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COMMENTARY

Magnesium Research (1996) 9, 2, 139-141


Commentary on recent epidemiological and clinical advances

Antioxidant dietary status and genetic cardiovascular risk, or how an adequate intake of a-tocopherol, selenium, taurine, magnesium and various other natural antioxidants may overcome the deleterious metabolic consequences related to the E4-4 type of apolipoprotein E

Key words: Apolipoprotein E, atherosclerosis, hypercholesterolaemia, antioxidants, magnesium, selenium, taurine, vitamin E

Magnesium deficit may well rank among the various cardiovascular risk factors. Finland has exceptionally high rates of cardiovascular disease, the prevalence of which may be directly corrected with the frequent marginal magnesium deficit that occurs in developed countries1, where, as is the case in Finland, a particularly high dietary Ca/Mg ratio is observed (3.75 instead of a physiological ratio close to 2)2-4.

Since atherosclerosis is now considered to be multifactorial, the importance of magnesium deficit among other dietary factors involved in the pathophysiology of cardiovascular diseases should be acknowledged.

Atherosclerosis is induced by the combined effects of genetic and environmental factors. Among the genetic variants that occur in lipoprotein disorders, apolipoprotein E polymorphism appears to have very important effects5,6. Early investigations of the apolipoprotein E phenotypes were time-consuming and unsatisfactory. However, a rapid, reliable and safe procedure is now available whereby apolipoprotein E genotypes can be investigated as a routine procedure7. Among genetic cardiovascular risk factors, subjects with the ApoE 4 allele and especially the homozygous apo E4-4 type type seem particularly prone to atherosclerosis5,8. The apo E 4 allele has an amino acid substitution at codon 112 that adds arginine in place of cysteine, and this region appears to reduce disulphide bonding of apoE with other free sulphydryl-containing proteins. Consequently a cascade of deleterious effects on lipoprotein metabolism results in hepatic cholesterol accumulation and raised concentrations of serum cholesterol9. Subjects with the apo E 4 allele are a diet-insensitive group, showing little response either to classical dietary intervention (lowered total fat intake, increased polyunsaturated/saturated fat ratio, and moderate decrease in cholesterol intake10,11, or to an increase in dietary fibre12,13. Subjects with apo E allele form a group with a genetic cardiovascular risk factor of the familial hypercholesterolaemia type5-13.

In northern Finland the frequency of the E4-4 type is higher in the Sami area, formerly known as the Lapp area (12 per cent), than in the rest of the country (3 per cent). The same is observed in Norway. But paradoxically in the Samis the E4-4 genotype together with a high serum cholesterol are associated with a lower occurrence of coronary heart disease mortality than in other communities in Finland or Norway14. The low mortality from coronary heart disease, in a population with genetic hypercholesterolaemia, could be explained by an adequate antioxidant status. The Samis of northern Finland have a higher α-tocopherol, albumin and selenium than Finns from neighbouring communities14. It seems that antioxidants occupy a prominent place in the prevention of human atherosclerosis15,16. This favourable antioxidant status may be credited to the local diet. Reindeer meat is lean, rich in protein and essential fatty acids, α-tocopherol and selenium. The same holds true for fish which provide a particularly high selenium intake14. This diet may also contain several other natural antioxidants such as taurine and magnesium, the importance of which needs to be assessed.

Taurine, a ubiquitous and stable sulphonic amino acid, constitutes an example of a water-soluble molecular antioxidant which may play an important role in cardiovascular protection15,17,18.

Magnesium may also play a physiological antioxidant role when it compensates a deficient intake, for example against lipoprotein oxidative stress16,17,19-21. In Greenland Eskimos, the serum calcium to magnesium ratio is significantly lower than in Danes, and death from ischaemic heart disease is 3-6 times lower than in Denmark. These high levels of serum calcium -- which might be cardioprotective in Eskimos -- could originate from the Ca/Mg ratios in their respective diets (2.0 in Greenland and 4.5 in Denmark)22.

To sum up, when a genetic risk factor linked with the Apo E 4-4 genotype is involved in hypercholesterolaemia, its harmful effects can be counteracted by nutritional means. The low cardiovascular mortality observed in the Lapp group does not seem to be connected with the type of dietary fats they consume, since lowering the total fat and cholesterol intake and increasing the polyunsaturated/saturated fat ratio is ineffective10,11. It seems, rather, to be related to a rich natural antioxidant intake14. Since we can hardly found our staple diet on reindeer meat and a daily fish catch, we may at least try to prevent such dyslipidaemias not only by a larger intake of vitamin E, selenium, taurine and magnesium14-17,19-21 but also with numerous other natural vitamin, metabolic and mineral antioxidants15,16,23,24 that are equally important in nutritional prophylaxis of atherosclerosis.

Jean Durlach
Editor-in-Chief, Magnesium Research
President SDRM
Hôp. St. Vincent-de-Paul, Paris, France

Anne Durlach
Unité de Biologie Cellulaire
Hôp. Maison Blanche, Reims, France

Vincent Durlach
Clinique Médicale
Hôp. Robert Debré, Reims, France


References

1. Durlach, J. (1989): Recommended dietary amounts of magnesium: Mg RDA. Magnes. Res.2, 195-203.

2. Karpannen, H. (1981): Epidemiological studies on the relationship between magnesium intake and cardiovascular diseases. Artery 9, 190-199.

3. Luoma, H. (1989): Risk of myocardial infarction in relation to magnesium and calcium in drinking water, with some aspects on the magnesium vs. fluoride interactions. In: Magnesium in health and disease, eds. Y. Itokawa and J. Durlach, pp. 183-190. London: John Libbey

4. Marier, J.R. (1991): Intakes of magnesium and fluoride, and some systemic effects. Proc. Finn. Dent. Soc. 87, 581-594.

5. Davignon, J., Gregg, R.E. & Sing, C.F. (1988): Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 8, 1-21.

6. Rall, S.S. & Mahley, R.W. (1992): The role of apolipoprotein E genetic variants in lipoprotein disorders. J. Intern. Med. 231, 653-659.

7. Clavel, C., Durlach, A., Durlach, V. & Birembaut, P (1995): Rapid and safe determination of human apolipoprotein E genotypes by miniaturised SDS-PAGE in noninsulin dependent diabetes mellitus. J. Clin. Pathol. 48, 295-299.

8. Lehtimaki, T., Moilanen, T., Solakivi, T., Laipalla, P. & Ehnholm, C. (1992): Cholesterol-rich diet induced changes in plasma lipids in relation to apolipoprotein E phenotype in healthy students. Ann. Med. 24, 61-66.

9. Boerwinkle, E., Brown, S.A., Rohrbach, K. & Gotto, A.M. (1991): Role of apolipoprotein E and B gene variation in determining response of lipid, lipoprotein and apolipoprotein levels to increase dietary cholesterol. Am. J. Hum. Gen. 49, 1145-1154.

10. Clifton, P.M., Kestin, M., Abbey, M., Drysdale, M. & Nestel, P.J. (1990): Relationship between sensitivity to dietary fat and dietary cholesterol. Arteriosclerosis 10, 394-401.

11. Marshall, J.A., Kamboh, M.I., Bessesen, D.H., Hoag, S., Hamman, R.P. & Ferrel, R.E. (1996): Associations between dietary factors and serum lipids by apolipoprotein E polymorphism. Am. J. Clin. Nutr. 63, 87-95.

12. Jenkins, D.J.A., Hegele, R.A. & Jenkins, A.L. (1993): The apolipoprotein E gene and the serum low-density lipoproteins cholesterol response to dietary fiber. Metabolism 42, 585-593. (cited in 11).

13. Uusitupa, M.I.J., Ruuskanen, E. & Makinen, E. (1992): A controlled study on the effect of beta-glucan-rich oat bran on serum lipids in hypercholesterolemic subjects: relation to apolipoprotein E phenotype. J.Am. Coll. Nutr. 11, 651-659. (cited in 11).

14. Luoma, P.V., Naha, S., Sikkila, K. & Hassi, J. (1995): High serum α-tocopherol, albumin, selenium and cholesterol and low mortality from coronary heart disease in northern Finland. J. Intern. Med. 237, 49-54.

15. Lecerf, J.M., Luc, G. & Fruchart, J.C. (1996): Antioxidants et athérosclérose. Med. Nutr. 32, 8-16.

16. Steinburg, D. (1992): Workshop participants. Antioxidants in the prevention of human atherosclerosis. Circulation 85, 2338-2334.

17. Durlach, J., Durlach, V., Bac, P., Rayssiguier, Y., Bara, M. & Guiet-Bara, A. (1993): Magnesium and aging. II. Clinical data: aetiological mechanisms and physiopathological consequences of magnesium deficit in the elderly. Magnes. Res. 6, 379-394.

18. Suleiman, M.S. (1994): New concepts in the cardioprotective action of magnesium and taurine during the calcium paradox and ischaemia of the heart. Magnes. Res. 7, 295-312.

19. Durlach, J. (1993): Present and future of magnesium research. J. Jpn. Soc. Magnes. Res. 12, 113-135.

20. Rayssiguier, Y., Gueux, E., Bussière, L., Durlach, J. & Mazur, A. (1993): Dietary magnesium affects susceptibility of lipoproteins and tisue to peroxydation. J. Am. Coll. Nutr. 12, 133-137.

21. Rayssiguier, Y., Durlach, J. & Mazur, A. (1993): Magnesium and ageing. I. Experimental data: importance of oxidative damage. Magnes. Res. 12, 369-378.

22. Jeppesen, B.B. (1987): Greenland, a soft-water area with a low incidence of ischemic heart death. Magnesium 6, 307-313.

23. Remsy, C., Manach, C., Texier. O. & Regerat, F. (1996): Intérêt nutritionnel des flavonoïdes. Med. Nutr. 32, 17-27.

24. Wiseman, H. (1996): Dietary influences on membrane function: importance in protection against oxidative damage and disease. J. Nutr. Biochem. 7, 2-15.

Address for correspondence: Dr. Jean Durlach Prf SDRM, Editor-in-Chief, Magnesium Research, 64 rue de Lonfchamp, F-92200 Neuilly/Seine, France. Tel: +33(1) 40-88-38-69; Fax: 33(1) 40-88-36-13.


All articles by Dr. Durlach are copyrighted, and permission is granted to Web users only to make single hard copies for personal use. Additional reprints should be obtained from the originating journals. Excerpts may be used by the media with attribution to Dr. Durlach.


This page was first uploaded to The Magnesium Web Site on August 11, 1997



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