B1 and Magnesium Supplements on Glucose Metabolism in Low-carb Dieters (B-Mag)

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

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.

Study Overview

• Status: Suspended
• Conditions: Diet, Carbohydrate-restricted
• Intervention / Treatment: Dietary supplement: vitamin B1 and magnesium supplements

Detailed Description

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

1. To investigate potential efficacy of Mg/B1 supplementation on glucose metabolism (mechanistic efficacy/proof of concept) in adults already voluntarily following LCHF
2. 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
3. To test capabilities of measures, procedures, recruitment criteria, and operational strategies that are under consideration for use in a subsequent, larger, study.
4. To identify barriers to successful study completion
5. 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:

1. 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).
2. 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).
3. Untreated: Participants with delayed entry (untreated) for 8 weeks (Con)

Assessment: Baseline, 4 weeks, and 8 weeks after intervention/untreated period

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom
    • University of Glasgow

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. aged 18 years and older
2. have been following LCHF diets for at least 2 months
3. carbohydrate intake is less than 130 g/day or less than 26% of energy intake
4. have stable body weight (weight change ≤ 2 kg within two months period)
5. no diagnosed or suspected eating disorder.

Exclusion Criteria:

1. currently taking Mg and B1 supplements within the last 3 months
2. underweight defined by BMI below 18.5 kg/m2
3. have been diagnosed with T1DM or other types of diabetes apart from T2DM.
4. 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.)
5. currently taking anti-diabetic drugs (e.g. metformin, sulfonylurea, GLP-1 agonist, DPP4-inhibitor, SGLT-2 inhibitor, etc) nor insulin use
6. currently taking medications that interact with Mg supplement
7. currently taking medications that may affect glucose metabolism such as steroids, hormonal therapy (e.g. hormone replacement therapy in postmenopausal), antipsychotics.
8. pregnant and lactating women.
9. have gastrointestinal tract diseases e.g. Inflammatory bowel diseases, irritable bowel syndrome, coeliac disease, including other diseases that involve malabsorption.
10. have kidney disease or impair renal function
11. have auto-immune/connective tissue diseases, malignancy.
12. currently dieting or losing 5% of body weight or more during the last 6 months (or planning to do so in the following year).
13. currently participating in other intervention studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Untreated; 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; 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; vitamin B1 - 100 mg/day magnesium - 400 mg/day
Experimental: B1-Mg early start; 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; vitamin B1 - 100 mg/day magnesium - 400 mg/day

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Glasgow
• Investigators: Principal Investigator: Chaitong Churuangsuk, MD, University of Glasgow

Publications and helpful links

General Publications

• Churuangsuk C, Griffiths D, Lean MEJ, Combet E. Impacts of carbohydrate-restricted diets on micronutrient intakes and status: A systematic review. Obes Rev. 2019 Aug;20(8):1132-1147. doi: 10.1111/obr.12857. Epub 2019 Apr 22.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2021
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: November 24, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (Actual): December 3, 2020

Study Record Updates

• Last Update Posted (Actual): April 30, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: supplement; glucose; thiamine; magnesium; low-carbohydrate
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Thiamine
• Other Study ID Numbers: 200180160

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No