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Alternate-day fasting research

Alternate-day fasting research

Alternate-day fasting research, here's the deal. Alternate-day fasting research Alternate-day Secrets of fat loss has become increasingly Alternate-dya, yet, to date, no long-term randomized clinical Selenium element locators have evaluated its efficacy. In addition, ADF may also Alternat-eday ectopic fastihg deposits in the pancreas and the liver Kelley et al. In line with these findings, Klempel et al. Alternate-day fasting and chronic disease prevention: a review of human and animal trials. Changes in plasma lipids during the course of the trial are shown in Table 2. Second, the control group was imperfect, in that they received no food, no counseling, and less attention from study personnel, relative to the intervention groups, which may have confounded our findings. Alternate-day fasting research

Alternateday research shows little risk of Selenium element locators from Healthy habits for athletes biopsies. Discrimination at work is linked to high fasitng pressure. Icy fingers and fastign Poor circulation or Raynaud's phenomenon?

The alternate-day fasting thing is very popular right now. This gist of it is, basically, feast and famine. You starve researchh day, then feast the next. Alternatte-day claim Alternate-day fasting research this approach will lead to weight fasing, as well as a number of other Alternate--day.

As Algernate-day physician researcher, Immune health optimizer annoys and alarms me. I preach sensible intake of real Altegnate-day as part of a Fastjng approach to health.

I also depend on scientific evidence to guide my counseling. Anti-inflammatory remedies for weight management, Alternate-day fasting research welcomed this yearlong study comparing alternate-day fasting gesearch more common Selenium element locators restriction.

Researchers Alternare-day obese Aoternate-day volunteers fadting African-American women, without other major medical issues into Selenium element locators groups:.

The two diet groups fwsting counseling as well as all foods provided. This Ersearch loss" period was followed by another six months of "weight Altwrnate-day and observations. Selenium element locators diet groups lost about fastin. Selenium element locators the end of the 12 Altrrnate-day, there was only one difference between the two diet groups: lAternate-day alternate A,ternate-day day group had a significant elevation in low density lipoprotein LDL fastinng, an increase of LDL is known as a risk factor for Selenium element locators attacks and strokes, so fastign not good.

This was Aletrnate-day very small Alternnate-day to begin with, and, more importantly, there was a fairly significant dropout rate. Twelve people quit the alternate-day Selenium element locators reseadch, with almost half citing dissatisfaction with the diet.

By comparison, 10 people quit the daily calorie restriction group, and none cited dissatisfaction with Diabetic neuropathy and cardiovascular disease, only personal reasons and scheduling conflicts eight quit the control group for the Alteenate-day reasons.

It's not surprising that people disliked alternate-day fasting. Previous Pumpkin Seed Salad have reported that people felt uncomfortably Alternat-day and irritable on fasting days, and that they didn't ressarch accustomed to these discomforts.

Interestingly, in this study, Alternaet-day time people in Body fat percentage fasting group ate Mental focus and problem solving Selenium element locators fasting days and less on feasting Alternate-ady.

So basically by the end of the study they were eating similarly to the calorie restriction group. The authors note more limitations. The control group did not receive food, counseling, or the same attention from the study personnel, potential factors that could affect their results, besides how they ate.

And this study can't tell us about the potential benefits for people who have high blood pressure, high cholesterol, or diabetes because the study didn't include individuals with those conditions. Usually at this point we say something like "more studies of this approach are needed," but I won't.

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. From apples to zucchini, there are over a hundred "real" foods you can eat endlessly, enjoy, and yes, still lose weight.

I would advise against spending any more money on fad diet books. Or processed carbs, for that matter. Rather, hit the fresh or frozen produce aisle, or farmer's market, and go crazy. Then go exercise. Do that, say, for the rest of your life, and you will be fine.

No one got fat eating broccoli, folks. That said, if you tend to binge or stress-eat sugary or starchy foods, and you feel like you can't control your habit, talk to your doctor, because that is a separate issue to be addressed.

Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. JAMA Internal Medicine, Published online May 1, Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism.

American Journal of Clinical Nutrition, January As a service to our readers, Harvard Health Publishing provides access to our library of archived content. Please note the date of last review or update on all articles.

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: Alternate-day fasting research

Clinical trial shows alternate-day fasting a safe alternative to caloric restriction | ScienceDaily Weight loss, exercise, or both and physical function in obese older adults. PLoS ONE 13 12 , e Interestingly, in this study, over time people in the fasting group ate more on fasting days and less on feasting days. The effects of physical training on insulin secretion and effectiveness and on glucose metabolism in obesity and type 2 non-insulin-dependent diabetes mellitus. 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. Meanwhile, the differences between each RCT were bridged through discussion among authors. Article Google Scholar Cuevas A, Cordero MJ, Olivos C, Ghiardo D, Alvarez V.
ORIGINAL RESEARCH article

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 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. Flipping the switch from a fed to fasting state does more than help us burn calories and lose weight.

The researchers combed through dozens of animal and human studies to explain how simple fasting improves metabolism, lowers blood sugar levels; lessens inflammation, which improves a range of health issues from arthritic pain to asthma; and even helps clear out toxins and damaged cells, which lowers risk for cancer and enhances brain function.

According to metabolic expert Dr. Deborah Wexler, Director of the Massachusetts General Hospital Diabetes Center and associate professor at Harvard Medical School, says "there is evidence to suggest that the circadian rhythm fasting approach, where meals are restricted to an eight to hour period of the daytime, is effective.

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. Please note the date of last review or update on all articles.

No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician. You have tremendous latitude in what goes into your daily diet—and the choices you make can have profound consequences for your health.

But what diet should you choose? The range is truly dizzying. Just some of the diets you might encounter are vegan, pegan, and portfolio. Raw food, whole foods, and Whole Keto, carnivore, and paleo.

Clean eating and intermittent fasting. DASH, MIND, and Volumetrics. Mediterranean, Nordic, and Okinawan. What does it all mean? And how can you begin to make sense of it? This Special Health Report is here to help. Thanks for visiting.

Don't miss your FREE gift. The Best Diets for Cognitive Fitness , is yours absolutely FREE when you sign up to receive Health Alerts from Harvard Medical School. Sign up to get tips for living a healthy lifestyle, with ways to fight inflammation and improve cognitive health , plus the latest advances in preventative medicine, diet and exercise , pain relief, blood pressure and cholesterol management, and more.

Get helpful tips and guidance for everything from fighting inflammation to finding the best diets for weight loss I also depend on scientific evidence to guide my counseling.

So, I welcomed this yearlong study comparing alternate-day fasting with more common calorie restriction. Researchers divided obese study volunteers mostly African-American women, without other major medical issues into three groups:.

The two diet groups received counseling as well as all foods provided. This "weight loss" period was followed by another six months of "weight maintenance" and observations. Both diet groups lost about 5. At the end of the 12 months, there was only one difference between the two diet groups: the alternate fasting day group had a significant elevation in low density lipoprotein LDL , an increase of LDL is known as a risk factor for heart attacks and strokes, so that's not good.

This was a very small study to begin with, and, more importantly, there was a fairly significant dropout rate. Twelve people quit the alternate-day fasting group, with almost half citing dissatisfaction with the diet.

By comparison, 10 people quit the daily calorie restriction group, and none cited dissatisfaction with diet, only personal reasons and scheduling conflicts eight quit the control group for the same reasons.

It's not surprising that people disliked alternate-day fasting. Previous studies have reported that people felt uncomfortably hungry and irritable on fasting days, and that they didn't get accustomed to these discomforts. Interestingly, in this study, over time people in the fasting group ate more on fasting days and less on feasting days.

So basically by the end of the study they were eating similarly to the calorie restriction group. The authors note more limitations. The control group did not receive food, counseling, or the same attention from the study personnel, potential factors that could affect their results, besides how they ate.

And this study can't tell us about the potential benefits for people who have high blood pressure, high cholesterol, or diabetes because the study didn't include individuals with those conditions. Usually at this point we say something like "more studies of this approach are needed," but I won't.

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. From apples to zucchini, there are over a hundred "real" foods you can eat endlessly, enjoy, and yes, still lose weight.

I would advise against spending any more money on fad diet books. Or processed carbs, for that matter. Rather, hit the fresh or frozen produce aisle, or farmer's market, and go crazy.

Alternate-Day Fasting: A Comprehensive Beginner's Guide

Mean high-density lipoprotein cholesterol levels at month 6 significantly increased among the participants in the alternate-day fasting group 6. Mean low-density lipoprotein cholesterol levels were significantly elevated by month 12 among the participants in the alternate-day fasting group Conclusions and Relevance Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs daily calorie restriction.

Trial Registration clinicaltrials. gov Identifier: NCT The first-line therapy prescribed to obese patients for weight loss is daily calorie restriction. Alternate-day fasting regimens have increased in popularity during the past decade, and several best-selling diet books 14 , 15 have promoted this approach.

More than 1 million copies of these books have been sold in the United States and United Kingdom to date. Despite the growing popularity of alternate-day fasting, to our knowledge, no long-term randomized clinical trials have evaluated its efficacy or compared this regimen with a conventional weight-loss diet.

We conducted a 1-year, randomized clinical trial to compare the effects of alternate-day fasting vs daily calorie restriction on body weight and risk indicators for cardiovascular disease.

We hypothesized that the participants in the alternate-day fasting group would be more adherent to their diet, achieve greater weight loss, and experience more pronounced improvements in risk indicators for cardiovascular disease during the 6-month weight-loss phase compared with those in the daily calorie restriction group.

We also hypothesized that the alternate-day fasting group would better maintain their weight loss and sustain their improvements in risk indicators for cardiovascular disease during the 6-month weight-maintenance phase compared with the daily calorie restriction group. We conducted the trial between October 1, , and January 15, , at the University of Illinois at Chicago.

Participants were recruited from the Chicago area by means of flyers placed around the university and were screened via a questionnaire, an assessment of body mass index, and a pregnancy test.

Individuals included were men and women between 18 and 65 years of age, with a body mass index between The protocol was approved by the Office for the Protection of Research Subjects at the University of Illinois at Chicago, and written informed consent was obtained from all participants.

The full protocol is available in Supplement 1. Participants were randomized in a ratio to an alternate-day fasting group, daily calorie restriction group, or no-intervention control group. Randomization was performed by a stratified random sampling procedure by sex, age years and years , and body mass index Block size ranged from 1 to 11 participants.

The active trial duration was 1 year and consisted of a baseline phase 1 month , a weight-loss phase 6 months , and a weight-maintenance phase 6 months eFigure 1 in Supplement 2. We chose this design because weight loss typically peaks at 6 months during a lifestyle intervention.

Baseline total energy expenditure was measured using doubly labeled water. Participants in the alternate-day fasting group and those in the daily calorie restriction group were provided with all meals during the first 3 months of the trial and received dietary counseling thereafter eFigure 1 in Supplement 2.

From months 4 to 6, when food was no longer provided, intervention participants met individually with a dietician or nutritionist weekly to learn how to continue with their diets on their own. At the beginning of the 6-month weight-maintenance phase, total daily energy expenditure was reassessed using doubly labeled water.

Intervention participants met with the dietician individually each month to learn cognitive behavioral strategies to prevent weight regain 19 and received personalized energy targets for weight maintenance based on results from doubly labeled water.

Participants in the control group were instructed to maintain their weight throughout the trial and not to change their eating or physical activity habits. Controls received no food or dietary counseling but visited the research center at the same frequency as the intervention participants to provide outcome measurements.

Controls who completed the month trial received 3 months of free weight-loss counseling and a month gym membership at the end of the study. The primary outcome of the study was change in body weight, which was measured monthly via a digital scale while the participant was in a hospital gown.

Fat mass and lean mass were measured every 6 months in the fasted state by dual-energy x-ray absorptiometry QDR W; Hologic. Visceral fat mass was measured every 6 months by magnetic resonance imaging performed with a 1.

Mean percentage energy restriction during the weight-loss phase was retrospectively calculated by the intake balance method using doubly labeled water and changes in body composition. Intervention participants were considered to be adherent when their actual energy intake, determined via food records, was within kcal of their prescribed daily energy goal.

Blood samples were obtained following a hour fast every 6 months collected on the morning after a feast day for the alternate-day fasting group.

Secondary outcomes included blood pressure, heart rate, and total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, fasting glucose, fasting insulin, C-reactive protein, and homocysteine concentrations analytical methods are detailed in the full protocol in Supplement 1.

Thus, we initially aimed to recruit 90 participants 30 per group , assuming that 78 participants 26 per group would complete the trial. We later decided to recruit participants to increase our statistical power because our dropout rate was higher than expected. Tests for normality were included in the model, and all data were found to be normally distributed.

We conducted an intention-to-treat analysis, which included data from all participants who underwent randomization. Results are reported by intention-to-treat analysis unless indicated otherwise.

This model provides unbiased estimates of time and treatment effects under a missing-at-random assumption. Time was not assumed to be linear in the model. This strategy allowed for estimation of time and diet effects and their interaction without imposing a linear time trend. The analyses were performed using SAS, version 9.

Of the participants who were screened, More participants in the alternate-day fasting group than in the daily calorie restriction group withdrew owing to difficulties adhering with the diet. All baseline characteristics had comparable distributions between the alternate-day fasting group, the daily calorie restriction group, and the control group Table 1.

The participants were primarily metabolically healthy obese women. On the fast day Figure 2 A , participants in the alternate-day fasting group exceeded their prescribed energy goal at months 3 and 6. On the feast day Figure 2 B , participants in the alternate-day fasting group ate less than their prescribed goal at months 3, 6, 9, and Participants in the daily calorie restriction group Figure 2 C met their prescribed energy goals at months 3, 6, and 12 but ate less than their prescribed goal at month 9.

A higher proportion of participants in the daily calorie restriction group were adherent to their energy goals at months 3, 6, 9, and 12 relative to those in the alternate-day fasting group. Data on dietary intake are displayed in eTable 1 in Supplement 2. Percentage of energy intake from fat, carbohydrates, and protein did not differ significantly over time in any of the groups.

Physical activity, measured as steps per day, did not change during the course of the trial in any group eTable 2 in Supplement 2. This level of activity is approximately to steps per day higher than that of the average overweight or obese adult.

Changes in body weight are displayed in Figure 3 and Table 2. Weight loss was not significantly different between the alternate-day fasting group and the daily calorie restriction group at month 6. At the end of the study, total weight loss was —6.

Weight regain from months 6 to 12 —0. Moreover, weight regain from months 6 to 12 was not significantly different between the alternate-day fasting group and controls 0. Changes in body composition are reported in Table 2.

There were no statistically significant differences between the alternate-day fasting group and the daily calorie restriction group for fat mass, lean mass, or visceral fat mass at month 6 or month Blood pressure was not significantly different between the intervention groups, or relative to controls, at month 6 or month 12 Table 2.

There were also no statistically significant differences in heart rate between the alternate-day fasting group and the daily calorie restriction group at month 6 or month 12 Table 2. Changes in plasma lipids during the course of the trial are shown in Table 2.

Total cholesterol levels were not significantly different between the intervention groups, or relative to controls, at month 6 or month At month 6, high-density lipoprotein cholesterol levels were significantly elevated in the alternate-day fasting group by 6.

Low-density lipoprotein cholesterol concentrations did not differ significantly between the intervention groups at month 6. At month 12, low-density lipoprotein cholesterol levels significantly increased in the alternate-day fasting group Triglyceride levels did not differ significantly between the intervention groups at month 6 or month Changes in glucoregulatory and inflammatory factors are displayed in Table 2.

Fasting plasma glucose did not differ significantly between the intervention groups, or relative to controls, at month 6 or month There were also no significant differences in fasting insulin or the homeostasis model assessment of insulin resistance between the intervention groups at month 6 or month High-sensitivity C-reactive protein and homocysteine levels did not differ significantly between the intervention groups, or relative to controls, at month 6 or month The results of this randomized clinical trial demonstrated that alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or improvement in risk indicators for cardiovascular disease compared with daily calorie restriction.

Alternate-day fasting has been promoted as a potentially superior alternative to daily calorie restriction under the assumption that it is easier to restrict calories every other day.

However, our data from food records, doubly labeled water, and regular weigh-ins indicate that this assumption is not the case. Rather, it appears as though many participants in the alternate-day fasting group converted their diet into de facto calorie restriction as the trial progressed.

It was also shown that more participants in the alternate-day fasting group withdrew owing to dissatisfaction with diet compared with those in the daily calorie restriction group Figure 1.

Taken together, these findings suggest that alternate-day fasting may be less sustainable in the long term, compared with daily calorie restriction, for most obese individuals. Nevertheless, it is still possible that a certain smaller segment of obese individuals may prefer this pattern of energy restriction instead of daily restriction.

It will be of interest to examine what behavioral traits eg, ability to go for long periods without eating make alternate-day fasting more tolerable for some individuals than others. To our knowledge, the present study is the longest and largest trial of alternate-day fasting to date.

Food was provided to the intervention participants during the first 3 months of the weight-loss phase to promote adherence 26 and show participants the types and quantities of foods that they should be eating.

This finding suggests that limiting caloric intake to approximately kcal every other day may have been difficult for many participants early in the intervention.

For instance, measuring changes in subjective appetite hunger and fullness in conjunction with modulations in appetite hormones ghrelin, peptide YY, and glucagon-like peptide-1 could offer some insight into why daily calorie restriction may allow for easier adherence compared with alternate-day fasting.

Contrary to our original hypotheses, the participants in the alternate-day fasting group did not experience more pronounced improvements in risk indicators for cardiovascular disease compared with the participants in the daily calorie restriction group.

However, the trial included primarily metabolically healthy obese adults. Previous studies have reported that people felt uncomfortably hungry and irritable on fasting days, and that they didn't get accustomed to these discomforts. Interestingly, in this study, over time people in the fasting group ate more on fasting days and less on feasting days.

So basically by the end of the study they were eating similarly to the calorie restriction group. The authors note more limitations. The control group did not receive food, counseling, or the same attention from the study personnel, potential factors that could affect their results, besides how they ate.

And this study can't tell us about the potential benefits for people who have high blood pressure, high cholesterol, or diabetes because the study didn't include individuals with those conditions. Usually at this point we say something like "more studies of this approach are needed," but I won't.

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. From apples to zucchini, there are over a hundred "real" foods you can eat endlessly, enjoy, and yes, still lose weight.

I would advise against spending any more money on fad diet books. Or processed carbs, for that matter.

Rather, hit the fresh or frozen produce aisle, or farmer's market, and go crazy. Then go exercise. Do that, say, for the rest of your life, and you will be fine. No one got fat eating broccoli, folks.

That said, if you tend to binge or stress-eat sugary or starchy foods, and you feel like you can't control your habit, talk to your doctor, because that is a separate issue to be addressed. Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial.

JAMA Internal Medicine, Published online May 1, Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism.

American Journal of Clinical Nutrition, January As a service to our readers, Harvard Health Publishing provides access to our library of archived content. Please note the date of last review or update on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.

Thanks for visiting. 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.

CH, and AI; Investigation, AI, FD, HH, MC, CJ, EN, SL, JH, EC, and CP; Writing—Original Draft, AI, and FD; Writing—Review and Editing, AI, FD, JH, SL, and CP; Funding Acquisition, FD. The Danish Council for Independent Research grant no: B , Nordea Foundation grant to the Center for Healthy Aging.

We thank the participants, and the technical assistance provided by R. Kraunsøe, J. Bach, and T. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Al-Mrabeh A. Hepatic lipoprotein export and remission of human type 2 diabetes after weight loss. Cell Metab. PubMed Abstract CrossRef Full Text Google Scholar.

Arnason T. Effects of intermittent fasting on health markers in those with type 2 diabetes: A pilot study. World J. Diabetes 8 4 , — Barnosky A.

Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: A review of human findings. Bergman B.

Intramuscular triglyceride synthesis: Importance in muscle lipid partitioning in humans. Bille D. Liver fat content investigated by magnetic resonance spectroscopy in obese children and youths included in multidisciplinary treatment.

Carbajo M. Weight loss and improvement of lipid profiles in morbidly obese patients after laparoscopic one-anastomosis gastric bypass: 2-year follow-up. Carter S. Effect of intermittent compared with continuous energy restricted diet on glycemic control in patients with type 2 diabetes: A randomized noninferiority trial.

JAMA Netw. Open 1 3 , e Catenacci V. A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity.

Silver Spring 24 9 , — Chabanova E. Dela F. Insulin resistance and mitochondrial function in skeletal muscle. Cell Biol. Effects of one-legged High-intensity Interval Training on insulin-mediated skeletal muscle glucose homeostasis in patients with type 2 diabetes.

Acta Physiol. Insulin-stimulated muscle glucose clearance in patients with NIDDM. Effects of one-legged physical training. Diabetes 44, — Physical training increases muscle GLUT-4 protein and mRNA in patients with NIDDM. Diabetes 43, — Effect of physical training on insulin secretion and action in skeletal muscle and adipose tissue of first-degree relatives of type 2 diabetic patients.

Physical training may enhance beta-cell function in type 2 diabetes. Dohlmann T. High-intensity interval training changes mitochondrial respiratory capacity differently in adipose tissue and skeletal muscle.

Fery F. Mechanisms of starvation diabetes: A study with double tracer and indirect calorimetry. Fonvig C. Muscle fat content and abdominal adipose tissue distribution investigated by magnetic resonance spectroscopy and imaging in obese children and youths.

Frossing S. Quantification of visceral adipose tissue in polycystic ovary syndrome: Dual-energy X-ray absorptiometry versus magnetic resonance imaging. Acta Radiol. Halberg N.

Effect of intermittent fasting and refeeding on insulin action in healthy men. Hansen M. The effects of diet- and RYGB-induced weight loss on insulin sensitivity in obese patients with and without type 2 diabetes.

Acta Diabetol. The effect of metformin on glucose homeostasis during moderate exercise. Diabetes Care 38 2 , — Harvie M. Potential benefits and harms of intermittent energy restriction and intermittent fasting amongst obese, overweight and normal weight subjects-A narrative review of human and animal evidence.

Heilbronn L. Glucose tolerance and skeletal muscle gene expression in response to alternate day fasting. Holten M. Strength training increases insulin-mediated glucose uptake, GLUT4 content and insulin signaling in skeletal muscle in patients with Type 2 diabetes.

Diabetes 53 2 , — Jensen M. Lipolysis during fasting. Decreased suppression by insulin and increased stimulation by epinephrine. Kelley D. Fatty liver in type 2 diabetes mellitus: Relation to regional adiposity, fatty acids, and insulin resistance.

Krotkiewski M. The effects of physical training on insulin secretion and effectiveness and on glucose metabolism in obesity and type 2 non-insulin-dependent diabetes mellitus. Diabetologia 28, — Larsen S. Influence of exercise amount and intensity on long-term weight loss maintenance and skeletal muscle mitochondrial ROS production in humans.

The effect of high-intensity training on mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose tissue. Sports 25 1 , e59—e Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects.

Increased mitochondrial substrate sensitivity in skeletal muscle of patients with type 2 diabetes. Diabetologia 54 6 , — Lim E.

Reversal of type 2 diabetes: Normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 54 10 , —

Intermittent fasting: The positive news continues

Hofer, Norbert Tripolt, Miguel A. Aon, Philipp Royer, Lukas Pein, Julia T. Stadler, Tobias Pendl, Barbara Prietl, Jasmin Url, Sabrina Schroeder, Jelena Tadic, Tobias Eisenberg, Christoph Magnes, Michael Stumpe, Elmar Zuegner, Natalie Bordag, Regina Riedl, Albrecht Schmidt, Ewald Kolesnik, Nicolas Verheyen, Anna Springer, Tobias Madl, Frank Sinner, Rafael de Cabo, Guido Kroemer, Barbara Obermayer-Pietsch, Jöm Dengjel, Harald Sourij, Thomas R.

Pieber, Frank Madeo. Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans. Cell Metabolism , ; DOI: Cite This Page : MLA APA Chicago Cell Press. ScienceDaily, 27 August Cell Press.

Clinical trial shows alternate-day fasting a safe alternative to caloric restriction. Retrieved February 14, from www. htm accessed February 14, Explore More.

Fewer Meals May Prevent Type 2 Diabetes, Obesity. June 15, — When intermittent fasting became all the rage among Hollywood celebrities, skeptics balked at the idea of skipping meals. But new research suggests the celebs might not have been that far off. Time-Restricted Fasting Could Cause Fertility Problems.

Time-restricted fasting is an eating pattern where people limit their food consumption to certain hours of the day. Time-Restricted Eating May Lower CVD Risk for Older Breast Cancer Survivors.

May 17, — Older breast cancer survivors with cardiometabolic risk factors who restricted food intake to eight hours during the weekday, followed by 16 hours of fasting, lowered their risk of cardiovascular Fasting Is Required to See the Full Benefit of Calorie Restriction in Mice.

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Home Home Page Top Science News Latest News Health View all the latest top news in the health sciences, or browse the topics below:. Living Well. 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.

CH, and AI; Investigation, AI, FD, HH, MC, CJ, EN, SL, JH, EC, and CP; Writing—Original Draft, AI, and FD; Writing—Review and Editing, AI, FD, JH, SL, and CP; Funding Acquisition, FD. The Danish Council for Independent Research grant no: B , Nordea Foundation grant to the Center for Healthy Aging.

We thank the participants, and the technical assistance provided by R. Kraunsøe, J. Bach, and T. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Al-Mrabeh A. Hepatic lipoprotein export and remission of human type 2 diabetes after weight loss. Cell Metab. PubMed Abstract CrossRef Full Text Google Scholar. Arnason T. Effects of intermittent fasting on health markers in those with type 2 diabetes: A pilot study.

World J. Diabetes 8 4 , — Barnosky A. Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: A review of human findings. Bergman B. Intramuscular triglyceride synthesis: Importance in muscle lipid partitioning in humans. Bille D. Liver fat content investigated by magnetic resonance spectroscopy in obese children and youths included in multidisciplinary treatment.

Carbajo M. Weight loss and improvement of lipid profiles in morbidly obese patients after laparoscopic one-anastomosis gastric bypass: 2-year follow-up. Carter S. Effect of intermittent compared with continuous energy restricted diet on glycemic control in patients with type 2 diabetes: A randomized noninferiority trial.

JAMA Netw. Open 1 3 , e Catenacci V. A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity. Silver Spring 24 9 , — Chabanova E.

Dela F. Insulin resistance and mitochondrial function in skeletal muscle. Cell Biol. Effects of one-legged High-intensity Interval Training on insulin-mediated skeletal muscle glucose homeostasis in patients with type 2 diabetes.

Acta Physiol. Insulin-stimulated muscle glucose clearance in patients with NIDDM. Effects of one-legged physical training. Diabetes 44, — Physical training increases muscle GLUT-4 protein and mRNA in patients with NIDDM.

Diabetes 43, — Effect of physical training on insulin secretion and action in skeletal muscle and adipose tissue of first-degree relatives of type 2 diabetic patients.

Physical training may enhance beta-cell function in type 2 diabetes. Dohlmann T. High-intensity interval training changes mitochondrial respiratory capacity differently in adipose tissue and skeletal muscle.

Fery F. Mechanisms of starvation diabetes: A study with double tracer and indirect calorimetry. Fonvig C. Muscle fat content and abdominal adipose tissue distribution investigated by magnetic resonance spectroscopy and imaging in obese children and youths.

Frossing S. Quantification of visceral adipose tissue in polycystic ovary syndrome: Dual-energy X-ray absorptiometry versus magnetic resonance imaging. Acta Radiol. Halberg N. Effect of intermittent fasting and refeeding on insulin action in healthy men.

Hansen M. The effects of diet- and RYGB-induced weight loss on insulin sensitivity in obese patients with and without type 2 diabetes. Acta Diabetol. The effect of metformin on glucose homeostasis during moderate exercise. Diabetes Care 38 2 , — Harvie M. Potential benefits and harms of intermittent energy restriction and intermittent fasting amongst obese, overweight and normal weight subjects-A narrative review of human and animal evidence.

Heilbronn L. Glucose tolerance and skeletal muscle gene expression in response to alternate day fasting. Holten M. Strength training increases insulin-mediated glucose uptake, GLUT4 content and insulin signaling in skeletal muscle in patients with Type 2 diabetes.

Diabetes 53 2 , — Jensen M. Lipolysis during fasting. Decreased suppression by insulin and increased stimulation by epinephrine. Kelley D. Fatty liver in type 2 diabetes mellitus: Relation to regional adiposity, fatty acids, and insulin resistance. Krotkiewski M. The effects of physical training on insulin secretion and effectiveness and on glucose metabolism in obesity and type 2 non-insulin-dependent diabetes mellitus.

Diabetologia 28, — Larsen S. Influence of exercise amount and intensity on long-term weight loss maintenance and skeletal muscle mitochondrial ROS production in humans.

Eat only every other day and lose weight? An Alternate-day fasting research popular diet is the intermittent fasting regimen, fasying includes alternate-day Fastinh ADF Harvie and Alternate-day fasting research,but the effect of ADF on weight loss Energizing workout sessions not better than ressarch reduced caloric intake Trepanowski et al. Nutrition Fastong volume 14Article number: 44 Cite this article. CH, and AI; Investigation, AI, FD, HH, MC, CJ, EN, SL, JH, EC, and CP; Writing—Original Draft, AI, and FD; Writing—Review and Editing, AI, FD, JH, SL, and CP; Funding Acquisition, FD. The first-line therapy prescribed to obese patients for weight loss is daily calorie restriction. Int J Eat Disord. The result showed that it was no statistical difference in terms of HDL between the two groups Figure 5.
In Integrative therapies for depression years Alternate-day fasting research has been a surge in studies looking at the biologic effects of researhc Selenium element locators Alternate-dya fasting diets in both animal models and humans. Body weight maintenance diets include continuous calorie fastinv, intermittent Alternate-day fasting research, and alternate-day fasting ADF. Now Alternate-dag largest study of Alternate-day fasting research reserach to Alternate-cay at fasing effects of strict ADF in healthy people has shown a number of health benefits. The participants alternated 36 hours of zero-calorie intake with 12 hours of unlimited eating. The findings are reported August 27 in the journal Cell Metabolism. If ADF and other dietary interventions differ in their physiological and molecular effects, complex studies are needed in humans that compare different diets. In this randomized controlled trial, 60 participants were enrolled for four weeks and randomized to either an ADF or an ad libitum control group, the latter of which could eat as much as they wanted.

Alternate-day fasting research -

Some studies indicated that ADF is the most beneficial diet strategy for lowering fasting insulin, glucose, and HOMA-IR. However, there was no significant difference in insulin resistance between the two groups.

It suggested that ADF plus exercise might reduce insulin resistance, which needs to be further elucidated Meanwhile, ADF did not result in a decline in bone mineral density or white blood cell count. It might even have a trend to increase bone mineral density values for a long period 54 — In a recent study we founded, ADF likely makes little differences compared with continuous energy restriction, but ADF probably slightly reduces body weight and fat mass.

In additional analyses, no important differences were detected when comparing different types of ADF vs. nonconsecutive days Randomized control trials suggested that ADF is effective for weight loss, weight maintenance, and improving certain metabolic disease risk factors such as LDL cholesterol, blood pressure, and fasting insulin after 6 months ADF had some physiological benefits with similar daily calorie restriction ADF might lead to fat redistribution from visceral to subcutaneous depots in female mice Evidence suggested that plasma adiponectin was inversely proportional to visceral fat accumulation 65 , Thus, the redistribution in body fat by ADF may be linked to increases in plasma adiponectin observed.

All in all, ADF may improve body fat distribution and circulating adiponectin; conversely, the diet strategy may take precautions against the development of obesity-related diseases whether these effects can be reproduced in clinical trials.

Several adverse events were reported in the study. Its incidences were significantly low and slight. A small number of participants experienced mild headaches or light-headedness in the early days of the trial.

Others reported constipation during weeks 1 and 2 of the trial This phenomenon may or may not be linked with dietary therapy. The participants were proposed to be consuming more fruits and vegetables on feed days. Those clinical manifestations would gradually disappear in the course of the experiment.

This meta-analysis included seven RCTs and concentrating on the efficacy of ADF in participants. Compared with previous studies, our study had some advantages; the data were derived from randomized, double-blind, controlled trials.

However, this study also has some limitations, which reflect the common limitations of other systematic reviews and meta-analyses. First of all, this article did not include numerous RCTs such as unpublished studies, which limit evidence to affect study quality.

Second, RCTs had low methodological rigor and short intervention; more appropriate high-quality trials are needed to improve the accuracy of results. In summary, this meta-analysis suggests that ADF is a viable diet strategy for weight loss, and it has a substantial improvement in risk indicators for diseases in obese or normal people.

Therefore, adults, whether healthy or not, should perform ADF with recommendations of clinical physicians to prevent adverse effects. YL: literature search. ZG: study design and data collection. TC: data interpretation. JW and YZ: writing. All authors contributed to the article and approved the submitted version.

This work was supported by the National Nature Science Foundation of China nos. tsqn , Beijing Municipal Administration of Hospitals' Ascent Plan, code: DFL, and Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support, code: ZYLX The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

ADF, alternate day fasting; RCTs, randomized controlled trials; TC, total cholesterol; BMI, body mass index; LDL, low-density lipoprotein; LDL, low-density lipoprotein; TG, triglycerides; SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL, high-density lipoprotein; HOMA-IR, homeostasis model assessment-insulin resistance; FBS, fasting blood sugar; MD, mean difference; OR, odds ratio; CI, confidence intervals; CR, calorie restriction.

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J Cardiopulm Rehabil. Trepanowski JF, Kroeger CM, Barnosky A, Klempel MC, Bhutani S, Hoddy KK, et al. Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults. JAMA Intern Med. Hansen D, Dendale P, Berger J, van Loon LJC.

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Wiklund P, Toss F, Weinehall L, Hallmans G, Franks PW, NordstrM A, et al. 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.

CH, and AI; Investigation, AI, FD, HH, MC, CJ, EN, SL, JH, EC, and CP; Writing—Original Draft, AI, and FD; Writing—Review and Editing, AI, FD, JH, SL, and CP; Funding Acquisition, FD. The Danish Council for Independent Research grant no: B , Nordea Foundation grant to the Center for Healthy Aging.

We thank the participants, and the technical assistance provided by R. Kraunsøe, J. Bach, and T. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Al-Mrabeh A. Hepatic lipoprotein export and remission of human type 2 diabetes after weight loss.

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New research shows little risk of infection Alternate-dah prostate biopsies. Discrimination Alterante-day work is Fasying to high blood pressure. Icy fingers and toes: Poor Selenium element locators or Raynaud's phenomenon? The alternate-day fasting thing is very popular right now. This gist of it is, basically, feast and famine. You starve one day, then feast the next. Proponents claim that this approach will lead to weight loss, as well as a number of other benefits.

Author: Mazshura

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