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Nutrition & Metabolism

Calorie Restriction and Fasting:
What Human Studies Actually Show About Eating Less and Ageing

Aevum Protocol8 min read

Eating less without malnutrition, known as calorie restriction, extends lifespan in many animals, and it has inspired a wave of fasting trends: intermittent fasting, alternate-day fasting, "fasting-mimicking" diets and multi-day fasts. Human evidence is more modest but real. In CALERIE, the first long-term randomised trial of calorie restriction in healthy, non-obese adults, participants aimed to eat 25% less but achieved about 12% over two years. They lost about 10% of their body weight and improved blood pressure, LDL cholesterol, insulin sensitivity and inflammation, and a later analysis found their pace of biological ageing slowed by 2-3%. However, fasting isn't magic. In a one-year trial, alternate-day fasting produced similar weight loss to simply eating less every day, but more people dropped out. In monkeys, long-term calorie restriction reduced age-related disease, although effects on lifespan differed between studies. For most people, the benefits come from eating somewhat less and maintaining a healthy weight, in whatever pattern they can sustain. This article explains what's known about calorie restriction and the main fasting approaches.

Key numbers

FindingDetail
CALERIE trial (218 healthy adults under 50, 2 years)Aimed for 25% fewer calories, achieved about 12%; about 10% weight loss with better blood pressure, LDL, insulin sensitivity and inflammation
Biological ageing in CALERIE (DunedinPACE)Pace of ageing slowed by 2-3%; other epigenetic clocks unchanged
Alternate-day fasting vs daily calorie restriction (100 adults, 1 year)Similar weight loss (6.0% vs 5.3%); dropout 38% vs 29%
Fasting-mimicking diet (100 adults, 5 days a month for 3 months)2.6 kg weight loss; systolic blood pressure down 4.5 mm Hg; no significant change in glucose, cholesterol or CRP
Monkey studies (NIA and Wisconsin)Both found fewer age-related diseases with calorie restriction

What calorie restriction and fasting mean

In animals, calorie restriction lowers insulin and growth-factor signalling, increases cellular repair processes such as autophagy and reduces inflammation. Whether these translate into longer human lives is still unknown.

Evidence strength

Moderate: modest calorie restriction improves cardiometabolic health in non-obese adults. The CALERIE trial, funded by the US National Institute on Aging, randomly assigned 218 healthy adults under 50, of normal weight or slightly overweight, to calorie restriction or their usual diet for two years. The target was a 25% reduction, but participants achieved about 12% on average. Even so, they lost about 10% of their body weight, mostly fat, and had lower LDL cholesterol, triglycerides and blood pressure, better insulin sensitivity and glucose control, and markedly lower inflammation. The researchers concluded that "modest calorie restriction may reduce the risk of heart disease and diabetes even in healthy adults who are not obese".

Stat tiles, eating a little less: the CALERIE trial. Participants aimed for a 25% calorie reduction, achieved 12%, lost 10% of body weight and slowed their pace of biological ageing by 2-3% (Kraus et al., 2019; Waziry et al., Nature Aging, 2023; 218 adults, 2 years)

Limited: calorie restriction may slow biological ageing. A 2023 analysis of CALERIE blood samples, published in Nature Aging, found that calorie restriction slowed participants' pace of ageing by 2-3% as measured by DunedinPACE, an epigenetic measure of how fast the body is ageing. The researchers estimated that this could translate into a 10-15% lower risk of death, an estimate based on other studies. However, two other epigenetic "clocks" showed no change, and the study couldn't show effects on actual disease or lifespan.

Moderate: in monkeys, calorie restriction reduces age-related disease. Two long-term rhesus monkey studies, at the US National Institute on Aging (NIA) and the University of Wisconsin, initially seemed to disagree about lifespan. A 2017 joint analysis concluded that both found fewer age-related diseases with calorie restriction, and the differences in survival were partly explained by diet: the Wisconsin control monkeys ate a high-sucrose purified diet, while the NIA monkeys ate a more natural diet, and the age at which restriction started differed.

Moderate: fasting schedules work mainly by reducing calories. A one-year trial in JAMA Internal Medicine randomly assigned 100 adults with obesity to alternate-day fasting, daily calorie restriction or no change. Weight loss was similar with both approaches: 6.0% with alternate-day fasting and 5.3% with daily restriction at one year, compared with controls. But 38% of the alternate-day fasting group dropped out, compared with 29% for daily restriction, and their LDL cholesterol was higher. The authors concluded that alternate-day fasting may be less sustainable for most people.

Grouped bar chart, fasting vs eating less every day, results after one year: weight loss 6.0% with alternate-day fasting vs 5.3% with daily calorie restriction; dropout 38% vs 29% (Trepanowski et al., JAMA Internal Medicine, 2017, 100 adults)

Limited: fasting-mimicking diets. In a 2017 trial in Science Translational Medicine, 100 healthy adults followed a fasting-mimicking diet for five consecutive days a month (about 1,100 calories on day one and 700 on days two to five) for three months, or ate normally. The diet group lost an average of 2.6 kg, their systolic blood pressure fell by 4.5 mm Hg and a growth factor, IGF-1, decreased, with larger benefits in those starting with obesity or higher blood pressure. There were no significant changes in fasting glucose, cholesterol or CRP. The diet products were supplied by a company in which some researchers held equity, and longer, independent trials are needed.

Important limitations and risks.

Comparison diagram, approaches to eating less: daily calorie restriction has the best evidence, time-restricted eating moderate evidence, alternate-day fasting similar results but harder to sustain, fasting-mimicking diet limited evidence, and prolonged fasting only under medical supervision

Recommendations by situation

SituationWhat the evidence supports
Overweight or obeseAny approach you can sustain that reduces calories; daily restriction and intermittent fasting give similar results
Healthy weight, interested in longevityAvoid overeating and keep a stable healthy weight; extreme restriction isn't recommended
Prefer a daily eating windowTime-restricted eating can help some people eat less
Taking insulin or other glucose-lowering medicinesDon't fast without medical advice because of the risk of low blood sugar
Pregnant or breastfeedingDon't follow calorie restriction or fasting regimens
History of an eating disorderAvoid fasting and restrictive diets; seek specialist support
Older adult or at risk of frailtyFocus on adequate protein and strength training rather than restriction
Considering a multi-day fastOnly with medical supervision
Religious fastingPlan meals to include enough protein, fluids and nutrients; seek advice if you have a medical condition

Practical notes

Calorie restriction is the most consistent anti-ageing intervention in animals, and in people, modest restriction improves heart and metabolic health and may slightly slow measures of biological ageing. Fasting schedules mainly work by helping people eat less; they aren't superior to daily calorie reduction, and some are harder to stick with. For most people, the practical lesson is to avoid habitual overeating, keep a healthy weight, eat a high-quality diet and choose an eating pattern you can maintain for life (see Eating Patterns for Longevity). Older adults should prioritise protein and strength rather than eating less (see Protein in the Sri Lankan Diet).

References
  1. Kraus WE, et al. 2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial. The Lancet Diabetes & Endocrinology, 2019;7(9):673-683.
  2. Waziry R, et al. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nature Aging, 2023;3(3):248-257.
  3. Mattison JA, et al. Caloric restriction improves health and survival of rhesus monkeys. Nature Communications, 2017;8:14063.
  4. Trepanowski JF, et al. Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults: a randomized clinical trial. JAMA Internal Medicine, 2017;177(7):930-938.
  5. Wei M, et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Science Translational Medicine, 2017;9(377):eaai8700.

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