Clinical trial NCT03632590: Magnesium and Vascular Stiffness
Official title: The Effects of Magnesium Salts on Vascular Stiffness: A Randomized Controlled Trial in Healthy Overweight and Slightly Obese Men and Women
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Vascular Stiffness
Blood Pressure
Keywords: Magnesium
Supplements
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Nedmag Industries Mining and Manufacturing B.V.
First posted: 2018-08-15
Enrollment: 162
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Change in vascular stiffness
timeFrame: Baseline, FU-1 (2 weeks), FU-2 (12 weeks), and FU-3 (24 weeks)
Secondary outcomes:
measure: Change in blood pressure
timeFrame: Baseline, FU-1 (2 weeks), FU-2 (12 weeks), and FU-3 (24 weeks)
measure: Change in gut microbiota
timeFrame: Baseline, FU-1 (2 weeks), FU-2 (12 weeks), and FU-3 (24 weeks)
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Stephan JL Bakker, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.