BACKGROUND: All types of caloric restriction are preventive against cardiovascular risk factors, but the best restriction method and most affected factors have not been identified.
OBJECTIVE: The objective of this study was to explore the effects of different caloric restriction methods on various cardiovascular risk factors by horizontally comparing program advantages and disadvantages via network meta-analysis.
METHODS: The PubMed, Web of Science, Cochrane Library, and Embase literature databases were searched (October 2013 to October 2023).
METHODS: Eligible randomized controlled trials involving participants who underwent caloric restriction and systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and high-density lipoprotein (HDL) cholesterol level measurements were included.
METHODS: Thirty-six of 13 208 records (0.27%) were included. Two researchers reviewed the articles, extracted data, and assessed article quality.
RESULTS: Alternate-day fasting (ADF) reduced SBP (4.88 mmHg; CI, 2.06-7.15) and DBP (5.10 mmHg; CI, 2.44-7.76). Time-restricted eating reduced SBP (2.46 mmHg; CI, 0.16-4.76) but not DBP. Continuous energy restriction (CER) significantly reduced BMI (1.11 kg/m2; CI = 0.16, 2.06) and waist circumference (3.28 cm; CI, 0.62-5.94).
CONCLUSIONS: This meta-analysis confirmed the preventive effect of CER and ADF on various cardiovascular risk factors. Additionally, CER is more likely to reduce obesity, and ADF is more likely to reduce blood pressure (BP). Based on this meta-analysis, CER is recommended to control obesity only for people who are obese and do not have elevated BP or other abnormal indicators. Additionally, ADF for early control or prevention is recommended for patients who have abnormal BP or other cardiovascular risk factors.
BACKGROUND: PROSPERO registration no. CRD42023455889.

Aging is a multifaceted process impacting cells, tissues, organs, and organ systems of the body. Like other systems, aging affects both the adaptive and the innate components of the immune system, a phenomenon known as immunosenescence. The deregulation of the immune system puts elderly individuals at higher risk of infection, lower response to vaccines, and increased incidence of cancer. In the Western world, overnutrition has increased the incidence of obesity (linked with chronic inflammation) which increases the risk of metabolic syndrome, cardiovascular disease, and cancer. Aging is also associated with inflammaging a sterile chronic inflammation that predisposes individuals to age-associated disease. Genetic manipulation of the nutrient-sensing pathway, fasting, and calorie restriction (CR) has been shown to increase the lifespan of model organisms. As well in humans, fasting and CR have also been shown to improve different health parameters. Yet the direct effect of fasting and CR on the aging immune system needs to be further explored. Identifying the effect of fasting and CR on the immune system and how it modulates different parameters of immunosenescence could be important in designing pharmacological or nutritional interventions that slow or revert immunosenescence and strengthen the immune system of elderly individuals. Furthermore, clinical intervention can also be planned, by incorporating fasting or CR with medication, chemotherapy, and vaccination regimes. This review discusses age-associated changes in the immune system and how these changes are modified by fasting and CR which add information on interventions that promote healthy aging and longevity in the growing aging population.

Mitochondria are central to cellular energy production, and their dysfunction is a major contributor to oxidative stress and chronic inflammation, pivotal factors in aging, and related diseases. With aging, mitochondrial efficiency declines, leading to an increase in ROS and persistent inflammatory responses. Therapeutic interventions targeting mitochondrial health show promise in mitigating these detrimental effects. Antioxidants such as MitoQ and MitoVitE, and supplements like coenzyme Q10 and NAD + precursors, have demonstrated potential in reducing oxidative stress. Additionally, gene therapy aimed at enhancing mitochondrial function, alongside lifestyle modifications such as regular exercise and caloric restriction can ameliorate age-related mitochondrial decline. Exercise not only boosts mitochondrial biogenesis but also improves mitophagy. Enhancing mitophagy is a key strategy to prevent the accumulation of dysfunctional mitochondria, which is crucial for cellular homeostasis and longevity. Pharmacological agents like sulforaphane, SS-31, and resveratrol indirectly promote mitochondrial biogenesis and improve cellular resistance to oxidative damage. The exploration of mitochondrial therapeutics, including emerging techniques like mitochondrial transplantation, offers significant avenues for extending health span and combating age-related diseases. However, translating these findings into clinical practice requires overcoming challenges in precisely targeting dysfunctional mitochondria and optimizing delivery mechanisms for therapeutic agents. Continued research is essential to refine these approaches and fully understand the interplay between mitochondrial dynamics and aging.

UNASSIGNED: Both 5:2 IF diet (intermittent fasting) and daily caloric restriction eating had been suggested for management of MAFLD (Metabolic-Associated Fatty Liver Disease), this study aimed to evaluate the effects of 5:2 IF diet on body weight and metabolic parameters in adults with MAFLD, in comparison to daily caloric restriction eating.
UNASSIGNED: This single-center, double-blind, prospective, randomized controlled trial included 60 patients with MAFLD, who were administered either a 5:2 IF diet limited calories consumed for 2 days each week with no restrictions on the remaining 5 (Group 5:2 IF diet) or a daily calorie restriction eating (Group daily calorie restriction). Fibrotouch-B instrument assessment, ultrasound assessment of hepatic steatosis, anthropometric indices and body composition analysis, blood sample measurements were conducted during two distinct visits: initially on the day of study commencement (T1), and subsequently at the conclusion of the 12-week intervention period (T2).
UNASSIGNED: In comparison to daily calorie restriction eating, the 5:2 IF diet significantly decreased the proportion of hepatic steatosis ≥moderate (29.6% vs. 59.3%, p = 0.028) and the degree of hepatic fibrosis F ≥ 2 (3.7% vs. 25.9%, p = 0.05), and fewer percentage of patients were diagnosed with fatty liver via upper abdominal ultrasound in the 5:2 intermittent fasting diet group (33.3% vs. 63.0%, p = 0.029). Additionally, the CAP (controlled attenuation parameter) and LSM (liver stiffness measurements) value were significantly lower in the 5:2 IF diet group (p < 0.05). No statistically significant differences were observed between the two groups in terms of weight, BMI (body mass index), WC (waist circumference), HC (hip circumference), and WHR (waist to hip ratio). Similarly, there were no significant differences in lipid profile, glycemic indices and adverse events (p > 0.05).
UNASSIGNED: In summary, although both 5:2 IF diet and daily caloric restriction eating achieved similar effect on body weight, liver enzymes, lipid profile and glycemic indices after 12 weeks treatment, 5:2 IF diet demonstrates better improvement in fibrosis and steatosis scores independently from weight regulation. Consequently, it is anticipated to emerge as a viable dietary modality for lifestyle intervention among patients diagnosed with MAFLD.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO, identifier ChiCTR2400080292.

Calorie restriction (CR) extends lifespan and healthspan in diverse species. Comparing ad libitum- and CR-fed mice is challenging due to their significantly different feeding patterns, with CR-fed mice consuming their daily meal in 2 h and then subjecting themselves to a prolonged daily fast. Here, we examine how ad libitum- and CR-fed mice respond to tests performed at various times and fasting durations and find that the effects of CR-insulin sensitivity, circulating metabolite levels, and mechanistic target of rapamycin 1 (mTORC1) activity-result from the specific temporal conditions chosen, with CR-induced improvements in insulin sensitivity observed only after a prolonged fast, and the observed differences in mTORC1 activity between ad libitum- and CR-fed mice dependent upon both fasting duration and the specific tissue examined. Our results demonstrate that much of our understanding of the effects of CR are related to when, relative to feeding, we choose to examine the mice.

There is a pressing need to develop new strategies for enhancing health in the elderly and preventing the rise in age-related diseases. Calorie restriction without malnutrition (CR) stands among the different antiaging interventions. Lifelong CR leads to increased expression and activity of plasma membrane CYB5R3, and male mice overexpressing CYB5R3 exhibit some beneficial adaptations that are also seen with CR. However, the mechanisms involved in both interventions could be independent since key aspects of energy metabolism and tissue lipid profile do not coincide, and many of the changes induced by CR in mitochondrial abundance and dynamics in the liver and skeletal muscle could be counteracted by CYB5R3 overexpression. In this study, we sought to elucidate the impact of CR on key markers of metabolic status, mitochondrial function, and pro-oxidant/antioxidant balance in transgenic (TG) female mice overexpressing CYB5R3 compared to their WT littermates. In females fed ad libitum, CYB5R3 overexpression decreased fat mass, led to a preferred utilization of fatty acids as an energy source, upregulated key antioxidant enzymes, and boosted respiration both in skeletal muscle and liver mitochondria, supporting that CYB5R3 overexpression is phenotypic closer to CR in females than in males. Whereas some markers of mitochondrial biogenesis and dynamics were found decreased in TG females on CR, as also found for the levels of Estrogen Receptor α, mitochondrial abundance and activity were maintained both in skeletal muscle and in liver. Our results reveal overlapping metabolic adaptations resulting from the overexpression of CYB5R3 and CR in females, but a specific crosstalk occurs when both interventions are combined, differing from the adaptations observed in TG males.

There is currently a growing interest in diets and physical activity patterns that may be beneficial in preventing and treating breast cancer (BC). Mounting evidence indicates that indeed, the so-called Mediterranean diet (MedDiet) and regular physical activity likely both help reduce the risk of developing BC. For those who have already received a BC diagnosis, these interventions may decrease the risk of tumor recurrence after treatment and improve quality of life. Studies also show the potential of other dietary interventions, including fasting or modified fasting, calorie restriction, ketogenic diets, and vegan or plant-based diets, to enhance the efficacy of BC therapies. In this review article, we discuss the biological rationale for utilizing these dietary interventions and physical activity in BC prevention and treatment. We highlight published and ongoing clinical studies that have applied these lifestyle interventions to BC patients. This review offers valuable insights into the potential application of these dietary interventions and physical activity as complimentary therapies in BC management.

The maintenance of germ cells is critical for the prosperity of offspring. The amount of food consumption is known to be closely related to reproduction, i.e., the number of eggs decreases under calorie-restricted conditions in various organisms. Previous studies in Caenorhabditis elegans have reported that calorie restriction reduces the number of eggs and the reduction can be rescued by methionine. However, the effect of methionine on the reproductive process has not been fully understood. In this study, to assess the gonadal function of methionine metabolism, we firstly demonstrated that a depletion in dietary methionine resulted in reduced levels of S-adenosyl-l-methionine (SAM) and S-adenosyl homocysteine (SAH) in wild-type N2, but not in glp-1 mutants, which possess only a few germ cells. Second, we found no recovery in egg numbers upon methionine administration in SAM synthase (sams)-1 mutants. Furthermore, a reduced number of proliferative zone nuclei exhibited in the sams-1 mutants was not rescued via methionine. Thus, our results have shown that dietary methionine is required for the normal establishment of both the germline progenitor pool and fecundity, mediated by sams-1.

BACKGROUND: Estrogen has a protective impact on acute kidney injury (AKI); moreover, reducing the daily intake of calories impedes developing diseases. The present study aimed to determine the effects of calorie restriction (CR) and time restriction (TR) diets on the expression of silent information regulator 2 homolog 1 (SIRT1), transforming growth factor beta 1 (TGF-β1), and other indicators in the presence and absence of ovaries in AKI female rats.
METHODS: The female rats were divided into two groups, ovariectomized (OVX) and sham, and were placed on CR and TR diets for eight weeks; afterward, AKI was induced by injecting glycerol, and kidney injury indicators and biochemical parameters were measured before and after AKI.
RESULTS: After AKI, the levels of urine albumin excretion rate, urea, and creatinine in serum, and TGF-β1 increased, while creatinine clearance and SIRT1 decreased in kidney tissue. CR improved kidney indicators and caused a reduction in TGF-β1 and an increase in SIRT1 in ovary-intact rats. Moreover, CR prevented total antioxidant capacity (TAC) decrease and malondialdehyde (MDA) increase resulting from AKI. Before AKI, an increase in body weight, fasting blood sugar (FBS), low-density lipoprotein (LDL), triglyceride (TG), and total cholesterol (TC), and a decrease in high-density lipoprotein (HDL) were observed in OVX rats compared to sham rats, but CR prevented these changes. The effects of TR were similar to those of CR in all indicators except for TGF-β1, SIRT1, urea, creatinine, and albumin.
CONCLUSIONS: The present study indicated that CR is more effective than TR in preventing AKI, probably by increasing SIRT1 and decreasing TGF-β1 in ovary-intact animals.

BACKGROUND: Obesity combined with heart failure with preserved ejection fraction (HFpEF) is the dominant form of HF among older persons. In a randomized trial, we previously showed that a 5-month calorie restriction (CR) program, with or without aerobic exercise training (AT), resulted in significant weight and fat loss and improved exercise capacity. However, little is known regarding the long-term effects of these outcomes after a short-term (5-month) intervention of CR with or without AT in older patients with obesity and HFpEF.
METHODS: Sixteen participants from either the CR or CR+AT who experienced significant weight loss ≥ 2 kg were reexamined after a long-term follow-up endpoint (28.0 ± 10.8 months) without intervention. The follow-up assessment included body weight and composition via dual-energy X-ray absorptiometry and exhaustive cardiopulmonary treadmill exercise testing.
RESULTS: Compared to the 5-month time-point intervention endpoint, at the long-term follow-up endpoint, mean body weight increased +5.2 ± 4.0 kg (90.7 ± 11.2 kg vs 95.9 ± 11.9; P < 0.001) due to increased fat mass (38.9 ± 9.3 vs 43.8 ± 9.8; P < 0.001) with no change in lean mass (49.6 ± 7.1 vs 49.9±7.6; P = 0.67), resulting in worse body composition (decreased lean-to-fat mass). Change in total mass was strongly and significantly correlated with change in fat mass (r = 0.75; P < 0.001), whereas there appeared to be a weaker correlation with change in lean mass (r = 0.50; P = 0.051). Additionally, from the end of the 5-month time-point intervention endpoint to the long-term follow-up endpoint, there were large, significant decreases in VO2peak (-2.2 ± 2.1 mL/kg/min; P = 0.003) and exercise time (-2.4 ± 2.6 min; P = 0.006). There appeared to be an inverse correlation between the change in VO2peak and the change in fat mass (r = -0.52; P = 0.062).
CONCLUSIONS: Although CR and CR+AT in older patients with obesity and HFpEF can improve body composition and exercise capacity significantly, these positive changes diminish considerably during long-term follow-up endpoints, and regained weight is predominantly adipose, resulting in worsened overall body composition compared to baseline. This suggests a need for long-term adherence strategies to prevent weight regain and maintain improvements in body composition and exercise capacity following CR in older patients with obesity and HFpEF.