Magnesium and Vascular Stiffness

The Effects of Magnesium on Vascular Stiffness: A Long-term Study in Healthy Overweight and Slightly Obese Men and Women

Observational epidemiologic studies have observed an inverse relationship between daily dietary magnesium intake and blood pressure (BP). Except for BP, 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. To examine the integrated effects of interventions on cardiovascular risk, vascular stiffness may therefore serve as a marker at the later stage of cardiovascular disease development.

Therefore, it is imperative to examine in a 24-week, randomized, double-blind, placebo-controlled, two-way parallel-group human intervention study, the effect of magnesium on vascular stiffness. Focus will be on carotid-femoral pulse wave velocity (PWV), the gold standard for the evaluation of vascular elasticity, to quantify vascular stiffness. Urinary excretion of magnesium will be used to assess dietary magnesium uptake. Furthermore, time courses of an increased magnesium intake on changes in BP, other markers reflecting vascular function, and plasma biomarkers related to low-grade inflammation and vascular activity will be measured to unravel possible cause-effect relationships.

Study Overview

• Status: Completed
• Conditions: Obesity; Metabolic Syndrome
• Intervention / Treatment: Dietary supplement: Magnesium Citrate; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • Maastricht University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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
• Serum triacylglycerol < 4.5 mmol/L
• 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 or medication known to treat blood pressure, serum lipid or glucose metabolism
• No use of dietary supplements or an investigational product within another biomedical within the previous 1-month
• 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

Exclusion Criteria:

• High habitual dietary magnesium intake
• 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 or medication known to treat blood pressure, serum lipid or glucose metabolism
• Use of dietary supplements or an investigational product within another biomedical within the previous 1-month
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: Placebo; One capsule thrice daily that contains placebo at breakfast, lunch and dinner for 24 weeks
Experimental: Magnesium Citrate	Dietary supplement: Magnesium Citrate; One capsule thrice daily that contains magnesium citrate (total daily dose: 350 mg elemental magnesium) at breakfast, lunch and dinner for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascular stiffness: effects of magnesium citrate supplementation	Carotid-femoral pulse wave velocity (PWV)	Baseline (0 weeks) and after medium-term (12 weeks) and long-term (24 weeks) magnesium citrate supplementation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascular function markers: effects of magnesium citrate supplementation	Flow-mediated dilation (FMD) of the brachial artery, pulse wave analysis (PWA) (also at 12 weeks), peripheral arterial tonometry (PAT) and retinal microvascular diameters (also at 12 weeks)	Baseline (0 weeks) and after long-term (24 weeks) magnesium citrate supplementation
Metabolic risk markers related to the metabolic syndrome: effects of magnesium citrate supplementation	Biomarkers for low-grade inflammation and endothelial activation	Baseline (0 weeks) and after medium-term (12 weeks) and long-term (24 weeks) magnesium citrate supplementation
Blood pressure: effects of magnesium citrate supplementation	Office (also at 12 weeks) and 24-hour ambulatory blood pressure	Baseline (0 weeks) and after long-term (24 weeks) magnesium citrate supplementation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dietary magnesium uptake	24-hour urine samples	Baseline (0 weeks) and after long-term (24 weeks) magnesium citrate supplementation

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Top Institute Food and Nutrition

Publications and helpful links

General Publications

• Schutten JC, Joris PJ, Minovic I, Post A, van Beek AP, de Borst MH, Mensink RP, Bakker SJL. Long-term magnesium supplementation improves glucocorticoid metabolism: A post-hoc analysis of an intervention trial. Clin Endocrinol (Oxf). 2021 Feb;94(2):150-157. doi: 10.1111/cen.14350. Epub 2020 Oct 26.
• Joris PJ, Plat J, Bakker SJ, Mensink RP. Long-term magnesium supplementation improves arterial stiffness in overweight and obese adults: results of a randomized, double-blind, placebo-controlled intervention trial. Am J Clin Nutr. 2016 May;103(5):1260-6. doi: 10.3945/ajcn.116.131466. Epub 2016 Apr 6.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: September 8, 2014
• First Submitted That Met QC Criteria: September 8, 2014
• First Posted (Estimate): September 10, 2014

Study Record Updates

• Last Update Posted (Estimate): September 15, 2015
• Last Update Submitted That Met QC Criteria: September 14, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Obesity; Metabolic Syndrome; Vascular Function; Vascular Stiffness; Magnesium Supplementation
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome; Gastrointestinal Agents; Cathartics; Magnesium citrate
• Other Study ID Numbers: MEC 14-3-021