The obesity epidemic has spawned a cottage industry of weight-loss schemes. Currently in vogue is intermittent fasting, which involves alternating intervals of extreme calorie reduction with periods of normal eating. Proponents of this regimen claim that it helps shed pounds faster than traditional diets, as well as reduce inflammation and other heart disease risks.
Harvard Health notes that all diets achieve weight loss through the same equation – you take in less food energy each day than your body burns for normal activity. Intermittent fasting achieves this goal by severely limiting calories during certain days of the week or during specified hours during the day. The theory is that this type of diet will help decrease appetite by slowing the body’s metabolism.
“One pattern that has become popular is the so-called 5:2 diet,” says Dr Frank Hu, chair of the department of nutrition at the Harvard TH Chan School of Public Health. With this system, you eat normally for five days of the week, but restrict food intake to just 500 to 600 calories on the two fasting days. Another variation calls for alternating “fast” days, in which you consume a quarter or less of your basic calorie requirement, with “feast” days, during which you eat whatever you choose.
The report says so far, the research studies evaluating intermittent fasting have been relatively short and have enrolled only a limited number of participants. In one, published 1 July, 2017, 100 overweight people were assigned to one of three eating plans: restricting daily calorie intake by the same amount every day (similar to a traditional diet plan), fasting on alternate days, and continuing with normal eating habits. At the end of the 12-month study, both diet groups had lost weight compared with the normal eaters. However, the fasters didn’t fare any better than the conventional calorie cutters.
A notable aspect of this trial was a very high dropout rate (38%) among the people assigned to the fasting regimen. This may reflect a real-life pitfall of fasting as a weight-loss approach. “It’s human nature for people to want to reward themselves after doing very hard work, such as exercise or fasting for a long period of time, so there is a danger of indulging in unhealthy dietary habits on non-fasting days,” says Hu. In addition, there’s a strong biological push to overeat following fasting periods. Your appetite hormones and hunger centre in your brain go into overdrive when you are deprived of food.
But intermittent fasting may have a beneficial effect on diet psychology for some people, says Kathy McManus, director of the department of nutrition at Harvard-affiliated Brigham and Women’s Hospital. “One of my patients felt strongly that he didn’t want to be bothered with tracking calories and filling out food records. Instead, he opted for a 5:2 fasting approach, which has worked well for him so far.” The main goal is to develop a healthy eating pattern that is sustainable and can support weight loss over time, McManus says. As of now, intermittent dieting has not been proved to meet this key criterion.
The report says some commercial companies have started marketing packaged meal plans designed specifically for intermittent fasting. While this may make the process easier for some people, these products tend to be expensive – around $300 for a week’s worth of food.
Part of the fascination with intermittent fasting arises from research with animals showing that fasting may reduce cancer risk and slow ageing. “One hypothesis is that fasting can activate cellular mechanisms that help boost immune function and reduce inflammation associated with chronic disease,” says Hu. While it’s true that getting rid of excess body fat will improve a person’s metabolic profile and lower cardiovascular risk, he says, there’s no strong evidence that fasting adds health benefits beyond any other weight-loss strategy.
The report says if you are considering this type of diet, make sure to discuss it with your doctor. Skipping meals and severely limiting calories can be dangerous for people with certain conditions, such as diabetes. People who take medications for blood pressure or heart disease also may be more prone to electrolyte abnormalities from fasting. Also, says Hu, we live in a toxic, obesogenic food environment. So you’ll need a strong social support network to endure very low-calorie days over the long haul.
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 Participants: A 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 Measures: The 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  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.
John F Trepanowski, Cynthia M Kroeger, Adrienne Barnosky, Monica C Klempel, Surabhir Bhutani, Kristin K Hoddy, Kelsey Gabel, Sally Freels, Joseph Rigdon, Jennifer Rood, Eric Ravussin, Krista A Varady
Manipulating mitochondrial networks inside cells – either by dietary restriction or by genetic manipulation that mimics it – may increase lifespan and promote health, according to research from Harvard TH Chan School of Public Health.
The study sheds light on the basic biology involved in cells’ declining ability to process energy over time, which leads to ageing and age-related disease, and how interventions such as periods of fasting might promote healthy ageing.
Mitochondria – the energy-producing structures in cells – exist in networks that dynamically change shape according to energy demand. Their capacity to do so declines with age, but the impact this has on metabolism and cellular function was previously unclear. In this study, the researchers showed a causal link between dynamic changes in the shapes of mitochondrial networks and longevity.
The scientists used C. elegans (nematode worms), which live just two weeks and thus enable the study of ageing in real time in the lab. Mitochondrial networks inside cells typically toggle between fused and fragmented states. The researchers found that restricting the worms’ diet, or mimicking dietary restriction through genetic manipulation of an energy-sensing protein called AMP-activated protein kinase (AMPK), maintained the mitochondrial networks in a fused or “youthful” state. In addition, they found that these youthful networks increased lifespan by communicating with organelles called peroxisomes to modulate fat metabolism.
“Low-energy conditions such as dietary restriction and intermittent fasting have previously been shown to promote healthy aging. Understanding why this is the case is a crucial step toward being able to harness the benefits therapeutically,” said Heather Weir, lead author of the study, who conducted the research while at Harvard Chan School and is now a research associate at Astex Pharmaceuticals. “Our findings open up new avenues in the search for therapeutic strategies that will reduce our likelihood of developing age-related diseases as we get older.”
“Although previous work has shown how intermittent fasting can slow aging, we are only beginning to understand the underlying biology,” said William Mair, associate professor of genetics and complex diseases at Harvard Chan School and senior author of the study. “Our work shows how crucial the plasticity of mitochondria networks is for the benefits of fasting. If we lock mitochondria in one state, we completely block the effects of fasting or dietary restriction on longevity.”
Next steps for the researchers including testing the role mitochondrial networks have in the effect of fasting in mammals, and whether defects in mitochondrial flexibility might explain the association between obesity and increased risk for age-related diseases.
Mitochondrial network remodeling between fused and fragmented states facilitates mitophagy, interaction with other organelles, and metabolic flexibility. Aging is associated with a loss of mitochondrial network homeostasis, but cellular processes causally linking these changes to organismal senescence remain unclear. Here, we show that AMP-activated protein kinase (AMPK) and dietary restriction (DR) promote longevity in C. elegans via maintaining mitochondrial network homeostasis and functional coordination with peroxisomes to increase fatty acid oxidation (FAO). Inhibiting fusion or fission specifically blocks AMPK- and DR-mediated longevity. Strikingly, however, preserving mitochondrial network homeostasis during aging by co-inhibition of fusion and fission is sufficient itself to increase lifespan, while dynamic network remodeling is required for intermittent fasting-mediated longevity. Finally, we show that increasing lifespan via maintaining mitochondrial network homeostasis requires FAO and peroxisomal function. Together, these data demonstrate that mechanisms that promote mitochondrial homeostasis and plasticity can be targeted to promote healthy aging.
Heather J Weir, Pallas Yao, Frank K Huynh, Caroline C Escoubas, Renata L Goncalves, Kristopher Burkewitz, Raymond Laboy, Matthew D Hirschey, William B Mair