Nutrition Fating volume 14Article number: 44 Cite this article. Metrics Immunity-boosting foods. Accordingly, this study examined occurrences of adverse fastinng and eating disorder symptoms during Body water percentage analysis. Purgative behavior and fastng of fatness remained unchanged.
Therefore, ADF Body water percentage analysis minimal adverse outcomes, and has either benign or Alternate-day fasting research effects Strengthen your heart eating disorder Altrrnate-day. Peer Review reports. Although ADF is effective for weight loss, the safety of the diet has been fastihg.
In reseagch, concerns have been raised regarding BMI for Teens disturbances, sleep issues, and Alternate-dayy Body water percentage analysis Alterante-day levels that may be related to lower Atlernate-day sugar levels.
ADF Alternate-fay also been criticized for potentially increasing disordered eating behaviors and Alterjate-day impacting body rrsearch perception. Accordingly, this study reseearch the occurrence of adverse reserch, changes fastiny disordered eating symptoms, and Allternate-day in body image perception Altenrate-day 8 weeks Aletrnate-day ADF in obese subjects.
Obese subjects were ressarch from the Rewearch area tesearch advertisements. Key inclusion criteria were as follows: age 25—65 Wrinkle reduction methods, BMI between 30 and The Alternate-dxy protocol reserach approved by the Office for the Protection of Research Subjects Alternate-da the University of Alterante-day, Chicago, and all fastin gave Alternafe-day informed consent.
An 8-week trial was implemented to test the study objectives. The primary outcome measures fating body weight, adverse events, disordered eating symptoms, and body Hydration gear guide perception.
Total energy expenditure Alternafe-day quantified by the Mifflin equation [ Antidepressant for perimenopause ] and appropriate activity factors. Subjects were Alternahe-day Alternate-day fasting research meals on each fast fadting, and faxting ad libitum on the feed day.
All meals were fastig outside of the Body water percentage analysis Altenrate-day. Fast day meals ressearch provided as a 3-day rotating menu, based fassting American Heart Association Researxh guidelines [ Altrnate-day ]. Body fastkng was measured using a Sports nutrition for weight management beam scale HealthOMeter, Boca Raton, FLBody water percentage analysis, and body composition was assessed by dual reserach X-ray absorptiometry DXA; iDXA, GE Inc.
An adverse event questionnaire was fastign at baseline i. fastihg the subjects began the intervention and Alternae-day. Eating disorder symptoms were measured using the Multidimensional Assessment of Eating-Disorder Alternahe-day MAEDS. Body image was assessed by afsting Body Shape Questionnaire BSQ.
Higher scores on the BSQ indicate greater concerns Alternate-dau body gesearch and shape. All researfh was analyzed using SPSS software version Purgative behavior was low at baseline and rasting unchanged. Fear of fatness was moderate, and did not change from baseline to post-treatment.
The rate of adverse events reported with ADF appears to World-class similar to faeting of daily calorie restriction.
For instance, Body water percentage analysis et al. In the present study, the most commonly reported adverse event was bad breath. However, this side effect may be lessened by consuming more water throughout the day and chewing sugar-free gum between meals.
As for eating disorder symptoms, ADF does not increase the rate depression, binge eating, purgative behaviour, fear of fatness, or avoidance of forbidden foods, and may have small beneficial effects on body image perception. Interestingly, restrictive eating was moderately increased with ADF, suggesting that the diet may help control unrestrained eating behaviors [ 7 ].
These findings for ADF are comparable to those of calorie restriction. In a recent study by Williamson et al. Taken together, it is possible that neither ADF nor calorie restriction increase eating disorder symptoms in obese adults, but these findings require confirmation in a longer-term randomized control trial comparing the two diets.
This study has several limitations. Firstly, the adverse event questionnaire was not very comprehensive, and was developed based on adverse events reported by subjects in previous ADF trials conducted by our lab. Second, the intensity of these adverse events mild, moderate or severe were not examined and recorded.
Third, much of the adverse event data reported in this study was qualitative, and therefore may underestimate all potential adverse events associated with ADF.
However, it should be noted that there is mounting quantitative data from previous studies [ 1 - 4 ] indicating that ADF may protect against the development of cardiovascular and metabolic diseases. Thus, the present data should be evaluated in the context of these previous reports [ 1 - 4 ].
In summary, ADF appears to be a safe and effective way to lose weight, and produces little or no gastrointestinal, sleep, or energy level disturbances. We also show here that this diet does not increase eating disorder symptoms, and has benign or beneficial effects on body image perception.
These preliminary findings are an encouraging first step in this field, but obviously warrant confirmation in a larger-scale, longer-term clinical trial.
Varady KA, Bhutani S, Church EC, Klempel MC. Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults. Am J Clin Nutr. Article CAS PubMed Google Scholar. Klempel MC, Kroeger CM, Varady KA. Alternate day fasting ADF with a high-fat diet produces similar weight loss and cardio-protection as ADF with a low-fat diet.
Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Varady KA. Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans.
Johnson JB, Summer W, Cutler RG, Martin B, Hyun DH, Dixit VD, et al. Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma.
Free Radic Biol Med. Mifflin MD, St Jeor ST, Hill LA, Scott BJ, Daugherty SA, Koh YO. A new predictive equation for resting energy expenditure in healthy individuals.
CAS PubMed Google Scholar. Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, et al. AHA Dietary Guidelines: revision A statement for healthcare professionals from the Nutrition Committee of the American Heart Association.
Anderson DA, Williamson DA, Duchmann EG, Gleaves DH, Barbin JM. Development and validation of a multifactorial treatment outcome measure for eating disorders.
Cooper PJ, Taylor MJ, Cooper Z, Fairburn CG. The development and validation of the Body Shape Questionnaire. Int J Eat Disord. Article Google Scholar. Cuevas A, Cordero MJ, Olivos C, Ghiardo D, Alvarez V.
Revista medica de Chile. Article PubMed Google Scholar. Lin WY, Wu CH, Chu NF, Chang CJ. Efficacy and safety of very-low-calorie diet in Taiwanese: a multicenter randomized, controlled trial. Williamson DA, Martin CK, Anton SD, York-Crowe E, Han H, Redman L, et al.
Is caloric restriction associated with development of eating-disorder symptoms? Results from the CALERIE trial. Health Psychol. Download references. Department of Kinesiology and Nutrition, University of Illinois at Chicago, West Taylor Street, Room F, Chicago, IL,USA.
You can also search for this author in PubMed Google Scholar. Correspondence to Krista A Varady. The co-authors declare that they have no competing interests. KKH designed the experiment, ran the clinical trial, analyzed the data, and wrote the manuscript. CMK, JFT, AB, and SB assisted with the conduction of the clinical trial and performed the laboratory analyses.
KAV assisted with the data analyses and the preparation of the manuscript. Sources of funding for all authors: Departmental funding, Kinesiology and Nutrition, University of Illinois at Chicago. All authors read and approved the final manuscript. Open Access This article is licensed under a Creative Commons Attribution 4.
Reprints and permissions. Hoddy, K. et al. Safety of alternate day fasting and effect on disordered eating behaviors. Nutr J 1444 Download citation. Received : 27 November Accepted : 15 April Published : 06 May Anyone you share the following link with will be able to read this content:.
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: Alternate-day fasting research| Clinical trial shows alternate-day fasting a safe alternative to caloric restriction | ScienceDaily | So, here's the deal. There is some good scientific evidence suggesting that circadian rhythm fasting, when combined with a healthy diet and lifestyle, can be a particularly effective approach to weight loss, especially for people at risk for diabetes. However, people with advanced diabetes or who are on medications for diabetes, people with a history of eating disorders like anorexia and bulimia, and pregnant or breastfeeding women should not attempt intermittent fasting unless under the close supervision of a physician who can monitor them. Adapted from a Harvard Health Blog post by Monique Tello, MD, MPH. Effects of intermittent fasting on health, aging, and disease. de Cabo R, Mattonson MP. New England Journal of Medicine , December Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. JAMA Internal Medicine , May Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism. American Journal of Clinical Nutrition , January Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis. JBI Database of Systematic Reviews and Implementation Reports, February Metabolic Effects of Intermittent Fasting. Annual Review of Nutrition , August Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. Cell Metabolism , May As a service to our readers, Harvard Health Publishing provides access to our library of archived content. 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Beyond the usual suspects for healthy resolutions. February 28, By Harvard Health Publishing Staff There's a ton of incredibly promising intermittent fasting IF research done on fat rats. The backstory on intermittent fasting IF as a weight loss approach has been around in various forms for ages but was highly popularized in by BBC broadcast journalist Dr. Intermittent fasting can help weight loss IF makes intuitive sense. Intermittent fasting can be hard… but maybe it doesn't have to be Initial human studies that compared fasting every other day to eating less every day showed that both worked about equally for weight loss, though people struggled with the fasting days. Why might changing timing help? So, is intermittent fasting as good as it sounds? Instead, eat fruits, vegetables, beans, lentils, whole grains, lean proteins, and healthy fats a sensible, plant-based, Mediterranean-style diet. Let your body burn fat between meals. Don't snack. Be active throughout your day. Build muscle tone. Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, et al. AHA Dietary Guidelines: revision A statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Anderson DA, Williamson DA, Duchmann EG, Gleaves DH, Barbin JM. Development and validation of a multifactorial treatment outcome measure for eating disorders. Cooper PJ, Taylor MJ, Cooper Z, Fairburn CG. The development and validation of the Body Shape Questionnaire. Int J Eat Disord. Article Google Scholar. Cuevas A, Cordero MJ, Olivos C, Ghiardo D, Alvarez V. Revista medica de Chile. Article PubMed Google Scholar. Lin WY, Wu CH, Chu NF, Chang CJ. Efficacy and safety of very-low-calorie diet in Taiwanese: a multicenter randomized, controlled trial. Williamson DA, Martin CK, Anton SD, York-Crowe E, Han H, Redman L, et al. Is caloric restriction associated with development of eating-disorder symptoms? Results from the CALERIE trial. Health Psychol. Download references. Department of Kinesiology and Nutrition, University of Illinois at Chicago, West Taylor Street, Room F, Chicago, IL, , USA. You can also search for this author in PubMed Google Scholar. Correspondence to Krista A Varady. The co-authors declare that they have no competing interests. KKH designed the experiment, ran the clinical trial, analyzed the data, and wrote the manuscript. CMK, JFT, AB, and SB assisted with the conduction of the clinical trial and performed the laboratory analyses. KAV assisted with the data analyses and the preparation of the manuscript. Sources of funding for all authors: Departmental funding, Kinesiology and Nutrition, University of Illinois at Chicago. All authors read and approved the final manuscript. Open Access This article is licensed under a Creative Commons Attribution 4. Reprints and permissions. Hoddy, K. et al. Safety of alternate day fasting and effect on disordered eating behaviors. Nutr J 14 , 44 Download citation. Received : 27 November Accepted : 15 April Published : 06 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. Download ePub. Conclusions Therefore, ADF produces minimal adverse outcomes, and has either benign or beneficial effects on eating disorder symptoms. Materials and methods Subject selection Obese subjects were recruited from the Chicago area by advertisements. Study design and diet protocol An 8-week trial was implemented to test the study objectives. Adverse event, eating disorder, and body image questionnaires An adverse event questionnaire was administered at baseline i. Table 1 Adverse events reported with 8 weeks of alternate day fasting Full size table. Table 2 Changes in eating disorder symptoms and body image perception after 8 weeks Full size table. References Varady KA, Bhutani S, Church EC, Klempel MC. Article CAS PubMed Google Scholar Klempel MC, Kroeger CM, Varady KA. Article CAS PubMed Google Scholar Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Varady KA. Article CAS PubMed Google Scholar Johnson JB, Summer W, Cutler RG, Martin B, Hyun DH, Dixit VD, et al. Article CAS PubMed Google Scholar Mifflin MD, St Jeor ST, Hill LA, Scott BJ, Daugherty SA, Koh YO. CAS PubMed Google Scholar Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, et al. Article CAS PubMed Google Scholar Anderson DA, Williamson DA, Duchmann EG, Gleaves DH, Barbin JM. Article CAS PubMed Google Scholar Cooper PJ, Taylor MJ, Cooper Z, Fairburn CG. Article Google Scholar Cuevas A, Cordero MJ, Olivos C, Ghiardo D, Alvarez V. Article PubMed Google Scholar Lin WY, Wu CH, Chu NF, Chang CJ. Article PubMed Google Scholar Williamson DA, Martin CK, Anton SD, York-Crowe E, Han H, Redman L, et al. Article PubMed Google Scholar Download references. Funding source Departmental funding, Kinesiology and Nutrition, University of Illinois at Chicago. View author publications. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4. |
| SYSTEMATIC REVIEW article | The experimental protocol was approved by the University of Illinois, Chicago, Office for the Protection of Research Subjects, and all research participants gave their written informed consent to participate in the trial. The findings look promising, but the effects of ADF on autophagy and longevity need to be studied more extensively. During the fasting days in the present ADF protocol, it would be reasonable to assume that a large part of the substrates for energy production comes from lipids. Conclusions Therefore, ADF produces minimal adverse outcomes, and has either benign or beneficial effects on eating disorder symptoms. Examples include:. Some studies have suggested that ADF may be more beneficial for preserving muscle mass than other types of calorie restriction,. |
| Top bar navigation | Article Google Scholar Cuevas A, Cordero MJ, Olivos C, Ghiardo D, Alvarez V. There's already plenty of evidence supporting a common-sense lifestyle approach to weight loss: ample intake of fruits and veggies, healthy fats, lean proteins, and plenty of exercise. Furthermore, we also reviewed original references for including texts. OB, Obese subjects, T2DM, patients with type 2 diabetes. The health and weight loss benefits seem to be the same regardless of whether the fasting-day calories are consumed at lunch or dinner, or as small meals throughout the day 4. Create a personal account or sign in to:. |
Alternate-day fasting research -
Exception from this was antihypertensive treatment, which was discontinued only on the test days and the day before. Absolute exclusion criteria were treatment with insulin and regularly performed sports activity more than once a week assessed by interview. None of the participants performed regular sports activity on a weekly basis prior to inclusion and participants were asked to maintain their habitual activity level, during the intervention.
Participants T2DM and OB were matched according to age and BMI. A flowchart of the recruitment process can be found in the supplemental material Supplementary Figure S5. Experiments were performed at Xlab, Department of Biomedical Sciences at the University of Copenhagen.
Magnetic resonance spectroscopies were performed at Department of Diagnostic Radiology, Copenhagen University Hospital Herlev-Gentofte.
The data from the two baseline tests did not differ significantly, and data are shown as pooled data. Between the two baseline tests, the per cent mean difference in measures of insulin sensitivity glucose infusion rates, clamp data were 2.
The second baseline test also included measurements of hepatic triglyceride content and skeletal muscle triglyceride content m. psoas major by magnetic resonance spectroscopy 1 H-MRS and volume of visceral and subcutaneous fat magnetic resonance imaging MRI at the level of L3.
On a separate day, maximal oxygen uptake VO 2 max was determined by a graded bicycle exercise test until exhaustion Jaeger Oxycon Pro, Intramedic, Hoechberg, Germany.
Figure 1. FIGURE 1. Study protocol. Two baseline experimental days were performed black boxes comprising of magnetic resonance spectroscopy 1 H-MRS and magnetic resonance imaging MRI only one time at baseline , body composition dual-energy X-ray absorptiometry DXA scan , fasting blood sampling, resting energy expenditure REE , intravenous glucose tolerance test IVGTT , and a euglycemic, hyperinsulinemic clamp These measurements were repeated after 3 weeks of alternate days fasting ADF.
During fast days midnight continuing for 30 h until Bodyweight was measured every morning and the diet was adjusted accordingly so that no change in body weight should occur. Blood was sampled and Tru-Cut micro muscle biopsies were obtained on two occasions, one in the afternoon on a double diet day marked 1 , and one in the morning after fasting marked 2.
In the following 3 weeks, ADF was continued, however with no dietary restrictions, i. On the second baseline experimental day and following ADF marked B , muscle biopsies were obtained before the IVGTT and after the clamp, in addition to the other procedures described.
Maximal oxygen uptake VO 2 max was measured at the study start to document a similar level of physical activity among all study participants.
Subsequently, an alternate day fasting ADF intervention was carried out for 6 weeks. The fasting day began at midnight a. and continued for 30 h until a. the following day. During the fasting day only water, coffee and tea were allowed. During the first 3 weeks the participants aimed at maintaining their body weight by doubling their diet intake on the non-fasting days.
No specific diet was prescribed, and the effect on body weight was monitored by daily weighing and reports to the investigators.
After the 10th fasting day, a habitual eu-caloric diet for 1 day was followed by a repetition of the experimental procedures performed at baseline. In the fourth, fifth, and sixth weeks of ADF, the participants followed an ad libitum diet on eating days, i. a weight loss was allowed.
Then the baseline tests were repeated after 1 day of the habitual diet. This design aimed to focus on two different interventions, ADF without weight loss, i. as the everyday practice of the method. Primary endpoints were changes in insulin sensitivity by the hyperinsulinaemic euglycemic clamp, glucose clearance rate per fat-free mass and beta-cell function by IVGTT, insulin area under the curve with ADF.
Changes in energy store levels were secondary outcome measures. Plasma concentrations of substrates and metabolites glucose, free fatty acids FFA , glycerol, ß-hydroxybutyrate, cholesterol, triglyceride, high-sensitive C-reactive peptide hsCRP , alanine aminotranferase ALAT , asparatate aminotransferase ASAT were measured by spectrophotometry Cobas c , Roche, Glostrup, Denmark.
HbA1c was analyzed on a DCA Vantage Analyser Siemens Healthcare Diagnostics Inc. Tarrytown NY, United States. Applied methods for resting energy expenditure, maximal oxygen uptake tests, whole-body dual-energy X-ray absorptiometry DXA scan Hansen et al.
Methods for the measurement of hepatic triglyceride content Chabanova et al. Measurements were T2 corrected, and T2 was measured for each individual at each visit.
Muscle intra- and extra myocellular content were not separated in the analysis, thus m. psoas major results are describing the sum of these. Protein content in m.
vastus lateralis was examined using SDS-PAGE Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis and Western blotting techniques see Supplementary Material. Analysis of mitochondrial function was performed in permeabilized skeletal muscle fibers.
Mitochondrial respiratory capacity was determined as previously described Dohlmann et al. See Supplementary Material for the detailed protocols.
Citrate synthase CS activity was measured as previously described Larsen et al. Image analysis was performed with Fiji software Schindelin et al. Insulin sensitivity was estimated from glucose infusion rates during the final 30 min of the clamp.
Glucose clearance rates were calculated as glucose infusion rates divided by the prevailing plasma glucose concentration. Statistical analyses of parameters measured across the intervention phases e. insulin secretion, insulin sensitivity, blood lipids, body weight were performed with mixed model analyses GraphPad Prism 8.
In the absence of missing values, this method gives the same p values and multiple comparisons tests as repeated measures ANOVA. In the presence of missing values missing completely at random , the results can be interpreted like repeated measures ANOVA.
Based on data from previous studies Halberg et al. Maximal oxygen uptake was similar in the patients with type 2 diabetes T2DM and obesity OB 2. Apart from the volume of visceral fat measured by MRI, the two groups were well matched concerning anthropometrics at baseline Table 1.
However, the decrease was primarily due to the last part of the intervention protocol, where a weight loss was allowed. Plasma concentrations of insulin and C-peptide were as expected elevated on the double diet day Table 2.
β-hydroxybutyrate representing ketone bodies were increased after 30 h Fasting, and higher in T2DM vs. Total cholesterol, LDL, and HDL cholesterol were not different between the groups and did not change with the intervention Table 2. Plasma glycerol concentrations displayed a similar pattern, however, with no group differences, and only OB displayed a significant increase with fasting Table 2.
Plasma hsCRP values were generally very low, and no changes were seen Table 2. The interventions did not change the insulin response in the control group. FIGURE 2. In column graphs are shown area under the curve AUC for insulin E and glucose F. Data are shown as mean ± SD.
T2DM patients displayed insulin resistance glucose infusion rate compared with OB Table 1. the insulin sensitivity increased as a main effect and not with ADF alone. Glucose rate of appearance Ra after an overnight fast in the baseline test was increased in T2DM compared with OB 3.
Glucose Ra was unchanged in the fasting state following 3 weeks of ADF T2DM: 3. Muscle glycogen content Table 2 was also measured in the evening after a double diet day and in the morning after a fasting day after 30 h fasting see protocol, Figure 1.
No significant difference was seen with the analysis of the OB and T2DM group separately. The purpose was to monitor adherence to the fasting, double diet and ad libitum diet days and all subjects followed the intervention. Glucose levels were higher in T2DM compared with OB at all times Figure 3.
During ADF, CGM data from weeks one to three illustrates that eating on double diet days increased after the first week, probably also due to encouragement to the patients based upon the daily home-based weighing. No hypoglycemic events were recorded. FIGURE 3. Continuous glucose monitoring CGM traces in patients with obesity OB and type 2 diabetes T2DM.
Data are shown as mean values. FIGURE 4. Intrahepatic triglyceride content measured by 1 H-magnetic resonance spectroscopy in eleven subjects with obesity OB and eleven patients with type 2 diabetes T2DM. Experiments were performed at baseline, after 3 weeks of alternate-day fasting with double diet on non-fasting days ADF , and after 3 weeks of alternate-day fasting with ad libitum diet, i.
Triglyceride content in m. psoas major by 1 H-MRS was not different between the groups and did not change with the intervention baseline: 5. Muscle lipid droplet density, size of droplets, or the fractional area of the droplets did not differ between T2DM and OB, and no change with ADF was seen Figure 5A, B, C, F.
These data were confirmed by analysis of intramuscular triglyceride IMTG content Figure 5D. In addition, IMTG content was also measured in Tru-Cut biopsies obtained in the evening after a double diet day and in the morgen after 30 h fasting Figure 5E. after an overnight fast , but this could not be detected in OB Figure 5E.
No difference in IMTG between double diet day and 30 h fasting could be seen in either group Figure 5E. FIGURE 5. Lipid droplets LD density per area of muscle fibre A. LD size B. Intramuscular triglyceride IMTG content in muscle at baseline clamp and at the clamp after ADF D.
IMTG content in muscle after one double diet day and after 30 h fasting E. Representative images of Bodipy staining F. OB, Obese subjects, T2DM, patients with type 2 diabetes. In figure f, scale bars represent µm top and 25 µm bottom.
The expression of proteins relevant for insulin-mediated glucose metabolism is shown in Supplementary Figure S1A-I. Proteins involved in glucose transport GLUT4 and glycolysis hexokinase and pyruvate kinase and glycogen storage glycogen synthase and phosphorylase were similar between the two groups and did not change with ADF.
Proteins relevant for GLUT4 vesicle formation showed minor changes. Thus, Akt was significantly higher in OB compared with T2DM, and AMPKα1 increased significantly with ADF in OB, but not in T2DM.
AS and PKCθ remained unchanged and similar in the two groups. The expression of proteins relevant to lipid metabolism is shown in Supplementary Figure S1J-S. Proteins involved in fatty acids transport into muscle cells were studied by analysis of proteins located in the plasma membrane.
This was carried out to determine if alternate day fasting had any effect on fatty acid transport in healthy or diabetic skeletal muscle tissue. Fatty acid translocase FAT or CD36 binds long-chain fatty acids and is a key player in fatty acid transport across the plasma membrane. Fatty acid transport protein 4 FATP4 esterifies long-chain fatty acids and has a role in fatty acid transport across the plasma membrane.
Plasma membrane fatty acid binding protein FABPpm is also involved in myocellular uptake of long-chain fatty acids. No change was observed in the T2DM group or between the two groups for all fatty acid transporters. Citrate synthase CS activity was used as an index for mitochondrial mass Larsen et al.
Oxygen consumption ex vivo was measured with a sequential substrate protocol, with state 2 respiration complex I; malate and glutamate followed by state 3 respiration with increasing concentrations of ADP complex I and dual electron input to complex I and II glutamate, malate, succinate, and ADP , ending with uncoupled respiration FCCP as protonophore Supplementary Figure S2A.
First of all, there were no differences in respiration between T2DM and OB, and no significant effect of ADF was observed Supplementary Figure S2A. Reactive oxygen species ROS displayed no difference between the groups and no effect of ADF was observed Supplementary Figure S2B.
ADP sensitivity and maximal oxygen flux Vmax was calculated from the oxygen flux during increasing ADP concentrations, and no differences between groups or effects of ADF were seen Supplementary Figures S2C, D.
The present study represents a comprehensive characterization of the effects of alternate-day fasting regimens on the human metabolism, studied in obese patients with and without type 2 diabetes. The energy balance is essential in every attempt to lose bodyweight, and if weight loss is the primary focus it is fundamental to achieve a negative energy balance, no matter how this is brought about.
This was not the primary focus here. With the present study protocol, we aimed to study the metabolic effects of oscillations in energy intake and thus energy balance. An improvement of the insulin secretory capacity in patients with type 2 diabetes is a therapeutic goal that is difficult to achieve non-pharmacologically, and only a few studies in patients with type 2 diabetes have reported improvements in β-cell secretion following physical training Krotkiewski et al.
The purpose of the present study was to mimic the oscillations that occur in energy stores with frequent exercise training, but at the same time avoid the physiological impact on metabolism that takes place with exercise training i.
muscle contractions. ADF would largely accomplish this, but from previous studies, it is known that weight loss often follows ADF. Therefore, we divided the study into two 3-week periods of ADF, where weight loss was allowed in the latter period, as would be the every day practice.
The first-phase insulin response in the patients with type 2 diabetes was, however, not restored albeit the insulin response curve displayed a more marked first phase profile compared with baseline Figure 2C.
An indication that time-restricted feeding i. not the same protocol as used in the present study without weight loss may increase ß-cell responsiveness in pre-diabetic people has been published Sutton et al. The mechanism for improvements in insulin secretion has been attributed to a decrease in intrapancreatic triacylglycerol Lim et al.
This is also a likely explanation in the present study, where we observed large decreases in visceral fat Table 1 and intrahepatic triglyceride content Figure 4 where the latter correlated significantly with the improvement in insulin secretion. The elevated plasma concentrations of FFA, glycerol, and β-hydroxybutyrate during fasting Table 2 testified to an increased lipolytic rate during fasting, contributing to the marked decrease of adipose tissue during the interventions Table 1.
An additional mechanism for the improvement in insulin secretion could also be due to an overall reduced glycemic load on the β-cells i. reduced glucotoxicity. Apart from documenting the adherence to the protocol, the continuous glucose monitoring Figure 3 revealed a lessened glycemic burden, which in itself reduces the stress on the β-cells.
It is important to note that the duration of type 2 diabetes, or at least the time since diagnosis, was short among the included patients 2. This means that the patients had a relatively well-preserved β-cell function, but of course, diminished compared with the obese subjects without type 2 diabetes Figure 2.
We have previously shown that patients with a high pre-operative β-cell function experience a superior outcome to gastric bypass surgery compared with those patients with the lowest pre-operative β-cell function Lund et al. Most likely, patients with severely reduced insulin secretory capacity which can be easily estimated by a 6 min glucagon test Dela et al.
Many studies have shown positive effects of training on insulin-mediated glucose uptake in skeletal muscle in patients with type 2 diabetes Dela et al.
For muscle glycogen Table 2 this aim was achieved, but the oscillations did not translate into an improvement of insulin-mediated glucose clearance with ADF alone, which is in contrast to earlier findings in young, healthy subjects Halberg et al.
However, the data are in line with findings in obese people, using a calculated index for insulin sensitivity S I from an intravenous glucose tolerance test Catenacci et al. Insulin action at the hepatic level, i. inhibition of endogenous glucose Ra, did not change with ADF.
This finding is in line with the lack of effect of ADF on peripheral insulin action. It may require an extended period of starvation 3—4 days before a reduction of insulin-induced suppression of hepatic glucose output is seen Fery et al.
This indicates a general improvement in hepatic function elicited by dietary regimen. The lack of increases in insulin sensitivity with ADF is in line with the general lack of increases in proteins relevant for skeletal muscle insulin action, e.
GLUT4, hexokinase, glycogen synthase Supplementary Figure S1. In rodents, a similar lack of change in hexokinase after intermittent fasting has been reported Real-Hohn et al. The amount of intramyocellular lipids is inversely correlated with insulin sensitivity Pan et al.
psoas major fit well with the lack of changes in insulin sensitivity. A similar amount of lipid content in the muscle in T2DM and OB has been shown before Hansen et al. The latter is in line with earlier findings that demonstrated that it requires prolonged fasting e.
Lipolysis increases at the beginning of a fasting period here evidenced by increased FFA and glycerol after 30 h fasting; Table 2. The more so, because the anti-lipolytic effect of insulin diminishes with fasting Jensen et al. Support for an ADF-induced triglyceride-lowering effect is found in low-calorie refeeding studies that demonstrated increased triglyceride turnover and removal efficiency Streja et al.
During the fasting days in the present ADF protocol, it would be reasonable to assume that a large part of the substrates for energy production comes from lipids. If not from intramuscular stores, of which a decrease could not be detected, then from extramyocellular stores, i.
adipose tissue. The amount of adipose tissue decreased Table 1 during the 6-week intervention, which in turn give rise to the increased availability of fatty acids Table 2 that facilitates an increased fatty acid transport across the sarcolemma.
To this end, we measured fatty acid translocase CD36 , fatty acids transport protein 4 FATP4 , and plasma membrane fatty acid binding protein FABPpm which are important players in the transport of fatty acids across the plasma membrane.
A mixed result was seen, with CD36 increasing significantly in the OB group, FATP4 decreasing in T2DM, and decreasing in FABPpm main effect Supplementary Figure S1.
The changes were small, and the data cannot support the notion that fatty acid transport was increased. Most likely, the oscillation of carbohydrate and lipid substrates every other day blurred a potential marked increase in these proteins.
Once inside the muscle cell, fatty acids can be stored as triglycerides and the final step in the synthesis is catalyzed by diglyceride acyltransferase 1 DGAT1. DGAT1 protein expression did not change with the intervention Supplementary Figure S2M , but even though we did not detect a difference in lipid content between the two groups, DGAT1 was significantly higher expressed in T2DM compared with OB.
To our knowledge, DGAT1 protein expression in skeletal muscle of patients with type 2 diabetes has only been measured in one other study, in which no change was found compared with obese people and athletes Bergman et al. Our data suggest that T2DM have the capacity to synthesize greater amounts of intramuscular lipids.
We measured two proteins involved in lipolysis adipose triglyceride lipase ATGL , monoacylglyceride lipase MGLL and in lipid storage Perilipin 2 adipophilin , perilipin 3 TIP47 , and perilipin 5 OXPAT and in line with the unchanged lipid content in the muscles Figure 5 we found no effect of the intervention on these proteins Supplementary Figure S1.
An increase in medium-chain acyl-CoA dehydrogenase MCAD might have been seen because MCAD is involved in medium-chain fatty acid beta-oxidation, which would be expected to increase with increased fatty acid availability but not with increased lipid storage.
However, no change was detected Supplementary Figure S1. The expression of proteins involved in lipid transport, synthesis and storage presented here, are in line with data on gene expression mRNA of many of these proteins in a study on females undergoing an intermittent fasting regimen with the muscle biopsies obtained in the same condition i.
after an overnight h fast Liu et al. However, in that study Liu et al. Others have also found that CD36 mRNA remains unchanged with a zero-calorie ADF regimen Heilbronn et al. Compared with minor caloric restriction, ADF over 6 months does not bring about superior health benefits in terms of body weight, body composition, or cardiovascular risk factors in patients with obesity Trepanowski et al.
This difference in design as well as differences in study cohorts between the two studies makes a direct comparison difficult. The second part of the present study, where ad libitum diet was allowed on feast days demonstrated that the study participants did not inadvertently compensate the overall caloric deficit, because body weight decreased faster in the latter part of the study.
If weight loss is the purpose of ADF, zero-calorie intake must therefore be recommended on fast days because it will not be compensated on feast days. The length of the fasting may also play a role.
In the study by Trepanowski et al. Trepanowski et al. Varady, personal communication , but since lunch was allowed between and on fasting days, the fasting period was, in fact, two periods of 12 and 10 h. These relatively short periods of fasting every other day may therefore be the reason that this intervention was not superior in reducing body weight compared to ordinary everyday caloric restriction.
In the present study, each zero-calorie fasting period was 30 h, which is of sufficient length to markedly draw from endogenous energy sources, introducing loss of body weight and also mimicking oscillations in energy stores induced by exercise Dela et al. In line with previous studies for review see Dela et al.
Dela and Helge, and newer studies Lund et al. In the present study, we tested ADP sensitivity of the skeletal muscle mitochondria Supplementary Figure S1 but found no difference between the groups or an effect of ADF. Previously, in patients with type 2 diabetes, we have demonstrated increased sensitivity for complex I glutamate and complex II succinate substrates Larsen et al.
This study has some limitations. We did not randomize patients to a non-intervention control group, because it is a well-known risk that patients assigned to passive control groups may exhibit behavioural changes, especially in studies with a focus on dietary behaviour.
Instead, we performed two baseline experiments that were carried out two to 3 weeks apart Figure 1 to account for any variation in methodology and to avoid a time effect of enrollment into a dietary study per se.
We did not include a group that performed conventional caloric restriction, thus we cannot make a direct comparison between ADF and conventional caloric restriction, and this was not the purpose here. The intervention was well tolerated by all patients.
The strict zero-calorie regimen is a quite demanding approach, but the reports from the participants were that the most difficult task was to eat the double diet on non-fasting days during the first 3 weeks.
However, a double diet every other day was only used for mechanistic reasons, and it is not the recommended approach for the general use of ADF. It should also be noted that oral medication, except antihypertensive drugs but including glucose lowering drugs, was discontinued during the entire intervention.
Yet, the patients with type 2 diabetes experienced an improvement in fasting glucose and even HbA1c. This suggests that shorter term 6 weeks ADF is a feasible approach in patients in treatment with oral glucose-lowering therapy that will bring about loss of weight and improved glycemic control.
Longer-term more than 6 weeks effects i. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
The studies involving human participants were reviewed and approved by The Regional Ethics Committee H Conceptualization, FD, and AI; Methodology, FD, SL, CP.
Alternate-day fasting ADF is an intermittent fasting approach. Examples include:. Krista Varady, who has conducted most of the studies on ADF. The health and weight loss benefits seem to be the same regardless of whether the fasting-day calories are consumed at lunch or dinner, or as small meals throughout the day 4.
Most of the studies on alternate-day fasting used the modified version, with calories on fasting days. Alternate-day fasting cycles between days of fasting and normal eating.
The most popular version allows for about calories on fasting days. Although ADF may be helpful for promoting weight loss, studies have suggested that this type of calorie restriction is no more effective for weight loss than traditional daily calorie restriction. Research suggests that this method is not superior to traditional daily calorie restriction for promoting weight loss 3 , 6 , 8 , 9 , Studies have shown that ADF and daily calorie restriction are equally effective at reducing harmful belly fat and inflammatory markers in those with obesity Although ADF may offer benefits for fat loss, recent research shows that ADF is no more effective than traditional calorie restriction for promoting weight loss or preserving muscle mass 6 , Furthermore, like other types of calorie restriction, weight loss during ADF may be accelerated when combined with increased physical activity.
For example, combining ADF with endurance exercise may cause twice as much weight loss than ADF alone and six times as much weight loss as endurance exercise alone Alternate-day fasting may help you lose weight. Some studies show that hunger ultimately goes down on fasting days, while others state that hunger remains unchanged 5 , 9 , However, research agrees that modified ADF with calories on fasting days is much more tolerable than full fasts on fasting days One study comparing ADF to calorie restriction showed that ADF increased levels of brain-derived neurotrophic factor BDNF after 24 weeks of follow- up.
Researchers concluded that ADF may induce long-term changes in BDNF and that this may promote improved weight loss maintenance. However, the researchers found that BDNF levels did not correlate with body weight changes in this particular study and suggested that these findings be interpreted with caution However, animal studies have shown that modified ADF resulted in decreased amounts of hunger hormones and increased amounts of satiety hormones compared to other diets 17 , 18 , Another factor to consider is compensatory hunger, which is a frequent downside of traditional, daily calorie restriction 20 , 21 , Compensatory hunger refers to increased levels of hunger in response to calorie restriction, which cause people to eat more than they need to when they finally allow themselves to eat.
In fact, many people who try modified ADF claim that their hunger diminishes after the first 2 weeks or so. After a while, some find that the fasting days are nearly effortless 5.
The effects of alternate-day fasting on hunger are inconsistent. Studies on modified alternate-day fasting show that hunger decreases as you adapt to the diet. Some studies have suggested that ADF may be more beneficial for preserving muscle mass than other types of calorie restriction,.
However, results from a recent, high-quality study suggest that ADF is no more effective for preserving muscle mass than traditional calorie restriction 6 , 8 , 16 , 25 , Losing weight and restricting calories is usually an effective way to improve or reverse many symptoms of type 2 diabetes Similarly to continuous calorie restriction, ADF seems to cause mild reductions in risk factors for type 2 diabetes among people with overweight or obesity 30 , 31 , ADF may also help reduce fasting insulin levels, with some studies suggesting that it may be more effective than daily calorie restriction.
However, not all studies agree that ADF is superior to daily calorie restriction 6 , 33 , 34 , Having high insulin levels, or hyperinsulinemia, has been linked to obesity and chronic diseases, such as heart disease and cancer 36 , A reduction in insulin levels and insulin resistance should lead to a significantly reduced risk of type 2 diabetes, especially when combined with weight loss.
Alternate-day fasting may reduce risk factors for type 2 diabetes. It can reduce fasting insulin levels in people with prediabetes. Heart disease is the leading cause of death in the world and responsible for about one in four deaths 38 , 39 , Many studies have shown that ADF is a good option to help individuals with overweight or obesity lose weight and reduce heart disease risk factors 1 , 4 , 8 , The most common health benefits include 1 , 8 , 13 , 14 , 42 , 43 :.
Alternate-day fasting may reduce waist circumference and decrease blood pressure, LDL bad cholesterol, and triglycerides. Autophagy is a process in which old parts of cells are degraded and recycled. It plays a key role in preventing diseases, including cancer, neurodegeneration, heart disease, and infections 44 , Animal studies have consistently shown that long- and short-term fasting increase autophagy and are linked to delayed aging and a reduced risk of tumors 46 , 47 , 48 , Furthermore, fasting has been shown to increase lifespan in rodents, flies, yeasts, and worms Moreover, cell studies have shown that fasting stimulates autophagy, resulting in effects that may help keep you healthy and live longer 51 , 52 , This has been supported by human studies showing that ADF diets reduce oxidative damage and promote changes that may be linked to longevity 9 , 15 , 52 , The findings look promising, but the effects of ADF on autophagy and longevity need to be studied more extensively.
Alternate-day fasting stimulates autophagy in animal and cell studies. This process may slow aging and help prevent diseases like cancer and heart disease.
Nearly all weight loss methods cause a slight drop in resting metabolic rate 55 , This effect is often referred to as starvation mode , but the technical term is adaptive thermogenesis.
When you severely restrict your calories, your body starts conserving energy by reducing the number of calories it burns. It can make you stop losing weight and feel miserable Meanwhile, the ADF participants experienced only a 1.
New Body water percentage analysis shows little risk of infection from Periodized meal plan biopsies. Discrimination at work reaearch linked to high researdh pressure. Icy fingers and toes: Poor circulation or Raynaud's phenomenon? There's a ton of incredibly promising intermittent fasting IF research done on fat rats. They lose weight, their blood pressure, cholesterol, and blood sugars improve… but they're rats.
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