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Clinical trial comparing daily consumption of water containing magnesium and bicarbonate ions to water without magnesium and bicarbonate ions

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Day RO, Liauw W, Tozer LMR, McElduff D, Beckett RJ, Williams KM

BMC Research Notes.  2010, 3:180

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Clinical trials listed

Internationally recognized clinical pharmacologist, toxicologist and rheumatologist Professor Richard Day, specialist oncologist Dr Winston Liauw, medical director Dr Lyn Tozer and medical statistician Dr Patrick McElduff have completed a clinical trial which certainly legitimates the call by physiologists for rigorous scientific proof of the claim that the daily consumption of extra water (eight glasses or 1.5 to 2 liters) is beneficial to health(1,2).  In the clinical trial, both soft water and hard water were consumed.  Soft water consisted of spring water devoid of electrolytes (minerals) and hard water consisted of spring water with added magnesium bicarbonate.  Multiple statistical analyses were performed on all results of interest to assist in the confirmation of results.

Each of the publications listed above emphasizes different aspects of the results of the clinical trial.

The investigators found that the daily consumption of approximately one to two liters of either soft water or hard water significantly increased the serum concentrations of sodium, potassium and magnesium. Increased hydration per se significantly increased serum electrolytes.   This finding is certainly counter intuitive but has positive health ramifications - particularly if the finding can be linked causally to decreased vasopressin levels in future studies. The authors did not measure serum concentrations of vasopressin (antidiuretic hormone, ADH). It is known that increased hydration blunts the secretion of vasopressin from the posterior pituitary gland. The absence of vasopressin results in solutes being reabsorbed from the kidney tubule system without the reabsorption of water from the collecting ducts (that is, results in water diuresis or 'aquaresis'). Vasopressin, as its name implies, is a potent vasopressor (vasoconstrictor). Vasopressin can cause significant vasoconstriction of coronary vessels and cerebral vessels. It also has effects on the release of coagulation factors by vascular endothelium and increases platelet aggregation.

Increased hydration per se significantly increased serum sodium, potassium and magnesium concentrations. Perhaps the simplest explanation is that body hydration increases intracellular hydration. The body prevents excess cell hydration and osmotic swelling by increasing the concentrations of sodium, potassium and magnesium in extracellular fluids (plasma, interstitial fluids).  At the end of the trial, serum sodium concentrations increased by nearly 1.0 per cent and serum potassium concentrations increased by 1.5 to 5.0 per cent.

In the clinical trial, the increase in serum potassium was greater with the consumption of hard water (magnesium bicarbonate). The increase in serum potassium was significant from Day 14 to the end of the trial at Day 84 (p < 0.04).  There have been numerous studies correlating either low dietary or low serum potassium with mortality in both heart failure patients and stroke patients(3,4,5).  Extracellular (interstitial) potassium concentrations are major determinants of the resting membrane potential across cell membranes.  The resting membrane potential is the basis for the action potential which is essential for optimal nerve and muscle function.  The higher the concentration of extracellular potassium, the lower the threshold for an action potential in brain, nerve and muscle cells.  This is particularly useful in maintaining function in older people.

Though serum potassium concentrations were not evaluated, a major review of epidemiological studies on drinking water concluded that a low intake of magnesium in drinking water increased the risk of dying from, and possibly developing, both cardiovascular disease and stroke.

Abstract in European Journal of Cardiovascular Prevention and Rehabilitation:

http://www.escardiocontent.org/periodicals/ejcpr/article/S1741-8267%2803%2913404-4/abstract

Following a meta-analysis of high quality case control studies, a statistically significant (p < 0.001) effect was found between low magnesium levels in drinking water and cardiovascular mortality.

Abstract in Journal of Water and Health:

http://www.ncbi.nlm.nih.gov/pubmed/18401109

A large case control study (17,133 and 17,133 controls) found a significant protective effect of moderate to high magnesium concentrations in drinking water on the risk of death from cerebrovascular disease (stroke).

Abstract in Stroke:

http://www.ncbi.nlm.nih.gov/pubmed/9472882

In the clinical trial, water with added magnesium bicarbonate was found to be a source of systemically available magnesium that significantly increased serum magnesium concentrations above the increase caused by increased hydration per se.

Are there other entities that increase in serum with consumption of sufficient water and increased hydration?  It was found in the clinical trial that consumption of soft water tended to steadily increase the serum concentration of parathyroid hormone.  This finding needs to be pursued further with both vigor and rigor. Increased hydration resulted in significantly increased secretion of parathyroid hormone in those women consuming soft water. In the women consuming hard water (magnesium bicarbonate), there was a statistically significant increase in serum magnesium which was sufficient to provide magnesium as an agonist ("calcimimetic") for the calcium-sensing receptors of the parathyroid glands.  As a consequence, parathyroid hormone concentrations did not increase in those women consuming magnesium bicarbonate. Recent medical research has shown that magnesium supplements decrease abnormal parathyroid hormone concentrations(6). The authors do not speculate how parathyroid hormone concentrations could increase with the consumption of soft water. It is well documented in the literature that parathyroid hormone secretion is very sensitive to plasma calcium concentrations. Theoretically, an increase in body hydration could decrease calcium ion concentrations sufficiently to depress calcium-sensing receptor activity and increase parathyroid hormone concentrations.

It is known that if parathyroid hormone is continuously elevated, even for a few hours, it initiates processes leading to the resorption of bone which overrides any anabolic effects in relation to bone formation(7).  Continuous elevation of parathyroid hormone, with consequent bone resorption, results in osteoporosis. Experimentally, exogenous parathyroid hormone is anabolic for bone when administered at a frequency that permits complete clearance between doses(8).  In chronic kidney disease, elevated serum parathyroid hormone levels occur which may be associated with vascular calcification, cardiovascular disease and mortality(9). Elevated parathyroid hormone increases pro-atherosclerotic lipid abnormalities such as increased VLDL cholesterol(10,11). It is known that the parathyroid hormone receptor is expressed extensively in various tissues including blood vessels and cartilage.  The receptor on cartilage cells (chondrocytes) is considered to play a role in the development of osteophytes in arthritis(12). The receptor on stem cells and smooth muscle cells in the walls of blood vessels may play a role in atherosclerosis and vascular calcification(13,14,15,16).

Several previous studies have identified that consumption of mineral waters containing magnesium and calcium (mainly) decrease the concentration of serum parathyroid hormone. With appropriate mineral water consumption, serum parathyroid hormone is decreased in a range of age groups - from acute decreases in young men to long term decreases in postmenpausal women.

Paper in The American Journal of Clinical Nutrition:

http://www.ajcn.org/content/71/4/999.full

Paper in Osteoporosis International:

http://www.springerlink.com/content/pd52c0g81bg33cwj/

Does the long term daily consumption of one to two liters of soft water, with consequent increases in parathyroid hormone concentration, contribute to the common chronic diseases of atherosclerosis, vascular calcification, osteoarthritis and osteoporosis?  Extrapolation of the parathyroid hormone result in the clinical trial indicates that serum parathyroid hormone concentrations may have exceeded upper normal levels (5 pmol/L) with a further six week consumption of soft water(17). A peak national medical body, the Australian Government National Health and Medical Research Council (NHMRC), states that the consumption of soft water may adversely affect mineral balance in the body(18).  Other health authorities make similar statements. As the authors note, water and electrolyte balance in the body are complex and further studies are warranted.  However, it appears that water can no longer be perceived as a passive player in life processes.  At the very least, in the interests of public health, it behooves the medical community to examine carefully the multitude of health claims made for water (and beverage?) consumption and to advise patients accordingly.

The authors state that the consumption of magnesium bicarbonate may be advocated potentially in various disease processes associated with aging. During normal human aging, progressive deficits in skin, kidney and intestinal function result in progressive inefficiency of vitamin D and calcium metabolism. This causes an increase in the secretion of parathyroid hormone from the parathyroid glands which frequently results in resorption of bone and osteoporosis(19). It is thought that parathyroid hormone, even within normal reference levels, may be associated with the development of atherosclerosis and cardiovascular disease in postmenopausal women(20). Elevated serum parathyroid levels, within normal reference levels, have been correlated to coronary heart disease over a wide range of ages in both sexes(21).

Abstract in The International Journal of Clinical Practice:

http://www.ncbi.nlm.nih.gov/pubmed/18657200

Abstract in European Journal of Cardiovascular Prevention and Rehabilitation:

http://www.ncbi.nlm.nih.gov/pubmed/15167209

Several moderately large prospective studies have identified high parathyroid hormone concentrations with either hypertension or cardiovascular mortality.

Abstract in Journal of Hypertension:

http://www.ncbi.nlm.nih.gov/pubmed/18551015

Abstract in Circulation:

http://www.ncbi.nlm.nih.gov/pubmed/19451355

Abstact in Clinical Endocrinology:

http://www.ncbi.nlm.nih.gov/pubmed/19250270

It may be appropriate for an aging population to consume water and beverages that contain magnesium bicarbonate in sufficient amounts to stabilize parathyroid hormone concentrations.

In the clinical trial, there was a significant increase in urine pH with the consumption of water containing magnesium bicarbonate. The significant increase in urine pH was an indicator of improved acid base balance. As the authors note, acidosis of the body increases with age and acidosis has been associated with diseases of aging. It has been identified previously that the consumption of water containing bicarbonate ions contributes to an alkali diet and decreases bone resorption biomarkers and parathyroid hormone concentrations.

Paper in The Journal of Nutrition:

http://jn.nutrition.org/content/138/2/435S.full

Abstract in Bone:

http://www.ncbi.nlm.nih.gov/pubmed/18926940

In the clinical trial, the consumption of water with added magnesium bicarbonate was found to significantly increase serum creatinine concentrations. In the absence of any biochemical indications of tissue pathology, this finding was interpreted by the authors to mean that the consumption of water with added magnesium caused an increase in the synthesis of creatine in the liver and kidneys or an increase in muscle mass or muscle energy stores (creatine phosphate). In other words, the consumption of water with added magnesium bicarbonate resulted in an increase in anabolic metabolism. It is known that aging results in an increase in catabolic metabolism and in a slow, continuous reduction in muscle mass and muscle strength.

In the clinical trial, water with added magnesium bicarbonate was a source of systemically available magnesium that increased serum magnesium concentrations.  The authors identify many diseases that have been associated with low magnesium status or low serum magnesium concentrations.  These diseases are the main causes of morbidity and mortality in Western societies and include Type 2 diabetes, hypertension, atherosclerosis, coronary heart disease, heart attack, stroke, the metabolic syndrome, osteoporosis and osteoarthritis.  Low magnesium status has also been associated with the development of cancer(22).  It is not known whether low magnesium is the cause or the result of these diseases(23).  Nevertheless, as the authors state, magnesium intake in the typical Western diet is below the Recommended Daily Allowance (RDA).  In the Women's Health Initiative Observational Study, a study involving 3,713 postmenopausal women, dietary magnesium intake was inversely associated with a range of biomarkers associated with inflammation and endothelial dysfunction.  High magnesium intakes were correlated significantly to low levels of interleukin 6 (p for linear trend<0.0001) and C-reactive protein (p for linear trend=0.003)(24).  Interleukin 6 is considered to be one of the main mediators of inflammation and strongly affects the inflammatory process involved in the development of atherosclerosis(14). C-reactive protein is an acute-phase reactant secreted by the liver and is an independent predictor of cardiovascular disease and Type 2 diabetes(24,25,26).

Paper in Diabetes Care:

http://care.diabetesjournals.org/content/33/2/304.full

In the clinical trial, water with added magnesium bicarbonate increased serum magnesium concentrations, stabilized parathyroid hormone concentrations and improved acid base balance.  The possible prevention, or adjunct treatment, of serious diseases by (the relatively cheap and simple) addition of magnesium bicarbonate to water or beverages needs urgent investigation.

1. Valtin H. 2002.  "Drink at least eight glasses of water a day."  Really? Is there scientific evidence for "8x8"?  Am J Physiol Regul Integr Comp Physiol 283: R993-R1004.

2. Negoianu D and Goldfarb S. 2008.  Just add water. J Am Soc Nephrol 19: 1-3.

3. Ahmed A, et al. 2007. A propensity-matched study of the association of low serum potassium levels and mortality in chronic heart failure. European Heart Journal 28: 1334-1343.

4. Khaw KT and Barrett-Connor E. 1987. Dietary potassium and stroke associated mortality. A 12-year prospective population study. New England Journal of Medicine 316(5): 235-240.

5. Green DM, et al. 2002.  Serum potassium level and dietary potassium intake as risk factors for stroke. Neurology 59: 314-320.

6. Turgut F, et al. 2008.  Magnesium supplementation helps to improve carotid intima media thickness in patients on hemodialysis. Int Urol Nephrol 40(4): 1075-1082.

7. Martin TJ, et al.  2006.  Mechanisms involved in skeletal anabolic therapies. Ann NY Acad Science 1068: 458-470.

8. Goltzman D. 2008. Studies on the mechanisms of the skeletal anabolic action of endogenous and exogenous parathyroid hormone. Arch Biochem Biophys 473(2): 218-224.

9. Kestenbaum B and Belozeroff V. 2007. Mineral metabolism disturbances in patients with chronic kidney disease. Eur J Clin Invest 37(8): 607-622.

10. Akmal M, et al. 1990. Excess parathyroid hormone adversely affects lipid metabolism in chronic renal failure. Kidney International 37: 854-858.

11. Hagstrom E, et al. 2002. Normalized dyslipidaemia after parathyroidectomy in mild primary hyperparathyroidism: population-based study over five years. Clinical Endocrinology 56(2): 253-260.

12. Huch K, et al. 2003. PTHrP, PTHr, and FGFR3 are involved in the process of endochondral ossification in human osteophytes. Histochem Cell Biol 119(4): 281-287.

13. Martin-Ventura JL, et al. 2008. LDL induces parathyroid hormone-related protein expression in vascular smooth muscle cells: Modulation by simvastatin. Atherosclerosis 198(2): 264-271.

14. Rashid G, et al. 2007. Parathyroid hormone stimulates endothelial expression of atherosclerotic parameters through protein kinase pathways. Am J Physiol Renal Physiol 292: F1215-F1218.

15. Martin-Ventura JL, et al. 2003. Possible role of parathyroid hormone-related protein as a proinflammatory cytokine in atherosclerosis. Stroke 34: 1783-1789.

16. Johnson RC, et al. 2006. Vascular calcification: pathobiological mechanisms and clinical implications. Circulation Research 99(10): 1044-1059.

17. Wallach J. 2000. Interpretation of Diagnostic Tests. Seventh Edition. Lippincott Williams & Wilkins, Philadelphia.

18. Australian Government, Australian Drinking Water Guidelines 6, 2004; NHMRC, 2003.

19. Basic & Clinical Endocrinology, Greenspan, FS and Gardner DG eds. Seventh Edition. 2004. McGraw-Hill, New York. Pg 338.

20. Choi HS, et al. 2008. Serum parathyroid hormone is associated with carotid intima-media thickness in postmenopausal women.  Int J Clin Pract 62(9): 1352-1357.

21. Kamycheva E, et al. 2004. Serum parathyroid hormone levels predict coronary heart disease: the Tromso Study. Eur J Cardiovasc Prev Rehabil 11(1): 69-74.

22. Larsson SC, et al. 2005.  Magnesium intake in relation to risk of colorectal cancer in women.  JAMA 293(1): 86-89.

23. Orchard TJ. 1999. Editorial: Magnesium and Type 2 Diabetes Mellitus. Arch Intern Med 159: 2119-2120.

24. Chacko SA, et al. 2010. Relations of dietary magnesium intake to biomarkers of inflammation and endothelial dysfunction in an ethnically diverse cohort of postmenopausal women. Diabetes Care 33(2): 304-310.

25. Danesh J, et al. 2000. Low grade inflammation and coronary heart disease:  prospective study and updated meta-analyses. BMJ 321: 199-204.

26. Ridker PM, et al. 2000. C reactive protein and other markers of inflammation . in the prediction of cardiovascular disease in women. N Engl J Med 342: 836-843.

Link to BioMed Central Research - Journal article:  BMC Research Notes 2010, 3:180

http://www.biomedcentral.com/1756-0500/3/180

Clinical trials listed

Link to PubMed: Abstract of publication in BioMed Central Research Notes, London

http://www.ncbi.nlm.nih.gov/pubmed/20579398