Magnesium and Vascular Stiffness

Not Applicable

Interventions: Drug: Placebo
Dietary Supplement: Magnesium Oxide
Dietary Supplement: Magnesium Citrate
Dietary Supplement: Magnesium Sulfate

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Magnesium Oxide	Magnesium Oxide	450 mg of Magnesium Oxide per day
Magnesium Citrate	Magnesium Citrate	450 mg of Magnesium Citrate per day
Magnesium Sulfate	Magnesium Sulfate	450 mg of Magnesium Sulfate per day

Primary Outcome Measures

Name	Time	Method
Change in vascular stiffness	Baseline, FU-1 (2 weeks), FU-2 (12 weeks), and FU-3 (24 weeks)	Measured from carotid-femoral pulse wave velocity (PWV). For this assessment, a SphygmoCor will be used (SphygmoCor v9, AtCor Medical).

Secondary Outcome Measures

Name	Time	Method
Change in blood pressure	Baseline, FU-1 (2 weeks), FU-2 (12 weeks), and FU-3 (24 weeks)	Measured from a semi continuous blood pressure monitoring device
Change in gut microbiota	Baseline, FU-1 (2 weeks), FU-2 (12 weeks), and FU-3 (24 weeks)	Measured from fecal samples

Locations (1): University Medical Center Groningen
🇳🇱
Groningen, Netherlands