Long-term Fasting: Multi-system Adaptations in Humans
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Changes in the composition of the quadriceps
研究概览
简要总结
The aim of this trial is to investigate the effects of long-term fasting on size, mass, composition and function of metabolic active tissues in several organs that reexpand possibly rejuvenated after 1-4 months. Additionally, the lipid metabolism is investigated in depth.
详细描述
Fasting displays numerous positive effects on metabolism, health and aging. Surprisingly, few considerations are given to long-term fasting periods.
The metabolic switch from food-derived glucose to adipose tissue-derived fatty acids and ketones as primary cellular fuel is the key to fasting metabolism. Fasting has been shown to improve cardiovascular risk factors and gut microbiota in humans. It provokes profound changes in lipid metabolism. However, many questions are still open concerning the mobilization, exchange, and function of lipids during long-term fasting. Furthermore, recent results show the ability of periodic restrictive nutritional strategies to trigger organ regeneration. This promising regenerative power has not been investigated comprehensively in humans. In addition, the knowledge about the role of human faecal microbiota in health and disease is increasing. Only little is known about its composition and function during fasting. We found indications that the gut microbiome could influence energy metabolism and consequently could influence the dynamic of the metabolic switch.
Long-term fasting under medical supervision according to the Buchinger Wilhelmi fasting program has been demonstrated to be safe and well-tolerated.
The current project investigates the effects of a 9±3 days fasting period by a multi-systemic approach focusing on lipid metabolism and the gut microbiome in 100 subjects. Additionally, the body composition in combination with muscle performance will be analyzed in-depth in a subgroup of 32 subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI between 22 - 35 kg/m2
排除标准
- •intake of medication (cardiovascular diseases, lipid and glucose metabolism)
- •chronic manifest psychical and psychiatric diseases
- •participation in another study
- •pregnancy or breastfeeding
- •in the MRI/MRS sub-study, any MRI contraindication (claustrophobia, pacemakers, MR-incompatible prosthetic valves, metallic implants, foreign metallic body)
- •active uncontrolled gastrointestinal disorders including ulcerative colitis, Crohn's disease, indeterminate colitis, severe irritable bowel syndrome, persistent infectious gastroenteritis, persistent or chronic diarrhea of unknown etiology, recurrent Clostridium difficile infection
- •major surgery of the GI tract, in the past five years. Any major bowel resection at any time
- •intake of antibiotics in the last 2 months
研究组 & 干预措施
Long-term fasting
The participants will undergo 6-12 fasting days according to the Buchinger Wilhelmi fasting program
干预措施: Long-term fasting according to the Buchinger Wilhelmi fasting program (Other)
结局指标
主要结局
Changes in the composition of the quadriceps
时间窗: Baseline and changes at the end of fasting as well as one and four months afterwards
Fat mass, lean mass, water content measured by magnetic resonance imaging
Changes in HDL cholesterol efflux capacity
时间窗: Baseline and changes at the end of fasting as well as one and four months afterwards
measured in serum by a standardized used radioisotopic technique
Changes in the composition of the heart
时间窗: Baseline and changes at the end of fasting as well as one and four months afterwards
Fat mass, lean mass, water content measured by magnetic resonance imaging
Changes in the composition of the kidney
时间窗: Baseline and changes at the end of fasting as well as one and four months afterwards
Fat mass, lean mass, water content measured by magnetic resonance imaging
Changes in HS-Omega-3 Index
时间窗: Baseline and changes at the end of fasting as well as one and four months afterwards
Determination of fatty acid (C 14:0; 16:0; 18:0; 20:0; 22:0; 24:0; 16:1 n-7; 18:1 n-9; 20:1 n-9; 24:1 n-9; 18:2 n-6; 18: 3 n-6; 20: 3 n-6; 22:2 n-6; 20:4 n-6; 22:4 n-6; 22:5 n-6; 18: 3 n-3; 20:5 n-3; 22:5 n-3; 22:6 n-3; 16:1 n-7t; 18:1 n-9t; 18:2 n-6tt; 18:2 n-6ct; 18:2 n-6tc) in erythrocyte membranes with highly standardized analytical procedure
Changes in the composition of the spleen
时间窗: Baseline and changes at the end of fasting as well as one and four months afterwards
Fat mass, lean mass, water content measured by magnetic resonance imaging
Changes in the composition of the adipose tissue
时间窗: Baseline and changes at the end of fasting as well as one and four months afterwards
Fat mass, lean mass, water content measured by magnetic resonance imaging
Changes in serum cholesterol loading capacity
时间窗: Baseline and changes at the end of fasting as well as one and four months afterwards
measured in serum using radioactive cholesterol loaded macrophages
Changes in whole body composition
时间窗: Baseline and changes at the end of fasting as well as one and four months afterwards
Fat mass, lean mass, water content measured by magnetic resonance imaging
Changes in the composition of the liver
时间窗: Baseline and changes at the end of fasting as well as one and four months afterwards
Fat mass, lean mass, water content measured by magnetic resonance imaging
Changes in faecal microbiota composition and function (carbohydrate metabolism)
时间窗: Baseline and changes after an average of 10 (+/-3) fasting days
Shotgun metagenomics, 5Gb of DNA sequencing data.
Changes in metabolome
时间窗: Baseline and changes after 3 fasting days, the end of fasting as well as one and four months afterwards
using an untargeted metabolomics approach to investigate changes in the metabolome, with a focus on the polyamine biosynthetic pathway at the cellular level in PBMCs and compare them with changes in the circulating plasma/serum metabolome
Changes in hydrogen sulfide production capacity
时间窗: Baseline and changes at the end of fasting as well as one and four months afterwards
measured in serum and urine using the lead acetate assay
次要结局
- Changes in oxidized phospholipids(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in persulfidation(Baseline, and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards)
- Changes in GlycA(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in mean diffusivity (MD)(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in cardiovascular fitness(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in muscle metabolism and mitochondrial oxidative capacity: TauPCr(s)(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in muscle metabolism and mitochondrial oxidative capacity: ATP concentration(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in muscle metabolism and mitochondrial oxidative capacity: T1 of metabolites at rest(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in fiber strain (Eff)(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in fractional anisotropy (FA)(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in systolic cardiac function(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in apparent diffusion coefficient (ADC)(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in muscle metabolism and mitochondrial oxidative capacity: PCr hydrolysis (%)(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in multiparametric muscle quantification: T2(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in multiparametric muscle quantification: T2 * relaxation time(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in brain morphometry(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in cardiac mass(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in lower limbs (quadriceps, hamstrings, calves)(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in diastolic cardiac function(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in muscle metabolism and mitochondrial oxidative capacity: PCr concentration(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in muscle metabolism and mitochondrial oxidative capacity: Pi concentration(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in lumbosacral muscle mass(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in helix angle (HA)(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in paraoxonase (PON-1) activity(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in proprotein convertase subtilisin/kexin type 9 (PCSK9)(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in enzymes(Baseline and changes after 3 fasting days, the end of fasting as well as one and four months afterwards)
- Changes in muscle metabolism and mitochondrial oxidative capacity: pH at rest and post exercise in mM(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in muscle metabolism and mitochondrial oxidative capacity: PCr consumption(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in sulfur compounds(Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards)
- Changes in multiparametric muscle quantification: susceptibility (chi)(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in DNA methylation(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in serum amyloid A levels(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in lipoprotein transfer enzymes(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in chylomicrons(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in multiparametric muscle quantification: fat fraction (PDFF)(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in quadricipital maximum voluntary contraction(Baseline and changes at the end of fasting as well as one and four months afterwards)
- Changes in thiosulfate levels(Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards)
- Changes in cysteine and cystine levels(Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards)
- Changes in amino acids(Baseline and changes after 3 fasting days, at the end of fasting as well as one and four months afterwards)
研究者
Françoise Wilhelmi de Toledo
Scientific Director; Principal Investigator
Buchinger Wilhelmi Development & Holding GmbH