Calorie restriction

• Slow biological aging and extend healthy lifespan.
• Lower cardiovascular risk factors such as LDL cholesterol and blood pressure.
• Improve insulin sensitivity and lower inflammation.
• Reduce body fat and keep weight low over the long term.
• Reduce the risk of cancer and other age-related diseases, as seen in animals.

Calorie restriction (CR) is the oldest and best studied longevity diet. The rule is simple to state: eat less than you would freely choose, consistently, without becoming malnourished. People who practice it for longevity often call it CRON, calorie restriction with optimal nutrition.

How much? Animal studies use deep cuts. Mice restricted by about 55 to 65% from weaning lived 35 to 65% longer than freely fed mice [15]. Human research uses far less.

• The CALERIE 2 trial prescribed 25% restriction for two years. Participants achieved about 19.5% in the first six months, then about 9% after that, averaging about 12% over two years [1] [10].
• Older Okinawans appear to have eaten about 10 to 15% below their needs for much of their lives [19].
• The Biosphere 2 crew ate 1,750 to 2,100 kcal a day of a nutrient-dense diet for most of two years [7].

The lesson from CALERIE is that even motivated volunteers with professional support slide from 25% toward about 10%. Practical CR for most people means a sustained cut in the range of 10 to 15%, which in CALERIE still produced weight loss of about 10% [10].

Across yeast, worms, flies and rodents, reduced food intake without malnutrition delays age-related decline. Researchers think it works through nutrient-sensing pathways that tell cells whether to grow or to protect and repair, and that protein intake and meal timing also matter, not only total calories [20].

Human trials give a glimpse of the same machinery:

• Slower metabolism. With about 15% restriction for two years, 24-hour energy expenditure was 80 to 120 kcal a day lower than weight loss alone predicted, with lower thyroid activity and less oxidative damage, measured as urinary F2-isoprostanes [12]. Two old theories of aging, rate of living and oxidative damage, predict exactly this.
• Hormones. T3, the active thyroid hormone, fell more with restriction at both 12 and 24 months [10]. IGF-1, central to the animal story, did not differ between groups in CALERIE [3].
• Immunity. About 14% restriction for two years improved thymus output of new T cells and suppressed PLA2G7, an inflammation-linked gene; deleting that gene in mice reduced age-related inflammation [11].

These are markers, not outcomes. Whether they add up to longer life in people is unknown.

CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) is the only long randomized trial of CR in healthy people of normal or slightly high weight. Phase 2 ran at three US centers and randomized 218 adults aged 21 to 50 with BMI 22 to 28, two to one, to 25% restriction or their usual diet [1].

Body. The CR group lost 7.5 kg against a 0.1 kg gain in controls, and 71% of the loss was fat [1]. Waist size fell 6.2 cm. Fat-free mass fell in proportion to the smaller body, and people who stayed more active kept more of it [8].

Heart and metabolism. Compared with controls at two years, CR lowered LDL cholesterol by about 10 mg/dL (0.26 mmol/L)0.26 mmol/L (10 mg/dL), triglycerides by 0.24 mmol/L, systolic blood pressure by 4.4 mm Hg and diastolic by 5.0 mm Hg, and improved hs-CRP, fasting insulin and insulin resistance. Fasting glucose did not change [1].

Mind. Mood, tension, general health and sexual drive were slightly better, and there were no negative effects on quality of life [16].

Aging markers. CR slowed the pace of aging on the DunedinPACE epigenetic measure, but did not change biological age on the PhenoAge or GrimAge clocks, and the effects were small [2].

Safety. CR was safe and well tolerated overall, but bone density fell at the spine and hip [3], 3 participants were withdrawn for safety, and the investigators advised monitoring for bone loss and anemia [18]. 82% of the CR group finished, against 95% of controls [10].

Rhesus monkeys live about as long relative to their size as people do, which made two parallel studies started in the late 1980s the closest test of CR in primates.

• Wisconsin (2009). After 20 years of adult-onset moderate CR, 80% of restricted monkeys were alive against 50% of controls when deaths from aging-related causes were counted. CR also delayed diabetes, cancer, cardiovascular disease and brain atrophy [13].
• National Institute on Aging (2012). CR started in young or older monkeys did not improve survival, although some health measures improved [14].
• Joint analysis (2017). The two teams pooled data from close to 200 monkeys. Both studies showed health benefits. The survival gap traced to design: NIA control monkeys ate less, and ate a more natural diet, than Wisconsin controls, who ate a more processed, higher sugar diet and were fatter; age at the start of restriction also mattered [4].

For people, the takeaway is that CR helps most when compared with overeating a poor diet. Against a lean, well-fed baseline, the extra gain may be small. Genetic background also matters: in mice, the same 40% restriction lengthened life in some strains and shortened it in more of them [5].

The costs of CR scale with how hard you push.

At moderate levels (about 12%).

• Bone. CALERIE participants lost bone mineral density at the lumbar spine, total hip and femoral neck over two years, and bone turnover markers rose; the authors called bone loss at fracture-prone sites a potential limitation of CR [3].
• Lean mass. Fat-free mass fell 2.2 kg against 0.2 kg in controls [3], though in proportion to the smaller body [8].
• Metabolism. Energy use dropped more than weight loss predicted, and thyroid activity fell [12]. That is good for aging theory and bad for keeping weight off later.
• Monitoring. Investigators recommended watching for bone loss and anemia [18].

Several common worries were not borne out at this level. Mood, sleep and sexual function were unchanged or slightly better [16].

At severe levels. In the Minnesota Starvation Experiment of the 1940s, 36 young men on semistarvation lost more than 25% of their weight and developed anemia, fatigue, apathy, extreme weakness, irritability, neurological problems and leg swelling [17]. Long-term CR Society practitioners reach BMIs near 19.6 [6], close to underweight.

Searches about calorie restriction and testosterone, libido, hair loss, depression, insomnia and feeling cold mostly reflect these severe or poorly planned versions. CR also overlaps with eating disorder behavior, so anyone with that history should not attempt it.

The CR Society, founded in 1994 according to its Wikipedia entry, counts Roy Walford, Lisa Walford and Brian Delaney among its founders, and its members became a natural experiment in long-term human CR.

Walford, a UCLA pathologist, had already tested CR in eight people. As physician to the crew sealed inside Biosphere 2, he and the others ate 1,750 to 2,100 kcal a day for most of two years. They lost 17% of their weight, systolic blood pressure fell 25%, cholesterol 30% and insulin 42% [7]. Those changes resembled calorie-restricted rodents and monkeys.

At Washington University in St Louis, researchers compared 18 CR Society members, who had restricted for about 6 years, with 18 age-matched people on typical American diets. The restrictors had BMI 19.6 against 25.9 and body fat of 8.7% against 24%. LDL, triglycerides, glucose, insulin, CRP and blood pressure were all markedly lower, and carotid artery wall thickness was about 40% less. Their medical records showed ordinary values before they started CR [6].

This is the strongest human evidence that years of CR protect the arteries. It is also a small, self-selected group of very committed people, and no study has followed CR practitioners long enough to measure lifespan. Walford himself died in 2004, aged 79, of complications of ALS; whether his diet played any role is unknown.

Most popular diets work, when they work, by making people eat less. The useful questions are which one you can sustain and whether any carries benefits beyond the calories.

• Intermittent fasting. A meta-analysis of 11 randomized trials found weight loss with intermittent and continuous restriction to be about the same, with no clear difference in cardiometabolic markers [9]. See intermittent fasting.
• Periodic fasting. The fasting-mimicking diet concentrates restriction into five days a month, and multi-day water fasting into days or weeks. Both were developed partly because daily restriction is hard to keep up [20].
• Keto and low-carb. These change what you eat; any CR effect comes through eating less overall.
• GLP-1 drugs. They work largely by reducing appetite and food intake, though they also have direct effects of their own. Whether they reproduce CR's effects on aging has not been studied.

For mortality, the best evidence comes from people with obesity: across 15 randomized trials lasting at least 18 months, intentional weight loss averaging 5.5 kg was linked to 15% lower all-cause mortality [21]. For lean people, there is no mortality evidence either way.

1. Find your baseline. Track what you eat for one to two weeks to estimate your usual intake.
2. Cut modestly. CALERIE asked for 25% and people settled near 12% [1]. A 10 to 15% cut is closer to what people can sustain.
3. Eat nutrient-dense food. CR without malnutrition is the definition. Prioritize vegetables, legumes, whole grains, fish and other protein foods, and check vitamins and minerals.
4. Keep protein and training up. More physical activity predicted better preservation of fat-free mass in CALERIE [8]. Strength training matters for bone too, given the density losses seen [3]. See strength training.
5. Monitor. Weigh in weekly. Ask your clinician about periodic blood counts and, over years, bone density, as CALERIE investigators advised [18]. Watch LDL cholesterol, fasting insulin and hs-CRP to see your response.
6. Know when to stop. Persistent fatigue, feeling cold, missed periods, low mood, hair loss or a BMI drifting toward 18.5 are signals to ease off.

Calorie restriction is not appropriate for children, teenagers, pregnant or breastfeeding women, people who are underweight or frail, or anyone with a current or past eating disorder.

• Aiming for very deep cuts that cannot be sustained, then rebounding.
• Cutting protein along with calories, which speeds lean mass loss.
• Stopping exercise because energy is low, which worsens muscle and bone loss.
• Assuming animal lifespan results apply directly to humans.
• Restricting when already lean, which adds risk with little evidence of benefit.
• Ignoring signs of disordered eating.

• Pregnancy or breastfeeding.
• A current or past eating disorder.
• Underweight (BMI under 18.5), frailty or older age with low muscle mass, without medical guidance.
• Children and teenagers who are still growing.
• Osteoporosis or low bone density.
• Anemia or other conditions where intake is already marginal.

• Hunger and lower energy, especially at first.
• Loss of bone mineral density.
• Loss of fat-free mass, including some muscle.
• Slower metabolism and lower thyroid hormone T3.
• Feeling cold, lower libido and low mood with severe restriction.
• Anemia, which CALERIE investigators advised monitoring.