ArticleLiterature Review

The Influence of Fasting and Energy Restricting Diets on IGF-1 Levels in Humans: A Systematic Review and Meta-Analysis

May 2019
Ageing Research Reviews 53:100910

DOI:10.1016/j.arr.2019.100910

Authors:

Hamed Kord Varkaneh

Shahid Beheshti University of Medical Sciences

Cain C. T. Clark

Coventry University

Hamid Zand

Shahid Beheshti University of Medical Sciences

Show all 8 authorsHide

Background: Fasting and energy restricting diets have a potential means of delaying or preventing the onset of a range of age-related metabolic and neoplastic diseases. Consistently at the centre of this effect appears to be a significant reduction in circulating IGF-1 levels. The aim of the current systematic review and meta-analysis was to determine the influence of fasting and energy restriction on IGF-1 levels in human subjects. Methods: A comprehensive systematic search was conducted from onset of the database to February 2019 in Embase, MEDLINE/PubMed, and SCOPUS to identify randomized clinical trials that investigating the impact of fasting or energy restriction circulating IGF-1 levels. Effect size was reported as weighted mean difference (WMD) and 95% confidence intervals (CI) using a random-effects models. Subgroup analysis was performed to identify the probable source of heterogeneity among trials. Results: Total pooling of fasting and energy restriction randomised controlled trials in WMD analysis revealed no significant effect on circulating IGF-1 levels (WMD: -16.41 ng/ml, 95% CI: -35.88, 3.07). Sub grouped analysis fasting regimens appeared to substantially reduce IGF-1 (WMD: -28.87 ng/ml, 95% CI: -43.69, -14.05, I2 = 00%), energy restricting regimens failed to do the same (WMD: -10.98 ng/ml, 95% CI: -33.08, 11.11, I2 = 90%). Within this final subgrouping, it was observed that only energy restriction regimens of 50% or greater of normal daily energy intake were capable of significantly reducing IGF-1 levels (WMD: -36.57 ng/ml, 95% CI: -59.19, -13.95, I2 = 00%). Finally, a meta regression were noted in which the percentage restriction of daily energy intake inversely correlated with plasma IGF-1 levels (p = 0.04). Conclusion: This study uncovered that fasting significantly reduced levels of IGF-1, while energy restriction diets were successful only when intake was reduced by 50% or more.

Effect of Epidemic Intermittent Fasting on Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Article

Full-text available

Oct 2021

Intermittent fasting (IF) has gained attention as a promising diet for weight loss and dysmetabolic diseases management. This systematic review aimed to investigate the effects of IF on cardiometabolic risk factors (CMRFs). A systematic literature search was carried out using three electronic databases, namely PubMed, Embase, and the Cochrane Library, until October 2020. Randomized controlled trials that compared the IF intervention with a control group diet were included. Fourteen effect sizes were expressed as weighted mean difference (WMD) using a fixed-effects model and 95% confidence intervals (CI). Compared to the ones within control groups, participants exposed to the IF intervention reduced their body weight (WMD, −1.78 kg; 95% CI, −2.21 to −1.35; p <0.05), waist circumference (WMD, −1.19 cm; 95% CI, −1.8 to −0.57; p <0.05), fat mass (WMD, −1.26 kg; 95% CI, −1.57 to −0.95; p <0.05), body mass index (WMD, −0.58 kg/m2; 95% CI, −0.8 to −0.37; p <0.05), systolic blood pressure (WMD, −2.14 mmHg; 95% CI: −3.54 to −0.73; p <0.05), diastolic blood pressure (WMD: −1.38 mmHg, 95% CI, −2.35 to −0.41, p <0.05), fasting blood glucose (WMD: −0.053 mmol/L; 95% CI: −0.105 to 0.001; p <0.05), fasting insulin (WMD, −0.8 mIU/L; 95% CI, −1.15 to −0.44; p <0.05), insulin resistance (WMD, −0.21; 95% CI, −0.36 to −0.05; p <0.05), total cholesterol (WMD, −0.10 mmol/L; 95% CI, −0.17 to −0.02; p <0.05), and triglycerides (WMD, −0.09 mmol/L; 95% CI, −0.13 to −0.04; p <0.05). No effects were observed for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or glycosylated hemoglobin. This meta-analysis supports the role of IF in improving the component composition of CMRFs, including weight, waist circumference, fat mass, BMI, blood pressure, total cholesterol, triglycerides, fasting insulin, and insulin resistance, compared to a control group diet. Further research on IF interventions should take into account long-term and well-designed administration to draw definitive conclusions.

The Effects of Intermittent Fasting on Brain and Cognitive Function

Article

Full-text available

Sep 2021

The importance of diet and the gut-brain axis for brain health and cognitive function is increasingly acknowledged. Dietary interventions are tested for their potential to prevent and/or treat brain disorders. Intermittent fasting (IF), the abstinence or strong limitation of calories for 12 to 48 h, alternated with periods of regular food intake, has shown promising results on neurobiological health in animal models. In this review article, we discuss the potential benefits of IF on cognitive function and the possible effects on the prevention and progress of brain-related disorders in animals and humans. We do so by summarizing the effects of IF which through metabolic, cellular, and circadian mechanisms lead to anatomical and functional changes in the brain. Our review shows that there is no clear evidence of a positive short-term effect of IF on cognition in healthy subjects. Clinical studies show benefits of IF for epilepsy, Alzheimer’s disease, and multiple sclerosis on disease symptoms and progress. Findings from animal studies show mechanisms by which Parkinson’s disease, ischemic stroke, autism spectrum disorder, and mood and anxiety disorders could benefit from IF. Future research should disentangle whether positive effects of IF hold true regardless of age or the presence of obesity. Moreover, variations in fasting patterns, total caloric intake, and intake of specific nutrients may be relevant components of IF success. Longitudinal studies and randomized clinical trials (RCTs) will provide a window into the long-term effects of IF on the development and progress of brain-related diseases.

Plant-Based Diet and IGF-1 Modulation on HER2-Positive Breast Cancer: A Lifestyle Medicine Nutrition Approach in Oncology

Article

Jun 2021

Breast cancer is the second most common type of cancer in women worldwide, where nutritional intervention should be part of a multidisciplinary lifestyle approach in oncology, promoting therapeutic success. Insulin-like growth factor 1 (IGF-1), along with estrogen, can promote the development of neoplastic cells in breast tissue. Cancers that develop under IGF-1 stimulation are often resistant to therapy. This case report describes a 47-year-old woman, body mass index 27.4 kg/m ² , with HER2-positive breast cancer, as well as elevated blood glucose, total cholesterol, and low-density lipoprotein cholesterol. Soon after her breast cancer diagnosis, she transitioned from a Western pattern diet (WPD) to a predominantly whole-food, plant-based diet (PWFPBD) for 1035 days, followed by 232 days of PWFPBD plus night fasting for 16 hours per day. IGF-1 decreased 22.38%, glycemia and total cholesterol decreased by −55.06% and −36.00% at the end of the first intervention and went up by 6.25%, and 3.87%, respectively, at the end of the second intervention. A PWFPBD, with or without 16-hour overnight fasting, seems to modulate plasma levels of IGF-1 on a 47-year-old woman diagnosed with breast cancer, type HER2-positive. Future research, should explore the physiologic and pathophysiological mechanisms and clarify whether this dietary strategy, may be clinically useful in preventing HER2-positive breast cancer.

Short- and long-term effects of nutritional state on IGF-1 levels in nestlings of a wild passerine

Article

Full-text available

Sep 2023
OECOLOGIA

Growth trajectories of young animals are intimately connected to their fitness prospects, but we have little knowledge of growth regulation mechanisms, particularly in the wild. Insulin-like growth factor 1 (IGF-1) is a central hormone in regulating resource allocation, with higher IGF-1 levels resulting in more growth. IGF-1 levels generally increase in conjunction with nutritional state, but whether IGF-1 levels are adjusted in response to current nutrient availability or to the nutrient availability integrated over a longer term is not well known. We tested for such effects by supplementary feeding the jackdaw (Corvus monedula) nestlings in experimentally reduced or enlarged broods with either water (control) or a food solution; these manipulations have long- and short-term effects on the nutritional state, respectively. Baseline plasma IGF-1 levels were higher in reduced broods. Food supplementation induced an increase in plasma IGF-1 levels measured one hour later, and this effect was significantly more substantial in nestlings in reduced broods. Changes in plasma IGF-1 levels increased with increased retention of the supplementary food, which was higher in reduced broods, explaining the stronger IGF-1 response. Thus, IGF-1 levels respond to short-term variations in the nutritional state, but this effect is amplified by longer-term variations in the nutritional state. We discuss our findings using a graphical model that integrates the results of the two treatments.

PROBIOTICS IN THE MAINTENANCE OF ORAL HEALTH

Chapter

Full-text available

Jun 2023

In light of recent in vitro and in vivo researches, probiotics have been shown to have a significant role in the prevention of a wide range of oral health problems, from dental caries to halitosis and periodontal disease. Studies declare a direct connection between the probiotics and the alteration of the oral microenvironment, which is the oral pathogens inhibited by the probiotics. In addition, choosing the most proper probiotic for improving oral health requires more study. Before consalidating probiotics into daily oral health regimes, more data are needed to analyze the mechanisms of probiotic effects on oral health, and continuing clinical trials are required

Towards Understanding the Direct and Indirect Actions of Growth Hormone in Controlling Hepatocyte Carbohydrate and Lipid Metabolism

Article

Full-text available

Sep 2021

Growth hormone (GH) is critical for achieving normal structural growth. In addition, GH plays an important role in regulating metabolic function. GH acts through its GH receptor (GHR) to modulate the production and function of insulin-like growth factor 1 (IGF1) and insulin. GH, IGF1, and insulin act on multiple tissues to coordinate metabolic control in a context-specific manner. This review will specifically focus on our current understanding of the direct and indirect actions of GH to control liver (hepatocyte) carbohydrate and lipid metabolism in the context of normal fasting (sleep) and feeding (wake) cycles and in response to prolonged nutrient deprivation and excess. Caveats and challenges related to the model systems used and areas that require further investigation towards a clearer understanding of the role GH plays in metabolic health and disease are discussed.

Expression of insulin-like growth factors depends on both mass and resource availability in female green anoles ( Anolis carolinensis )

Article

Full-text available

Jul 2021

The insulin and insulin-like signaling (IIS) network is an important mediator of cellular growth and metabolism in animals, and is sensitive to environmental conditions such as temperature and resource availability. The two main hormones of the IIS network, insulin-like growth factor 1 (IGF1) and insulin-like growth factor 2 (IGF2), are present in all vertebrates, yet little is known regarding the responsiveness of IGF2 in particular to external stimuli in non-mammalian animals. We manipulated diet (low quantity of food or high quantity of food) in adult green anole (Anolis carolinensis) females to test the effect of energetic state on hepatic gene expression of IGF1 and IGF2. The absolute expression of IGF2 in female green anoles is 100X higher than IGF1 regardless of diet treatment, and IGF1 and IGF2 expression interact with post-treatment body mass and treatment, as do the purported housekeeping genes glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and eukaryotic elongation factor 2 (EEF2). The Low Diet group showed a negative relationship between body mass and gene expression for all genes, whereas the relationships between body mass and gene expression in the High Diet group were either absent (in the case of IGF1) or positive (for all other genes). After accounting for total change in mass the Low Diet group expressed IGF2, GAPDH and EEF2 at higher levels compared to individuals in the High Diet group of similar ▵ mass. These results illustrate that expression of IGF1 and IGF2, and housekeeping genes are affected by energetic status in reptiles.

MicroRNA-30a-3p inhibits malignant progression of hepatocellular carcinoma through regulating IGF1

Article

Full-text available

Dec 2020

Objective: The purpose of this study was to investigate the expression level of microRNA-30a-3p in hepatocellular carcinoma (HCC), and to further study its relationship with HCC clinical parameters and prognosis and the underlying mechanisms. Patients and methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine microRNA-30a-3p level in 44 tumor tissue specimens and paracancerous normal ones collected from HCC patients, and the interplay between microRNA-30a-3p expression and clinical indicators, as well as prognosis of HCC patients was analyzed. Meanwhile, qPCR was also used to further verify microRNA-30a-3p expression in HCC cell lines. In addition, microRNA-30a-3p overexpression and knockdown models were constructed in HCC cell lines, and the impacts of microRNA-30a-3p on HCC cell functions was evaluated by cell counting kit-8 (CCK-8), transwell and cell wound healing assays. Finally, the Luciferase reporting assay was conducted to uncover the underlying mechanism. Results: In this study, qRT-PCR results showed that the expression level of microRNA-30a-3p in tumor tissues of HCC patients was markedly lower than that in adjacent ones. Compared with patients with high expression of microRNA-30a-3p, the patients with low expression of microRNA-30a-3p had a higher incidence of lymphatic or distant metastasis and a lower overall survival rate. In the Bel-7402 cell line, the proliferation, invasion, and metastasis ability of HCC cells were decreased markedly after microRNA-30a-3p overexpression, while in Hep3B cell line, knockdown of microRNA-30a-3p enhanced the cell proliferation and invasion capacity. In addition, Luciferase reporting assay demonstrated that microRNA-30a-3p could specifically bind to IGF1. Furthermore, Western Blot results also verified a reduced expression of IGF1 after overexpression of microRNA-30a-3p, and an elevated one after knockdown of microRNA-30a-3p. Finally, cell recovery experiment verified that microRNA-30a-3p and IGF1 may regulate each other and thereby together inhibit the malignant progression of HCC. Conclusions: MicroRNA-30a-3p expression is significantly decreased in HCC tumor tissue samples, which is associated with lymph node or distant metastasis rate, as well as the poor prognosis of HCC. In addition, this research suggests that microRNA-30a-3p may inhibit the malignant progression of HCC by regulating IGF1.

The influence of fasting and energy-restricted diets on leptin and adiponectin levels in humans: A systematic review and meta-analysis

Article

Oct 2020
CLIN NUTR

Background & aims Fasting and energy-restricted diets have been evaluated in several studies as a means of improving cardiometabolic biomarkers related to body fat loss. However, further investigation is required to understand potential alterations of leptin and adiponectin concentrations. Thus, we performed a systematic review and meta-analysis to derive a more precise estimate of the influence of fasting and energy-restricted diets on leptin and adiponectin levels in humans, as well as to detect potential sources of heterogeneity in the available literature. Methods A comprehensive systematic search was performed in Web of Science, PubMed/MEDLINE, Cochrane, SCOPUS and Embase from inception until June 2019. All clinical trials investigating the effects of fasting and energy-restricted diets on leptin and adiponectin in adults were included. Results Twelve studies containing 17 arms and a total of 495 individuals (intervention = 249, control = 246) reported changes in serum leptin concentrations, and 10 studies containing 12 arms with a total of 438 individuals (intervention = 222, control = 216) reported changes in serum adiponectin concentrations. The combined effect sizes suggested a significant effect of fasting and energy-restricted diets on leptin concentrations (WMD: −3.690 ng/ml, 95% CI: −5.190, −2.190, p ≤ 0.001; I² = 84.9%). However, no significant effect of fasting and energy-restricted diets on adiponectin concentrations was found (WMD: −159.520 ng/ml, 95% CI: −689.491, 370.451, p = 0.555; I² = 74.2%). Stratified analyses showed that energy-restricted regimens significantly increased adiponectin (WMD: 554.129 ng/ml, 95% CI: 150.295, 957.964; I² = 0.0%). In addition, subsequent subgroup analyses revealed that energy restriction, to ≤50% normal required daily energy intake, resulted in significantly reduced concentrations of leptin (WMD: −4.199 ng/ml, 95% CI: −7.279, −1.118; I² = 83.9%) and significantly increased concentrations of adiponectin (WMD: 524.04 ng/ml, 95% CI: 115.618, 932.469: I² = 0.0%). Conclusion Fasting and energy-restricted diets elicit significant reductions in serum leptin concentrations. Increases in adiponectin may also be observed when energy intake is ≤50% of normal requirements, although limited data preclude definitive conclusions on this point.

The Influence of Fasting and Energy Restricting Diets on Blood Pressure in Humans: A Systematic Review and Meta-Analysis

Article

Jun 2020

IntroductionTo the best of our knowledge, no comprehensive meta-analysis has been carried out to investigate the effect of different approaches of fasting and calorie restriction on blood pressure. AimThus, the present systematic review and meta-analysis was designed to examine the effect of fasting and energy restricting diets on blood pressure in adult subjects.Methods We searched PubMed/Medline, Scopus, the Cochrane Library, and Google Scholar up to June 2019. The clinical trials that examined the effects of fasting and energy restricting diets on Blood Pressure was identified using MESH and non-MESH terms.Results23 studies, including a total of 1397 participants, reported SBP and DBP as an outcome measure. Overall results from the random-effects model indicated that fasting and energy restricting administration elicited significant changes in SBP (weight mean difference (WMD): − 1.88 mmHg, 95% CI − 2.50, − 1.25) and DBP (WMD − 1.32 mmHg, 95% CI − 1.81, − 0.84, p = 0.000). Subgroup analyses displayed that intervention duration ≤ 12 weeks more effectively reduced SBP (WMD: -3.26 mmHg) and DBP (WMD − 1.32 mmHg). In addition, these analyses showed that fasting regimens (WMD − 3.26 mmHg) more effectively reduced SBP than energy restricting diets (WMD − 1.09 mmHg).Conclusion The principal finding of this study was that fasting and energy restricting diets elicited, overall, significant reductions in SBP and DBP. Subsequent subgroup analyses revealed that intervention duration ≤ 12 weeks and fasting regimens more effectively reduced SBP and DBP.

The treatment of chronic anemia in heart failure: a global approach

Article

Full-text available

Sep 2023
CLIN RES CARDIOL

Chronic anemia is an independent risk factor for mortality in patients with heart failure (HF). Restoring physiological hemoglobin (Hb) levels is essential to increase oxygen transport capacity to tissues and improve cell metabolism as well as physical and cardiac performance. Nutritional deficits and iron deficiency are the major causes of chronic anemia, but other etiologies include chronic kidney disease, inflammatory processes, and unexplained anemia. Hormonal therapy, including erythropoietin (EPO) and anabolic treatment in chronic anemia HF patients, may contribute to improving Hb levels and clinical outcomes. Although preliminary studies showed a beneficial effect of EPO therapy on cardiac efficiency and in HF, more recent studies have not confirmed this positive impact of EPO, alluding to its side effect profile. Physical exercise significantly increases Hb levels and the response of anemia to treatment. In malnourished patients and chronic inflammatory processes, low levels of anabolic hormones, such as testosterone and insulin-like growth factor-1, contribute to the development of chronic anemia. This paper aims to review the effect of nutrition, EPO, anabolic hormones, standard HF treatments, and exercise as regulatory mechanisms of chronic anemia and their cardiovascular consequences in patients with HF. Graphical abstract

Efficacy and safety of modified fasting therapy for weight loss in 2054 hospitalized patients

Article

Full-text available

May 2023

Objective: The aim of this study was to evaluate the efficacy and safety of modified fasting therapy, and a retrospective study was conducted to analyze changes in clinical indicators of hospitalized fasting patients. Methods: A total of 2054 hospitalized fasting patients were enrolled in this observational study. All participants underwent 7 days of modified fasting therapy. The clinical efficacy biomarkers, safety indicators, and body composition were measured before and after fasting. Results: The modified fasting therapy reduced body weight, BMI, abdominal circumference, systolic blood pressure, and diastolic blood pressure significantly. Blood glucose and indicators of body composition were improved to various extents (all p < 0.05). There was a small increase in liver function, kidney function, uric acid, electrolytes, blood count, coagulation, and uric biomarkers. Subgroup analysis results showed that cardiovascular diseases benefited from modified fasting therapy. Conclusions: At present this study is the largest retrospective population-based study about modified fasting therapy. The results from 2054 patients showed that the modified fasting therapy lasting 7 days was efficient and safe. It led to improvements in physical health and body weight-associated indicators, as well as body composition and relevant cardiovascular risk factors.

Intermittent Fasting and Cancer

Article

Full-text available

Jan 2022

Intermittent Fasting has shown several physiological benefits, such as improved glucose regulation, stress resistance, suppression of inflammation, and in relation to cancer, tumor growth inhibition. These benefits can be accomplished through several mechanisms, such as induction of autophagy, mitophagy, autophagic cell death, and changes in the cellular metabolic environment. Nutritional restriction is a promising protocol to modulate autophagy and enhance the efficacy of anticancer therapies while protecting normal cells. Intermittent Fasting may offer cancer patients an effective and less toxic adjuvant treatment for cancer. In addition, Intermittent Fasting has shown benefits when combined with the use of chemotherapeutic drugs resulting in a decrease in side effects and an increase in the effectiveness of the drugs. Throughout this article, literature pertaining to Intermittent Fasting, and cancer is reviewed and analyzed. The evidence of dietary restriction, specifically fasting, is discussed as a tool that provides physiological and epigenetic benefits in the management of cancer.

Food Restriction Reveals Individual Differences in Insulin-Like Growth Factor-1 Reaction Norms

Article

Full-text available

Jul 2022

Most organisms have to cope with unpredictable environmental challenges such as fluctuations in nutritional resources. Insulin-like growth factor-1 (IGF-1) is an evolutionarily conserved hormone that is highly sensitive to the individual nutritional status and regulates major life-history traits including lifespan and reproduction across vertebrates. We investigated the role of IGF-1 during periods of food shortages by altering between two feeding regimes (110 and 70% of daily food intake) after a period of ad libitum feeding in captive bearded reedlings (Panurus biarmicus). Each dietary treatment was repeated twice. Birds lost mass under food restriction, but the magnitude of mass change depended on the preceding dietary conditions. Moreover, bearded reedlings showed large, repeatable individual differences in their IGF-1 reaction norms with some individuals increasing IGF-1 levels in response to a restricted diet, whereas others showed no responses or decreased IGF-1 levels. This variation was explained by differences in average body mass: heavier individuals had higher IGF-1 levels during the control treatment and were more likely to decrease IGF-1 levels in response to the dietary restriction than did lighter ones. This result uncovers an individual by environment interaction (I × E) and may have important implications for the evolution of IGF-1 related hormonal phenotypes in this species.

Sprint training interacts with body mass to affect hepatic insulin-like growth factor expression in female green anoles (Anolis carolinensis)

Article

May 2022
GEN COMP ENDOCR

Locomotor performance is a key predictor of fitness in many animal species. As such, locomotion integrates the output of a number of morphological, physiological, and molecular levels of organization, yet relatively little is known regarding the major molecular pathways that bolster locomotor performance. One potentially relevant pathway is the insulin and insulin-like signaling (IIS) network, a significant regulator of physiological processes such as reproduction, growth, and metabolism. Two primary hormones of this network, insulin-like growth factor 1 (IGF1) and insulin-like growth factor 2 (IGF2) are important mediators of these processes and, consequently, of life-history strategies. We sprint-trained green anole (Anolis carolinensis) females to test the responsiveness of IGF1 and IGF2 hepatic gene expression to exercise training. We also tested how sprint training would affect glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and eukaryotic elongation factor 2 (EEF2). The former is a crucial enzyme for glycolytic function in a cell, and the latter is necessary for protein synthesis. Resistance exercise forces animals to increase investment of resources towards skeletal muscle growth. Because IGF1 and IGF2 are important hormones for growth, and GAPDH and EEF2 are crucial for proper cellular function, we hypothesized that these four genes would be affected by sprint training. We found that sprint training affects IGF and EEF2 expression, such that larger sprint-trained lizards express hepatic IGF1, IGF2, and EEF2 to a lesser extent than similarly sized untrained lizards. These results demonstrate that the IIS, and pathways connected to it, can react in a size-dependent manner and are implicated in the exercise response in reptiles.

Intermittent methionine restriction reduces IGF‐1 levels and produces similar healthspan benefits to continuous methionine restriction

Article

Full-text available

May 2022
AGING CELL

A sustained state of methionine restriction (MR) dramatically extends the healthspan of several model organisms. For example, continuously methionine-restricted rodents have less age-related pathology and are up to 45% longer-lived than controls. Promisingly, MR is feasible for humans, and studies have suggested that methionine-restricted individuals may receive similar benefits to rodents. However, long-term adherence to a methionine-restricted diet is likely to be challenging for many individuals. Prompted by this, and the fact that intermittent variants of other healthspan-extending interventions (i.e., intermittent fasting and the cyclic ketogenic diet) are just as effective, if not more, than their continuous counterparts, we hypothesized that an intermittent form of MR might produce similar healthspan benefits to continuous MR. Accordingly, we developed two increasingly stringent forms of intermittent MR (IMR) and assessed whether mice maintained on these diets demonstrate the beneficial metabolic changes typically observed for continuous MR. To the best of our knowledge, we show for the first time that IMR produces similar beneficial metabolic effects to continuous MR, including improved glucose homeostasis and protection against diet-induced obesity and hepatosteatosis. In addition, like continuous MR, IMR confers beneficial changes in the plasma levels of the hormones IGF-1, FGF-21, leptin, and adiponectin. Together, our findings demonstrate that the more practicable intermittent form of MR produces similar healthspan benefits to continuous MR, and thus may represent a more appealing alternative to the classical intervention.

The Complementary Role of Exercise and Fasting in the Treatment of Cancer: A Narrative Review of Mechanisms Related to Metabolic Stress Elements

Article

Full-text available

Apr 2022

Background: Complementary methods such as physical activity (PA) and fasting are particularly important for cancer patients. The present study reviewed the effects of regular PA and fasting on cancer patients and attempted to explain the relevant mechanisms. Methods: Several electronic databases such as PubMed, Elsevier, and Google Scholar were searched for keywords. After reviewing, 412 articles were identified until February 1, 2021. The inclusion criteria included meta-analysis, clinical intervention studies that considered different effects of fasting and various types of exercise on health indicators. After carefully reviewing and eliminating duplicates, 68 articles were identified based on the PICO format (participants, intervention, comparison, and results). Results: The short-term fasting (STF) before chemotherapy (48-72 hours) or rehabilitation exercise could be modulating fasting blood sugar, growth factors, oxidative stress (OS), and inflammatory pathways. In addition, physiological metabolic stress induced by STF or rehabilitation exercise could regulate sex hormone-binding globulin, fat oxidation, leptin secretion, hyperinsulinemia, maintaining mass muscle, and bone density, boosting the immune system, and improving the therapeutic index of cancer. Conclusion: Metabolic stress in cancer cells leads to the intake of high doses of chemotherapy. The rehabilitation exercise prevents the complications of the disease and improves the patient’s quality of life. Thus, these interventions can be used to improve the cancer-based therapeutic index on individual differences.

The Complementary Role of Exercise and Fasting in the Treatment of Cancer: A Narrative Review of Mechanisms Related to Metabolic Stress Elements

Article

Full-text available

Apr 2022

Impact du niveau d'apport protéino-glucidique sur l’homéostasie et le contrôle de l’ingestion des protéines et de l’énergie

Thesis

Nov 2021

Joséphine Gehring

Le niveau d’apport protéique est contrôlé de façon très précise par des signaux agissant sur le comportement alimentaire qui visent à atteindre et réguler un niveau d’apport « cible », communément de 10-20% de l’apport énergétique, pour équilibrer le bilan azoté. Cependant, les études d’auto-sélection alimentaire montrent que les rats, mais aussi d’autres espèces, ayant la possibilité de séparer le contrôle de l’ingestion des protéines du contrôle de l’ingestion des glucides et des lipides consomment en moyenne 30% de protéines. L’homéostasie protéique ne semble donc pas être le seul critère qui régule le niveau d’apport protéique. Certaines études suggèrent en effet que l’ingestion d’un niveau élevé de protéines au dépend des glucides aurait des effets métaboliques positifs permettant de réduire la dépendance du métabolisme vis-à-vis de l’insuline, de limiter la prise de poids et de gras, et de réduire le développement de syndromes métaboliques. L’objectif de cette thèse était de mieux comprendre les mécanismes de contrôle de l’ingestion de protéine et leur interaction avec le contrôle énergétique. Les travaux réalisés ont montré que même si une teneur en protéine de 15% était suffisante pour assurer le métabolisme protéique, elle ne l’était pas pour optimiser le métabolisme énergique par rapport au niveau sélectionné par les rats. Le niveau protéique choisi était en moyenne de 30%, et était défendu en s’ajustant à la quantité et à la qualité des glucides proposés, notamment en diminuant proportionnellement à la baisse de l’index glycémique des régimes. Nos résultats suggèrent aussi que FGF21 joue un rôle dans l'orientation des choix alimentaires vers les protéines, puisque les rats en auto-sélection alimentaire maintiennent des taux plasmatiques de FGF21 très bas. Enfin, les taux de FGF21 n’étaient régulés que part le niveau d’apport protéique, et étaient insensibles à l’apport glucidique.

Protein-carbohydrate interaction effects on energy balance, FGF21, IGF-1, and hypothalamic gene expression in rats

Article

Sep 2021

Amino acids are involved in energy homeostasis, just as are carbohydrates and lipids. Therefore, mechanisms controlling protein intake should operate independently and in combination with systems controlling overall energy intake to coordinate appropriate metabolic and behavioural responses. The objective of this study was to quantify the respective roles of dietary protein and carbohydrate levels on energy balance, plasma FGF21 and IGF-1 concentrations, and hypothalamic neurotransmitters (POMC, NPY, AgRP and CART). In a simplified geometric framework, 7-week-old male Wistar rats were fed 12 diets containing 3 to 30% protein for 3 weeks, in which carbohydrates accounted for 30 to 75% of the carbohydrate and fat part of the diet. As a result of this study, most of the studied parameters (body composition, energy expenditure, plasma FGF21 and IGF-1 concentrations and Pomc/Agrp ratio) responded mainly to the protein content and to a lesser extent to the carbohydrate content in the diet.

The GH-IGF-1 Axis in Circadian Rhythm

Article

Full-text available

Sep 2021

Organisms have developed common behavioral and physiological adaptations to the influence of the day/night cycle. The CLOCK system forms an internal circadian rhythm in the suprachiasmatic nucleus (SCN) during light/dark input. The SCN may synchronize the growth hormone (GH) secretion rhythm with the dimming cycle through somatostatin neurons, and the change of the clock system may be related to the pulsatile release of GH. The GH—insulin-like growth factor 1 (IGF-1) axis and clock system may interact further on the metabolism through regulatory pathways in peripheral organs. We have summarized the current clinical and animal evidence on the interaction of clock systems with the GH—IGF-1 axis and discussed their effects on metabolism.

Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer

Article

Full-text available

Jun 2021
INT J MOL SCI

Aldona Kasprzak

Colorectal cancer (CRC) is one of the most common aggressive carcinoma types worldwide, characterized by unfavorable curative effect and poor prognosis. Epidemiological data re-vealed that CRC risk is increased in patients with metabolic syndrome (MetS) and its serum components (e.g., hyperglycemia). High glycemic index diets, which chronically raise post-prandial blood glucose, may at least in part increase colon cancer risk via the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. Hyperactivated glucose uptake and aerobic glycolysis (the Warburg effect) are considered as a one of six hallmarks of cancer, including CRC. However, the role of insulin/IGF-1 signaling during the acquisition of the Warburg metabolic phenotypes by CRC cells is still poorly understood. It most likely results from the interaction of multiple processes, directly or indirectly regulated by IGF-1, such as activation of PI3K/Akt/mTORC, and Raf/MAPK signaling pathways, activation of glucose transporters (e.g., GLUT1), activation of key glycolytic enzymes (e.g., LDHA, LDH5, HK II, and PFKFB3), aberrant expression of the oncogenes (e.g., MYC, and KRAS) and/or overexpression of signaling proteins (e.g., HIF-1, TGF-β1, PI3K, ERK, Akt, and mTOR). This review describes the role of IGF-1 in glucose metabolism in physiology and colorectal carcinogenesis, including the role of the insulin/IGF system in the Warburg effect. Furthermore, current therapeutic strategies aimed at repairing impaired glucose metabolism in CRC are indicated.

Association Between Serum Insulin-Like Growth Factor 1 Levels and the Clinical Symptoms of Chronic Schizophrenia: Preliminary Findings

Article

Full-text available

Mar 2021

Purpose: Insulin-like growth factor 1 (IGF-1) is a trophic mediator that is regulated by growth hormone and associated with the proliferation, development, and growth of neural cells. IGF-1 may be associated with the pathophysiology of schizophrenia, but this association remains controversial. This study aimed to investigate the relationship between serum IGF-1 levels and psychiatric symptoms in patients with chronic schizophrenia. Patients and Methods: A total of 65 patients were recruited from the University of Occupational and Environmental Health, Komine Eto Hospital, Moji Matsugae Hospital, Shin-Moji Hospital, and Tsutsumi Hospital in Kitakyushu between September 2019 and June 2020. Further, 20 healthy age- and sex-matched control participants were recruited from the Komine Eto Hospital and the University of Occupational and Environmental Health. Patients with schizophrenia were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Drug-Induced Extrapyramidal Symptoms Scale. Serum levels of free plus albumin-bound IGF-1 (IGF-1) were measured by immunoradiometric assay. The measurements were performed using antibody beads for bound/free separation. Associations between serum IGF-1 levels and the PANSS scores were determined. We also examined the associations between serum IGF-1 levels and diabetes, antipsychotic drug use, and disease duration. Results: No significant difference was found in the serum IGF-1 level between patients with schizophrenia and healthy controls. Serum IGF-1 levels were significantly negatively correlated with the PANSS total score ( R ² = 0.06, p = 0.015) and PANSS general score ( R ² = 0.088, p = 0.008), but not with the PANSS positive scores and PANSS negative scores. Serum IGF-1 levels were not related to the prevalence of diabetes ( p = 0.64). However, a significant correlation was observed between serum IGF-1 levels and age ( B = −1.88, p < 0.0001). Serum IGF-1 levels could not distinguish patients with schizophrenia and healthy controls. Conclusion: The association between serum IGF-1 levels and psychiatric symptoms may be complicated in patients with chronic schizophrenia.

Energy hormone response to fasting-induced dyslipidemia in obese and non-obese donkeys

Article

Mar 2021

Metabolic and endocrine disorders, such as dyslipidemia, are common in donkeys. Negative energy balance due to fasting, stressful conditions, or disease is a major trigger for fat mobilization often leading to dyslipidemia. The hormonal response to fasting has not been well characterized in donkeys. Therefore, this work aimed to study variations in insulin, glucagon, leptin, total adiponectin, ghrelin, and insulin-like growth factor-1 concentrations, insulin-to-glucagon (IGR) and glucagon-to-insulin (GIR) molar ratios, and lipid and carbohydrate parameters during a 66 h fasting period in 8 adult donkeys, and to determine differences depending on body condition. Obese donkeys developed earlier lipid mobilization (increased plasma total triglyceride and total cholesterol concentrations) compared to non-obese donkeys. Plasma glucose and leptin concentrations decreased in obese animals. After 60 h fasting, obese donkeys showed a significant increase in glucagon and decrease in leptin. GIR significantly increased, while insulin and IGR decreased in both groups. These findings support faster lipid mobilization in response to negative energy status in obese donkeys during fasting, which could be linked to greater glucagonemia and could explain the predisposition of these animals to dyslipidemia.

The effects of lycopene supplementation on serum insulin-like growth factor 1 (IGF-1) levels and cardiovascular disease: A dose-response meta-analysis of clinical trials

Article

Full-text available

Jan 2021
COMPLEMENT THER MED

Background The results of human studies assessing the efficacy of lycopene on insulin-like growth factor 1 (IGF-1) levels are inconsistent. Thus, we performed a systematic review and meta-analysis to examine the effects of lycopene supplementation on serum IGF-1 levels and cardiovascular disease. Methods The literature published up to January 2020 was searched using the electronic databases Scopus, PubMed/Medline, Web of Science, Embase and Google Scholar. Results Seven qualified trials were included in the current meta-analysis. IGF-1 levels were non-significantly decreased in lycopene group compared to the control (WMD: −6.74 ng/mL, 95 % CI: −23.01 to 9.52, p = 0.42; I² = 94.3 %). Subgroup analysis revealed a significantly decrease in IGF-1 levels upon lycopene supplementation at doses ≥15 mg/d (WMD: −6.40 ng/mL), intervention period <12 weeks (WMD: −6.49 ng/mL), and subjects aged ≥60 years (WMD: −24.98 mg/dl). In addition, lycopene intake significantly reduced IGF-1 levels upon healthy conditions (WMD: −25.59 ng/mL) when compared with cancer patients (WMD: 0.35 ng/mL). In addition, the effect of lycopene supplementation was significant in patients diagnosed with cardiac disorders. Conclusion Overall, lycopene intake was not associated with reduced serum IGF-1 levels. However, association was significant when lycopene was administrated at doses >15 mg/d, for <12 weeks, as well as for healthy conditions and patients aged ≥60 years. In addition, lycopene supplementation exhibited potential health benefits in the management of patients with cardiac disorders.

Can Blood-Circulating Factors Unveil and Delay Your Biological Aging?

Article

Full-text available

Dec 2020

According to the World Health Organization, the population of over 60 will double in the next 30 years in the developed countries, which will enforce a further raise of the retirement age and increase the burden on the healthcare system. Therefore, there is an acute issue of maintaining health and prolonging active working longevity, as well as implementation of early monitoring and prevention of premature aging and age-related disorders to avoid early disability. Traditional indicators of biological age are not always informative and often require extensive and expensive analysis. The study of blood factors is a simple and easily accessible way to assess individual health and supplement the traditional indicators of a person’s biological age with new objective criteria. With age, the processes of growth and development, tissue regeneration and repair decline; they are gradually replaced by enhanced catabolism, inflammatory cell activity, and insulin resistance. The number of senescent cells supporting the inflammatory loop rises; cellular clearance by autophagy and mitophagy slows down, resulting in mitochondrial and cellular damage and dysfunction. Monitoring of circulated blood factors not only reflects these processes, but also allows suggesting medical intervention to prevent or decelerate the development of age-related diseases. We review the age-related blood factors discussed in recent publications, as well as approaches to slowing aging for healthy and active longevity.

Key Molecular Mechanisms of Aging, Biomarkers, and Potential Interventions

Article

Nov 2020

The mechanisms of aging are described at the molecular, cell, tissue, and systemic levels. Primary age-dependent molecular lesions activate the cell stress response to compensate for the resulting defects, but the mechanisms that recover and maintain homeostasis are gradually deteriorated. When the amount of errors reaches a critical threshold in regulatory networks, a phase transition from health to disease occurs at the systemic level. The review considers the approaches to quantitative assessment of the aging process (bio-markers of aging) and promising interventions to slow down the aging process and to reduce the risk of age-dependent diseases.

Ключевые молекулярные механизмы старения, биомаркеры и потенциальные интервенции

Article

Oct 2020

В обзоре рассмотрены механизмы старения на молекулярном, клеточном, тканевом и системном уровнях. Первичные молекулярные повреждения вызывают клеточный ответ, направленный на компенсацию нарушений, однако постепенно выходят из строя сами механизмы восстановления и поддержания гомеостаза. Когда количество ошибок в регуляторных сетях достигает критического порога, на системном уровне происходит фазовый переход из состояния здоровья в состояние бо-лезни. Рассмотрены подходы к количественной оценке процесса старения (биомаркеры старения), а также интервенции, перспективные с точки зрения возможности замедления процессов старения и уменьшения риска развития возрастзависимых заболеваний. Ключевые слова: старение, возрастзависимые заболевания, биомаркеры старения, геропротекторы ВВЕДЕНИЕ В связи с увеличением среднего возраста насе-ления проблема профилактики преждевременного старения и лечения возрастных заболеваний выхо-дит на первый план в современном здравоохране-нии [1]. Перспективным подходом к реализации этой цели считается воздействие на ключевые молекулярные механизмы, связанные со старением - основным фактором риска возрастзависимых заболеваний, направленное на подавление патологических процессов и активацию защитных систем клетки и организма в целом [2, 3]. В настоящее время практически отсутствуют клинически прове-ренные терапевтические вмешательства в ход мо-лекулярных процессов естественного и ускоренного старения, однако имеется большое количество перспективных доклинических исследований [1, 4]. Кроме того, для трансляции в клинику потребуется разработка системы биомаркеров старения, пригодных как для оценки состояния организма, так и для определения эффективности геропротек-торной терапии [5]. Основатель геронтологии Бенджамин Гомперц вывел закон смертности, впоследствии названный его именем: "Возможно, что смерть может быть следствием двух обычно сосуществующих причин: одна -случайность, без предшествующей предрасположенности к смерти или изнашиванию; другая - изнашивание или возрастающая неспо-собность противостоять разрушению" [6]. Тем самым Гомперц не только отделил внешние при-чины смертности от внутренних (старения), но и предвосхитил разделение механизмов старения на накопление повреждений и ошибок ("изнашивание") и утрату способности восстанавливать ошибки из-за поломок самих систем репарации. В обзоре с современных позиций рассмотрена комплексная динамика процесса старения на разных уровнях биологической организации - от первичных повреждений на молекулярном уровне и ответа клетки на них, который отчасти компенсирует нарушения, но может вносить новые ошибки (в том числе, приводящие к нарушению регулирования систем поддержания гомеостаза), до системного уровня, когда количество накопленных ошибок вызывает фазовый переход из состояния здоровья в состояние болезни. Цель обзора состояла в обобщении современных взглядов на ключевые механизмы старения, а также на биомаркеры, характеризующие биоло-гический возраст организма и связанные со ста-рением патологические процессы, и на геропротекторные интервенции, нацеленные на профилактику преждевременного старения.

Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats

Article

Full-text available

Aug 2020
INT J MOL SCI

Food deprivation resulting in muscle atrophy may be detrimental to health. To better understand how muscle mass is regulated during such a nutritional challenge, the current study deciphered muscle responses during phase 2 (P2, protein sparing) and phase 3 (P3, protein mobilization) of prolonged fasting in rats. This was done using transcriptomics analysis and a series of biochemistry measurements. The main findings highlight changes for plasma catabolic and anabolic stimuli, as well as for muscle transcriptome, energy metabolism, and oxidative stress. Changes were generally consistent with the intense use of lipids as fuels during P2. They also reflected increased muscle protein degradation and repressed synthesis, in a more marked manner during P3 than P2 compared to the fed state. Nevertheless, several unexpected changes appeared to be in favor of muscle protein synthesis during fasting, notably at the level of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, transcription and translation processes, and the response to oxidative stress. Such mechanisms might promote protein sparing during P2 and prepare the restoration of the protein compartment during P3 in anticipation of food intake for optimizing the effects of an upcoming refeeding, thereby promoting body maintenance and survival. Future studies should examine relevance of such targets for improving nitrogen balance during catabolic diseases.

Unravelling the health effects of fasting: a long road from obesity treatment to healthy life span increase and improved cognition

Article

Full-text available

Jun 2020

In recent years a revival of interest has emerged in the health benefits of intermittent fasting and long-term fasting, as well as of other related nutritional strategies. In addition to meal size and composition a new focus on time and frequency of meals has gained attention. The present review will investigate the effects of the main forms of fasting, activating the metabolic switch from glucose to fat and ketones (G-to-K), starting 12–16 h after cessation or strong reduction of food intake. During fasting the deactivation of mTOR regulated nutrient signalling pathways and activation of the AMP protein kinase trigger cell repair and inhibit anabolic processes. Clinical and animal studies have clearly indicated that modulating diet and meal frequency, as well as application of fasting patterns, e.g. intermittent fasting, periodic fasting, or long-term fasting are part of a new lifestyle approach leading to increased life and health span, enhanced intrinsic defences against oxidative and metabolic stresses, improved cognition, as well as a decrease in cardiovascular risk in both obese and non-obese subjects. Finally, in order to better understand the mechanisms beyond fasting-related changes, human studies as well as non-human models closer to human physiology may offer useful clues. • KEY-MESSAGES • Biochemical changes during fasting are characterised by a glucose to ketone switch, leading to a rise of ketones, advantageously used for brain energy, with consequent improved cognition. • Ketones reduce appetite and help maintain effective fasting. • Application of fasting patterns increases healthy life span and defences against oxidative and metabolic stresses. • Today’s strategies for the use of therapeutic fasting are based on different protocols, generally relying on intermittent fasting, of different duration and calorie intake. • Long-term fasting, with durations between 5 and 21 days can be successfully repeated in the course of a year.

Ramadan intermittent fasting and immunity: An important topic in the era of COVID-19

Article

Full-text available

Apr 2020
Ann Thorac Med

With the growing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-related coronavirus (SARS-CoV-2) infection, a parallel growing interest arose concerning the preventive therapies, dietary behaviors, and remedies that may boost the immunity of against SARS-CoV-2 infection. Further, as Ramadan intermittent religious fasting that is practiced by about one and a half billion people throughout the globe is coincide this year with COVID-19 pandemic, a growing debate rose concerning the expected impact of fasting during Ramadan month and the associated dietary and lifestyle behaviors on the body's immunity against the pandemic infection. Published literature was searched to find out how intermittent fasting and its model of Ramadan affect the various aspects related to the body's immunity against microbial infections. Intermittent fasting was found to impact immunity by changing different related elements, including oxidative stress and inflammation, metabolism, body weight, and body composition. Dietary and lifestyle modifications during Ramadan month and their impact on immunity, such as water intake and hydration status, sleep duration and timing, caloric intake and mealtime, and social and religious activities, were addressed. Further research is warranted to figure out how intermittent fasting during Ramadan affects immunity against SARS-CoV-2 infection.

Ramadan intermittent fasting and immunity: An important topic in the era of COVID-19

Article

Full-text available

Jul 2020
Ann Thorac Med

Impact of dehydroepianrosterone (DHEA) supplementation on serum levels of insulin-like growth factor 1 (IGF-1): A dose-response meta-analysis of randomized controlled trials

Article

Apr 2020
EXP GERONTOL

Background and aim Inconsistencies exist with regard to the influence of dehydroepiandrosterone (DHEA) supplementation on insulin-like growth factor 1 (IGF-1) levels. The inconsistencies could be attributed to several factors, such as dosage, gender, and duration of intervention, among others. To address these inconsistencies, we conducted a systematic review and meta-analysis to combine findings from randomized controlled trials (RCTs) on this topic. Methods Electronic databases (Scopus, PubMed/Medline, Web of Science, Embase and Google Scholar) were searched for relevant literature published up to February 2020. Results Twenty-four qualified trials were included in this meta-analysis. It was found that serum IGF-1 levels were significantly increased in the DHEA group compared to the control (weighted mean differences (WMD): 16.36 ng/ml, 95% CI: 8.99, 23.74; p = .000). Subgroup analysis revealed that a statistically significant increase in serum IGF-1 levels was found only in women (WMD: 23.30 ng/ml, 95% CI: 13.75, 32.87); in participants who supplemented 50 mg/d DHEA (WMD: 15.75 ng/ml, 95% CI: 7.61, 23.89); in participants undergoing DHEA intervention for >12 weeks (WMD: 17.2 ng/ml, 95% CI: 8.02, 26.22); in participants without an underlying comorbidity (WMD: 19.11 ng/ml, 95% CI: 10.69, 27.53); and in participants over the age of 60 years (WMD: 19.79 ng/ml, 95% CI: 9.86, 29.72). Conclusion DHEA supplementation may increase serum IGF-I levels especially in women and older subjects. However, further studies are warranted before DHEA can be recommended for clinical use.

Effect of dietary L-carnitine supplementation to sows during gestation and/or lactation on sow productivity, muscle maturation and lifetime growth in progeny from large litters

Article

Full-text available

Mar 2020

Genetic selection for increased sow prolificacy has resulted in decreased mean piglet birth-weight. This study aimed to investigate the effect of L-carnitine (CAR) supplementation to sows during gestation and/or lactation on sow productivity, semitendinosus muscle (STM) maturity, and lifetime growth in progeny. Sixty-four sows were randomly assigned to one of four dietary treatments at breeding until weaning; CONTROL (0mg CAR/d), GEST (125mg CAR/d during gestation), LACT (250mg CAR/d during lactation), and BOTH (125mg CAR/d during gestation & 250mg CAR/d during lactation). The total number of piglets born per litter was greater for sows supplemented with CAR during gestation (17.3 v 15.8 ± 0.52; P<0.05). Piglet birth-weight (total and live) was unaffected by sow treatment (P>0.05). Total myofibre number (P=0.08) and the expression level of selected myosin heavy chain genes in the STM (P<0.05) was greater in piglets of sows supplemented with CAR during gestation. Pigs from sows supplemented with CAR during gestation had lighter carcasses at slaughter than pigs from non-supplemented sows during gestation (83.8 v 86.7 ± 0.86kg; P<0.05). In conclusion, CAR supplementation during gestation increased litter size at birth without compromising piglet birth-weight. Results also showed that the STM of piglets born to sows supplemented with CAR during gestation was more developed at birth. However, carcass weight at slaughter was reduced in progeny of sows supplemented with CAR during gestation. The CAR supplementation strategy applied during gestation in this study could be utilized by commercial pork producers to increase sow litter size and improve offspring muscle development.

Muscle fibre transition and transcriptional changes of horse skeletal muscles during traditional Mongolian endurance training

Article

Full-text available

Jun 2023
EQUINE VET J

Background: Traditional Mongolian endurance training is an effective way to improve the athletic ability of the horse for endurance events and is widely used. This incorporates aerobic exercise and intermittent fasting and these altered physiologic conditions are associated with switches between muscle fibre types. Objectives: To better understand the adaption of horse skeletal muscle to traditional Mongolian endurance training from muscle fibre characteristics and transcriptional levels and to explore possible molecular mechanisms associated with the endurance performance of horses. Study design: Before-after study. Methods: Muscle fibre type switches and muscle transcriptome changes in six Mongolian horses were assessed during 4 weeks of training. Transcriptomic and histochemical analyses were performed. The activities of oxidative and glycolytic metabolic enzymes were analysed and we generated deep RNA-sequencing data relating to skeletal muscles. Results: A fast-to-slow muscle fibre transition occurred in horse skeletal muscles, with a concomitant increase of oxidative enzyme activity and decreased glycolytic enzyme activity. Numerous differentially expressed genes were involved in the control of muscle protein balance and degradation. Differential alternative splicing events were also found during training which included exon-skipping events in Ttn that were associated with muscle atrophy. Differentially expressed noncoding RNAs showed connections with muscle protein balance-related pathways and fibre type specification via the post-transcriptional regulation of miRNA. Main limitations: The study focuses on horse athletic ability only from the aspect of muscular adaptation. Conclusion: Traditional Mongolian endurance training-induced muscle fibre transition and metabolic and transcriptional changes. Muscle-specific non-coding RNAs could contribute to these transcriptomic changes during training.

Ketogenic diet acutely improves gas exchange and sleep apnoea in obesity hypoventilation syndrome: A non‐randomized crossover study

Article

May 2023

Background and objective: Obesity hypoventilation syndrome (OHS) causes hypercapnia which is often refractory to current therapies. We examine whether hypercapnia in OHS can be improved by a ketogenic dietary intervention. Methods: We conducted a single-arm crossover clinical trial to examine the impact of a ketogenic diet on CO2 levels in patients with OHS. Patients were instructed to adhere to 1 week of regular diet, 2 weeks of ketogenic diet, followed by 1 week of regular diet in an ambulatory setting. Adherence was assessed with capillary ketone levels and continuous glucose monitors. At weekly visits, we measured blood gases, calorimetry, body composition, metabolic profiles, and sleep studies. Outcomes were assessed with linear mixed models. Results: A total of 20 subjects completed the study. Blood ketones increased from 0.14 ± 0.08 during regular diet to 1.99 ± 1.11 mmol/L (p < 0.001) after 2 weeks of ketogenic diet. Ketogenic diet decreased venous CO2 by 3.0 mm Hg (p = 0.008), bicarbonate by 1.8 mmol/L (p = 0.001), and weight by 3.4 kg (p < 0.001). Sleep apnoea severity and nocturnal oxygen levels significantly improved. Ketogenic diet lowered respiratory quotient, fat mass, body water, glucose, insulin, triglycerides, leptin, and insulin-like growth factor 1. Rebound hypercapnia was observed after resuming regular diet. CO2 lowering was dependent on baseline hypercapnia, and associated with circulating ketone levels and respiratory quotient. The ketogenic diet was well tolerated. Conclusion: This study demonstrates for the first time that a ketogenic diet may be useful for control of hypercapnia and sleep apnoea in patients with obesity hypoventilation syndrome.

Intermittent fasting—the future treatment in NASH patients?

Article

Apr 2023
HEPATOLOGY

Non-alcoholic steatohepatitis (NASH) is one of the leading causes of chronic liver disease with the potential of evolving towards end-stage liver disease and hepatocellular carcinoma (HCC), even in the absence of cirrhosis. Apart from becoming an increasingly prevalent indication for liver transplantation in cirrhotic and HCC patients, its burden on the healthcare system is also exerted by the increased number of non-cirrhotic NASH patients. Intermittent fasting (IF) has recently gained more interest in the scientific community as a possible treatment approach for different components of the metabolic syndrome. Basic science and clinical studies have shown that apart from inducing body weight loss, improving cardio-metabolic parameters, namely blood pressure, cholesterol and triglyceride levels, insulin and glucose metabolism, IF can reduce inflammatory markers, endoplasmic reticulum (ER) stress, oxidative stress, autophagy, and endothelial dysfunction, as well as modulate gut microbiota. This review aims to further explore the main NASH pathogenetic metabolic drivers on which IF can act upon and improve the prognosis of the disease, and summarize the current clinical evidence.

The influence of Arginine supplementation on IGF-1: A systematic review and meta-analysis

Article

Full-text available

Mar 2023

Background: Insulin-like growth factor-1 (IGF-1) secretion is thought to be induced by a semi-essential amino acid called arginine (Arg). Existing research on the effect of Arg on IGF-1 levels has provided conflicting results. This systematic review and meta-analysis investigated the efficacy of acute and chronic Arg supplementation on IGF-1 levels. Methods: PubMed, Web of Science, and Scopus were systematically searched until November 2022. The meta-analysis was performed using random- and fixed-effects models. Sensitivity and subgroup analyses were also carried out. Publication bias was assessed using Begg's test. Results: Nine studies were included in this meta-analysis. Chronic Arg supplementation did not significantly change IGF-1 levels (SMD = 0.13 ng/ml; %95 CI: -0.21, 0.46; p = 0.457). Furthermore, the IGF-1 level was not significantly affected by acute Arg supplementation (SMD = 0.10 ng/mL; CI: -0.42, 0.62; p = 0.713). The meta-analysis results did not change following subgroup analyses based on the duration, dosage, age, placebo, and study population. Conclusion: In conclusion, there was no significant effect of Arg supplementation on IGF-1 concentration. The meta-analyses revealed no acute or chronic Arg supplementation impact on IGF-1 levels.

Conditioned place avoidance is associated with a distinct hippocampal phenotype, partly preserved pattern separation, and reduced reactive oxygen species production after stress

Article

Full-text available

Feb 2023
GENES BRAIN BEHAV

Stress is associated with contextual memory deficits, which may mediate avoidance of trauma-associated contexts in posttraumatic stress disorder. These deficits may emerge from impaired pattern separation, the independent representation of similar experiences by the dentate gyrus-Cornu Ammonis 3 (DG-CA3) circuit of the dorsal hippocampus, which allows for appropriate behavioral responses to specific environmental stimuli. Neurogenesis in the DG is controlled by mitochondrial reactive oxygen species (ROS) production, and may contribute to pattern separation. In Experiment 1, we performed RNA sequencing of the dorsal hippocampus 16 days after stress in rats that either develop conditioned place avoidance to a predator urine-associated context (Avoiders), or do not (Non-Avoiders). Weighted genome correlational network analysis showed that increased expression of oxidative phosphorylation-associated gene transcripts and decreased expression of gene transcripts for axon guidance and insulin signal-ing were associated with avoidance behavior. Based on these data, in Experiment 2, we hypothesized that Avoiders would exhibit elevated hippocampal (HPC) ROS production and degraded object pattern separation (OPS) compared with Non-Avoiders. Stress impaired pattern separation performance in Non-Avoider and Avoider rats compared with nonstressed Controls, but surprisingly, Avoiders exhibited partly preserved pattern separation performance and significantly lower ROS production compared with Non-Avoiders. Lower ROS production was associ- ated with better OPS performance in Stressed rats, but ROS production was not associated with OPS performance in Controls. These results suggest a strong neg- ative association between HPC ROS production and pattern separation after stress, and that stress effects on these outcome variables may be associated with avoidance of a stress-paired context.

Short- and Long-Term Effects of Nutritional State on IGF-1 Levels in Nestlings of a Wild Passerine

Article

Jan 2022

The effect of long-term ketogenic diet on serum adiponectin and insulin-like growth factor-1 levels in mice

Article

Oct 2021

Objectives Noncommunicable disease (NCD) including obesity, cancer, and diabetes has become particular concern worldwide due to its morbidity and mortality which keep increasing annually. Adiponectin and insulin-like growth factor-1 (IGF-1) are known to be substances that are involved in the development of NCD. Several diet regimens have been developed to treat NCD, one of which is the ketogenic diet (KD). This study aimed to analyze the long-term KD effect on serum adiponectin and IGF-1 levels in mice. Methods This study was a real experimental with post-test only controls group design. The subjects were 14 male mice (2–3 months, 20–30 g) were randomly divided into two groups, K1 (n=7, standard diet) and K2 (n=7, KD with a composition of 60% fat, 30% protein, and 10% fiber). All subjects were given diet intervention for 8 weeks ad libitum . Serum adiponectin and IGF levels were measured in post-intervention using Enzyme-Linked Immunosorbent Assay. Distribution of normality was analyzed by the Shapiro–Wilk Test, mean difference using Independent T-Test, and linear correlation using Pearson’s Correlation Test. Data analysis was performed using Statistic Package for Social Science Version 16. Results Serum adiponectin levels in K1 (0.080 ± 0.012) pg/mL and K2 (0.099 ± 0.005) pg/mL, with p=0.003. Serum IGF-1 levels in K1 (133.535 ± 25.702) ng/mL and K2 (109.987 ± 27.118) ng/mL, with p=0.121. Coefficient correlation between serum adiponectin and serum IGF-1 levels [r]=−0.401, with p=0.155. Conclusions Long-term KD increases serum adiponectin levels and has no effect on serum IGF-1 levels. There was no significant correlation between serum adiponectin and serum IGF-1 levels.

Effects of raloxifene administration on serum levels of insulin-like growth factor-1 and insulin-like growth factor-binding protein 3 levels: A systematic review and meta-analysis of randomized controlled trials

Article

Jul 2021
GROWTH HORM IGF RES

Objective To ascertain the clinical magnitude of raloxifene administration on insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) levels. Methods A systematic comprehensive search was performed without language limitation up to 14 December 2020. We included only trials that assessed the effect of raloxifene on IGF-1 and IGFBP-3 in adults. Meta-analysis was performed using the Stata software (Stata Corp. College Station, Texas, USA). Results Seven arms were included, encompassing postmenopausal women with type 2 diabetes mellitus, postmenopausal women with breast cancer, healthy postmenopausal women, and healthy elderly men. Raloxifene therapy significantly reduced IGF-1 levels (WMD: −2.92 nmol/L, 95% CI: −3.49, −2.35, p < 0.001) compared to placebo. Raloxifene dosage ˃60 mg/day (WMD: −3.29 ng/mL, 95% CI: −3.50 to −3.08, I² = 0.0%) decreased IGF-1 levels more than 60 mg/day (WMD: −2.29 ng/mL, 95% CI: −2.90 to −1.69, I² = 16%). Moreover, intervention duration ˃26 weeks (WMD: −3.48 ng/mL, 95% CI: −5.26 to −1.69, I² = 0.0%) reduced IGF-1 levels more than ˂26 weeks (WMD: −2.55 ng/mL, 95% CI: −3.31 to −1.79, I² = 92%). In contrast, overall results from the random-effects model did not suggest a significant change in IGFBP-3 levels upon raloxifene therapy. Conclusion Raloxifene therapy significantly reduced serum levels of IGF-1 levels but without changes in IGFPB-3 levels.

Selenium supplementation inhibits IGF-1 signaling and confers methionine restriction-like healthspan benefits to mice

Article

Full-text available

Mar 2021
eLife

Methionine restriction (MR) dramatically extends the healthspan of several organisms. Methionine-restricted rodents have less age-related pathology and increased longevity as compared with controls, and recent studies suggest that humans might benefit similarly. Mechanistically, it is likely that the decreased IGF-1 signaling that results from MR underlies the benefits of this regimen. Thus, we hypothesized that interventions that decrease IGF-1 signaling would also produce MR-like healthspan benefits. Selenium supplementation inhibits IGF-1 signaling in rats, and has been studied for its putative healthspan benefits. Indeed, we show that feeding mice a diet supplemented with sodium selenite results in an MR-like phenotype, marked by protection against diet-induced obesity, as well as altered plasma levels of IGF-1, FGF-21, adiponectin, and leptin. Selenomethionine supplementation results in a similar, albeit less robust response, and also extends budding yeast lifespan. Our results indicate that selenium supplementation is sufficient to produce MR-like healthspan benefits for yeast and mammals.

Insulin-like Growth Factor-1, Bone Mineral Density, and Fracture: A Mendelian Randomization Study

Article

Full-text available

Jan 2021
J CLIN ENDOCR METAB

Abstract Context The associations of circulating insulin-like growth factor-1 (IGF-1) levels with bone mineral density and fracture risk are inconclusive in observational studies. Objective We conducted a mendelian randomization study to assess the associations of serum IGF-1 levels with estimated bone mineral density (eBMD) and fracture. Methods Genetic instruments for IGF-1 were selected at the genome-wide significance level (P < 5 × 10–8) from a genome-wide association study including 358 072 individuals of European ancestry. Summary-level data for eBMD (426 824 individuals) and fracture (53 184 fracture cases and 373 611 noncases) were obtained from the UK Biobank study. Univariable and multivariable mendelian randomization analyses methods were used to estimate the associations of IGF-1 with eBMD and fracture. The main outcome measure included the change of eBMD and odds ratio of fracture per genetically predicted 1-SD increase of serum IGF-1 levels. Results For 1-SD increase in IGF-1, the change of eBMD levels was 0.04 g/cm2 (95% CI, 0.01-0.07; P = .011) and the odds ratio of fracture was 0.94 (95% CI, 0.91-0.98; P = .003). The associations persisted with similar magnitude after adjustment for height. The association was consistent for fracture but not for eBMD after excluding genetic instruments that might directly influence these outcomes. The association between IGF-1 and fracture was somewhat attenuated after adjustment for eBMD (odds ratio 0.96; 95% CI, 0.92-0.99; P = .012). Conclusion The present study supports a role for IGF-1 in preventing fracture, possibly and partly mediated by greater bone mineral density.

Obesity and malnutrition – risk factors in prediagnostic and later phases of colorectal cance

Article

Full-text available

Dec 2020

Racho S. RIBAROV

Obesity and malnutrition are subjected to comprehensive studies as risk factors in the pathogenesis of colorectal cancer (CRC). Nevertheless, the most recent scientific evidence revealed that a number of issues associated with risk impact processes remain to be clarified. The aim of the current review is to discuss the action mechanisms of obesity and malnutrition, their effect in the prediagnosis and later phases of CRC, with emphasis on concomitant oxidative stress. The relationship obesity-CRC is considered in three aspects: low-grade inflammation and role of adipocytokines, development of metabolic syndrome, lipid peroxidation and oxidative stress. Malnutrition effect is discussed in two aspects – metabolic dysregulation and oxidative stress. Data are presented on the specificity of action of the two risk factors referring to the periods of disease course. Oxidative stress is a characteristic indicator of obesity, malnutrition and CRC. This fact enables us to recommend its inclusion together with nutritional status indicators in CRC screening.

Clinical Hormonal Guidelines for the Research of the Endocrinology in Sports and Athletes: Beyond Overtraining Syndrome

Chapter

Sep 2020

Cadegiani Flávio

The importance of physical activity has achieved levels that have been recognized by as a major world public health game changer, which positively engaged a growing number of subjects to become physically active. While effects of exercise on cardiovascular and musculoskeletal systems are well described, little is known regarding hormonal adapted physiology in athletes, as well as how to detect and manage endocrine abnormalities in physically active subjects. Methodological issues and inconsistent findings precluded from a structured understanding of the endocrinology physiology of physical activity and sport. The objective of the present guideline is to uniformize the design and assessment methods of further studies in the field, based on standardized hormonal and metabolic parameters, and dynamic tests.

Diverging metabolic programmes and behaviours during states of starvation, protein malnutrition, and cachexia

Article

Full-text available

Sep 2020

Background: Our evolutionary history is defined, in part, by our ability to survive times of nutrient scarcity. The outcomes of the metabolic and behavioural adaptations during starvation are highly efficient macronutrient allocation, minimization of energy expenditure, and maximized odds of finding food. However, in different contexts, caloric deprivation is met with vastly different physiologic and behavioural responses, which challenge the primacy of energy homeostasis. Methods: We conducted a literature review of scientific studies in humans, laboratory animals, and non-laboratory animals that evaluated the physiologic, metabolic, and behavioural responses to fasting, starvation, protein-deficient or essential amino acid-deficient diets, and cachexia. Studies that investigated the changes in ingestive behaviour, locomotor activity, resting metabolic rate, and tissue catabolism were selected as the focus of discussion. Results: Whereas starvation responses prioritize energy balance, both protein malnutrition and cachexia present existential threats that induce unique adaptive programmes, which can exacerbate the caloric insufficiency of undernutrition. We compare and contrast the behavioural and metabolic responses and elucidate the mechanistic pathways that drive state-dependent alterations in energy seeking and partitioning. Conclusions: The evolution of energetically inefficient metabolic and behavioural responses to protein malnutrition and cachexia reveal a hierarchy of metabolic priorities governed by discrete regulatory networks.

Serum concentrations of insulin-like growth factor-1 as a biomarker of improved circadian rhythm sleep-wake disorder in school-aged children

Article

Sep 2020

Study objectives: We aimed to investigate whether improvements in the symptoms of circadian rhythm sleep-wake disorder following treatment were associated with an increase in serum insulin-like growth factor 1 (IGF-1) concentration. Methods: Eighty-seven school-aged children (32 males, 55 females), aged 14.31±1.50 years (mean ± standard deviation), who were admitted to our hospital with circadian rhythm sleep-wake disorder, received treatment for 6-8 weeks consisting of the following protocol: 1) lights-out for sleep occurred at 21:00, 2) phototherapy for waking started at 6:00 or 7:00, and 3) light exercise every day (e.g., a 20-30 min walk). Blood samples were collected at 08:00 to measure the serum concentrations of IGF-1, pre- and post-treatment. Results: The mean times of day of sleep onset and offset at the pre- and post-treatment timepoints were 23:32±4.21 and 10:27±2.98, and 21:26±0.55 and 6:50±0.70, respectively. The mean times of day of sleep onset and offset measured at the post-treatment timepoint were significantly earlier compared to the pre-treatment baselines (P<0.01). The mean serum levels of IGF-1 significantly increased from 315.59±68.26 ng/mL pre-treatment to 335.09±69.78 ng/mL post-treatment (P<0.01). Conclusions: Improvements in the symptoms of patients with circadian rhythm sleep-wake disorders were associated with increased serum concentrations of IGF-1, suggesting that serum IGF-1 may be a biomarker of improvements in school-aged children with circadian rhythm sleep-wake disorder.

Effects of intermittent fasting diets on plasma concentrations of inflammatory biomarkers: A systematic review and meta-analysis of randomized controlled trials

Article

Aug 2020
NUTRITION

Purpose Intermittent fasting (IF) and energy-restricted diets (ERDs) have emerged as dietary approaches to decrease the inflammatory status; however, there are no consistent results regarding humans. In order to achieve a comprehensive conclusion, we aimed to conduct a meta-analysis of randomized control trials (RCTs) to evaluate the effects of IF or ERDs on plasma concentrations of inflammatory biomarkers. Methods We systematically searched online medical databases including Web of Sciences, PubMed, SCOPUS, and Google Scholar up to June 2019. Evaluations of effect sizes were described employing in weighted mean difference (WMD) and 95% confidence interval (CI) from the random-effects model. Findings Eighteen eligible RCTs were included in this meta-analysis. The pooled estimation from the random-effect model showed that IF regimens and ERDs significantly reduced C-reactive protein (CRP) concentrations (WMD: -0.024 mg/dl; 95% CI: -0.044 to -0.005, I² = 7.0%). In addition, IF regimens (WMD: -0.029; 95% CI: -0.058, -0.000, I² = 17.9%) were more effective in reducing CRP levels than ERDs (WMD: -0.001 mg/dl; 95% CI: -0.037, 0.034, I² = 0.0%). Moreover, based on the treatment duration and types of the studies’ population, a greater reduction was observed in overweight and obese individuals (WMD: -0.03 mg/dl; 95% CI: -0.05, 0.01, I² = 42.1%), and in treatment duration ≥8 weeks (WMD: -0.03 mg/dl; 95% CI: -0.05, 0.01, I² = 0.0%) as well. However, IF and ERDs did not significantly reduced tumor necrosis factor alpha (TNF-α) (WMD: -0.158 pg/mL; p = 0.549, I² = 98.3) and interleukin-6 (IL-6) concentrations (WMD: -0.541 pg/mL; p = 0.080, I² = 94.7%). Conclusions This meta-analysis showed that IF regimens and ERDs may reduce CRP concentrations, particularly in overweight and obese subjects and through a considerable length of intervention (at least ≥2 months). However, both dietary models did not affect the concentrations of TNF-α and IL-6.

Effects of intermittent fasting and energy-restricted diets on lipid profile: A systematic review and meta-analysis

Article

Mar 2020
NUTRITION

BACKGROUND To the best of our knowledge, no systematic review and meta-analysis has evaluated the cholesterol-lowering effects of intermittent fasting (IF) and energy-restricted diets (ERD) compared with control groups. OBJECTIVE The aim of the present systematic review and meta-analysis was to summarize the effects of controlled clinical trials examining the influence of IF and ERD on lipid profiles. METHODS A systematic review of four independent databases (PubMed/Medline, Scopus, Web of Science and Google Scholar) was performed to identify clinical trials reporting the effects of IF or ERD, relative to non-diet controls, on lipid profiles in humans. A random-effects model, employing the method of DerSimonian and Laird, was used to evaluate effect sizes, and results were expressed as weighted mean difference (WMD) and 95% confidence intervals (CI). Heterogeneity between studies was calculated using Higgins I², with values ≥50% considered to represent high heterogeneity. Subgroup analyses were performed to examine the influence of intervention type, baseline lipid concentrations, degree of energy deficit, sex, health status and intervention duration. RESULTS For the outcomes of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), there were 34, 33, 35, and 33 studies meeting all inclusion criteria, respectively. Overall, results from the random-effects model indicated that IF and ERD interventions resulted significant changes in TC (WMD: -6.93 mg/dL, 95% CI: -10.18, -3.67, p <0.001; I² = 78.2%), LDL-C (WMD: -6.16 mg/dL, 95% CI: -8.42, -3.90, p ˂0.001; I² = 52 %), and TG concentrations (WMD: -6.46 mg/dL, 95% CI: -10.64, -2.27, p = 0.002; I² = 61%). HDL-C concentrations did not change significantly following IF or ERD (WMD: 0.50 mg/dL, 95% CI: -0.69, 1.70, p = 0.411; I² = 80%). Subgroup analyses indicated potentially differential effects between subgroups for one or more lipid parameter in the majority of analyses. CONCLUSION Relative to a non-diet control, IF and ERD are effective for the improvement of circulating TC, LDL-C and TG concentrations, but have no meaningful effects on HDL-C concentration. These effects are influenced by several factors which may inform clinical practice and future research. The present results suggest that these dietary practices are a means of enhancing the lipid profile in humans.

Circulating insulin-like growth factor-1: A new clue in the pathogenesis of age-related macular degeneration

Article

Full-text available

Dec 2018

In order to investigate Insulin-like growth factor-1 (IGF-1) blood levels in male and female age-matched patients affected by early, intermediate, neovascular age related macular degeneration (AMD) and healthy subjects (no AMD) were enrolled in a prospective, observational study. All patients enrolled were classified according to 4 stages classification of AMD from Age-related eye disease study (AREDS). Each subject underwent a complete ophthalmic examination including best corrected visual acuity (BCVA), applanation tonometry, slit-lamp biomicroscopic examination, color fundus photography, optical coherence tomography (OCT) and, if needed, fluorescein angiography. Overall, 224 anti-VEGF naïve subjects including 56 patients in early AMD group, 56 patients in intermediate AMD group, 56 patients in neovascular AMD group and 56 patients in no AMD group were recruited. For each group 28 male patients and 28 female patients were enrolled. IGF-1 hematic levels were significantly higher (p < 0.005) in the neovascular AMD group and in the intermediate AMD group in comparison to no AMD group; no significant difference between early AMD group and no AMD group was found. Our analysis has shown an increment of IGF-1 levels in both neovascular and intermediate stage of AMD supporting the hypothesis that IGF-1 may play a role in the pathogenesis of AMD.

Programmed longevity, youthspan, and juventology

Article

Full-text available

Oct 2018
AGING CELL

Valter D. Longo

The identification of conserved genes and pathways that regulate lifespan but also healthspan has resulted in an improved understanding of the link between nutrients, signal transduction proteins, and aging but has also provided evidence for the existence of multiple “longevity programs,” which are selected based on the availability of nutrients. Periodic fasting and other dietary restrictions can promote entry into a long‐lasting longevity program characterized by cellular protection and optimal function but can also activate regenerative processes that lead to rejuvenation, which are independent of the aging rate preceding the restricted period. Thus, a “juventology”‐based strategy can complement the traditional gerontology approach by focusing not on aging but on the longevity program affecting the life history period in which mortality is very low and organisms remain youthful, healthy, and fully functional.

Effect of alternate day fasting on markers of bone metabolism: An exploratory analysis of a 6-month randomized controlled trial

Article

Full-text available

Oct 2017

BACKGROUND Alternate day fasting (ADF) is a novel diet therapy that reduces body weight, but its effect on bone health remains unknown. OBJECTIVE This study examined the impact of ADF versus traditional daily calorie restriction (CR) on markers of bone metabolism in a 6-month randomized controlled trial. METHODS Overweight and obese subjects (n = 100) were randomized to 1 of 3 groups for 6 months: 1) ADF (25% energy intake fast day, alternated with 125% intake feast day; 2) CR (75% intake every day); or 3) control (usual intake every day). RESULTS Body weight decreased similarly (P < 0.001) by ADF (–7.8±1.2%) and CR (–8.8±1.5%), relative to controls by month 6. Lean mass, total body bone mineral content and total body bone mineral density remained unchanged in all groups. Circulating osteocalcin, bone alkaline phosphatase, and C-terminal telopeptide type I collagen (CTX) did not change in any group. IGF-1 increased (P < 0.01) in the CR group, with no change in the ADF or control group. When the data were sub-analyzed according to menopausal status, there were no differences between premenopausal or postmenopausal women for any marker of bone metabolism. CONCLUSION These findings suggest that 6 months of ADF does not have any deleterious impact on markers of bone metabolism in obese adults with moderate weight loss.

Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease

Article

Full-text available

Feb 2017

Calorie restriction or changes in dietary composition can enhance healthy aging, but the inability of most subjects to adhere to chronic and extreme diets, as well as potentially adverse effects, limits their application. We randomized 100 generally healthy participants from the United States into two study arms and tested the effects of a fasting-mimicking diet (FMD)—low in calories, sugars, and protein but high in unsaturated fats—on markers/risk factors associated with aging and age-related diseases. We compared subjects who followed 3 months of an unrestricted diet to subjects who consumed the FMD for 5 consecutive days per month for 3 months. Three FMD cycles reduced body weight, trunk, and total body fat; lowered blood pressure; and decreased insulin-like growth factor 1 (IGF-1). No serious adverse effects were reported. After 3 months, control diet subjects were crossed over to the FMD program, resulting in a total of 71 subjects completing three FMD cycles. A post hoc analysis of subjects from both FMD arms showed that body mass index, blood pressure, fasting glucose, IGF-1, triglycerides, total and low-density lipoprotein cholesterol, and C-reactive protein were more beneficially affected in participants at risk for disease than in subjects who were not at risk. Thus, cycles of a 5-day FMD are safe, feasible, and effective in reducing markers/risk factors for aging and age-related diseases. Larger studies in patients with diagnosed diseases or selected on the basis of risk factors are warranted to confirm the effect of the FMD on disease prevention and treatment.

Caloric restriction improves health and survival of rhesus monkeys

Article

Full-text available

Jan 2017

Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late 1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health.

Reduced Insulin/IGF-1 Signaling Restores the Dynamic Properties of Key Stress Granule Proteins during Aging

Article

Full-text available

Jan 2017

Low-complexity “prion-like” domains in key RNA-binding proteins (RBPs) mediate the reversible assembly of RNA granules. Individual RBPs harboring these domains have been linked to specific neurodegenerative diseases. Although their aggregation in neurodegeneration has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. We show that a wide variety of RNA granule components, including stress granule proteins, become highly insoluble with age in C. elegans and that reduced insulin/insulin-like growth factor 1 (IGF-1) daf-2 receptor signaling efficiently prevents their aggregation. Importantly, stress-granule-related RBP aggregates are associated with reduced fitness. We show that heat shock transcription factor 1 (HSF-1) is a main regulator of stress-granule-related RBP aggregation in both young and aged animals. During aging, increasing DAF-16 activity restores dynamic stress-granule-related RBPs, partly by decreasing the buildup of other misfolded proteins that seed RBP aggregation. Longevity-associated mechanisms found to maintain dynamic RBPs during aging could be relevant for neurodegenerative diseases.

Impact of Intermittent Fasting on Health and Disease Processes

Article

Full-text available

Oct 2016

Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state. Intermittent fasting (IF) encompasses eating patterns in which individuals go extended time periods (e.g., 16–48 hours) with little or no energy intake, with intervening periods of normal food intake, on a recurring basis. We use the term periodic fasting (PF) to refer to IF with periods of fasting or fasting mimicking diets lasting from 2 to as many as 21 or more days. In laboratory rats and mice IF and PF have profound beneficial effects on many different indices of health and, importantly, can counteract disease processes and improve functional outcome in experimental models of a wide range of age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer’s disease Parkinson’s disease and stroke. Studies of IF (e.g., 60% energy restriction on 2 days per week or every other day), PF (e.g., a 5 day diet providing 750–1100 kcal) and time-restricted feeding (TRF; limiting the daily period of food intake to 8 hours or less) in normal and overweight human subjects have demonstrated efficacy for weight loss and improvements in multiple health indicators including insulin resistance and reductions in risk factors for cardiovascular disease. The cellular and molecular mechanisms by which IF improves health and counteracts disease processes involve activation of adaptive cellular stress response signaling pathways that enhance mitochondrial health, DNA repair and autophagy. PF also promotes stem cell-based regeneration as well as long-lasting metabolic effects. Randomized controlled clinical trials of IF versus PF and isoenergetic continuous energy restriction in human subjects will be required to establish the efficacy of IF in improving general health, and preventing and managing major diseases of aging.

Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males

Article

Full-text available

Oct 2016
J TRANSL MED

Background Intermittent fasting (IF) is an increasingly popular dietary approach used for weight loss and overall health. While there is an increasing body of evidence demonstrating beneficial effects of IF on blood lipids and other health outcomes in the overweight and obese, limited data are available about the effect of IF in athletes. Thus, the present study sought to investigate the effects of a modified IF protocol (i.e. time-restricted feeding) during resistance training in healthy resistance-trained males. Methods Thirty-four resistance-trained males were randomly assigned to time-restricted feeding (TRF) or normal diet group (ND). TRF subjects consumed 100 % of their energy needs in an 8-h period of time each day, with their caloric intake divided into three meals consumed at 1 p.m., 4 p.m., and 8 p.m. The remaining 16 h per 24-h period made up the fasting period. Subjects in the ND group consumed 100 % of their energy needs divided into three meals consumed at 8 a.m., 1 p.m., and 8 p.m. Groups were matched for kilocalories consumed and macronutrient distribution (TRF 2826 ± 412.3 kcal/day, carbohydrates 53.2 ± 1.4 %, fat 24.7 ± 3.1 %, protein 22.1 ± 2.6 %, ND 3007 ± 444.7 kcal/day, carbohydrates 54.7 ± 2.2 %, fat 23.9 ± 3.5 %, protein 21.4 ± 1.8). Subjects were tested before and after 8 weeks of the assigned diet and standardized resistance training program. Fat mass and fat-free mass were assessed by dual-energy x-ray absorptiometry and muscle area of the thigh and arm were measured using an anthropometric system. Total and free testosterone, insulin-like growth factor 1, blood glucose, insulin, adiponectin, leptin, triiodothyronine, thyroid stimulating hormone, interleukin-6, interleukin-1β, tumor necrosis factor α, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured. Bench press and leg press maximal strength, resting energy expenditure, and respiratory ratio were also tested. ResultsAfter 8 weeks, the 2 Way ANOVA (Time * Diet interaction) showed a decrease in fat mass in TRF compared to ND (p = 0.0448), while fat-free mass, muscle area of the arm and thigh, and maximal strength were maintained in both groups. Testosterone and insulin-like growth factor 1 decreased significantly in TRF, with no changes in ND (p = 0.0476; p = 0.0397). Adiponectin increased (p = 0.0000) in TRF while total leptin decreased (p = 0.0001), although not when adjusted for fat mass. Triiodothyronine decreased in TRF, but no significant changes were detected in thyroid-stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, or triglycerides. Resting energy expenditure was unchanged, but a significant decrease in respiratory ratio was observed in the TRF group. Conclusions Our results suggest that an intermittent fasting program in which all calories are consumed in an 8-h window each day, in conjunction with resistance training, could improve some health-related biomarkers, decrease fat mass, and maintain muscle mass in resistance-trained males.

Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement

Article

Full-text available

Jan 2015

Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.

Circulating adiponectin levels in various malignancies: An updated meta-analysis of 107 studies

Article

Full-text available

Apr 2016

Early detection of cancers is challenging for lack of specific biomarkers. Adiponectin is an adipokine predominantly derived from adipocytes and hypoadiponectinemia has been reported to associate with risk of many types of cancers. However, available evidence is controversial. Some studies show that increased adiponectin levels correlate with cancer risk. Therefore, we performed a meta-analysis of the association between circulating adiponectin levels and cancer development. A systematic search of PubMed, EMBASE, Wiley Online Library and Cochrane Library was conducted for eligible studies involving circulating adiponectin and malignancies from inception to August 8, 2015. Standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated by use of a random-effect model. Funnel plot and Egger's linear regression test were conducted to examine the risk of publication bias. 107 studies were included with 19,319 cases and 25,675 controls. The pooled analysis indicated that circulating adiponectin levels were lower in patients with various cancers than in controls, with a pooled SMD of -0.334 μg/ml (95% CI, -0.465 to -0.203, P = 0.000). No evidence of publication bias was observed. Circulating high molecular weight adiponectin levels were also lower in cancer patients than in controls, with a pooled SMD of -0.502 μg/ml (95% CI, -0.957 to -0.047, P = 0.000). This meta-analysis provides further evidence that decreased adiponectin levels is associated with risk of various cancers. Hypoadiponectinemia may represent a useful biomarker for early detection of cancers.

A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk

Article

Full-text available

Feb 2016
CANCER RES

The role of insulin-like growth factors (IGFs) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the odds ratios (ORs) for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all {less than or equal to} 0.005), and IGFBP-1 was weakly inversely associated with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval=1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development.

Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: A randomized clinical trial

Article

Full-text available

Oct 2015
AGING CELL

Young-onset calorie restriction (CR) in rodents decreases serum IGF-1 concentration and increases serum corticosterone levels, which have been hypothesized to play major roles in mediating its anticancer and anti-aging effects. However, little is known on the effects of CR on the IGF-1 system and cortisol in humans. To test the sustained effects of CR on these key hormonal adaptations, we performed a multicenter randomized trial of a 2-year 25% CR intervention in 218 nonobese (body mass index between 22 and 27.8 kg m(-2) ) young and middle-aged (20-50 years age range) men and women. Average CR during the first 6 months was 19.5 ± 0.8% and 9.1 ± 0.7% over the next 18 months of the study. Weight loss averaged 7.6 ± 0.3 kg over the 2-years period of which 71% was fat mass loss (P < 0.0001). Average CR during the CR caused a significant 21% increase in serum IGFBP-1 and a 42% reduction in IGF-1:IGFBP-1 ratio at 2 years (P < 0.008), but did not change IGF-1 and IGF-1:IGFBP-3 ratio levels. Serum cortisol concentrations were slightly but significantly increased by CR at 1 year only (P = 0.003). Calorie restriction had no effect on serum concentrations of PDGF-AB and TGFβ-1. We conclude, on the basis of the present and previous findings, that, in contrast to rodents, humans do not respond to CR with a decrease in serum IGF-1 concentration or with a sustained and biological relevant increase in serum cortisol. However, long-term CR in humans significantly and persistently increases serum IGFBP-1 concentration.

A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan

Article

Full-text available

Jun 2015

Prolonged fasting (PF) promotes stress resistance, but its effects on longevity are poorly understood. We show that alternating PF and nutrient-rich medium extended yeast lifespan independently of established pro-longevity genes. In mice, 4 days of a diet that mimics fasting (FMD), developed to minimize the burden of PF, decreased the size of multiple organs/systems, an effect followed upon re-feeding by an elevated number of progenitor and stem cells and regeneration. Bi-monthly FMD cycles started at middle age extended longevity, lowered visceral fat, reduced cancer incidence and skin lesions, rejuvenated the immune system, and retarded bone mineral density loss. In old mice, FMD cycles promoted hippocampal neurogenesis, lowered IGF-1 levels and PKA activity, elevated NeuroD1, and improved cognitive performance. In a pilot clinical trial, three FMD cycles decreased risk factors/biomarkers for aging, diabetes, cardiovascular disease, and cancer without major adverse effects, providing support for the use of FMDs to promote healthspan.

Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement

Article

Full-text available

Jan 2015

Roles of Caloric Restriction, Ketogenic Diet and Intermittent Fasting during Initiation, Progression and Metastasis of Cancer in Animal Models: A Systematic Review and Meta-Analysis

Article

Full-text available

Dec 2014
PLOS ONE

The role of dietary restriction regimens such as caloric restriction, ketogenic diet and intermittent fasting in development of cancers has been detected via abundant preclinical experiments. However, the conclusions are controversial. We aim to review the relevant animal studies systematically and provide assistance for further clinical studies. Literatures on associations between dietary restriction and cancer published in PubMed in recent twenty years were comprehensively searched. Animal model, tumor type, feeding regimen, study length, sample size, major outcome, conclusion, quality assessment score and the interferential step of cancer were extracted from each eligible study. We analyzed the tumor incidence rates from 21 studies about caloric restriction. Fifty-nine studies were involved in our system review. The involved studies explored roles of dietary restriction during initiation, progression and metastasis of cancer. About 90.9% of the relevant studies showed that caloric restriction plays an anti-cancer role, with the pooled OR (95%CI) of 0.20 (0.12, 0.34) relative to controls. Ketogenic diet was also positively associated with cancer, which was indicated by eight of the nine studies. However, 37.5% of the related studies obtained a negative conclusion that intermittent fasting was not significantly preventive against cancer. Caloric restriction and ketogenic diet are effective against cancer in animal experiments while the role of intermittent fasting is doubtful and still needs exploration. More clinical experiments are needed and more suitable patterns for humans should be investigated.

Fasting: Molecular Mechanisms and Clinical Applications

Article

Full-text available

Jan 2014

Fasting has been practiced for millennia, but, only recently, studies have shed light on its role in adaptive cellular responses that reduce oxidative damage and inflammation, optimize energy metabolism, and bolster cellular protection. In lower eukaryotes, chronic fasting extends longevity, in part, by reprogramming metabolic and stress resistance pathways. In rodents intermittent or periodic fasting protects against diabetes, cancers, heart disease, and neurodegeneration, while in humans it helps reduce obesity, hypertension, asthma, and rheumatoid arthritis. Thus, fasting has the potential to delay aging and help prevent and treat diseases while minimizing the side effects caused by chronic dietary interventions.

Effect of 6Month Calorie Restriction on Biomarkers of Longevity, Metabolic Adaptation, and Oxidative Stress in Overweight Individuals A Randomized Controlled Trial

Article

Full-text available

Nov 2005

The GH/IGF-1 axis in ageing and longevity

Article

Full-text available

Apr 2013
NAT REV ENDOCRINOL

Secretion of growth hormone (GH), and consequently that of insulin-like growth factor 1 (IGF-1), declines over time until only low levels can be detected in individuals aged ≥60 years. This phenomenon, which is known as the 'somatopause', has led to recombinant human GH being widely promoted and abused as an antiageing drug, despite lack of evidence of efficacy. By contrast, several mutations that decrease the tone of the GH/IGF-1 axis are associated with extended longevity in mice. In humans, corresponding or similar mutations have been identified, but whether these mutations alter longevity has yet to be established. The powerful effect of reduced GH activity on lifespan extension in mice has generated the hypothesis that pharmaceutically inhibiting, rather than increasing, GH action might delay ageing. Moreover, mice as well as humans with reduced activity of the GH/IGF-1 axis are protected from cancer and diabetes mellitus, two major ageing-related morbidities. Here, we review data on mouse strains with alterations in the GH/IGF-1 axis and their effects on lifespan. The outcome of corresponding or similar mutations in humans is described, as well as the potential mechanisms underlying increased longevity and the therapeutic benefits and risks of medical disruption of the GH/IGF-1 axis in humans.

Obesity, Energy Balance, and Cancer: New Opportunities for Prevention

Article

Full-text available

Oct 2012
CANCER PREV RES

Obesity is associated with increased risk and poor prognosis for many types of cancer. The mechanisms underlying the obesity-cancer link are becoming increasingly clear and provide multiple opportunities for primary to tertiary prevention. Several obesity-related host factors can influence tumor initiation, progression and/or response to therapy, and these have been implicated as key contributors to the complex effects of obesity on cancer incidence and outcomes. These host factors include insulin, insulin-like growth factor-1, leptin, adiponectin, steroid hormones, cytokines, and inflammation-related molecules. Each of these host factors is considered in the context of energy balance and as potential targets for cancer prevention. The possibility of prevention at the systems level, including energy restriction, dietary composition and exercise is considered as is the importance of the newly-emerging field of stem cell research as a model for studying energy balance and cancer prevention.

Growth Hormone Receptor Deficiency Is Associated with a Major Reduction in Pro-Aging Signaling, Cancer, and Diabetes in Humans

Article

Full-text available

Feb 2011

Mutations in growth signaling pathways extend life span, as well as protect against age-dependent DNA damage in yeast and decrease insulin resistance and cancer in mice. To test their effect in humans, we monitored for 22 years Ecuadorian individuals who carry mutations in the growth hormone receptor (GHR) gene that lead to severe GHR and IGF-1 (insulin-like growth factor-1) deficiencies. We combined this information with surveys to identify the cause and age of death for individuals in this community who died before this period. The individuals with GHR deficiency exhibited only one nonlethal malignancy and no cases of diabetes, in contrast to a prevalence of 17% for cancer and 5% for diabetes in control subjects. A possible explanation for the very low incidence of cancer was suggested by in vitro studies: Serum from subjects with GHR deficiency reduced DNA breaks but increased apoptosis in human mammary epithelial cells treated with hydrogen peroxide. Serum from GHR-deficient subjects also caused reduced expression of RAS, PKA (protein kinase A), and TOR (target of rapamycin) and up-regulation of SOD2 (superoxide dismutase 2) in treated cells, changes that promote cellular protection and life-span extension in model organisms. We also observed reduced insulin concentrations (1.4 μU/ml versus 4.4 μU/ml in unaffected relatives) and a very low HOMA-IR (homeostatic model assessment-insulin resistance) index (0.34 versus 0.96 in unaffected relatives) in individuals with GHR deficiency, indicating higher insulin sensitivity, which could explain the absence of diabetes in these subjects. These results provide evidence for a role of evolutionarily conserved pathways in the control of aging and disease burden in humans.

The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: A randomized trial in young overweight women

Article

Full-text available

Oct 2010
INT J OBESITY

The problems of adherence to energy restriction in humans are well known. To compare the feasibility and effectiveness of intermittent continuous energy (IER) with continuous energy restriction (CER) for weight loss, insulin sensitivity and other metabolic disease risk markers. Randomized comparison of a 25% energy restriction as IER (∼ 2710 kJ/day for 2 days/week) or CER (∼ 6276 kJ/day for 7 days/week) in 107 overweight or obese (mean (± s.d.) body mass index 30.6 (± 5.1) kg m(-2)) premenopausal women observed over a period of 6 months. Weight, anthropometry, biomarkers for breast cancer, diabetes, cardiovascular disease and dementia risk; insulin resistance (HOMA), oxidative stress markers, leptin, adiponectin, insulin-like growth factor (IGF)-1 and IGF binding proteins 1 and 2, androgens, prolactin, inflammatory markers (high sensitivity C-reactive protein and sialic acid), lipids, blood pressure and brain-derived neurotrophic factor were assessed at baseline and after 1, 3 and 6 months. Last observation carried forward analysis showed that IER and CER are equally effective for weight loss: mean (95% confidence interval ) weight change for IER was -6.4 (-7.9 to -4.8) kg vs -5.6 (-6.9 to -4.4) kg for CER (P-value for difference between groups = 0.4). Both groups experienced comparable reductions in leptin, free androgen index, high-sensitivity C-reactive protein, total and LDL cholesterol, triglycerides, blood pressure and increases in sex hormone binding globulin, IGF binding proteins 1 and 2. Reductions in fasting insulin and insulin resistance were modest in both groups, but greater with IER than with CER; difference between groups for fasting insulin was -1.2 (-1.4 to -1.0) μU ml(-1) and for insulin resistance was -1.2 (-1.5 to -1.0) μU mmol(-1) l(-1) (both P = 0.04). IER is as effective as CER with regard to weight loss, insulin sensitivity and other health biomarkers, and may be offered as an alternative equivalent to CER for weight loss and reducing disease risk.

Evaluation of an alternating-calorie diet with and without exercise in the treatment of obesity

Article

Full-text available

Sep 1989

This study examined the effects of calorie alternation and exercise on weight loss. Moderately obese women (130-160% of ideal body weight) were randomly assigned to an alternating- or constant-calorie diet with or without aerobic exercise. Both diets provided an average of 1200 kcal/d over a 12-wk period; daily intake of subjects in the alternating-diet condition varied in a prescribed pattern from 600 to 1800 kcal/d. Exercising subjects walked 5 d/wk. All subjects participated in an intensive outpatient behavior-modification program. At the end of the study, exercised subjects had greater reductions in body weight and body fat percentage than did nonexercised subjects. The type of caloric restriction did not affect weight or fat loss. Changes in resting metabolic rate did not differ among groups. Alternating calories was neither beneficial nor detrimental as a weight-loss strategy whereas exercise was clearly beneficial in weight-loss therapy.

Rapid Insulin-Like Growth Factor (IGF)-Independent Effects of IGF Binding Protein-3 on Endothelial Cell Survival

Article

Full-text available

The Influence of Fasting and Energy Restricting Diets on IGF-1 Levels in Humans: A Systematic Review and Meta-Analysis

Abstract

No full-text available