FEBRUARY 6, 2009
By Emilie Lamb , Research Assistant, PXE International
In January, Dr. Uitto´s group published an article about the effects of altered magnesium or phosphate diets on tissue mineralization in mice in which the ABCC6 gene has been ‘knocked out´ (KO). In other words, these mice have been engineered to be affected by PXE. In mammals, the amounts of minerals such as calcium, magnesium, and phosphate circulating in the blood and tissue are all connected and highly controlled. Calcium and phosphate are stored in the bones whereas magnesium travels throughout the body helping with over 300 different processes.
At this time, the exact way in which magnesium and calcium interact is not known. However, previous research has shown that high levels of magnesium in tissue can lead to a calcium overload and conversely low levels of magnesium can lead to a calcium deficiency. One possible explanation involves the channel in the cell wall that allows calcium to enter and leave the cell, controlling the level of calcium inside of a cell. High levels of magnesium can compete with the calcium and prevent it from entering the cell, leaving lots of calcium outside of the cell and in the bloodstream. However, if the levels of magnesium are low, then a large amount of calcium enters the cell causing the tissue to become calcified. It is also possible that magnesium and calcium interact with each other directly to form specific crystal structures and if magnesium is not present, the calcium forms a different type of crystal that gets deposited in the tissue.
Dr. Uitto´s experiments involved comparing a KO mouse to a Wild Type (WT) mouse, where the ABCC6 gene functions normally, with no mutations. This study placed 5 groups of both KO and WT mice, before mineralization had occurred in the KO mice, on 5 different diets: a control diet, a high phosphate diet, a low phosphate diet, a high magnesium diet, and a low magnesium diet.
The researchers followed each group of mice for 12 weeks to study the effects of the diets on the progression of tissue mineralization. The KO mice on the control diet showed the expected tissue calcification. Both KO mice fed the high and low phosphate diets showed no difference in the calcification when compared to the KO mice fed the control diet. However, the mineralization process in KO mice fed the high magnesium diet was completely prevented, and the levels of mineralization were essentially the same as the WT mice. The KO mice fed the low magnesium diet showed tissue calcification similar to that of the KO mice on the control diet. Dr. Uitto also studied the effect of adding magnesium to cultured tissue cells already calcified, and there was no change.
While this data shows that magnesium can prevent the calcification of tissue in mice, it also shows that magnesium does not have an effect on already calcified cultured mouse tissues. Once the calcification develops, high levels of magnesium cannot reverse it. The researchers also studied the effects of the diets on the rest of the body and did not find any significant changes, but they suggest long-term studies to look at the effects of a high magnesium diet over time. While this data is exciting, it is only a hypothesis and does not represent a medical treatment for PXE. The safety of magnesium supplementation to this degree, and whether magnesium supplementation would even have any beneficial effects in humans with PXE, is unknown. More studies are needed to confirm these findings and to study these effects in humans.
PXE International recommends that individuals affected by PXE follow the Recommended Dietary Allowance (RDA) for all vitamins and minerals. There is no scientific evidence to the contrary at this time.
Larusso J, Li Q, Jiang Q, Uitto J. Elevated Dietary Magnesium Prevents Connective Tissue Mineralization in a Mouse Model of Pseudoxanthoma Elasticum (Abcc6(-/-)) . J Invest Dermatol. Free article in PubMed . 2009 Jun;129(6):1388-94.
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