Lactate in the Gut

Lactate is formed naturally in the body in example during physical activity. However, lactate is also formed during food fermentation where certain bacterial strains form lactate. Lactate can also be produced chemically. An example of this is Ringer-lactate which is used for volume replacement when treating dehydrated patients. As a source of carbon-molecules, lactate is believed to be an important oxidative fuel source in all major organs and yields adenosine triphosphate (ATP) production through Krebs cycle, the Electron Transport Chain in the mitochondria as well as by being a key precursor for gluconeogenesis. Metformin is the first drug of choice for type 2 diabetes treatment. Use of metformin often results in a small but significant weight loss in overweight users. It is known that metformin increases the lactate concentration in the gut. It is also known also know that metformin use is associated with an increase in blood concentrations of growth differentiation factor 15 (GDF-15). Receptors for GDF-15 can be found in parts of the brain associated with control of appetite. In rats increases in [GDF-15] results in a decrease in appetite and thus weight loss. GDF-15 is thought to be involved in the normal energy homeostasis. With this study the investigators want to examine the hormonal, metabolic and mechanical effects of lactate in the gut in healthy volunteers. Our hypothesis is that lactate has beneficial effects which may be though an increase in GDF-15 in the blood. Volunteers will undergo two study days separated by at least 7 days and a maximum of 1 month. On day one volunteers will drink a sodium-lactate solution (intervention). The investigators will also administrate 1500mg paracetamol to assess gastric emptying and do blood samples over 4 hours. The investigators measure [lactate] every 15 min. Every hour the investigators will ask volunteers questions regarding hunger and thoughts of future food intake (questionnaire). After 4 hours of blood sampling the investigators will serve volunteers an all-you-can-eat meal of sandwich and measure how must they ate. On day two volunteers will drink a sodium chloride solution. Furthermore, the investigators administrate intravenous D/L sodium lactate in order to reach the same plasma [lactate] on day 2 as was done on day 1. The rest of day two is identical to day 1.

iv sodium D/L lactate to elevate [lactate] to the same levels as measured on day 1 + oral sodium chloride, 300 mL

Inclusion Criteria: Male gender Age 18-50 years BMI 20-30 kg/m2 In good health with no daily use of prescription medicine based on medical history, clinical examination and blood samples. Spoken and written informed consent Exclusion Criteria: Chronic illness or daily use of prescription medicine . Abnormal screening blood samples as judged by the PI Does not understand or speak Danish

Pedersen MGB, Sondergaard E, Nielsen CB, Johannsen M, Gormsen LC, Moller N, Jessen N, Rittig N. Oral lactate slows gastric emptying and suppresses appetite in young males. Clin Nutr. 2022 Feb;41(2):517-525. doi: 10.1016/j.clnu.2021.12.032. Epub 2021 Dec 24.