The effects of magnesium salts 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. 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. In the current study, we intend to
(1) reproduce the result of the earlier study and to (2) investigate whether
there is a difference between different commonly used magnesium salts, i.e.
magnesium citrate, magnesium sulphate and magnesium chloride in terms of
effects on gut microbiota, metabolism, gastro-intestinal comfort and vascular
stiffness.

1.What is the long-term (24 weeks) effect of magnesium citrate (total daily
dose: 450 mg elemental magnesium) on vascular stiffness measured from
carotid-femoral pulse wave velocity (PWV) in healthy overweight and slightly
obese men and women?

2. Is the effect of magnesium sulphate supplementation (total daily dose: 450
mg elemental magnesium) non-inferior to the effect of magnesium citrate
supplementation on vascular stiffness measured from carotid-femoral PWV in
healthy overweight and slightly obese men and women?

3. Is the effect of magnesium oxide supplementation (total daily dose: 450 mg
elemental magnesium) non-inferior to the effect of magnesium citrate
supplementation on vascular stiffness measured from carotid-femoral PWV in
healthy overweight and slightly obese men and women?

At baseline, all participants have to attend the research facilities to perform
the measurements. Before the test day 24-hour urine will be collected. After
the first test day (baseline (BL) measurement), the overweight and slightly
obese participants will be randomly assigned to receive magnesium citrate,
magnesium sulphate, magnesium oxide or a placebo. After 2, 12 and 24 weeks
(follow-up (FU) measurements), measurements will be repeated.

After the first test day, the overweight and slightly obese subjects will be
randomly assigned to magnesium citrate, magnesium sulphate, magnesium oxide or
to placebo for 24 weeks.
Subjects assigned to the oral magnesium treatment will be instructed to take
one capsule thrice daily that contains magnesium citrate, magnesium sulphate or
magnesium oxide (total daily dose: 450 mg elemental magnesium) at breakfast,
lunch and dinner for 24 weeks.
Subjects assigned to the placebo treatment will undergo the same tests, but
will be instructed to take one capsule thrice daily that contains placebo
(identical in color, shape, taste and smell to the capsules containing
magnesium) for 24 weeks.

Before the start of the study, subjects will attend the research facilities for
a screening visit. During this visit, anthropometric measurements (weight,
length, body mass index) will be performed and blood pressure will be
determined. Dietary magnesium intake will be assessed using a questionnaire. In
addition, a venous blood sample will be drawn for analysis of serum total
cholesterol and triacylglycerol concentrations, and plasma glucose
concentrations.
Following screening, all participants will visit our research facilities at the
UMCG for 45 minutes (BL measurements). During this period, subjects will remain
at the UMCG. Before each test day, 24-hour urine samples will be collected.
After 2, 12 and 24 weeks, measurements will be repeated (FU measurements). Time
investment at 2, 12 and 24 weeks will be approximately 45 minutes. Total time
investment for the overweight and slightly obese subjects will be approximately
300 minutes (5 hours).

The amount of blood drawn will be 216.5 mL (6.5 mL during the screening visit
and 52.5 mL at each test day) during the whole study.
Subjects assigned to receive magnesium citrate, magnesium sulphate or magnesium
oxide will consume safe and commercially available products. Only diarrhea, and
unspecific mild abdominal pain have been reported after consumption of
magnesium supplements.