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The Safety of Novel Therapies in Chronic Lymphocytic Leukemia in the Era of Intermittent Fasting: A Pharmacology-Based Review
Intermittent fasting (IF) has recently gained popularity due to its emerging benefits in reducing weight and improving metabolic health. Concurrently, novel agents (NAs) like venetoclax and Bruton tyrosine kinase inhibitors (BTKIs) have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Unfortunately, it is unclear whether the associated risks of tumor lysis syndrome (TLS) and gastrointestinal bleeding (GIB) are increased in IF practitioners receiving NAs. This review explored the literature available on the permissibility of IF in CLL patients undergoing treatment with first-line NAs (FLNAs). Literature was scoped to identify IF patterns and the available data on TLS and GIB risks associated with food and fluid intake in CLL patients receiving FLNAs. Although current evidence is insufficient to recommend IF in this population, it may be possible for patients on venetoclax to conservatively practice fluid-liberal IF, provided that adequate hydration and the consistent administration of food are achieved. In contrast, considering the significant risk of TLS and the pharmacokinetics of venetoclax, patients should be discouraged from practicing fluid-restricted IF, especially during the ramp-up phase. Moreover, patients on BTKIs ought to refrain from IF due to the possible risk of GIB until further data are available. Further research is needed to provide conclusive recommendations.
Journal Article
Does Energy Restriction and Loss of Body Fat Account for the Effect of Intermittent Fasting on Cognitive Function?
Intermittent fasting (IF) and caloric restriction (CR) have garnered attention for their potential to enhance cognitive function, particularly in aging and metabolically compromised populations. This narrative review critically examines whether the cognitive benefits of IF are attributable to its specific fasting patterns or are instead mediated by the production of weight loss, fat loss, and improvements in insulin sensitivity. Evidence from human trials suggests that reductions in body weight, especially visceral adiposity, and improvements in insulin resistance are key factors linked to enhanced cognitive performance. Comparisons between the results of IF and CR trials show comparable cognitive outcomes, supporting the idea that negative energy balance, rather than fasting or altered eating patterns, drive these effects. However, further investigation of specific types of IF patterns, as well as possible cognitive domains to be affected, may identify mechanisms through which IF can yield benefits on neurocognitive health beyond those of loss of body fat and its accompanying inflammatory state.
Journal Article
Adverse events profile associated with intermittent fasting in adults with overweight or obesity: a systematic review and meta-analysis of randomized controlled trials
Background
There is little evidence to comprehensively summarize the adverse events (AEs) profile of intermittent fasting (IF) despite its widespread use in patients with overweight or obesity.
Methods
We searched the main electronic databases and registry websites to identify eligible randomized controlled trials (RCTs) comparing IF versus control groups. A direct meta-analysis using a fixed-effect model was conducted to pool the risk differences regarding common AEs and dropouts. Study quality was assessed by using the Jadad scale. Pre-specified subgroup and sensitivity analyses were conducted to explore potential heterogeneity.
Results
A total of 15 RCTs involving 1,365 adult individuals were included. Findings did not show a significant difference between IF and Control in risk rate of fatigue [0%, 95% confidence interval (CI), -1% to 2%;
P
= 0.61], headache [0%, 95%CI: -1% to 2%;
P
= 0.86] and dropout [1%, 95%CI: -2% to 4%;
P
= 0.51]. However, a numerically higher risk of dizziness was noted among the IF alone subgroup with non-early time restricted eating [3%, 95%CI: -0% to 6%;
P
= 0.08].
Conclusions
This meta-analysis suggested that IF was not associated with a greater risk of AEs in adult patients affected by overweight or obesity. Additional large-scale RCTs stratified by key confounders and designed to evaluate the long-term effects of various IF regimens are needed to ascertain these AEs profile.
Journal Article
An Intermittent Fasting Mimicking Nutrition Bar Extends Physiologic Ketosis in Time Restricted Eating: A Randomized, Controlled, Parallel-Arm Study
There has been increasing interest in time-restricted eating to attain intermittent fasting’s metabolic benefits. However, a more extended daily fast poses many challenges. This study was designed to evaluate the effects of a 200-calorie fasting-mimicking diet (FMD) energy bar formulated to prolong ketogenesis and mitigate fasting-associated side effects. A randomized, controlled study was conducted comparing the impact of consuming an FMD bar vs. continued water fast, after a 15-h overnight fast. Subjects in the FMD group showed a 3-h postprandial beta-hydroxybutyrate (BHB) level and 4-h postprandial BHB area under the curve (AUC0–4) that were non-inferior to those who continued with the water fast (p = 0.891 and p = 0.377, respectively). The postprandial glucose AUC0–4 in the FMD group was non-inferior to that in the water fast group (p = 0.899). A breakfast group served as a control, which confirmed that the instrument used in home glucose and ketone monitoring functioned as expected. The results indicate that FMD bar consumption does not interfere with the physiological ketogenesis associated with overnight fasting and could be used to facilitate the practice of time-restricted eating or intermittent fasting.
Journal Article
The effect of intermittent fasting on preventing obesity-related early aging from a molecular and cellular perspective
Obesity is a global health concern owing to its association with numerous degenerative diseases and the fact that it may lead to early aging. Various markers of aging, including telomere attrition, epigenetic alterations, altered protein homeostasis, mitochondrial dysfunction, cellular senescence, stem cell disorders, and intercellular communication, are influenced by obesity. Consequently, there is a critical need for safe and effective approaches to prevent obesity and mitigate the onset of premature aging. In recent years, intermittent fasting (IF), a dietary strategy that alternates between periods of fasting and feeding, has emerged as a promising dietary strategy that holds potential in counteracting the aging process associated with obesity. This article explores the molecular and cellular mechanisms through which IF affects obesity-related early aging. IF regulates various physiological processes and organ systems, including the liver, brain, muscles, intestines, blood, adipose tissues, endocrine system, and cardiovascular system. Moreover, IF modulates key signaling pathways such as AMP-activated protein kinase (AMPK), sirtuins, phosphatidylinositol 3-kinase (PI3K)/Akt, mammalian target of rapamycin (mTOR), and fork head box O (FOXO). By targeting these pathways, IF has the potential to attenuate aging phenotypes associated with obesity-related early aging. Overall, IF offers promising avenues for promoting healthier lifestyles and mitigating the premature aging process in individuals affected by obesity.
Journal Article
Effects of intermittent fasting on the histology and mRNA expression of major drug-metabolizing cyp450s in the liver of diabetic mice
There is a variation in drug response among patients who practice intermittent fasting. Alteration in the expression of drug-metabolizing enzymes (DMEs) can affect the pharmacokinetics and drug response.
This research aimed to determine the effect of intermittent fasting on the mRNA expression of major drug-metabolizing cyp450s in the liver of diabetic mice.
Thirty-two male Balb/c mice were divided into four groups; control, nonfasting diabetic, non-diabetic fasting, and diabetic fasting mice. Insulin-dependent diabetes was induced in mice by a single high-dose (250 mg/kg) streptozocin. Mice of non-diabetic and diabetic fasting groups were subjected to 10-day intermittent fasting for 17 hours daily. Then, the mRNA expression of mouse phase I DMEs cyp1a1, cyp2c29, cyp2d9, and cyp3a11 was analyzed using real-time polymerase chain reaction. In addition, the liver of mice in all groups was examined for pathohistological alterations.
Diabetes downregulated the mRNA expression of hepatic drug-metabolizing cyp450s in diabetic mice, while intermittent fasting significantly (
< 0.05) increased it. Also, cyp2d9 and cyp3a11 were upregulated in the liver of diabetic fasting mice. These alterations in the gene expression were correlated with the pathohistological alterations, where livers of diabetic mice showed dilatation in the blood sinusoids and inflammatory cells leukocyte infiltrations. Whereas livers of diabetic fasting mice showed almost comparable histological findings to control mice.
Intermittent fasting can protect the liver against diabetes-induced hepatotoxicity and the down-regulation of DME genes in the diabetic liver. These results can explain, at least partly, the inter-individual variation in the drug response during practicing fasting.
Journal Article
Remodeling of Gut Microbiome of Pakistani Expats in China After Ramadan Fasting
Time‐restricted intermittent fasting (TRIF) has gained popularity as an intervention for addressing overweight, obesity, and metabolic syndrome. It may influence the composition of the gut microbiome, potentially affecting various microbiome‐mediated functions in humans. However, limited studies have been conducted involving TRIF and microbiome on developing and underdeveloped populations. Here, we investigated the impact of TRIF/Ramadan fasting (16:8) on the changes of gut microbiome and functional profiling of microbial communities during and after the month of Ramadan in Pakistani Expats living in China. We observed substantial change in alpha diversity during TRIF; the changes in gut microbial structure by the end of TRIF were higher vis‐a‐vis in the beginning. Significant differences were observed among individuals; several bacteria (Clostridium perfringens, Coprococcus comes, and Lactococcus lactis, among others) were changed significantly (p < 0.05). Additionally, amino acid, carbohydrate, and energy metabolism; glycan biosynthesis; and metabolism of cofactors and vitamins were significantly affected by TRIF. Pyridoxamine, glutamate, citrulline, arachidonic acid, and short‐chain fatty acids showed substantial differences at different time points based on the predicted metabolic pathways. The preliminary results from this study demonstrate significant potential for elucidating the mechanisms underlying gut microbiome stability and enhancing the effectiveness of microbiome‐tailored interventions among the Pakistani populace to ameliorate metabolic disorders. Time‐restricted intermittent fasting (TRIF) significantly changed the microbial structure and compositions of Pakistani Expats living in China. TRIF mainly affected the gut microbial pathways of amino acid, carbohydrate, and energy metabolism and glycan biosynthesis metabolism of cofactors and vitamins.
Journal Article
Time-restricted Eating for the Prevention and Management of Metabolic Diseases
Abstract
Time-restricted feeding (TRF, animal-based studies) and time-restricted eating (TRE, humans) are an emerging behavioral intervention approach based on the understanding of the role of circadian rhythms in physiology and metabolism. In this approach, all calorie intake is restricted within a consistent interval of less than 12 hours without overtly attempting to reduce calories. This article will summarize the origin of TRF/TRE starting with concept of circadian rhythms and the role of chronic circadian rhythm disruption in increasing the risk for chronic metabolic diseases. Circadian rhythms are usually perceived as the sleep-wake cycle and dependent rhythms arising from the central nervous system. However, the recent discovery of circadian rhythms in peripheral organs and the plasticity of these rhythms in response to changes in nutrition availability raised the possibility that adopting a consistent daily short window of feeding can sustain robust circadian rhythm. Preclinical animal studies have demonstrated proof of concept and identified potential mechanisms driving TRF-related benefits. Pilot human intervention studies have reported promising results in reducing the risk for obesity, diabetes, and cardiovascular diseases. Epidemiological studies have indicated that maintaining a consistent long overnight fast, which is similar to TRE, can significantly reduce risks for chronic diseases. Despite these early successes, more clinical and mechanistic studies are needed to implement TRE alone or as adjuvant lifestyle intervention for the prevention and management of chronic metabolic diseases.
Graphical Abstract
Graphical Abstract
Journal Article
The ups and downs of caloric restriction and fasting: from molecular effects to clinical application
Age‐associated diseases are rising to pandemic proportions, exposing the need for efficient and low‐cost methods to tackle these maladies at symptomatic, behavioral, metabolic, and physiological levels. While nutrition and health are closely intertwined, our limited understanding of how diet precisely influences disease often precludes the medical use of specific dietary interventions. Caloric restriction (CR) has approached clinical application as a powerful, yet simple, dietary modulation that extends both life‐ and healthspan in model organisms and ameliorates various diseases. However, due to psychological and social‐behavioral limitations, CR may be challenging to implement into real life. Thus, CR‐mimicking interventions have been developed, including intermittent fasting, time‐restricted eating, and macronutrient modulation. Nonetheless, possible side effects of CR and alternatives thereof must be carefully considered. We summarize key concepts and differences in these dietary interventions in humans, discuss their molecular effects, and shed light on advantages and disadvantages.
Graphical Abstract
Can dietary modulations promote better health? The current article comprehensively reviews key concepts of dietary interventions, their clinical application and the beneficial and disadvantageous effects of caloric restriction and fasting on human health.
Journal Article