Fasting and Reduced Risk of Chronic Disease -
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Request Appointment. Fasting diet: Can it improve my heart health? Products and services. Is it true that occasionally following a fasting diet can reduce my risk of heart disease?
Answer From Francisco Lopez-Jimenez, M. With Francisco Lopez-Jimenez, M. Show references Regular fasting could lead to longer, healthier life. American Heart Association. Accessed July 25, Dong TA, et al. Intermittent fasting: A heart healthy dietary pattern?
American Journal of Medicine. Malinowski B, et al. Intermittent fasting in cardiovascular disorders: An overview. Perrault L. Obesity in adults: Dietary therapy. Patikorn C, et al. Intermittent fasting and obesity-related health outcomes: An umbrella review of meta-analyses of randomized clinical trials.
JAMA Network Open. Allaf M, et al. Intermittent fasting for the prevention of cardiovascular disease. The Cochrane Database of Systematic Reviews.
Lopez-Jimenez F expert opinion. Mayo Clinic. Ofori-Asenso R, et al. Skipping breakfast and the risk of cardiovascular disease and death: A systematic review of prospective cohort studies in primary prevention settings.
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However, a greater reduction was observed in fasting NEFA in iTRE versus CR at months 2 and 6, and versus standard care at month 6 Table 2. There were no qualitative differences between the frequentist and Bayesian secondary analyses of postprandial glucose and HbA1c change Supplementary Table 1 and Extended Data Fig.
AUC values were compared between iTRE and CR at 6 months adjusted for sex, AUSDRISK and baseline values. P values are two-sided and not adjusted for multiple testing. There were greater reductions in systolic blood pressure in iTRE and CR versus standard care at month 2, and CR versus standard care only at month 6 Table 2.
A greater reduction in diastolic blood pressure also occurred in both iTRE and CR versus standard care at month 6. Fasting triglycerides were lower in iTRE versus CR and standard care at month 2 and 6.
There were no between-group differences detected in postprandial triglycerides. Total cholesterol and low-density lipoprotein LDL were lower in iTRE versus standard care at month 6. A greater reduction in the cholesterol to HDL ratio was observed in iTRE versus CR at month 2, and versus standard care at months 2 and 6.
There was no significant difference between groups in the reduction in alanine aminotransferase ALT or aspartate aminotransferase AST at month 6 Table 2. Body weight and fat mass loss were greater in both iTRE and CR versus standard care over the first 6 months Table 3.
There were no detectable differences in weight trajectories between the iTRE and CR groups Supplementary Table 2 and Extended Data Figs. Waist circumference was reduced in iTRE and CR versus standard care at month 6 Table 3.
Physical activity did not differ between groups Supplementary Table 3. However, self-reported energy intake was modestly lower in iTRE versus CR at month 2. Protein and fiber intakes were also lower at months 2 and 6 in iTRE versus CR.
Energy intake during iTRE and ad libitum days at month 2 did not differ from month 6, indicating comparable adherence over time in iTRE Supplementary Table 4.
However, there was no difference in weight or body composition between groups at month 18 Extended Data Fig. There were also no between-group differences in the reported biomarkers of health Table 2 , except for lower waist circumference in CR versus standard care.
We calculated insulin sensitivity using the Matsuda index and insulin secretion using the insulinogenic index, neither reached statistical significance Table 2.
We also combined iTRE with CR and observed lower insulin AUC, and a trend for differences in glucose and NEFA AUC versus standard care Supplementary Table 6.
In the first 6 months, 56 of participants reported at least one adverse event, with flu-like symptoms most frequently reported, and there was no difference in the incidence between groups Table 4.
Four serious adverse events with hospitalization were reported, one in first 6 months and three during follow-up; none were considered to be related to the intervention. This randomized controlled trial demonstrated that iTRE was superior to CR for improving postprandial glucose tolerance in adults at increased risk of developing type 2 diabetes.
Our findings are in alignment with past studies of IF versus CR showing similar effectiveness for body weight, fat mass, fasting glucose and insulin 22 , However, postprandial responses to a mixed-nutrient meal are a better assessment of glycemic control than simple fasting assessments, more highly predictive of type 2 diabetes and cardiovascular disease, and provide more physiological relevance than oral glucose tolerance tests 24 , 25 , 26 , In this large trial, superior improvements in glucose tolerance were observed in iTRE versus CR after 6 months, independently of body weight loss.
Only three pilot studies have previously compared the effects of IF versus CR on postprandial glucose and lipid metabolism in humans.
Improvements in glucose tolerance can occur through improved insulin sensitivity, insulin secretion, glucose mass action or slower gastric emptying. We observed a greater reduction in postprandial insulin AUC, which could indicate greater improvements in insulin sensitivity.
In the current study, greater reductions in fasting NEFA were observed, which suggest greater improvements in adipose tissue insulin sensitivity, which could also reduce ectopic lipid and increase peripheral glucose uptake There was no difference in insulin secretion as calculated by the insulinogenic index The greater improvements in glucose tolerance did not result in a greater reduction in HbA1c.
HbA1c is influenced by both postprandial and fasting glucose, although postprandial glucose is most strongly predictive of HbA1c in adults without diabetes.
Although HbA1c was marginally elevated, it is minimally shifted with dietary interventions in those without type 2 diabetes Few studies have specified morning meal timing during IF in humans 13 , potentially masking its possible health benefits.
Eating at an early time in the day is associated with health benefits in humans in short-term trials 37 , including improved h glucose control 38 and insulin sensitivity in response to an oral glucose tolerance test 39 and glucose mass action Delaying food intake is associated with reduced weight loss in retrospective cohort studies 37 and increased hunger and reduced energy expenditure in an acute metabolic ward study Delayed food intake also delayed adipose tissue clocks and expression of Period-2 in humans Thus, although a delayed eating plan may be more socially acceptable and sustainable, it may not be optimal for glycemic health 22 , In contrast to previous long-term IF trials 23 , 29 , we provide preliminary evidence that prescription of iTRE elicits favorable alterations in lipid profiles versus CR, including reductions in fasting triglycerides, which are strongly associated with an increased risk of cardiovascular diseases 42 , Fatty liver is also commonly associated with increased very-LDL triglycerides secretion and hypertriglyceridemia, and thus might also reflect an increased reduction in liver fat Interventions that improve glycemic control reduce β-hexosaminidase activity 45 , Here, iTRE was more effective in reducing β-hexosaminidase activity.
This exploratory finding could also reflect superior restoration of lipid metabolism 12 , 47 and liver health compared with CR, but the clinical relevance of a change in β-hexosaminidase with a dietary intervention is uncertain.
Adverse events were generally mild and resolved over the course of the trial. Higher fatigue was observed in iTRE versus CR during the first 6 months, which might increase difficulty in maintaining iTRE. Fasting protocols that require people to skip dinner several times per week could also lead to poor adherence.
Fewer than half of the iTRE participants indicated they would continue their current weight loss plan when they were given the option to modify to a weight maintenance plan that included two iTRE days per week at month 6.
However, weight loss maintenance at month 18 did not differ between iTRE and CR, suggesting that neither regimen was more sustainable when support from the investigators was withdrawn.
The increased health benefits in the active intervention groups were also lost by 18 months. A post hoc subanalysis that divided the iTRE cohort into those that chose to continue versus change the diet plan did not alter outcomes.
As an exploratory analysis, we also combined iTRE and CR, and observed sustained reductions in insulin AUC versus standard care. Future studies should investigate whether intermittent prescription of a longer daily eating window for example, to hours retains the benefit of iTRE versus CR, and if these interventions are more sustainable long-term.
Strengths of the study include that it is the largest to date, with a high proportion of men enrolled. This trial also included assessments of glucose tolerance and aligned meal timing from breakfast during IF. At month 6, we allowed participants in the active groups to choose whether they changed to a weight maintenance plan during the additional month follow-up.
This trial decision has hindered the clinical interpretation of that period because more participants in the iTRE group chose to alter their diet plans. Whether h post refeeding is sufficient to entirely wash out the acute effect of the h fasting period is not clear, although the washout period is in line with past studies of IF CR and standard care participants were not provided with any instruction on meal timing, and adoption of a shortened daily eating period might have lessened the differences between groups.
The extrapolation of a clinically relevant change in glucose from an oral glucose tolerance test to a mixed-meal tolerance test requires further study. Finally, although we theorized that limiting meals to the morning during iTRE was responsible for the greater health benefits that were observed versus CR, we did not include an iTRE group with a late eating window as a comparator.
In conclusion, iTRE provided modest benefit for postprandial glycemia in response to mixed-meal tolerance test compared with daily CR without timing advice in adults at elevated risk of type 2 diabetes after 6 months. This study adds to the growing body of evidence to indicate that meal timing and fasting advice might be influential in clinical practice.
This open-label, three-arm, parallel group sequential randomized controlled trial was conducted between 26 September and 30 November and involved a 6-month intervention phase followed by a month follow-up.
The primary objective for this study was to assess differences in glucose tolerance in response to a mixed-meal in iTRE versus CR at 6 months.
Because it was expected that weight loss for iTRE and CR would be similar, a standard care group was included to ensure weight losses occurred and to aid quantification of the magnitude of change in the active intervention groups. Secondary aims were to compare iTRE versus CR versus standard care on body weight, body composition, fasting and postprandial markers of glycemia, cardiovascular health and liver health at 6 months, and with a further month follow-up in adults at elevated risk of developing type 2 diabetes.
The detailed study protocol including inclusion and exclusion criteria was reported 49 , 50 , and the statistical analysis plan is available ClinicalTrials. gov, NCT Ethics approval was obtained from the Central Adelaide Local Health Network Human Research Ethics Committee and participants provided written informed consent.
The study was performed at the South Australian Health and Medical Research Institute by researchers from The University of Adelaide and South Australian Health and Medical Research Institute. An independent data and safety monitoring committee provided oversight. In response to the coronavirus pandemic, a lockdown was in place in South Australia from mid-March to May , which brought a halt to recruiting.
The primary outcome visits continued, but the diet consults were shifted from face-to-face to telehealth. Other than this period, the Australian border force laws in place meant the study visits remained largely unaffected, with the final follow-up visit completing around the time that Adelaide relaxed its border rules.
The prescribed menu included two meal replacements at breakfast approximately hours and lunch approximately hours to aid adherence and to ensure adequate nutrient intake. iTRE participants were instructed to consume their regular prestudy diet during each nonfasting day.
The prescribed menu included one meal replacement per day to aid adherence and to ensure adequate nutrient intake. The standard care group was given current guidelines in a booklet, with no counseling or meal replacements.
All participants were instructed to maintain their usual physical activity levels throughout the trial. At month 6, they were provided with the option to continue with the same weight loss plan or to modify to a weight maintenance plan. The secondary outcomes included changes in body weight, waist circumference, hip circumference, fat mass, fat-free mass, blood pressure, blood lipids cholesterol, low-density lipoprotein LDL , high-density lipoprotein HDL , plasma triglycerides , NEFA, HbA1c, plasma glucose, plasma insulin, serum high-sensitivity C-reactive protein hs-CRP , ALT, AST, β-hexosaminidase activity, physical activity and dietary intake.
During each metabolic visit, body weight, and waist and hip circumference were measured in a gown after voiding. Body weight was measured to the nearest 0.
Waist circumference was measured at the mid-axillary line halfway point between lowest rib and the top of iliac crest , and hip circumference was measured at the widest circumference of the buttocks. Body mass index was calculated as weight in kilograms per height in meters squared.
Whole-body composition was measured by dual-energy X-ray absorptiometry DXA Lunar Prodigy; GE Health Care and was analyzed using enCORE software v.
These were assessed in completers who lost at least 3. The mean of the two lowest blood pressure readings was used. Prescribed daily energy requirements were calculated by averaging predicted daily energy expenditure from a published equation that uses gender, age, height and weight variables Participants were asked to self-report all their dietary intake via a smartphone application Easy Diet Diary, Xyris Software before each metabolic testing at baseline, and at months 2, 6 and The energy and macronutrients intakes were calculated by using FoodWorks Professional v.
Perceptions of diet easiness and satisfaction were assessed at months 2 and 6 using visual analog scales. ActiGraph data was downloaded and analyzed by using ActiLife 6 software by the investigators upon collection of the devices. Participants attended the research facility at baseline, month 6 and month 18 for metabolic testing.
Additional fasting samples were obtained following a h fast at month 2. Blood glucose was assayed by the hexokinase method Cobas Integra plus, Roche. Plasma insulin was measured by radioimmunoassay HIK, Millipore. Whole-blood HbA1c, plasma triglycerides, NEFA, hs-CRP, ALT and AST, were measured using commercially available enzymatic kits on an automated clinical analyzer Indiko Plus, Thermo Fisher Scientific.
AUC values were calculated using the trapezoidal rule. The Matsuda index was calculated for insulin sensitivity estimation Insulin secretion was estimated using the insulinogenic index A subset of individuals had additional fasting bloods drawn at baseline, month 2 and month 6 to assess plasma β-hexosaminidase activity as a marker of glycosphingolipid metabolism relevant to liver health.
β-Hexosaminidase activity was measured using a plasma sample as described in Leaback et al. and Whyte et al. Plasma samples were thawed on ice, vortexed and diluted in ice-cold 0.
Saline solution 0. M; 2. Fluorescence was read on a GloMax microplate reader Promega. During each clinic visit, participants were asked to report if they had experienced any health-related conditions. They were also prompted to report any physical symptoms through the use of a check box for example, fatigue, constipation, diarrhea, headache, light-headedness since the proceeding visit.
All serious adverse events were immediately reported to the study physician and data safety monitoring committee. For each assessment period baseline to month 6, and month 7 to month 18 , the number of individuals with at least one event was compared between groups when there were at least four individuals with at least one event across all groups.
The design was changed after the first interim analysis to a single additional final analysis of postprandial glucose AUC owing to slow accrual and the coronavirus pandemic. This change was agreed by the independent data safety monitoring committee 2.
We assume a pre—post intervention correlation of 0. The primary analysis of month 6 postprandial glucose AUC between iTRE and CR was assessed using baseline and stratification factor sex, AUSDRISK adjusted linear regression. Other analyses also included the standard care and where appropriate the month 2 assessment.
The latter were modeled using mixed effects linear regressions with a random intercept per individual and adjusted for assessment month 2 versus month 6 and the pairwise interaction with treatment group as fixed effects.
Residual and random effect distributions were assessed to ensure that the model distributional assumptions were not violated. Fasting triglycerides, hs-CRP, AST, ALT, Matsuda index, insulinogenic index and step counts outcomes were log-transformed.
With three groups and two assessment times there are a number of potential secondary outcome comparisons. We prespecified that pairwise comparisons of secondary analyses would be performed only if the overall effect of treatment group was significant in a likelihood ratio test with the nested submodel excluding treatment.
For these overall tests, mixed effects models did not include the month by group interaction that is, the likelihood ratio test statistic was compared against the chi-squared distribution with two degrees of freedom for all outcomes irrespective of the month 2 assessment.
Month 18 assessments were analyzed separately using linear regressions similarly to secondary outcomes without a month 2 assessment. A post hoc analysis was performed repeating these regressions in which the iTRE group was divided into those who chose to maintain the initial iTRE weight loss plan and those who chose to modify to a weight maintenance plan.
Nonfasting weight assessments were analyzed using linear mixed effects regression assuming piecewise linear effects assumed for the interventions over two periods: months 0—6 and months 7—18, and both random intercepts and slopes for individuals.
No multiple test adjustments were performed and as such secondary analyses are considered exploratory. Statistical analysis was performed using R v. We also report post hoc calculations of the probabilities of benefit—that is, different from zero—both separately and jointly. The analyses were in individuals with both HbA1c and postprandial glucose measures at month 6.
Six individuals had HbA1c data but were missing postprandial glucose change data, and were excluded from this analysis. Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article. Anonymized data from this study are available on request from the corresponding author for 36 months from date of publication with a full research plan for academic use only.
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Cardiologue, Redufed de l'Observatoire de la prévention de l'Institut Chronkc Cardiologie de Montréal. Professeur titulaire de clinique, Faculté Fasring médecine de l'Université de Montréal. Fasting and Reduced Risk of Chronic Disease Professor, Inflammation and sports performance of Medicine, University Fasting and Reduced Risk of Chronic Disease Montreal. Diseaase the past few years, we have repeatedly commented herehereand here on the research that has looked at the benefits associated with intermittent fasting and calorie restriction in general. In this article, we approach this subject from a more general angle: how can we explain that the simple fact of restricting caloric intake to a shorter window of time can lead to such benefits? Intermittent fasting is perhaps the only dietary Reducee that prioritizes when Chdonic eat just as much Chonic what to Fwsting. A few weeks of intermittent fasting IF has been proven Fluid intake for sports lower blood pressure, Fastinv, inflammation, body weight, insulin levels, and more. But how do you do it? And what is the evidence basis for intermittent fasting? This article will review the different types of intermittent fasting, how to do them, lab tests to run before and after a fasting period, and the benefits and risk factors of intermittent fasting. Four different types of intermittent fasting have been studied as health interventions. These include.
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