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

IF 7.4 2区医学 Q1 NUTRITION & DIETETICS

Clinical nutrition Pub Date : 2025-08-06 DOI:10.1016/j.clnu.2025.08.004

Lucy Burns , Scott Cooper , Sarir Sarmad , Guido Funke , Antonio Di Mauro , George C. Gaitanos , Kostas Tsintzas

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引用次数: 0

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 kg^.m⁻²); LP-FMD (850 Calories per day: 10 % protein/45 % fat), n = 15, (age 38.2 ± 10.7 yrs, BMI 23.4 ± 3.2 kg^.m⁻²); HP-FMD (850 Calories per day: 30 % protein/25 % fat), n = 15, (age 41.4 ± 8.8 yrs, BMI 25.1 ± 3.7 kg^.m⁻²). 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) mmol^.L⁻¹, P = 0.038; HP-FMD: [-0.46 (−0.74 to −0.17) mmol^.L⁻¹, P = 0.003] and IGF1 by ∼35 % [LP=FMD: −9.0 (−12.4 to −5.5) nmol^.L⁻¹, P < 0.0001; HP-FMD: −5.4 (−8.6 to −2.1) nmol^.L⁻¹, 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) mmol^.L⁻¹, 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.

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低蛋白和高蛋白模拟禁食饮食对心脏代谢健康和自噬的影响：一项随机、平行组研究

背景,非常低热量、模拟禁食的饮食（FMD）已被证明可以促进心脏代谢健康和自噬。然而，大多数研究都集中在低蛋白饮食刺激自噬和减少衰老相关因素上。本研究的目的是研究7天低蛋白/高脂肪（LP）和高蛋白/低脂肪含量（HP）的植物性口蹄疫对健康人的生理、代谢和分子效应，并将这些反应与非干预比较对照组进行比较。方法46名健康男性和女性随机分为3组：对照组（等能饮食），n = 16（平均±SD年龄35.0±9.5岁，BMI 23.3±2.7 kg.m−2）；LP-FMD（每天850卡路里：10%蛋白质/ 45%脂肪），n = 15,（年龄38.2±10.7岁，BMI 23.4±3.2 kg.m−2）；HP-FMD（每天850卡路里：30%蛋白质/ 25%脂肪），n = 15,（年龄41.4±8.8岁，BMI 25.1±3.7 kg.m−2）。在每7天治疗前后分别进行血液和粪便取样、DEXA扫描和心血管健康功能测试。结果两种fmd均能降低体重和脂肪量（相互作用）；0.0001)，但只有HP-FMD相对于对照组减少了内脏脂肪质量[95% CI: - 0.09(- 0.15至- 0.03)kg, P = 0.006]。两种fmd均可使空腹血糖降低约10% [LP-FMD: -0.41(- 0.80至- 0.02)mmol]。L−1,p = 0.038；HP-FMD: [-0.46 (- 0.74 ~ - 0.17) mmol。L−1，P= 0.003]和IGF1降低~ 35% [LP=FMD:−9.0(−12.4至−5.5)nmol]。L−1,P <；0.0001;HP-FMD:−5.4(−8.6 ~−2.1)nmol。L−1,P = 0.024]相对于CONTROL。LP-组血清羟丁酸的升高高于HP-FMD组[0.64 (0.13 ~ 1.15)mmol]。L−1,p = 0.015]。心率变异性(P <；仅HP-FMD组改善了肠道微生物多样性（P = 0.003）、循环甘油三酯（P = 0.009）和饱和脂肪酸（P = 0.008）。两种FMDs均在分子水平诱导自噬。结论两种fmd均可促进心脏代谢健康和诱导自噬，HP-FMD在机体组成、循环脂质谱、心率变异性和肠道微生物群健康方面具有选择性的新益处。这些发现表明，可以根据个人健康目标和偏好定制具有不同宏量营养素组成的膳食补充剂。临床试验注册编号clinicaltrials .gov标识符NCT06560996。注册URL: https://clinicaltrials.gov/study/NCT06560996。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical nutrition 医学-营养学

CiteScore

14.10

自引率

6.30%

发文量

356

审稿时长

28 days

期刊介绍： Clinical Nutrition, the official journal of ESPEN, The European Society for Clinical Nutrition and Metabolism, is an international journal providing essential scientific information on nutritional and metabolic care and the relationship between nutrition and disease both in the setting of basic science and clinical practice. Published bi-monthly, each issue combines original articles and reviews providing an invaluable reference for any specialist concerned with these fields.