A double-blind, placebo-controlled study of the short term effects of a spring water supplemented with magnesium bicarbonate on acid/base balance, bone metabolism and cardiovascular risk factors in postmenopausal women

Epidemiological observational studies have found an inverse association between the incidence of, and mortality from, cardiovascular disease and increased drinking of water containing mineral salts of calcium and magnesium [1–3]; particularly in women [4]. In case control studies, drinking water with greater than 8 mg/L of magnesium was associated with lower risk of death from myocardial infarction [4–6]. A recent meta-analysis of such epidemiology studies further supported the inverse association between magnesium levels in drinking water and cardiovascular mortality [7]. A lower risk of myocardial infarction among men drinking water with magnesium and bicarbonate with concentrations of greater than 110 mg/L compared to those who consumed magnesium in water with minimal bicarbonate was imputed from epidemiological studies in Sweden [6, 8]. It is possible, therefore, that any beneficial effects from the magnesium content of waters may be enhanced by bicarbonate.

Clinical studies have reported that bicarbonate from mineral waters lowers bone resorption [reviewed in [9]] and may reduce cardiovascular risk as evidenced by associated decreases in early markers of atherosclerosis in healthy postmenopausal women [10]. Western diets generally have a high dietary acid load and are associated with in a low intake of minerals such as magnesium, calcium and potassium. Such diets can induce a chronic, low-level, metabolic acidosis [11–13]. The degree of acidosis also increases with age and, therefore, it has been postulated that acidosis may be associated with some of the diseases of aging [12]. Drinking water containing bicarbonate may represent a means of regulating acid base balance.

Magnesium is a cofactor for approximately 300 enzymes. About 50% of magnesium in the body resides in bone where it is directly involved in calcium and bone homeostasis. Magnesium affects the function of the parathyroid glands [14] where it acts as an agonist at the calcium-sensing receptors and, like calcium, can decrease parathyroid hormone (PTH) secretion [15]. Low magnesium status has been associated with cardiovascular disease, hypertension, diabetes [16] and osteoporosis [17]. Magnesium supplementation has been linked with suppression of bone turnover [18] and improvements in lipid profile and blood pressure [19, 20].

This randomised double-blind, placebo-controlled study was conducted in postmenopausal women to investigate whether the short term regular ingestion of spring water supplemented with magnesium bicarbonate could contribute to the intake of magnesium and influence acid base balance, metabolic parameters of bone turnover and cardiovascular risk factors (blood pressure and serum lipids).

A randomised, double-blind, placebo-controlled, parallel-arm study comparing the daily intake of 1500 mL - 1800 mL of magnesium bicarbonate supplemented spring water with non supplemented spring water (placebo) was undertaken in postmenopausal women, while on their usual diet, over an 84 day period. The study was conducted from 31 August 2005 to 3 November 2006 and approved by the St Vincent's Hospital Human Research Ethics Committee.

Sixty-seven eligible subjects received at least one dose of magnesium bicarbonate supplemented spring water {supplemented water group; n = 34} or one dose of spring water without supplement {control group; n = 33}, had a valid baseline measurement and returned for at least one post-baseline visit. All analyses were carried out on this population which was identical to the safety population.

The most common pre-existing conditions in both groups were self-reported drug hypersensitivity, osteoarthritis and lipid disorders for which subjects used hypolipidaemics, anti-inflammatory and antirheumatic products and analgesics. The compliance rate was high in both groups {28 (84.8%) in the control and 29 (85.3%) and supplemented water groups} according to daily diary records. The 1500 mL -1800 mL of water volume was well tolerated by all subjects.

Outcome Analyses

There were no statistically significant differences in change between the supplemented water group and the water control group from baseline to Day 14, 42 and 84 in any of the measures of bone mineral turnover (n-telopeptides, hydroxyproline, osteocalcin and 1,25-dihydroxyvitamin D) (Table 2, Additional file 2) or in cardiovascular parameters of serum lipid profile measures (triglycerides, LDL HDL and total cholesterol) (Table 3, Additional file 3) and blood pressure (Table 4, Additional file 4). Measurements of bicarbonate, calcium, creatinine, sodium (Table 5, Additional file 5) and most serum biochemistry also did not show significant differences between the two groups remaining within normal ranges (data not shown). Haematology parameters remained unaltered through study period for both water groups (data not shown).

The concentration of serum PTH increased from Day 0 (3.85 pmol/L) to Day 84 (4.57 pmol/L) with control water consumption compared to supplemented water for which the concentration remained relatively constant (4.24 and 4.21 pmol/L, respectively). There was a trend towards a difference in the change in PTH concentration between the two groups from Day 0 to Day 84 (0.74 pmol/L; 95% Confidence Interval (CI): -0.03 to 1.52 pmol; p = 0.059) (Figure 1, Table 2). There was no significant difference in the change in PTH concentration between the two groups at Day 0 to Day 14 or Day 42 (see Additional file 2).

The serum concentration of magnesium increased with the intake of the supplemented water compared to that of control water intake {0.022 mmol/L (95% CI: 0.003 to 0.041 mmol/L)} (Table 5, Additional file 5). The difference between the two groups in the change from Day 0 to Day 84 in the serum concentrations of magnesium was statistically significant (p = 0.027) (Figure 2, Table 5). When data from all time points were analysed using a repeated measures analysis of variance the difference between groups in the serum concentrations of magnesium remained statistically significant (p = 0.015). Serum potassium was also increased by Day 84 with the intake of supplemented water (p = 0.054) (Additional File 5).

Consumption of the supplemented water also significantly increased the urinary pH at 84 days (p = 0.0182) (Figure 3, Table 4). The venous pH remained unaltered (Additional file 4) over the study period. There were no other statistically significant differences in change from Day 0 to Day 84 comparing control and supplemented water groups in any of the other 24-hour urinary analytes (data not shown).

The present study did not show any effect of the consumption of spring water supplemented with magnesium and bicarbonate, as part of a daily routine including usual dietary habits, on clinically relevant bone parameters or cardiovascular indices over a period of 12 weeks.

The bicarbonate component was sufficient to change urinary pH values, statistically significantly by Day 84, as an indicator of acid base balance [21]. The blood bicarbonate as an indirect parameter was not different between the groups. Other studies of mineral waters containing bicarbonate at greater concentrations (approximately 1 - 2 g/L) than employed here (650 mg/L) have shown a decrease in bone resorption markers in young women [22, 23] and a lowering of markers of atherosclerosis in postmenopausal women [24, 25]. It is likely that the level of 650 mg/L bicarbonate in the present study was too low to elicit an effect on bone metabolic and cardiovascular parameters over a short period. In addition, the consumption of a high calcium mineral water has shown that bone modelling parameters were only affected when the study population had low dietary mineral intakes [26].

The present study showed that consumption of magnesium in alkaline aqueous formulation (magnesium bicarbonate supplemented spring water) provided a source of orally available magnesium as evidenced by the increase in serum magnesium concentrations over the 12 weeks of the study period. Other metabolic studies have shown that magnesium mineral waters with magnesium content (110 mg/L and 282 mg/L) similar to this study water of 120 mg/L could be easily absorbed and retained in healthy men and women [27, 28]. It has been suggested that absorption becomes impaired with increasing age [29], thus the magnesium bicarbonate supplemented spring water could provide a source of magnesium particularly in older women. However, since this study did not measure dietary magnesium intake or excreted magnesium, the absolute contribution of the magnesium from the supplemented spring water remains unknown.

It is acknowledged that other parameters measured in this study will be influenced by the composition of diet and energy loads. Accordingly the rise in serum potassium by Day 84 with the consumption of the supplemented water remains observational. Thus, despite the requested maintenance of usual dietary habits by all subjects in the study, the lack of dietary records in the study population is a limitation of this exploratory investigation.

In this present study, PTH concentrations remained stable over 12 weeks in the magnesium bicarbonate water group. This finding is consistent with other studies in normal subjects where intake of oral alkaline [28] and magnesium [30] loads do not alter PTH levels in the short term. It remains to be determined, if the trend to increase in PTH with the consumption of spring water alone becomes sufficient to potentiate the action of PTH on bone metabolism in a clinically meaningful way and if magnesium bicarbonate supplemented spring water has favourable effects on PTH concentrations and bone metabolism with longer-term consumption.

In summary, these results suggest that the consumption of magnesium rich bicarbonate spring water may provide a source of magnesium to contribute to total magnesium intake. Changes in urinary pH may, in the longer term, lead to improved acid base balance. Longer term studies, that include assessment of diet, urinary volume and mineral excretion, are required to determine the clinical relevance of these findings.

Short term consumption of magnesium bicarbonate supplemented spring water increased serum magnesium and urinary pH in postmenopausal women. There was no effect on bone metabolism or cardiovascular risk factors. Whether the former changes are of clinical relevance with respect to various processes, such as those associated with aging which have been linked to magnesium insufficiency and/or acidosis, remains to be determined by further research.