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
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magnesium: Mg RDA. Magnes. Res.2,
195-203.
2. Karpannen, H. (1981): Epidemiological studies on the
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4. Marier, J.R. (1991): Intakes of magnesium and fluoride, and
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5. Davignon, J., Gregg, R.E. & Sing, C.F. (1988):
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7. Clavel, C., Durlach, A., Durlach, V. & Birembaut, P
(1995): Rapid and safe determination of human apolipoprotein E
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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.
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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.
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19. Durlach, J. (1993): Present and future of magnesium
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20. Rayssiguier, Y., Gueux, E., Bussière, L., Durlach,
J. & Mazur, A. (1993): Dietary magnesium affects
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Am. Coll. Nutr. 12, 133-137.
21. Rayssiguier, Y., Durlach, J. & Mazur, A. (1993):
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23. Remsy, C., Manach, C., Texier. O. & Regerat, F.
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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.
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