Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults

Abstract

IMPORTANCE Alternate-day fasting has become increasingly popular, yet, to date, no long-term randomized clinical trials have evaluated its efficacy.OBJECTIVE To compare the effects of alternate-day fasting vs daily calorie restriction on weight loss, weight maintenance, and risk indicators for cardiovascular disease. DESIGN, SETTING, AND PARTICIPANTSA single-center randomized clinical trial of obese adults (18 to 64 years of age; mean body mass index, 34) was conducted between October 1, 2011, and January 15, 2015, at an academic institution in Chicago, Illinois.INTERVENTIONS Participants were randomized to 1 of 3 groups for 1 year: alternate-day fasting (25% of energy needs on fast days; 125% of energy needs on alternating "feast days"), calorie restriction (75% of energy needs every day), or a no-intervention control. The trial involved a 6-month weight-loss phase followed by a 6-month weight-maintenance phase. MAIN OUTCOMES AND MEASURESThe primary outcome was change in body weight. Secondary outcomes were adherence to the dietary intervention and risk indicators for cardiovascular disease. RESULTS Among the 100 participants (86 women and 14 men; mean [SD] age, 44 [11] years), the dropout rate was highest in the alternate-day fasting group (13 of 34 [38%]), vs the daily calorie restriction group (10 of 35 [29%]) and control group (8 of 31 [26%]). Mean weight loss was similar for participants in the alternate-day fasting group and those in the daily calorie restriction group at month 6 (-6.8% [95% CI, -9.1% to -4.5%] vs -6.8% [95% CI, -9.1% to -4.6%]) and month 12 (-6.0% [95% CI, -8.5% to -3.6%] vs -5.3% [95% CI, -7.6% to -3.0%]) relative to those in the control group. Participants in the alternate-day fasting group ate more than prescribed on fast days, and less than prescribed on feast days, while those in the daily calorie restriction group generally met their prescribed energy goals. There were no significant differences between the intervention groups in blood pressure, heart rate, triglycerides, fasting glucose, fasting insulin, insulin resistance, C-reactive protein, or homocysteine concentrations at month 6 or 12. Mean high-density lipoprotein cholesterol levels at month 6 significantly increased among the participants in the alternate-day fasting group (6.2 mg/dL [95% CI, 0.1-12.4 mg/dL]), but not at month 12 (1.0 mg/dL [95% CI, -5.9 to 7.8 mg/dL]), relative to those in the daily calorie restriction group. Mean low-density lipoprotein cholesterol levels were significantly elevated by month 12 among the participants in the alternate-day fasting group (11.5 mg/dL [95% CI, 1.9-21.1 mg/dL]) compared with those in the daily calorie restriction 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: NCT00960505

Differential Effects of Alternate‐Day Fasting Versus Daily Calorie Restriction on Insulin Resistance

“…The impact of intermittent fasting versus daily CR on glucoregulatory factors has been tested in a handful of clinical trials . Studies performed in metabolically healthy individuals generally demonstrate either superior improvements by fasting compared with daily restriction or no effect . For instance, Harvie et al and Hutchison and Heilbronn noted greater decreases in insulin resistance (~ 25%‐35% reductions) by intermittent fasting versus daily restriction (~ 15% reductions) after 2 to 6 months of intervention in healthy participants with overweight and obesity.…”

“…Another form of dietary restriction that has gained attention in recent years is alternate‐day fasting (ADF) . ADF regimens generally consist of an ad libitum “feast day” alternated with a 25% energy intake “fast day.” Accumulating evidence has suggested that ADF and CR produce similar weight loss (6%‐8%) over 2 to 12 months in healthy adults with overweight and obesity . Research has also indicated that both diets are safe and well tolerated .…”

Lysosomes Mediate Benefits of Intermittent Fasting in Cardiometabolic Disease: The Janitor Is the Undercover Boss

“…Time-restricted feeding resulted in dramatically lowered insulin levels and improved insulin sensitivity and β cell responsiveness, and lower blood pressure without altering circulating lipoprotein levels or markers of inflammation, without adverse effects. Taken together, while these clinical studies have demonstrated a beneficial effect of intermittent fasting in the setting of diabetes and pre-diabetes, it remains unclear if this strategy is sustainable (as the longest clinical trial lasted one year (220)) and if the beneficial effects are durable. It is also important to note that fasting strategies may be detrimental in individuals with type 1 diabetes which is characterized by primary beta cell failure and insulin deficiency, and provoke potentially fatal hypoglycemia; and therefore not a subject of clinical investigation.…”

“…In general, this study supports the concept that once weekly intermittent fasting is safe and well tolerated in healthy individuals. Recently, ADF (25% of energy needs on fasting days, 125% on feast days) and chronic caloric restriction (75% of energy needs daily) were compared in a randomized controlled clinical trial of 100 patients (220). Overall, although both groups were associated with weight loss compared with control patients, there were no significant differences between ADF and chronic caloric restriction, although caloric restriction was better tolerated, with fewer drop outs.…”

Short‐term intermittent energy restriction interventions for weight management: a systematic review and meta‐analysis

“…However, there is no clear definition provided of IER, which acts as an umbrella term that encompasses various dietary regimens. These include diverse interventions such as alternate day fasting (1 d of energy restriction followed by a day of ad libitum energy intake) , the 5:2 diet (2 d of energy restriction per week) and longer cyclic IER periods .…”