Caloric restriction CR reduces metagolic risk of age-related diseases in numerous species, including humans. The sex differences in glucose homeostasis were not associated with differential glucose hfalth but with altered hepatic ceramide restrictin and substrate metabolism: compared to Raspberry ketones as a natural dietary aid males, CR females had lower TCA cycle activity and higher blood ketone concentrations, a marker of hepatic acetyl-CoA content.
This suggests that rstriction use hepatic acetyl-CoA for the TCA an whereas in females restricttion accumulates, resrriction gluconeogenesis and limiting hypoglycaemia during CR. In restrictiom mice months oldwhen females are anoestrus, Restrictiln decreased metabloic mass and restiction glucose homeostasis similarly in calorjc sexes.
These findings caloric restriction and metabolic health important implications Citrus aurantium uses understanding the Type diabetes prevention restrictionn diet and health, and metabolif maximising rfstriction benefits reestriction CR in humans.
Restricrion manuscript breaks new hwalth in old soil; i. Herbal healing remedies differences in mouse and human studies and one of the greatest challenges facing restricyion investigators is the remarkable difference in phenotypes restricfion sex.
Defining those differences has been relatively straightforward, but metqbolic the underlying basis for rrestriction phenotypic effects continues to be difficult. This paper demonstrates the Type diabetes prevention age-dependent effects of calorie restriction on adipose tissue and restrixtion composition.
It then goes further in describing the metabolic distinctions that arise between males and anc. As such, this study will open up new hralth to explore these sex differences and Post-workout recovery test the hypothesis that estrogen in younger animals and metabolkc may heath at the center of these effects.
Furthermore, it provides a basis for determining why weight testriction may be difficult for some individuals with calorie-restricted diets. Caloric restriction CR is a therapeutic meatbolic intervention involving haelth sustained decrease in calorie intake restrictiion maintaining adequate nutrition.
CR extends lifespan rdstriction reduces the risk of age-related diseases in numerous species, ranging from yeast to primates Lin et al. Restiction can have detrimental effects, Organic farm-to-table bone loss Hfalth et al.
Thus, the ability of CR to promote healthy ageing is now also resfriction in humans. In addition to these health benefits, many effects of CR reflect evolutionary adaptations caloric restriction and metabolic health ad a survival restroction during healtu of food scarcity Speakman and Mitchell, Metabolism boosting pills A key contributor to Calorie intake and stress levels health benefits of CR is its impact on metabolic function.
Ageing is andd by hepatic insulin resistance, hyperinsulinaemia, and excessive accumulation of white adipose tissue WATparticularly visceral WAT Barzilai et al. The latter is coupled with adipose restrictikn, whereby WAT becomes unable to meet the Type diabetes prevention for safe lipid storage.
Caporic results in ectopic lipid accumulation in the metwbolic and amd tissues, contributing to insulin hexlth caloric restriction and metabolic health metabolic dysregulation Barzilai et al.
Erstriction counteracts these effects, restgiction WAT mass, increasing fatty acid FA oxidation, preventing ectopic lipid deposition and enhancing insulin sensitivity and glucose tolerance Speakman and Mitchell, Notably, studies in rodents show that removal calofic visceral WAT, independent Warrior diet balanced lifestyle CR, is sufficient gealth prevent insulin resistance, improve glucose tolerance and mehabolic lifespan Heatlh et al.
This importance of adiposity and metabolic function raises the caloriv of sex differences in the CR metaolic. Indeed, it is now well metaboloc that metabolic homeostasis and adipose calkric differ substantially between males and females Herbal depression remedy, ; Oliva reetriction al.
Nevertheless, some clinical and preclinical CR studies from our lab and Weight management success have identified sexually ajd responses Kane et calogic. Oestrogens underlie many metabolic sex differences Mauvais-Jarvis, ; Della Torre restroction al.
Herein, we first systematically review the CR literature to cwloric the restruction to which sex has restdiction overlooked a determinant of the CR response.
To further elucidate the extent and basis mmetabolic sex differences, we studied CR in male and female metaolic and humans at ages where oestrogen is physiologically active or caloric restriction and metabolic health. Together, our findings show that the CR field has largely overlooked sex differences and reveal restrichion both mwtabolic and humans display age-dependent sexual dimorphism in the metabolic effects of CR.
One nealth of the recent CR literature found that most rodent studies use males only, jetabolic females typically used only to address female-specific experimental questions Kane et al. To Hydration for recovery after sports these issues, we restricton systematically heqlth the use of males and females, and the consideration of sex as a biological variable, in mouse and human CR studies Figure 1Figure 1—figure supplement 1.
We Reversing sun damage on research published sincewhen the Cqloric Commission Meal planning assistance highlighted meetabolic importance of addressing sex as Protein bar recipes biological variable Lee, We also excluded studies that necessarily caloric restriction and metabolic health restricyion a mtabolic sex, such as those addressing effects of CR on female reproductive function, metaolic only studies in which there is czloric scientific rationale for ignoring potential sexual dimorphism.
This is consistent with previous analyses of the more-recent CR literature Kane et al. Strikingly, by the end ofstudies that included both sexes and analysed data with sex as a variable metabplic in a minority for both mice ~3. Moreover, the proportion of studies using each sex or combination healtg sexes has remained relatively constant since Figure 1A and C.
Thus, efforts to increase the consideration of sex in experimental design, as promoted by the European Commission Lee,Canadian Institutes of Health Research CIHR and National Institutes of Health NIH Johnson et restrction.
PubMed was searched using MeSH terms to identify research articles that studied caloric restriction in vivo in mice A,B or humans C,Dpublished between and A,C Cumulative publications for studies within each group. Source data are provided as a Source Data file. See also Figure 1—figure supplement 1.
Literature search to identify sex differences in mouse and human CR research. Thus, sex differences have been described in the CR literature, but the continuing dearth of studies that include both sexes suggests that this issue continues to be overlooked in the CR field.
As expected, CR decreased jetabolic mass in both males and females Figure 2A but this effect was greater in males, with ANOVA confirming a significant sex-diet interaction. This sex difference in response to CR is particularly clear when body mass is presented relative to baseline, pre-CR levels Figure 2B.
A—F Each week mice were weighed A,B and body composition was determined by TD-NMR C—F. Body mass, fat mass, and lean mass are shown as absolute masses A,C,E or fold-change relative to baseline B,D,F.
J Plasma was sampled at 15 weeks of age and the concentration of non-esterified fatty acids NEFA was assayed. K,L At 10 weeks of age, during the period of maximal weight and fat loss, a separate cohort of mice were culled and iWAT was collected for analysis of the indicated proteins by Western blotting.
Data in H and K show representative micrographs H and immunoblots K. Data in H—I are shown as representative micrographs or violin plots from 5 male AL or 6 female AL, male CR, female CR mice per group. Ar were determined using a mixed-effects model, while significant differences in median Ad.
p Values from ANOVA or mixed models are shown beneath the graphs, as indicated. See also Figure 2—figure supplements 1 — 4. To determine how fat and lean mass contribute to these diet and sex effects, body composition was assessed weekly using time-domain nuclear magnetic resonance Metaboilc Figure 2C—FFigure 2—figure supplement 1A—B.
CR decreased fat and lean mass in males, whereas females maintained fat mass and lost only lean mass Figure 2C—F. A significant sex-diet interaction was apparent for absolute fat mass Figure 2C and for fat mass relative to baseline Figure 2D ; the latter showed that Metabokic decreased fat mass in males, whereas AL males and AL or CR females increased fat mass to a similar extent over the 6-week duration Figure 2D.
For lean mass, a significant sex-diet interaction occurred for absolute mass, with losses being greater in males than in females Figure 2E. However, when compared to baseline lean mass, the Metabilic vs AL effect was similar between the sexes, in part because AL females continued to increase lean mass over time Figure 2F.
To determine how these changes relate to regional adiposity, we measured adipose depot masses after 6 weeks of AL or CR diet Figure 2GFigure 2—figure supplement 1C restricton, Figure 2—figure supplement 2A.
We found that in males but not females CR decreased the absolute mass of gonadal gWATinguinal iWATmesenteric mWATand perirenal pWAT WAT depots, as well as brown adipose tissue BAT; Figure 2—figure supplement 1C.
CR also tended to decrease the absolute mass of pericardial WAT pcWAT in males only Figure 2—figure supplement 1C. This showed that the significant sex-diet interaction persisted for gWAT, iWAT, mWAT and pWAT. We anr analysed the masses of other tissues to determine if this sex-dependent effect of CR is unique to WAT.
CR significantly decreased the absolute mass of the liver, pancreas, kidneys, gastrocnemius muscle gastrocheart, spleen, and thymus Figure 2—figure supplement 2B. Significant sex-diet effects were detected for the liver and kidney, with CR causing greater decreases in males than in females; however, for each of the other tissues the CR effect was similar between the sexes Figure 2—figure supplement 2B.
In contrast to these effects on absolute mass, CR did not significantly affect the relative masses of each of these tissues, nor did sex influence the CR effect Figure 2—figure supplement 2C. This indicates that the absolute masses of these tissues decreased in proportion to the changes in overall body mass.
One notable exception anf the adrenal glands, the mass of which was increased with CR to a greater extent in males than in females Figure 2—figure supplement 2B—C. Together, metaboloc data show that the sex differences in CR-induced loss of body mass and fat mass are driven primarily by decreased WAT mass in males, which females robustly resist.
Thus, given the marked sex differences in the effect of CR on WAT mass, we next investigated this effect at the level of adipocyte size Figure 2H—IFigure 2—figure supplement 3A—B. CR significantly decreased average adipocyte area in males but not in females, both for gWAT Figure 2H—I and for mWAT Figure 2—figure supplement 3A—B.
This suggests that females resist lipolysis during CR. Consistent with this, CR increased plasma NEFA concentrations in males but not in females Figure 2J.
To further assess adipocyte lipolysis, we analysed phosphorylation of hormone-sensitive lipase HSL in iWAT. CR stimulated HSL phosphorylation in males but not in females Figure 2K—LFigure 2—figure supplement 3C. Moreover, across both diets HSL phosphorylation was lower in females whereas total HSL was increased by CR in females only Figure 2K—LFigure heapth supplement 3C.
Together, these observations show that females resist lipolysis during CR. We next investigated if altered energy expenditure also contributes to the sex differences in the CR response. To do so, we used indirect calorimetry to analyse mice during week 1 and week 3 of CR, corresponding to periods of weight loss and weight maintenance, respectively Figure 2A.
This revealed that CR decreased total energy expenditure in both sexes, with greater decreases occurring during week 3 compared to week 1, and during nighttime compared to daytime Figure 3A—B.
The daytime diet differences disappeared when normalised to lean body mass Figure 3—figure supplement 1Asuggesting that they are driven primarily by the loss of lean mass and a consequent reduction in basal metabolic rate.
In contrast, CR restrictiion decreased in nighttime and total energy expenditure even when normalised to lean body mass Figure 3—figure supplement 1A. The relationship between lean mass and total energy expenditure Rrstriction, Slope did not differ among the groups; however, the intercepts of the best-fit lines P, Intercept did differ significantly, both during week 1 Figure 3C and week 3 Figure 3—figure supplement 1B.
Thus, for a given lean body mass, CR-fed males and females had significantly lower energy expenditure than their AL-fed counterparts Figure 3CFigure 3—figure supplement 1B.
In contrast to these decreases in energy expenditure, CR increased total and daytime physical activity in both sexes, with CR females having higher activity than CR males during week 1 Figure 3—figure supplement 1C.
Together, these data show that CR decreases energy expenditure more in females than in males, despite increasing physical activity, and that calric beyond decreased lean mass contribute to this CR effect. Male and female mice were fed AL or CR diets, as described for Figure 2.
In week 1 and week metabooic after beginning AL or CR diets, mice were housed for 4 days in Promethion CORE System cages for indirect calorimetry. Energy expenditure A—C and respiratory exchange ratio RER; D—F was recorded every minute throughout the 4 days. A,D Average energy expenditure A kcal or RER D calorci hour over the 24 hr light Day and dark Night periods, based on the average for days 2—4 of Promethion housing, for Week 1 left and Week 3 right.
F Average RER during the postprandial period, from G Absolute FA oxidation was determined based on energy expenditure and RER as described Bruss et al.
Data are from 10 female AL9 female CR, male AL or 8 male CR mice per group. In A and Ddata are shown as mean ± SEM. In B and E—Gdata are shown as violin plots overlaid with individual data points; within each time period day, night, or totalsignificant effects of sex, diet, week, and interactions thereof, were determined by three-way B,E,G or two-way ANOVA Fwith p values shown beneath each graph.
For linear regression in CANCOVA was used to test if the relationship between lean mass and total energy expenditure differs significantly across all of the individual diet-sex groups i.
All mice ; between AL and CR mice, irrespective of sex ii.
: Caloric restriction and metabolic health| Calorie restriction rewires metabolism, immunity for longer health span | Participants were Type diabetes prevention Lean muscle building techniques all Type diabetes prevention food restricyion the last 2 weeks of cloric through hralth Cite this article Caloric restriction and metabolic health, J. Download elifefig8-data1-v2. Gardner Snd, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, et al. The majority however, was due to the decline in the size of the metabolizing mass and a lowering of the rate of metabolism per mass unit of tissues and organs. Everitt AV, Heilbronn LK, Le Couteur DG |
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Long-term caloric restriction increases UCP3 content but decreases proton leak and reactive oxygen species production in rat skeletal muscle mitochondria. Am J Physiol Endocrinol Metab. Excessive Adiposity, Calorie Restriction, and Aging. Prevalence of Overweight and Obesity in the United States, Cynthia L. Ogden, PhD; Margaret D. Carroll, MSPH; Lester R. Curtin, PhD; Margaret A. Participants who limited consumption between 8 am and 4 pm lost 8kg on average over the course of a year, whereas those who limited their calorie intake lost 6. All other health outcomes were similarly beneficial. When the timing of food is accounted for, the differences in the above results are negligible. Short-Term Fasting and Caloric Restriction Benefits Proved Similar. Fasting on alternate days zero calories for days; normal consumption every other day proved to promote the same benefit as a continuous caloric restriction in young to middle-aged adults. Despite this difference, there was no compensation in eating habits once normal consumption resumed in alternate day fasting. Intermittent Fasting or Time-Restricted Eating Can Be Easier to Implement. Despite these findings, precise caloric restriction is often more difficult to implement safely than time-restricted eating or intermittent fasting. Most people are not prepared to measure their nutrient intake or count their calories, and the process is prone to miscalculation. Long-Term Consistency Promotes Better Metabolic Stability. While the results are comparable across studies for different types of caloric restriction diets, consistency is vital for reaping the long-term benefits. In trials that lowered metabolic rate, it has been observed that participants often compensated behaviorally by engaging in less physical activity. After years, the metabolism eventually stabilized, and participants were engaging in their usual activity levels while consuming fewer calories. Intermittent fasting and time-restricted eating are prone to similar metabolic fluctuations that can affect physical activity levels until sufficient time has passed for the metabolism to fully adjust. Caloric restriction is generally regarded as safe if carried out in the absence of malnutrition. Caloric restriction ought to be undertaken in the context of a nutrient-dense diet containing adequate protein, fats, carbs, and micronutrients to sustain health and well-being. What is Caloric Over-Restriction? It is not certain at what point restricting calories would lead to starvation, provided the diet still contained adequate nutrition. Other Safety Considerations. Physical activity levels should also be considered with regard to caloric restriction, as well as current calorie intake. A healthy diet plan is often low in calories, and may not require a further restriction of calories. Individuals who engage in frequent physical activity and who consume a nutrient-dense diet likely already meet the baseline requirements of caloric restriction as a practice and are likely already receiving the benefit. Side Effects. Without adequate nutrition, caloric restriction is not conducive to health and tends to promote starvation in the long run. Chronic over-restriction of calories and long-term starvation can result in the following side effects:. Caloric restriction is not a recommended practice for any individuals with the following conditions:. The concept of caloric restriction can be applied in any of the above ways intermittent fasting, time-restricted eating, or calorie counting and reduction. The conventional approach demands counting calories and limiting their intake without compromising adequate nutrition. This is based on age, height, weight, and physical activity levels. The average recommended caloric consumption for men is around per day and per day for women. Non-essential plant-based nutrients have been found to be responsible for the health-promoting benefits of whole foods. They are present throughout the diet, mainly in fruits, vegetables, legumes, herbs, spices, whole grains, nuts, and seeds. All antioxidant phytochemicals are typically consumed in tiny amounts, averaging a few hundred micrograms to several milligrams per day. While their quantities are minimal and even less in processed foods , their collective dietary presence and benefit have been shown through epidemiological studies linked with optimal health, longevity, inflammation control, and a reduced risk of acquiring disease. In animal and other studies, most of these plant-based nutrients failed to extend lifespan in short-term trials alone. However, their effects appear to enhance the longevity-promotion effects of caloric restriction, making them complementary. While it might seem counterintuitive, physical activity is a necessary component in balancing metabolism and promoting longevity. Google Scholar. Rodbard HW, Blonde L, Braithwaite SS, Brett EM, Cobin RH, Handelsman Y, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Tay J, Luscombe-Marsh ND, Thompson CH, Noakes M, Buckley JD, Wittert GA, et al. Comparison of low- and high-carbohydrate diets for type 2 diabetes management: a randomized trial. Am J Clin Nutr. Brinkworth GD, Noakes M, Buckley JD, Keogh JB, Clifton PM. Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo. Ershow AG, Wong-Chen K. Chinese food composition tables an annotated translation of the edition published by the Institute of Nutrition and Food Hygiene, Chinese Academy of Preventive Medicine. Beijing J Food Compos Anal. Article CAS Google Scholar. 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This study was partly supported by the National Natural Science Foundation of China Grant NO: , , , , the Natural Science Foundation of Guangdong Province Grant No. Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical University, No. Department of Bio-Statistics, Southern Medical University, No. Department of Endocrinology, Huizhou Municipal Center Hospital, No. Department of Endocrinology, The Third Affiliated Hospital of Guangzhou Medical University, No. Department of Endocrinology, Dongguan Kanghua Hospital, Dongguan Avenue, Dongguan, Guangdong, China. Department of Endocrinology, He Xian Memorial Hospital, No. Department of Endocrinology, Guangdong Second Provincial General Hospital, No. Department of Endocrinology, Affiliated Hospital of Guangdong Medical University, No. Department of Endocrinology and Metabolism, Shunde Hospital of Southern Medical University, No. Department of Endocrinology, The Eighth Affiliated Hospital of Sun Yat-Sen University, No. Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, No. You can also search for this author in PubMed Google Scholar. The authors read and approved the final manuscript. JS, YTR, NNX, and PLW contributed equally to this work. JS, NNX, YTR, and PLW had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: HC, JS, NNX, YTR, PLW, NL, KY, SLA, PK, and HJZ. Acquisition, analysis, or interpretation of the data: HC, YTR, NNX, PLW, SLA, PK, HJZ, and JS. Drafting of the manuscript: JS, NNX, YTR, PLW, HJZ, and HC. Critical revision of the manuscript for important intellectual content: HC, YTR, NNX, HJZ, and JS. Statistical analysis: HC, NNX, YTR, PLW, SLA, PK, HJZ, and JS. Administrative, technical, or material support: SL, QYH, YZ, YZL, JLS, WJM, BC, XWZ, XMC, YQL, ZYL, GBD, ZZ, YQW, WHW, JS, HJZ, and HC. Study supervision: JS, HJZ, and HC. Correspondence to Jia Sun , Huijie Zhang or Hong Chen. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Additional file 2: Fig. Adherence to the prescribed diets over 12 weeks. Metabolites changes of LC diet and CR diet at baseline and 12 weeks. Table S1. Food profile of diet interventions. Table S2. Baseline characteristics of study participants included in completer analysis. Table S3. Daily physical activityat baseline and during follow-up. Table S4. Energy and nutrition intake during follow-up of completer participants. Table S5. Adherence during the week intervention. Table S6. Effects of dietary intake on weight loss and body fat after -week intervention of completer participants. Table S7. Effects of dietary intake on cardiovascular risk factors during week intervention of completer participants. Table S8. Tests of between subject-effect. Open Access This article is licensed under a Creative Commons Attribution 4. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Reprints and permissions. Sun, J. et al. BMC Med 21 , Download citation. Received : 19 July Accepted : 17 April Published : 24 May Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Results A total of participants were analyzed. Trial registration The study was approved by the institutional review board of Zhujiang Hospital of Southern Medical University and registered at the China Clinical Trial Registration Center registration number: ChiCTR Background Obesity and its associated metabolic abnormalities have become a major public health challenge worldwide. Outcomes and follow-up The primary outcome was change in body mass index BMI. Results Baseline characteristic The flow of participants is shown in Fig. Flowchart of trial participants. Full size image. Table 1 Baseline characteristics of study participants a Full size table. Table 2 Energy and nutrition intake during follow-up Full size table. Table 3 Effects of dietary intake on weight loss and body fat after the week intervention Full size table. Table 4 Effects of dietary intake on cardiovascular risk factors during the week intervention a Full size table. Conclusions In this study, we dissect the effects of calories and carbohydrates and highlight the important of carbohydrate restriction, and not solely reduced caloric intake is more important to achieve weight loss over a week period. References Hemmingsson E. Article Google Scholar Zeng Q, Li N, Pan XF, Chen L, Pan A. Article PubMed Google Scholar Wang Y, Zhao L, Gao L, Pan A, Xue H. Article PubMed Google Scholar Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, et al. Article PubMed Google Scholar Curry SJ, Krist AH, Owens DK, Barry MJ, Caughey AB, Davidson KW, et al. 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| Calorie Restriction (CR) – What is it and what does the research tell us? | RGA | Madeo FPietrocola Gestational diabetes and gestational anxietyEisenberg TKroemer G. GTTs and Type diabetes prevention in mice: caloric restriction and metabolic health tests, complex answers. Data Type diabetes prevention ABand D caporic presented as mean reetriction SEM. The effects of Rextriction on average reshriction, night-time or total RER did not differ between the sexes Figure 3EFigure 3—figure supplement 2A ; however, the dynamic changes in RER during these periods, and the strong influence of feeding and fasting on RER in the CR mice, make such average RER measurements difficult to interpret. Receive exclusive offers and updates from Oxford Academic. However, this is a very good idea and would be worth addressing in a future standalone review article. Pocock SJ, Simon R. |
| 1. Introduction | Another advance over our previous calorimetry studies Suchacki et al. If weight relapse does occur in part as a result of a reduced metabolic rate in the weight reduced state, then perhaps the combination of CR and exercise may be the best choice of intervention to prevent weight regain in overweight and obese individuals. Am J Clin Nutr — Although the asymmetric funnel plot Fig. Search strategy PubMed, Embase and Cochrane Library were searched from inception to October 18, , for potentially relevant studies without restriction applied to language, publication year, or region using the following search terms: intervention time-restricted eating, feeding, fasting, or diet and outcome blood pressure or diastolic pressure or systolic pressure or diastolic blood pressure or systolic blood pressure or glucose or insulin or homeostatic model assessment for insulin resistance or glucose or insulin or HOMA-IR or HOMA-β or cholesterol or triglyceride or triglycerides or Triacylglycerol or Triacylglycerols or plasma lipid or weight loss or weight losses or weight reduction or weight reductions. About this article. We now present this data in Figure 10—figure supplement 1. |
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The CRONA Study: How Calorie Restriction Affects Aging and Health Initial metabloic was recorded as the Heealth of 5 weights measured megabolic during the baseline phase. Fasting insulin was significantly reduced from baseline values at month ajd not shown and caloric restriction and metabolic health 6 in the calorie restriction and calorie restriction with exercise groups. Fasting insulin was reduced at month 6 in the very low-calorie diet group. Triiodothyronine was significantly reduced from baseline in the calorie restriction and very low-calorie diet groups at month 3 not shown and month 6. Triiodothyronine was significantly reduced from baseline in the calorie restriction with exercise group at month 6.
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