Lactate in the Gut

Study Overview
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Brief Summary
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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.

Official Title
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Lactate in the Gut

Conditions
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Lactate, Healthy, Hyperlactatemia

Intervention / Treatment
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* Drug: Oral Sodium Lactate
* Drug: Intravenous sodium lactate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oral lactate<br>Sodium D/L lactate solution, 25g/L in 300mL water | Drug: Oral Sodium Lactate<br>* 25 grams of D/L lactate dissolved in 300mL water.<br>|
| Placebo Comparator: Iso-lactic intravenous lactate infusion<br>iv sodium D/L lactate to elevate [lactate] to the same levels as measured on day 1 + oral sodium chloride, 300 mL | Drug: Intravenous sodium lactate<br>* intravenous sodium lactate + oral sodium-chlorid solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GDF-15 | Difference in [GDF-15] between intervention and placebo | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glucagon-like peptide -1 | Difference in [glucagon-like peptide -1] between intervention and placebo | 4 hours | 
| Gastric inhibitory peptide (GIP) | Difference in plasma [GIP] between intervention and placebo | 4 hours | 
| free fatty acid | Difference in [free fatty acid ] between intervention and placebo | 4 hours | 
| cholecystokinin | Difference in [cholecystokinin] between intervention and placebo | 4 hours | 
| Ghrelin | Difference in [Ghrelin] between intervention and placebo | 4 hours | 
| Gastrin | Difference in [Gastrin] between intervention and placebo | 4 hours | 
| C-peptide | Difference in [C-peptide] between intervention and placebo | 4 hours | 
| glucose | Difference in [glucose] between intervention and placebo | 4 hours | 
| gastric emptying | [Paracetamol] to asses gastric emptying | 4 hours | 
| Evaluation of hunger | Evaluation of hunger, thoughts of future food intake ect using a questionnaire | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lactate, metabolism, Gastric emptying, GDF-15, insulin, incretin hormones