B1 and Magnesium Supplements on Glucose Metabolism in Low-carb Dieters

Study Overview
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Brief Summary
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Magnesium (Mg) and thiamine (vitamin B1) are micronutrients involved in the regulation of blood sugar level. Avoidance of wholegrains or fruits and starchy vegetables could impact on Mg and vitamin B1 intakes and status. Although supplementation can be recommended alongside low-carbohydrate high fat diets (LCHF) diets, its benefits have never been studied before. This study aims to test the effect of Mg and vitamin B1 supplements on glucose metabolism in people following any LCHF diet.

Detailed Description
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It is clear that Mg involves in both type 2 diabetes (T2D) prevention and management, and following LCHF diets, avoidance of wholegrains, fruits and starchy vegetables, could have a negative impact on Mg and B1 intakes and status. A systematic review of LCHF diets and micronutrients confirmed that Mg and B1 intakes were reduced by 50% and 70% following LCHF diets compared to baseline normal carbohydrate diets, and could be as low as 40% and 75% of recommended intakes for Mg and B1 respectively. Although supplementation can be recommended alongside LCHF diets, not all LCHF dieters take supplements, and their benefits during LCHF diets have never been studied before. Rationale We hypothesise that people who have been following LCHF diets without taking supplement are potentially at risk of Mg/B1 insufficiency, with negative impact on glucose metabolism. Objective To investigate potential efficacy of Mg/B1 supplementation on glucose metabolism (mechanistic efficacy/proof of concept) in adults already voluntarily following LCHF To investigate effect of Mg/B1 supplementation on Mg/B1 status in adults already voluntarily following LCHF, who are at risk of Mg/B1 inadequacy To test capabilities of measures, procedures, recruitment criteria, and operational strategies that are under consideration for use in a subsequent, larger, study. To identify barriers to successful study completion To evaluate acceptability of methods and instruments to participants Study design: This is a mechanistic efficacy/proof of concept, intervention study with a use of a randomised-start design. All participants will be assigned to the same intervention but at different times. There are 3 groups of the study - 2 interventions and 1 control group: 400 mg of Mg per day for 4 weeks then add on 100 mg of B1 per day for another 4 weeks, a total duration of 8 weeks (MB). 100 mg of B1 per day for 4 weeks then add on 400 mg of Mg per day for another 4 weeks, a total duration of 8 weeks (BM). Untreated: Participants with delayed entry (untreated) for 8 weeks (Con) Assessment: Baseline, 4 weeks, and 8 weeks after intervention/untreated period

Official Title
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Effects of Vitamin B1 and Magnesium Supplements on Glucose Metabolism in Adults Voluntarily Following Reduced-carbohydrate Diets: a Proof of Concept Intervention Study

Conditions
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Diet, Carbohydrate-restricted

Intervention / Treatment
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* Dietary Supplement: vitamin B1 and magnesium supplements


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 18 years and older have been following LCHF diets for at least 2 months carbohydrate intake is less than 130 g/day or less than 26% of energy intake have stable body weight (weight change ≤ 2 kg within two months period) no diagnosed or suspected eating disorder. Exclusion Criteria: currently taking Mg and B1 supplements within the last 3 months underweight defined by BMI below 18.5 kg/m2 have been diagnosed with T1DM or other types of diabetes apart from T2DM. if potential participants have been diagnosed with T2DM, they will be excluded if they are on anti-diabetic drugs and/or insulin (see 7.) or if they are currently following a complete diet for weight loss (e.g. meal replacement, Slimfast, etc.) currently taking anti-diabetic drugs (e.g. metformin, sulfonylurea, GLP-1 agonist, DPP4-inhibitor, SGLT-2 inhibitor, etc) nor insulin use currently taking medications that interact with Mg supplement currently taking medications that may affect glucose metabolism such as steroids, hormonal therapy (e.g. hormone replacement therapy in postmenopausal), antipsychotics. pregnant and lactating women. have gastrointestinal tract diseases e.g. Inflammatory bowel diseases, irritable bowel syndrome, coeliac disease, including other diseases that involve malabsorption. have kidney disease or impair renal function have auto-immune/connective tissue diseases, malignancy. currently dieting or losing 5% of body weight or more during the last 6 months (or planning to do so in the following year). currently participating in other intervention studies.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Untreated<br>This control group will be untreated for 8 weeks as to be a controlled group. Then all participants in the control group will be randomised again to either Mg-B1 or B1-Mg groups for another 8 weeks (delayed-start intervention). | |
| Experimental: Mg-B1 early start<br>Participants in the Mg-B1 are the 'early start' group where they will receive 400 mg of Mg per day for 4 weeks then add on 100 mg of B1 per day for another 4 weeks, a total duration of 8 weeks (MgB1). | Dietary Supplement: vitamin B1 and magnesium supplements<br>* vitamin B1 - 100 mg/day magnesium - 400 mg/day<br>|
| Experimental: B1-Mg early start<br>Participants in the B1-Mg are the 'early start' group where they will receive 100 mg of B1 per day for 4 weeks then add on 400 mg of Mg per day for another 4 weeks, a total duration of 8 weeks (B1Mg). | Dietary Supplement: vitamin B1 and magnesium supplements<br>* vitamin B1 - 100 mg/day magnesium - 400 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fasting plasma glucose | changes from baseline and after supplementation | 8 weeks | 
| fasting insulin | changes from baseline and after supplementation | 8 weeks | 
| homeostatic model assessment of insulin resistance (HOMA-IR) | changes from baseline and after supplementation | 8 weeks | 
| incremental area under the curve (iAUC) of glucose and insulin after 75 g oral glucose tolerance test | changes from baseline and after supplementation | 8 weeks | 
| magnesium status | changes from baseline and after supplementation | 8 weeks | 
| vitamin B1 status | changes from baseline and after supplementation | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lipid profile: plasma Triglyceride, Total cholesterol, LDL-cholesterol, HDL-cholesterol | changes from baseline and after supplementation | 8 weeks | 
| plasma hs-CRP | changes from baseline and after supplementation | 8 weeks | 
| plasma IL-6 | changes from baseline and after supplementation | 8 weeks | 
| sRAGE | changes from baseline and after supplementation | 8 weeks | 
| Urine 8-isoprostane | , MDA, glycation markers (fructosamine and HbA1c, dermal glycation by skin fluorescence) | 8 weeks | 
| plasma 8-isoprostane | changes from baseline and after supplementation | 8 weeks | 
| plasma fructosamine | changes from baseline and after supplementation | 8 weeks | 
| HbA1c | changes from baseline and after supplementation | 8 weeks | 
| dermal glycation by skin fluorescence | changes from baseline and after supplementation | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glucose, low-carbohydrate, magnesium, thiamine, supplement