Article - Effects of fasting-mimicking diets with low and high protein content on cardiometabolic health and autophagy: A randomized, parallel group study.

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Take home message

FMD’s may be of benefit to cardiometabolic health. However, individuals given a FMD with a high protein:fat ratio may see additional benefits to body composition, heart rate variability, lipids, and blood glucose levels. FMD’s could be tailored to individual health goals

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

Introduction -

Fasting Mimicking Diets (FMD) are associated with improved risk factors for cardiovascular disease (CVD) and metabolic syndrome through weight loss, ketogenesis, hepatic fat loss, and improved glucose control. The aim of the study was to investigate the effects of a very low-calorie FMD with differing protein and fat ratios in healthy individuals.

Methods –

A randomised, parallel group, 3 arm study:

FMD with low protein/high fat (LP-FMD) n=15
FMD with high protein/low fat (HP-FMD) n=15
Weight maintaining diet (control) n=16

FMD meals for 7 days were plant-based, whole foods, with 850 calories.
LP-FMD had 10% energy from protein and 45% from fat
HP-FMD had 30% energy from protein and 25% from fat.
Control had 20% energy from protein and 40% from fat.
Blood and faecal sampling, DEXA scans, and cardiovascular health tests were performed before and after each 7-day treatment.

Results –

Body weight decreased in both LP-FMD and HP-FMD compared to CONTROL (−2.44; −3.26 to −1.62 kg; P= < 0.0001 and −2.73; −2.01 to −3.44 kg; P= < 0.0001 respectively).
Visceral adipose tissue decreased in HP-FMD compared to control (−0.09; −0.15 to −0.03 kg, P = 0.006).
Subcutaneous adipose tissue reduced in both groups compared to control (−0.07; −0.14 to 0.00 kg, P = 0.072, and −0.08; −0.15 to −0.02 kg, P = 0.012, respectively).
Systolic blood pressure, mean arterial pressure, and heart rate were not affected regardless of treatment compared to control.
Diastolic blood pressure was reduced in HP-FMD (−6.1; −11.4 to −0.8 mmHg, P = 0.027).
Heart rate variability, circulating triglycerides, and saturated fatty acids improved in HP-FMD (P= < 0.0001, P=0.003, and P=0.009 respectively).
Fasting plasma glucose reduced in both groups compared to control LP-FMD: -0.41; −0.80 to −0.02 mmol.L−1, P = 0.038; HP-FMD: -0.46; −0.74 to −0.17 mmol.L−1, P = 0.003).

Gut microbiome diversity Increased in HP-FMD (P=0.003).

Conclusion –

Both FMDs improved cardiometabolic health but HP-FMD had additional benefits for body composition, lipid profiles, and heart rate variability.

Clinical practice applications

FMDs, regardless of macronutrient content, may improve cardiometabolic health with improvements to blood glucose levels and fat loss.
FMDs high in protein may improve visceral adipose tissue, diastolic blood pressure, heart rate variability, circulating triglycerides, and saturated fatty acids.
FMDs with varied macronutrient content can be personalised to individual health goals.

Considerations for future research

Research should focus on the effects of both LP-FMD and HP-FMD on skeletal muscle content, low levels of which may contribute to poorer cardiometabolic outcomes.
Studies should also look at the effects of both FMD’s on individuals with pre-existing poor cardiometabolic health.

Abstract

BACKGROUND & AIM

Very low-calorie, fasting-mimicking diets (FMD) have been shown to promote cardiometabolic health and autophagy. However, most studies have focused on low protein diets to stimulate autophagy and reduce ageing-related factors. The aim of this study was to investigate the physiological, metabolic and molecular effects of a 7-day plant-based FMD with low protein/high fat (LP) and high protein/low fat content (HP) in healthy humans and compare those responses to a non-intervention comparator control group.

METHODS

Forty six healthy men and women were randomly assigned to one of three groups: CONTROL (isoenergetic diet), n = 16 (mean ± SD age 35.0 ± 9.5 yrs, BMI 23.3 ± 2.7 kgm); LP-FMD (850 Calories per day: 10 % protein/45 % fat), n = 15, (age 38.2 ± 10.7 yrs, BMI 23.4 ± 3.2 kgm); HP-FMD (850 Calories per day: 30 % protein/25 % fat), n = 15, (age 41.4 ± 8.8 yrs, BMI 25.1 ± 3.7 kgm). Blood and faecal sampling, DEXA scans and functional tests of cardiovascular health were performed before and after each 7-day treatment.

RESULTS

Both FMDs reduced body weight and fat mass (interaction effects P < 0.0001) but only HP-FMD reduced visceral fat mass relative to CONTROL [mean difference (95 % CI): -0.09 (-0.15 to -0.03) kg, P = 0.006]. Both FMDs reduced fasting plasma glucose by ∼10 % [LP-FMD: -0.41 (-0.80 to -0.02) mmolL, P = 0.038; HP-FMD: [-0.46 (-0.74 to -0.17) mmolL, P = 0.003] and IGF1 by ∼35 % [LP=FMD: -9.0 (-12.4 to -5.5) nmolL, P < 0.0001; HP-FMD: -5.4 (-8.6 to -2.1) nmolL, P = 0.024] relative to CONTROL. The increase in serum hydroxybutyrate was higher in the LP- than HP-FMD [0.64 (0.13 to 1.15) mmolL, P = 0.015]. Heart rate variability (P < 0.0001), gut microbiome diversity (P = 0.003), circulating triglycerides (P = 0.009) and saturated fatty acids (P = 0.008) were improved in HP-FMD only. Both FMDs induced autophagy at the molecular level.

CONCLUSION

Both FMDs promoted cardiometabolic health and induction of autophagy, with HP-FMD selectively conferring novel benefits in body composition, circulating lipid profiles, heart rate variability and gut microbiome health. These findings suggest that FMDs with varied macronutrient compositions could be customised to better align with individual health goals and preferences.

CLINICAL TRIAL REGISTRY NUMBER

ClinicalTrials.gov Identifier NCT06560996. URL OF REGISTRATION: https://clinicaltrials.gov/study/NCT06560996.