Table 1 Key studies investigating the effects of caloric restriction on brain health in humans

Witte et al. 2009 [15]

Healthy overweight elderly.

n = 49 (M/F = 21/29).

Age = 60.5 ± 7.6 SD.

BMI = 28 ± 3.7 SD.

Parallel RCT.

Memory performance, BP, CRP, TNF- α, BDNF, glucose, insulin and lipid profile.

Duration: three months.

Three groups:

1. CR (30% reduction in EI) n = 19.

2. Increase UFAs (20%) n = 20.

3. Control n = 10.

CR increases memory score significantly (20%; p < 0.001), and it has a significant inverse association with insulin, glucose and CRP among the high compliance subjects. No significant difference in UFAs and control.

Zotova et al. 2015 [114]

Arterial hypertension (AH) and cerebral ischemia (CI) patients.

n = 42 into two arms:

1. CR (M/F = 6/16),

age = 54.4 ± 2.4 SD.

2. Antihypertensive drugs (M/F = 8/12),

age = 55.6 ± 1 SD.

Parallel controlled clinical trial.

Cognitive function, cerebral haemodynamic (Doppler ultrasound), QoL, glucose, and lipid profile.

Duration: six months.

Two groups:

1. CR n = 22. Level of CR not reported.

2. Antihypertensive therapy (ACE inhibitors, thiazide diuretics), neurometabolic drugs, drugs that improve cerebral hemodynamics) n = 20.

CR significantly improves the cognitive function, cerebral haemodynamic and QoL in both AH and CI compared to the second group and baseline.

Prehn et al. 2017 [115]

Healthy postmenopausal obese women.

n = 37.

Age = 61 ± 5 SD.

BMI = 34.9 ± 4 SD.

Parallel RCT.

Memory performance, cognitive function, fMRI (BOLD; oxygenation metabolism), physical activity, BP and glucose.

Duration: three months (CR) + one month of sustained weight loss (Isocaloric diet).

Two groups:

1. CR (formula-diet 800 kcal/d) n = 19.

2. Control n = 18.

Improved recognition memory significantly and grey matter in the CR group compared to the control at the second time point (after the three months CR); p < 0.05, and it returned to non-significant at the endpoint, but it remained higher in CR.

Kim et al. 2020 [116]

Healthy adults with central obesity.

n = 43.

Age = 52.8 ± 2 SD.

BMI = 31.4 ± 5.1 SD.

Parallel RCT.

Memory performance, cognitive function, cardiometabolic, BP, glucose and lipid profile

Duration: one month.

Two groups:

1. Continuous CR (500 kcal reduction), n = 22.

2. Intermittent CR (5:2 pattern; consuming 600 kcal for two consecutives days), n = 21.

Both groups enhanced the pattern separation significantly (p < 0.0005), but the intermittent CR group were significantly lower in recognition memory (p < 0.007).

Leclerc et al. 2020 [117]

Healthy non-obese adults.

n = 220.

Age = 21–50 (males), 21–47 (female).

BMI = 22–28.

Parallel RCT (part of CALERIE study).

Working memory, cognitive function, mood state, sleep quality and energy expenditure.

Duration: two years.

Two groups:

1. CR (25% reduction).

2. Control.

CR improve working memory significantly compared to the control at second (12 months) and third (24 months) time points (p < 0.001).

Teong et al. 2021 [118]

Healthy overweight and obese women.

n = 46.

Age = 50 ± 9 SD.

BMI = 32.9 ± 4.4 SD.

Parallel RCT (secondary analysis).

Cognitive function, mood state, sleep quality and QoL.

Duration: two months.

Two groups:

1. CR (30% reduction in EI) n = 24.

2. Intermittent fasting (IF; 30% reduction in EI) n = 22.

Both groups increase cognitive function significantly (CR; p < 0.006, IF; p < 0.03). There was no significant difference in the other measurement, except that weight loss was significant in the IF group (p < 0.001).