Prevention, autophagy, fasting simulation by dietary methionine restriction
Conditions
Interventions
Sponsors
Eligibility
Inclusion criteria
Inclusion criteria: - Men and women in a ratio of 1:1 - Body Mass Index 18.5 - 29.9 kg/m2 - Ability to provide informed consent - Existing health insurance to cover any necessary clarification and treatment of incidental findings.
Exclusion criteria
Exclusion criteria: - Diseases or functional disorders which, in the opinion of the study doctor preclude participation in the study - Severe, manifest and treatment-requiring diseases - Permanent use of prescription drugs (except hormonal contraception) - Vitamin B6, B12 and folic acid levels below the normal range - Homocysteinemia - Postoperative phases - Acute and chronic infections - Special diet for medical reasons - Taking food supplements - Food intolerances - Vegetarian or vegan diet - Pregnancy and breastfeeding - Smoker - Following a diet or weight reduction programme - Change in body weight of more than 2 kg in the previous month of the study - Habitual methionine intake < 20 mg/kg bw/d - Known medication, drug or alcohol abuse - Incapacity or other circumstances that do not allow the subject to fully understand the nature, meaning and implications of this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Detection of autophagy activation by autophagic flux (LC3-II) and mTOR (p-S6 and p-4EBP1) by flow cytometry after 14 days of dietary methionine reduction (10 mg/kg bw/d) | — |
Secondary
| Measure | Time frame |
|---|---|
| - Change of Methionine concentration in plasma and urine measured by LC-MS mass spectroscopy - Change of body fat content, measured by air displacement plethysmography - Change of Office Blood pressure (mmHg), non-invasively measured (NIBP) - Change of pulse wave velocity (m/s), measured by PulsePen - Change of frequency of pro- and anti-inflammatory immune cells; immunophenotyping of PBMCs using flow cytometry - Changed immune cell function (cytokines, proliferation after in vitro stimulation of different PBMC populations) measured by flow cytometry - Changed metabolite patterns in plasma and urine, measured by non-targeted (H-NMR spectroscopy) and targeted metabolomics (LCMS) - Changed concentrations of inflammatory or anti-inflammatory circulating cytokines in blood plasma, measured by multiplex cytokine analysis - Changed expression of senescence markers in various immune cell populations, measured by flow cytometry - Changed expression profile of key methionine cycle genes measured by qPCR in specific immune cell types - Histone methylation patterns of key genes, assessed by DNA methylation patterns in specific immune cell types | — |
Countries
Germany
Contacts
Charité - Universitätsmedizin Berlin, Experimental and Clinical Research Center (ECRC), Clinical Research Unit