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The primary aims of the current study:
The secondary aim is to evaluate the effect of carnitine supplementation on gut microbiome composition.
Subjects will be randomly divided in two groups: supplemented by L-carnitine 2g/day for 12 weeks, and placebo group receiving leucine in identical gelatine capsules.
Subjects who successfully complete the protocol will be divided into four subgroups - two with a changed circadian cycle and two controls (supplemented and placebo). Subgroups with a changed daily cycle will be able to sleep between 8:00 and 17:00 for four consecutive days, while during the night they will stay active in the laboratory. The oral glucose tolerance test (OGTT) will be performed before and after the circadian cycle modification. Glucose levels will be monitored by FreeStyle Libre Sensor. Moreover, the activity of the participants will be monitored by wearable activity trackers.
Before supplementation, as well as before circadian cycle modification and after finishing the whole experimental procedure, fasting blood samples will be collected for determination of plasma trimethylamine N-oxide (TMAO), trimethylamine (TMA), carnitine (free and acyl derivatives), protein markers of diabetes and inflammation.
Moreover, the stool samples will be collected before and after 12 weeks of supplementation, to determine the composition of the gut microbiome. In addition diet of participants will be monitored.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| carnitine | Experimental | 2 grams of L-carnitine per day for 12 weeks |
|
| leucine | Placebo Comparator | 2 grams of L-leucine per day for 12 weeks |
|
| modified circadian cycle | Experimental | no sleep at night for four consecutive days (enabling sleep between 8:00 and 17:00). |
|
| normal circadian cycle | Active Comparator | sleep at night for four consecutive days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-carnitine | Dietary Supplement | L-carnitine-L-tartrate |
|
| Measure | Description | Time Frame |
|---|---|---|
| Circulating microbiome metabolites | Determination of plasma trimethylamine and trimethylamine N-oxide using ultra performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS) method | 13 weeks |
| Circulating carnitine metabolites | Determination of plasma free, total, and acyl-L-carnitines using ultra performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS) method | 13 weeks |
| Circulating diabetes biomarkers | insulin, C-peptide, ghrelin, leptin, resistin using enzyme-linked immunosorbent assay | 13 weeks |
| Circulating inflammatory biomarkers | tumor necrosis factor, C-reactive protein using enzyme-linked immunosorbent assay | 13 weeks |
| Oral Glucose Tolerance Test | The subjects will consume 75 g of glucose solution drink within a 5-minute time frame. The glucose level will be continuously monitored with the FreeStyle Libre Sensor. | 1 week |
| Measure | Description | Time Frame |
|---|---|---|
| gut microbiome composition | 16 S rRNA sequencing will be used to analyze the gut microbiome in the stool samples | 13 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert Olek, PhD | Poznan University of Physical Education | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Akademia Wychowania Fizycznego | Poznan | 61-871 | Poland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30485835 | Background | Samulak JJ, Sawicka AK, Hartmane D, Grinberga S, Pugovics O, Lysiak-Szydlowska W, Olek RA. L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women. Ann Nutr Metab. 2019;74(1):11-17. doi: 10.1159/000495037. Epub 2018 Nov 28. | |
| 29356345 | Background |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D002331 | Carnitine |
| D007930 | Leucine |
| ID | Term |
|---|---|
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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| L-leucine | Dietary Supplement | L-leucine |
|
| Change of the circadian cycle | Behavioral | Reducing sleep at night for four consecutive days (enabling sleep between 8:00 and 17:00) |
|
| Bescos R, Boden MJ, Jackson ML, Trewin AJ, Marin EC, Levinger I, Garnham A, Hiam DS, Falcao-Tebas F, Conte F, Owens JA, Kennaway DJ, McConell GK. Four days of simulated shift work reduces insulin sensitivity in humans. Acta Physiol (Oxf). 2018 Jun;223(2):e13039. doi: 10.1111/apha.13039. Epub 2018 Feb 12. |
| D000597 |
| Amino Acids, Branched-Chain |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000601 | Amino Acids, Essential |