in blinding participants and researchers, and search for possible mechanisms of action, so we can have better evidence to guide clinical mental care of adults with ADHD.