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Atherosclerosis unequivocally contributes to more mortality - approximately half or more of all deaths - and more serious morbidity in the Western world than any other disorder(1). Dr Turgut and associates have successfully tested the hypothesis that magnesium supplementation may help to improve atherosclerosis in dialysis patients. By definition, dialysis patients have limited kidney function and aberrant hydration control. To the best of the authors' knowledge, the clinical trial was the first prospective clinical trial to explore the effect of magnesium consumption on atherosclerosis.  However, an assumption has been made that atherosclerotic changes in the carotid artery mirror pathologic events of generalized atherosclerosis.  There is mounting scientific and medical evidence supporting this assumption.

In the clinical trial, magnesium supplementation at a rate of 98 mg magnesium every second day significantly increased serum magnesium levels and significantly decreased serum parathyroid hormone levels.  In addition, carotid artery intima media thickness due to atherosclerosis was significantly decreased.  The authors consider that atherosclerotic changes in the carotid arteries may reflect atherosclerosis of the coronary arteries - as described elsewhere(2).  Atherosclerosis of coronary arteries is the leading cause of death (ischemic heart disease, myocardial infarction or heart attack) in Western societies.  Atherosclerosis of cerebral arteries is the second most common cause of death (cerebral infarction or stroke). There is evidence now that Alzheimer's disease has risk factors similar to cardiovascular diseases including the presence of atherosclerosis, insulin resistance and diabetes(3,4).

The authors found that magnesium consumption decreased serum parathyroid hormone levels.  Constant elevated levels of parathyroid hormone or its fragments over stimulate parathyroid hormone receptors on the surface of body cells.  It is considered that the parathyroid hormone receptors on stem cells and smooth muscle cells in the walls of blood vessels may play a role in atherosclerosis and vascular calcification(5,6,7,8).  In atherosclerosis, calcifications occur in the intima and media of blood vessels supplying the heart, brain, kidneys, lower extremities and small intestine.  Myocardial infarction (heart attack) cerebral infarction (stroke) and aortic aneurysms are the major consequences of this disease.  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(9).  Elevated serum parathyroid levels, within normal reference levels, have been correlated to coronary heart disease over a wide range of ages in both sexes(10). In addition, it has been found that a high magnesium intake in postmenopausal women is associated with lower concentrations of biomarkers of inflammation and endothelial dysfunction, particularly lower concentrations of C-reactive protein and interleukin 6(11).

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

Paper in Diabetes Care:

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

It is known that magnesium acts as an agonist to the calcium-sensing receptors of the parathyroid glands(12,13). Calcium-sensing receptors are crucial to the regulation of calcium metabolism. Polymorphism of the calcium-sensing receptor gene has been associated with increased concentrations of parathyroid hormone, osteoporosis, coronary heart disease and myocardial infarction(14). It is known that calcimimetics can decrease serum parathyroid hormone concentrations by activation of calcium-sensing receptors(15). It appears from the clinical trial conducted by Dr Turgut and associates that magnesium may be regarded now as a calcium agonist or "calcimimetic" to decrease parathyroid hormone concentrations and to decrease atherosclerotic lesions.

In the past decade, the calcium-sensing receptor has been identified in a range of cells, tissues and organs. In the brain, the calcium-sensing receptor appears to participate in the central control of systemic water and electrolyte balance(16). In monocytes and macrophages, the calcium-sensing receptor appears to modulate the immune response(17). Increased expression of the calcium-sensing receptor during inflammation may indicate a role in vascular inflammation and atherosclerosis(18).  Could bioavailable magnesium supplements function as calcium agonists or antagonists in these situations to produce beneficial outcomes?

The authors make clear that magnesium supplementation may improve atherosclerotic lesions.  As stated in another editorial on this website, the possible prevention or adjunct treatment of serious diseases by the consumption of bioavailable magnesium needs further investigation.  In particular, because magnesium homeostasis relies on the complexities of proper kidney function, the consumption of bioavailable magnesium coupled with optimal water intake and optimal body hydration to prevent or treat serious diseases needs urgent investigation.

1. Robbins Pathologic Basis of Disease. Cotran RS, Kumar V and Collins T eds. Sixth Edition. 1999. WB Saunders Company, Philadelphia. Pgs 498-504.

2. Fabbian F, et al. 2007. The relationship between carotid and coronary atherosclerotic damage in dialysis patients. Int J Artif Organs 30(4): 315-320.

3. Casserly I and Topol EJ.  2004. Convergence of atherosclerosis and Alzheimer's disease: inflammation, cholesterol, and misfolded proteins. The Lancet 363(9415): 1139-1146.

4. Alzheimer's Disease International.  World Alzheimer Report 2009. Prince M and Jackson J, eds. Pg 17.

5. 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.

6. 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.

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

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

9. 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.

10. 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.

11. 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.

12. Ruat M, et al. 1996. Cloned and expressed rat calcium-sensing receptor. J Biol Chem 271(11): 5972-5975.

13. Riccardi D. 2002. Cell surface, ion-sensing receptors. Exp Physiol 87(4): 403-411.

14. Marz W, et al. 2007. Alanine to serine polymorphism at position 986 of the calcium-sensing receptor associated with coronary heart disease, myocardial infarction, all-cause, and cardiovascular mortality. J Clin Endocrinol Metab 92(6): 2363-2369.

15. Ivanovski O, et al. 2009. The calcimimetic R-568 retards uremia-enhanced vascular calcification and atherosclerosis in apolipoprotein E deficient (apoE-/-) mice. Atherosclerosis 205(1): 55-62.

16. Yano S, et al. 2004. Calcium-sensing receptor in the brain. Cell Calcium 35(3): 257-264.

17. Olszak IT, et al. 2000. Extracellular calcium elicits a chemokinetic response from monocytes in vitro and vivo. J Clin Invest 105: 1299-1305.

18. Molostvov G, et al. 2009. Expression and role of the calcium-sensing receptor in the blood vessel wall. Curr Pharm Biotechnol 10(3): 282-288.

Comments from the Water Clinical Trials editors

Link to PubMed- Abstract of publication in International Urology and Nephrology

http://www.ncbi.nlm.nih.gov/pubmed/ 18568412

Link to Int Urol Nephrol - Journal article:  2008, 40(4): 1075-82

http://www.springerlink.com/content/ q57575kw57116g31/fulltext.pdf

Links to

publication

Clinical trials listed

Clinical trial comparing magnesium supplementation to non-supplementation in dialysis patients

Turgut F, Kanbay M, Metin MR, Uz E, Akcay A, Covic A.

Int Urol Nephrol. 2008; 40(4):1075-82

Clinical trials listed