Magnesium and Vascular Stiffness

NCT ID: NCT03632590

Last Updated: 2018-08-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 162 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-27
• Study Completion Date: 2020-01-31

Brief Summary

This four-arm randomized controlled trial was designed to study the effects of magnesium supplements (total daily dose: 450 mg elemental magnesium) on vascular stiffness in healthy overweight and slightly obese men and women. In addition, the effects of magnesium supplements on blood pressure and gut microbiota will be evaluated. Three groups will receive magnesium supplements (magnesium oxide, magnesium citrate or magnesium sulphate) and one group will receive a placebo.

Detailed Description

Observational epidemiologic studies have observed an inverse relationship between daily dietary magnesium intake and blood pressure. Except for blood pressure, magnesium may also beneficially affect other cardiovascular risk markers. Whether all these effects translate into improved vascular function is not known. Different vascular function markers at various stages on the pathway between diet and disease exist. One of these markers, vascular stiffness, is closely related to the process of atherosclerosis, an independent cardiovascular risk factor, and predictive of future cardiovascular events and mortality. A recently published intervention study showed that oral magnesium citrate supplementation of 350 mg per day for 24 weeks was well-tolerated and improved vascular stiffness by 1.0 m/s. Importantly, it was not established whether the beneficial effect on vascular stiffness was due to the supplementation of magnesium or due to citrate. This may involve effects on gut microbiota and systemic metabolic effects. The current study was designed to (1) reproduce the result of the earlier study and to (2) investigate whether there is a difference between different commonly used magnesium salts (magnesium citrate, magnesium sulphate and magnesium oxide) in terms of effects on vascular stiffness, blood pressure and gut microbiota.

Conditions

Vascular Stiffness; Blood Pressure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Magnesium Citrate

450 mg of Magnesium Citrate per day

Group Type: EXPERIMENTAL

Magnesium Citrate

Intervention Type: DIETARY_SUPPLEMENT

450 mg of Magnesium Citrate per day (6 capsules per day) for 24 weeks

Magnesium Sulfate

450 mg of Magnesium Sulfate per day

Group Type: EXPERIMENTAL

Magnesium Sulfate

Intervention Type: DIETARY_SUPPLEMENT

450 mg of Magnesium Sulfate per day (6 capsules per day) for 24 weeks

Magnesium Oxide

450 mg of Magnesium Oxide per day

Group Type: EXPERIMENTAL

Magnesium Oxide

Intervention Type: DIETARY_SUPPLEMENT

450 mg of Magnesium Oxide per day (6 capsules per day) for 24 weeks

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

The placebo capsules will contain starch (Amylum solani) for 24 weeks

Interventions

Magnesium Citrate

450 mg of Magnesium Citrate per day (6 capsules per day) for 24 weeks

Intervention Type: DIETARY_SUPPLEMENT

Magnesium Sulfate

450 mg of Magnesium Sulfate per day (6 capsules per day) for 24 weeks

Intervention Type: DIETARY_SUPPLEMENT

Magnesium Oxide

450 mg of Magnesium Oxide per day (6 capsules per day) for 24 weeks

Intervention Type: DIETARY_SUPPLEMENT

Placebo

The placebo capsules will contain starch (Amylum solani) for 24 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Aged between 45-70 years
• Women postmenopausal: two or more years after last menstruation
• BMI between 25-35 kg/m2 (overweight and slightly obese)
• Plasma glucose < 7.0 mmol/L
• Serum total cholesterol < 8.0 mmol/L (further testing is recommended for excessive hyperlipidemia (serum total cholesterol ≥ 8.0 mmol/L) according to the Standard for cardiovascular risk management of the Dutch general practitioners community (NHG))
• Serum triacylglycerol < 4.5 mmol/L (Friedewald formula)
• No current smoker
• No diabetic patients
• No familial hypercholesterolemia
• No abuse of drugs
• Less than 21 alcoholic consumptions per week
• Stable body weight (weight gain or loss <3 kg in the past three months)
• No use of proton pump inhibitors
• No use of magnesium supplements
• No severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis
• No active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebro vascular accident
• Willingness to give up being a blood donor (or having donated blood) from 8 weeks before the start of the study and during the study
• No difficult venipuncture as evidenced during the screening visit
• Written informed consent

Exclusion Criteria

• High habitual dietary magnesium intake (defined as urinary magnesium excretion of 7.0 or 5.9 mmol/24-h or more for men and women, respectively)
• Plasma glucose ≥ 7.0 mmol/L
• Serum total cholesterol ≥ 8.0 mmol/L
• Serum triacylglycerol ≥ 4.5 mmol/L
• Current smoker, or smoking cessation <12 months
• Diabetic patients
• Familial hypercholesterolemia
• Abuse of drugs
• More than 21 alcoholic consumptions per week
• Unstable body weight (weight gain or loss > 3 kg in the past three months)
• Use of proton pump inhibitors
• Use of magnesium supplements
• Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis
• Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebro vascular accident
• Not willing to give up being a blood donor (or having donated blood) from 8 weeks before the start of the study and during the study
• Not or difficult to venipuncture as evidenced during the screening visit

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Nedmag Industries Mining and Manufacturing B.V.

UNKNOWN

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Stephan J.L. Bakker

Prof. dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephan JL Bakker, MD-PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

University Medical Center Groningen

Groningen, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Joëlle C Schutten, MSc

Role: CONTACT

j.c.schutten@umcg.nl

+31 50 3612679

Facility Contacts

Joëlle C Schutten, MSc

Role: primary

j.c.schutten@umcg.nl

+31 50 3612679

Stephan JL Bakker, MD-PhD

Role: backup

s.j.l.bakker@umcg.nl

+31 50 3613677

References

Schutten JC, Joris PJ, Groendijk I, Eelderink C, Groothof D, van der Veen Y, Westerhuis R, Goorman F, Danel RM, de Borst MH, Bakker SJL. Effects of Magnesium Citrate, Magnesium Oxide, and Magnesium Sulfate Supplementation on Arterial Stiffness: A Randomized, Double-Blind, Placebo-Controlled Intervention Trial. J Am Heart Assoc. 2022 Mar 15;11(6):e021783. doi: 10.1161/JAHA.121.021783. Epub 2022 Mar 5.

Reference Type: DERIVED

PMID: 35253448 (View on PubMed)

Schutten JC, Joris PJ, Mensink RP, Danel RM, Goorman F, Heiner-Fokkema MR, Weersma RK, Keyzer CA, de Borst MH, Bakker SJL. Effects of magnesium citrate, magnesium oxide and magnesium sulfate supplementation on arterial stiffness in healthy overweight individuals: a study protocol for a randomized controlled trial. Trials. 2019 May 28;20(1):295. doi: 10.1186/s13063-019-3414-4.

Reference Type: DERIVED

PMID: 31138315 (View on PubMed)

Other Identifiers

METc2017/220

Identifier Type: -

Identifier Source: org_study_id