Mitochondrial Effects of C18:0 Supplementation in Humans

The purpose of this crossover study is to determine whether nutritional supplementation of C18:0 in humans has mitochondrial effects as shown in Drosophila and human cell culture. We will compare a study cohort of patients with diagnosed type 2 diabetes with non-diabetics. Participants will undergo a 2-day low-fat vegan diet and will then be supplemented with a bolus of C18:0. Changes in the mitochondrial morphology and function of white blood cells will be scored by immunofluorescence and FACS analysis.

The purpose of this study is to determine whether nutritional supplementation of C18:0 in humans has mitochondrial effects as shown in Drosophila and human cell culture. We will compare a study cohort of patients with diagnosed type 2 diabetes with non-diabetics. Participants will undergo a 2-day low-fat vegan diet to reach baseline levels of C18:0 and will then be fed a milkshake supplemented with 24g of C18:0, which corresponds roughly to the C18:0 content of a fast-food meal. Blood samples will be taken at baseline and several hours after intake. We will look at changes in mitochondrial morphology of neutrophils by immunofluorescence, and score mitochondrial function via FACS analysis. Since this study is designed as a crossover study, participants will also receive a mock milk shake after another 2 days of low-fat vegan diet.

Transferrin Receptor, Type 2 Diabetes, Stearic Acid (C18:0), Mitochondrial Morphology, Crossover Study

Non-diabetic volunteers with HbA1c < 6.5%. Subjects will be treated with C18:0 supplementation or mock.

Type 2 Diabetes according to common definitions, but we exclude insulin-treated Type 2 diabetics because nutritional intervention is more difficult/risky. Subjects will be treated with C18:0 supplementation or mock.

Mitochondria of neutrophils are stained and scored via immunofluorescence microcsopy, either as "fragmented", "intermediate" or "fused". Statistical calculations will be performed on changes in fragmentation status after treatment.

Mitochondrial membrane potential and ROS production in neutrophils will be analyzed via FACS. Statistical calculations will be performed on changes in the respective levels after treatment.

Measurement of iron, transferrin, ferritin, hepcidin and ferroportin from serum at all timepoints via ELISA. Changes in plasma levels will be correlated to primary endpoints.

Methylglyoxal levels in plasma analyzed via liquid chromatography-mass spectrometry. Changes will be correlated to primary endpoints.

Fatty acids along with other lipid parameters like triglycerides and cholesterol for normalization purposes will be measured.

Patients with confirmed HbA1c > 6,5% will be considered diabetic. Then albumin in urine will be measured and diabetic neuropathy will be assessed clinically via NDS/NSS scoring.

Inclusion Criteria: type 2 diabetes, either dietary treatment or oral medication must be able to give consent Exclusion Criteria: insulin treated diabetes mellitus severe diseases inducing wasting (e.g. cancer, liver cirrhosis, renal failure) conditions of malnourishment severe anemia pregnancy alcohol abuse

Senyilmaz D, Virtue S, Xu X, Tan CY, Griffin JL, Miller AK, Vidal-Puig A, Teleman AA. Regulation of mitochondrial morphology and function by stearoylation of TFR1. Nature. 2015 Sep 3;525(7567):124-8. doi: 10.1038/nature14601. Epub 2015 Jul 27.