Intermittent calorie restriction alters T cell subsets and metabolic markers in people with multiple sclerosis

Background: Intermittent fasting or calorie restriction (CR) diets provide anti-inflammatory and neuroprotective advantages in models of multiple sclerosis (MS); data in humans are sparse. Methods: We conducted a randomized-controlled feeding study of different CR diets in 36 people with MS over 8 weeks. Patients were randomized to receive either: a daily CR diet (22% reduction in calories, 7 days/week), an intermittent CR diet (75% reduction, 2 days/week; 100%, 5 days/week), or a weight-stable diet (100%, 7 days/week). Untargeted metabolomics was performed on plasma samples at weeks 0, 4 and 8 at Metabolon Inc (Durham, NC). Flow cytometry of cryopreserved peripheral blood mononuclear cells at weeks 0 and 8 were used to identify CD4+ and CD8+ T cell subsets including effector memory, central memory, and naïve cells. Results: 31 (86%) completed the trial. Over time, individuals randomized to intermittent CR had significant reductions in CD4+CM -4.87%; 95%CI: -8.59%, -1.15%; p=0.01), CD4+EM (-3.82%; 95%CI: -7.44, -0.21; p=0.04), and CD8+EM (-6.96%; 95%CI: -11.96, -1.97; p=0.006) with proportional increases in naïve subsets (CD4+Naïve: 5.81%; 95%CI: -0.01, 11.63%; p=0.05; CD8+Naïve: 10.11%; 95%CI: 3.30, 16.92%; p=0.006). No changes were observed for daily CR or weight-stable diets. Larger within-person changes in lysophospholipid and lysoplasmalogen metabolites in intermittent CR were associated with larger reductions in memory T cell subsets and larger increases in naïve T cell subsets. Conclusions: In people with MS, an intermittent CR diet was associated with reduction in memory T cell subsets. The observed changes may be mediated by changes in specific classes of lipid metabolites. Trial Registration: This study is registered on Clinicaltrials.gov with identifier NCT02647502. Funding: National MS Society, NIH, Johns Hopkins Catalyst Award

Glucose Limitation Sensitizes Cancer Cells to Selenite-Induced Cytotoxicity via SLC7A11-Mediated Redox Collapse

Combination of intermittent fasting and chemotherapy has been drawn an increasing attention because of the encouraging efficacy. In this study, we evaluated the anti-cancer effect of combination of glucose limitation and selenite (Se), a representative inorganic form of selenium, that is preferentially accumulated in tumors. Results showed that cytotoxic effect of selenite on cancer cells, but not on normal cells, was significantly enhanced in response to the combination of selenite and glucose limitation. Furthermore, in vivo therapeutic efficacy of combining selenite with fasting was dramatically improved in xenograft models of lung and colon cancer. Mechanistically, we found that SLC7A11 expression in cancer cells was up-regulated by selenite both in vitro and in vivo. The elevated SLC7A11 led to cystine accumulation, NADPH depletion and the conversion of cystine to cysteine inhibition, which in turn boosted selenite-mediated reactive oxygen species (ROS), followed by enhancement of selenite-mediated cytotoxic effect. The findings of the present study provide an effective and practical approach for increasing the therapeutic window of selenite and imply that combination of selenite and fasting holds promising potential to be developed a clinically useful regimen for treating certain types of cancer.

Walking Football During Ramadan Fasting for Cardiometabolic and Psychological Health Benefits to the Physically Challenged and Aged Populations

Concurrent exercise and intermittent fasting regimens for long periods have been shown to enhance cardiometabolic health in healthy individuals. As exercise and fasting confer health benefits independently, we propose that Muslims who are fasting, especially those experiencing health and clinical challenges, continually engage in physical activity during the Ramadan month. In this opinion piece, we recommend walking football (WF) as the exercise of choice among Muslims who are fasting. WF can be played by any individual regardless of the level of fitness, skills, and age. WF has been shown to elicit cardiovascular and metabolic stress responses, which are suitable for populations with low fitness levels. Most importantly, WF has the inherent characteristics of being a fun team activity requiring social interactions among participants and, hence, likely to encourage long-term consistent and sustainable participation.

Sex-specific regulation of metabolic health and vertebrate lifespan by AMP biosynthesis

The loss of energy homeostasis seen during aging, is causally linked to multiple age-related pathologies. The AMP-activated protein kinase (AMPK) directly senses cellular energy levels, which are reflected in the ratio between AMP:ATP. However, the genetic regulation of vertebrate aging by the AMPK pathway remains poorly understood. Here, we manipulate ATP production by mutating APRT, a key enzyme in AMP biosynthesis, and extend vertebrate lifespan in a male-specific manner. Using a multi-omics approach, we demonstrate that the APRT mutation restores metabolic plasticity, and identify a distinct transcriptional signature linking mitochondria with the sex-related differences in longevity. Accordingly, APRT mutant cells display a reduction in mitochondrial functions and ATP levels, and an increase in AMPK activity, resembling a persistent state of energy starvation. In-vivo, a fasting-like response was observed exclusively in male mutants, including resistance to a high-fat diet. Finally, intermittent fasting eliminated the longevity benefits mediated by the APRT mutation in males. Together, these data identify AMP biosynthesis as a sex-specific mediator of vertebrate longevity and metabolic health.

Intermittent Fasting and Fat Mass: What Is the Clinical Magnitude?

Clinical studies addressing the benefits of intermittent fasting (IF) diets have evoked interest in the treatment of obesity. Herein, the overall effects of IF regimens on fat-mass loss are explained in a brief review through a recent literature update. To date, human studies show a reduction in fat mass from 0.7 to 11.3 kg after IF regimens, in which the duration of interventions ranges from two weeks to one year. In light of this, IF regimens can be considered a reasonable approach to weight (fat mass) loss. However, the benefits of IF regimens occur thanks to energy restriction and cannot hence be considered the best dietary protocol compared to conventional diets.

Intermittent Fasting Improves High-Fat Diet-Induced Obesity Cardiomyopathy via Alleviating Lipid Deposition and Apoptosis and Decreasing m6A Methylation in the Heart

Intermittent fasting (IF) plays an essential role in improving lipid metabolism disorders caused by metabolic cardiomyopathy. Growing evidence revealed that N6-methyladenosine (m6A) RNA methylation is related to obesity and lipid metabolic. Our study aimed to assess the beneficial effects of IF on lipid deposition, apoptosis, and m6A methylation in high-fat diet (HFD)-induced obesity cardiomyopathy. Male C57BL/6J mice were fed a normal diet (ND) or HFD ad libitum for 13 weeks, after which time a subgroup of HFD mice were subjected to IF for 24 h and fed HFD in the other day for 8 weeks. We found that IF intervention significantly improved cardiac functional and structural impairment and serum lipid metabolic disorder induced by HFD. Furthermore, IF intervention decreased the mRNA levels of the fatty acid uptake genes of FABP1, FATP1, and CD36 and the fatty acid synthesis genes of SREBF1, FAS, and ACCα and increased the mRNA levels of the fatty acid catabolism genes of ATGL, HSL, LAL, and LPL in cardiac tissueof HFD-induced obese mice. TUNEL-positive cells, Bax/Bcl-2 ratio, and Cleaved Caspase-3 protein expression in HFD-induced obese mice hearts was down-regulated by IF intervention. In addition, IF intervention decreased the m6A methylation levels and METTL3 expression and increased FTO expression in HFD-induced obesity cardiomyopathy. In conclusion, our findings demonstrate that IF attenuated cardiac lipid deposition and apoptosis, as well as improved cardiac functional and structural impairment in HFD-induced obesity cardiomyopathy, by a mechanism associated with decreased m6A RNA methylation levels.

The Effect of Fasting on Human Metabolism and Psychological Health

Fasting is a prevalent approach to weight loss and is a feasible method for treating some diseases, such as type 2 diabetes. Meanwhile, the effects of intermittent fasting on health, aging, and disease process are hot issues and are of concern by researchers of multiple areas, even the public. This article introduces the effects of fasting on human lipid metabolism, glucose metabolism, protein metabolism, and neuroendocrine metabolism; demonstrates the metabolic conversion caused by fasting; and describes the effects of fasting on human psychological health, the relationship between mood regulation and glucose, and the emotional enhancing effect induced by fasting.

Intermittent fasting: eating by the clock for health and exercise performance

Intermittent fasting (IF) is an increasingly popular dietary practice, and its implementation is found throughout human civilisation in various cultural, spiritual and religious traditions. Emerging evidence has shown that the health benefits of IF stretch beyond calorie restriction and weight loss. These benefits include metabolic shifts in energy production, the optimisation of peripheral circadian clocks, and overall improvement in physiological markers of metabolic health. IF has been proposed to reduce systemic inflammation and have a role in the prevention and treatment of chronic disease. For the athlete, IF protocols offer a potential new frontier for maintaining performance in the fasted state. They may allow athletes to optimise training adaptions, while respecting individual cultural, religious, and/or spiritual preferences to fast and exercise. Below, we discuss the physiological impact of fasted exercise while highlighting areas for future work to improve our understanding and implementation of the practice for the benefit of both the active general community and sporting populations.

The Effects of Caloric Restriction and/or Intermittent Fasting on Bone Health

This mini-review summarizes the available information regarding the impact of caloric restriction (CR) and/or intermittent fasting (IF) on bone health. CR and IF are dietary interventions used in rehabilitative healthcare for augmenting weight loss and also proposed for recovery of conditions such as stroke and heart failure. CR restricts the total number of calories rather than different food groups or periods of eating. In contrast, IF severely restricts caloric intake for a period of time followed by a period of ad libitum intake. Here, we discuss the available information regarding the impact of these rehabilitation diets on bone metabolism, highlighting areas of consistency and discrepancy and suggesting future areas of study to advance the understanding of CR and/or IF on bone health.