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Journal of the American College of Nutrition, Vol. 19, No. 3, 374-382 (2000)
Published by the American College of Nutrition

Original Research

Magnesium Status and Parameters of the Oxidant-Antioxidant Balance in Patients with Chronic Fatigue: Effects of Supplementation with Magnesium

Begoña Manuel y Keenoy, MD, PhD, Greta Moorkens, MD, Jan Vertommen, Mia Noe, Jean Nève, PhD and Ivo De Leeuw, MD, PhD, FACN,

Laboratory of Endocrinology, University of Antwerp (B.M.K., J.V., I.D.L.), Antwerp, BELGIUM
Department of Internal Medicine, University Hospital (G.M., M.N., I.D.L.), Antwerp, BELGIUM
Institute of Pharmacy, Free University of Brussels (J.N.), BELGIUM

Address reprint requests to: B. Manuel y Keenoy, University of Antwerp (UA), Laboratory of Endocrinology, Universiteitsplein 1, B-2610 Wilrijk-Antwerp, BELGIUM.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Objective: Magnesium deficiency and oxidative stress have both been identified as pathogenic factors in aging and in several age-related diseases. The link between these two factors is unclear in humans although, in experimental animals, severe Mg deficiency has been shown to lead to increased oxidative stress.

Methods: The relationship between Mg body stores, dietary intakes and supplements on the one hand and parameters of the oxidant-antioxidant balance on the other was investigated in human subjects.

Results: The study population consisted of 93 patients with unexplained chronic fatigue (median age 38 years, 25% male, 16% smokers and 54% with Chronic Fatigue Syndrome (CFS). Mg deficient patients (47%) had lower total antioxidant capacity in plasma (p=0.007) which was related to serum albumin. Mg deficient patients whose Mg body stores did not improve after oral supplementation with Mg (10 mg/kg/day) had persistently lower blood glutathione levels (p=0.003). In vitro production of thiobarbituric acid reactive substances (TBARS) by non-HDL lipoproteins incubated with copper was related to serum cholesterol (p<0.001) but not to Mg or antioxidants and did not improve after Mg supplementation. In contrast, velocity of formation of fluorescent products of peroxidation (slope) correlated with serum vitamin E (p<0.001), which was, in turn, related to Mg dietary intakes. Both slope and serum vitamin E improved after Mg supplementation (p<0.001).

Conclusions: These results show that the lower antioxidant capacity found in moderate Mg deficiency was not due to a deficit in Mg dietary intakes and was not accompanied by increased lipid susceptibility to in vitro peroxidation. Nevertheless, Mg supplementation was followed by an improvement in Mg body stores, in serum vitamin E and its interrelated stage of lipid peroxidation.

Key words: magnesium, chronic fatigue, antioxidant capacity, lipid peroxidation


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Magnesium deficiency has been associated with a wide variety of clinical conditions such as atherosclerosis, cardiovascular disorders and diabetes mellitus [1–5]. One of the major pathogenic factors also associated with these diseases and with the closely related process of aging is increased oxidative stress [6–10]. However, it is not clear whether there is a direct causal link between Mg deficiency, oxidative stress and the resulting disease process or whether the Mg deficiency and the increased oxidative stress observed in these conditions are parallel but unrelated phenomena. Several lines of evidence suggest such a relationship. For example, increased susceptibility to oxidative stress has been shown in cell cultures [11] and in experimental animals with extreme Mg deficiency [12]. Moreover, Mg supplementation has been beneficial in a wide variety of conditions, such as neuropsychiatric disorders, ischemic heart disease and cardiac arrhythmias, asthma, diabetes and chronic fatigue, in which Mg deficiency has not always been substantiated [13,14]. The physiopathological processes linking Mg status and these pathologies are not totally known. It is also not clear whether the beneficial effects of Mg supplementation are due to the replenishment of possibly depleted body stores or whether these effects are pharmacological. For example, the effect of Mg supplements on energy metabolism is independent of the state of Mg body stores [15].

In order to address these questions, the relationship between Mg status and some parameters of the oxidant-antioxidant balance was investigated in a group of human subjects before and after receiving Mg supplements. In order to include a sufficient number of subjects with Mg deficiency, a population of patients suffering from chronic fatigue was selected. Chronic fatigue is a heterogeneous syndrome with no clear cut causality and no consistent pathognomonic markers [16,17]. In the more well-defined subgroup of these patients, diagnosed as having Chronic Fatigue Syndrome (CFS) [18], the involvement of Mg in the pathogenesis remains controversial [14,19,20,21]. However, in patients with chronic fatigue in general and with CFS in particular, Mg supplementation has been empirically shown to be beneficial [14,22]. It was therefore assumed that a higher proportion of Mg deficient patients would be found among chronic fatigue patients than among other groups. Moreover, and in contrast with other pathologies such as atherosclerosis and diabetes, these patients do not suffer from dyslipidemias, hyperglycaemia and cell damage. It is well-known that these factors contribute to the accumulation of oxidative damage and thus they might distort the relationship between Mg and the oxidant-antioxidant balance. Nevertheless, it should be kept in mind that chronic fatigue, with its unknown etiology and pathogenesis, might in itself also contribute other, so far unknown, distorting factors.

By monitoring Mg status and dietary intakes as well as several antioxidant parameters before and after Mg supplementation, we aimed to investigate whether moderate Mg deficiency is directly related to increased oxidative stress. We also aimed to analyse the separate roles played by the Mg dietary intakes, by supplements and by levels of Mg in blood and in body stores.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
I. Study Population and Design
Ninety-three consecutive patients (25% male, 16% smokers, ages ranging from 14 to 73 years, median 38 years), who were referred to the outpatient clinic of Internal Medicine at the Antwerp University Hospital with a complaint of chronic fatigue lasting for at least one month, were enrolled in the study after written consent. Patients with diagnosis of any known medical condition and with psychiatric disorders were excluded, as well as patients taking drugs interfering with Mg status such as diuretics, antihypertensives and the like. As 37% of the patients were taking vitamin supplements once in a while this factor was taken into account during the statistical analysis. Apart from the routine clinical examination and blood tests, patients were examined for the presence of the following conditions.

Magnesium deficiency (deficiency in body stores) was evaluated with an intravenous Mg retention test according to the guidelines of Ryzen [23,24]. In short, 0.2 mEq of Mg per kg of body weight were infused in 5% glucose for four hours. Mg was measured in the urine preceding the infusion (preinfusion urine) and during the 24 hours starting with the infusion (postinfusion urine). Mg retention was calculated from the difference between these two urinary excretions of Mg and expressed as a percentage of the total elemental Mg infused during the test. The following formula was used:

where,

Patients with 20% or more Mg retention were diagnosed as moderately Mg deficient and those with 50% or more as severely deficient.

Chronic fatigue syndrome (CFS) was diagnosed according to the CDC criteria [18,25].

In the course of their first retention test, 64 patients were submitted to an extensive dietary anamnesis using the "dietary history method" in which consumption during the week and during the weekend were separated and confirmed by the "cross-check method" [26]. The questionnaire was expanded to include specific intakes of Mg-containing foodstuffs and mineral waters. Quantitative analysis of energy and nutrient consumption was done using the Nevo 93-BECEL program [27] based on values obtained from the Netherlands and the Belgian food tables (NUBEL 95) [28].

Patients with a retention of 20% or more of the Mg infused were diagnosed to be Mg deficient and were asked to take part in a study to investigate the effect of Mg supplementation at nutritional doses (aiming at daily intakes of 10 mg of Mg/kg body weight) for a period of at least three months in order to ensure slow replenishment of Mg body stores. Of the first 34 patients diagnosed as being Mg deficient and accepting Mg supplementation, 24 returned for a second intravenous Mg retention test and the parameters measured in the first visit were remeasured.

II. Analytical Methods
Magnesium concentrations in plasma, RBC and urine and copper, selenium and zinc concentrations in serum were measured by atomic absorption spectrophotometry (Varian Spectra-100 AAS and Perkin Elmer 23030). Routine blood tests (blood count, urea nitrogen, creatinine, uric acid, glucose, liver enzymes, protein, albumin, total and HDL cholesterol, triglycerides, sodium, potassium, calcium, paratohormone and alkaline phosphatase) were analysed in the routine laboratory of the clinic. Oxidant-antioxidant balance was evaluated by measuring total antioxidant capacity of plasma, concentrations of individual antioxidants and susceptibility of lipoproteins to oxidative attack in vitro (susceptibility to in vitro peroxidation). Total antioxidative capacity of plasma was measured using the TEAC (Trolox Equivalents Antioxidant Capacity) method developed by Miller et al. [29] in which the formation of the coloured ABTS radical (ABTS+•) due to the oxidation by ferrylmyoglobin and hydrogen peroxide is followed spectrophotometrically. The degree of inhibition is calibrated with different concentrations of the water soluble vitamin E analogue Trolox. TEAC in fresh plasma obtained from blood anticoagulated with heparin was measured using a kit (Randox laboratories Ltd, Crumlin, UK). The assay was adapted by measuring absorbance at 734 nm and by distinguishing between three types of inhibitory effects: prolongation of the lagtime (TEAC LT); inhibition of the formation of ABTS+• after three minutes (TEAC 3) and after six minutes of reaction (TEAC 6). TEAC LT values for plasma did not correlate with TEAC 3 (r=-0.10, p=0.30) nor with TEAC 6 (r=-0.16, p=0.20), whereas TEAC 3 and TEAC 6 correlated with each other (r=0.83, p<0.001, n=29), suggesting that TEAC LT is measuring the effect of some individual plasma antioxidants which are different from those having an effect on TEAC 3 and TEAC 6. Transferrin and ceruloplasmin in serum were measured by nephelometry (Behring diagnostics). Vitamins E and A in serum were measured by HPLC (Shimadzu, Bio-Rad reverse phase C18 with 100% methanol mobile phase) and detection at 292 and 325 nm respectively. Glutathione (GSH) in blood was measured using the colorimetric method according to Beutler [30]. Glutathione peroxidase activity in hemolysate was measured with a commercial kit (Randox laboratories Ltd, Crumlin, UK). The susceptibility of low density (LDL) and very low density lipoproteins (VLDL) to copper catalysed oxidation was measured by isolating these two groups of lipoproteins (non-HDL) by dextran sulphate/MgCl2 precipitation. As confirmed by electrophoresis, the LDL and VLDL fraction was free of albumin and globulins and of the alpha band. A suspension of this fraction, containing 200 µg/ml of cholesterol, was incubated with 46 µM CuSO4 for up to 180 minutes at 37°C, during which aliquots were taken every 30 minutes for the measurement of thiobarbituric reactive substances (TBARS). Fluorescence at 360 nm excitation and 430 nm emission was monitored continuously. Three phases were measured: the lagtime, during which fluorescence does not increase significantly and which indicates the capacity of the lipoprotein antioxidants to prevent initiation of oxidation; the slope of the propagation phase, during which fluorescence increases rapidly and which indicates the velocity of oxidative changes in the apo B and the saturation phase during which fluorescence reaches a plateau and which denotes the total amount of lipid oxidised [31]. Lipid hydroperoxides in plasma were measured spectrophotometrically using the xylenol orange method [32].

III. Statistical Methods
Data were analysed using SPSS/PC software. Differences between groups were assessed by Student’s t test and the Mann-Whitney test (for non-normally distributed data) and the paired comparisons on the effect of Mg supplementation were done using the Wilcoxon test. The relationship between the various parameters was assessed by correlation, stepwise multiple regression and analysis of covariance. Data were expressed as mean ±SD or as median (range) where appropriate and two-tailed p-values<0.05 (or adjusted for multiple comparisons according to Bonferroni) were considered statistically significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 CONCLUSION
 REFERENCES
 
This study population was middle-aged and did not suffer from any major illness. 54% of these patients were diagnosed as having CFS according to the CDC criteria. Eating habits and routine blood biochemistry values were within the ranges found in non-hospitalised subjects. The concentrations of Mg measured in plasma (with only three cases having <0.6 mmol/L) and in erythrocytes (Table 1) indicate that this group can be considered as normomagnesemic. The frequency distribution of % Mg retention after the intravenous test, which was taken in this project as a reliable parameter to measure body Mg stores, was Gaussian, with a median retention of 19% (range -40% to 88%). When 20% retention was taken as the cut-off value to diagnose a deficiency in body Mg stores, 47% of the cases were classified as being Mg deficient.


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  		Table 1. Parameters of Oxidant-Antioxidant Balance in Patients with or without Mg Deficiency

 
As summarised in Table 1, patients with Mg deficiency had significantly lower TEAC 3, TEAC 6 and serum albumin concentrations. Moreover, TEAC 3 and 6 values related positively to Mg status and serum albumin, whereas the other total antioxidant component, TEAC LT, was predominantly related to serum uric acid concentrations (Table 2). Lipid profiles and susceptibility to in vitro peroxidation were not significantly different in the Mg deficient group and did not relate significantly to % Mg retention. Patients with higher Mg in erythrocytes had higher total cholesterol in serum (r=0.31, p=0.005) and total cholesterol was the parameter most strongly determinant of lipid susceptibility to in vitro peroxidation since its variance explained 15% to 22% of the variance of TBARS production after 90–180 minutes of incubation with copper and also of the variance in the lagtime of fluorescence (r=-0.45, p<0.001). In contrast, the slope of fluorescence formation correlated positively with Mg concentration in plasma (r=0.44, p<0.001) and negatively with serum vitamin E (r=-0.46, p<0.001).


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  		Table 2. Relationship between the Two Components of Total Antioxidant Capacity in Plasma (TEAC LT and TEAC 6) and Mg Status, Albumin and Uric Acid

 
The acute effect of intravenous Mg was investigated by measuring parameters before and after the retention test. Although plasma Mg increased from 0.82±0.09 to 1.03±0.11 mmol/L (p<0.0001), erythrocyte Mg, TEAC parameters and concentrations of lipid hydroperoxides were not significantly affected. Intravenous Mg did not affect TBARS formation after 0–120 minutes of incubation with copper (initiation and early propagation step) or the lagtime and slope of fluorescence. In contrast TBARS formation was significantly increased after 150 and 180 minutes of incubation with copper (the saturation phase): 88±15 versus 83±14 nmol MDA equivalents/mg of non-HDL cholesterol after 180 minutes, p=0.008 (Fig. 1).



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  		Fig. 1. Production of TBARS in non-HDL lipoproteins incubated with copper before (closed circles, interrupted line) and after (closed triangles, closed line) intravenous Mg given during the retention test. Values shown are mean±SEM, n=22; *p=0.01, **p=0.008 in the paired comparison before versus after the Mg infusion. Note the lack of effect of Mg on the lagphase and the significant increase of lipid peroxidation in the saturation phase.

 
Dietary intakes of Mg and other foodstuffs (Table 3) were within the acceptable ranges in the study group and did not differ significantly in the Mg deficient group. The proportion of patients with Mg deficiency tended to be lower in the group taking sporadic vitamin supplements (39% vs. 63% of the non-vitamin supplement takers, ns). Mg stores and blood concentrations were not related to dietary Mg intakes [33]. Males had significantly higher intakes of Mg (when expressed as total Mg/day). However, intakes of calories, carbohydrates, alcohol, all types of fats as well as iron were also significantly higher, so that when Mg intakes were corrected for these factors, Mg intake in males was not significantly higher and even lower when expressed as Mg/mg cholesterol (Table 3).


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  		Table 3. Dietary Intakes according to Gender

 
When the relationship between Mg intake (corrected for body weight) and the different blood antioxidant concentrations was examined, significant correlations were found only with serum vitamin E, uric acid and transferrin. This relationship was influenced by gender (Table 4) and by other dietary intakes; for example, the variance in fiber intake explained 37% of the variance in Mg intake and 12% of the variance in serum vitamin E. Mg intake was also positively related to HDL-cholesterol concentrations (r=0.31, p=0.017) and negatively to serum triglycerides (r=-0.27, p=0.04).


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  		Table 4. Relationship between Dietary Mg Intake and Serum Antioxidants according to Gender

 
In the group of 24 Mg deficient patients who received oral Mg supplementation for three months or more, the retention decreased from a median of 46% (range 21% to 88%) to 17% (range -79% to 95%) (n=24, p=0.002). Blood Mg concentrations or fluctuations in Mg concentrations during the intravenous test were not significantly different after supplementation [33]. Eleven patients ("the non-responders") maintained a Mg retention of 20% or more despite supplementation. The same parameters of antioxidative capacity, lipid profiles and susceptibility to peroxidation were remeasured after supplementation. The only parameters of antioxidant status which were significantly affected were the serum vitamin E (from 8.5±3.4 to 13.2±5.4 µg/mL, p<0.001) and transferrin (from 274±52 to 250±54 mg/dL, p=0.032) as well as the slope of fluorescence production (from 0.97±0.23 to 0.84±0.25, p=0.026) (Fig. 2). Lipid profiles, lipid hydroperoxides, TBARS production and lagtime of fluorescence remained remarkably stable after Mg supplements. In vitro TBARS production and serum iron even tended to increase after supplementation (ns, data not shown). The only parameter which distinguished non-responders was GSH concentration, which was significantly lower both before (5.9±0.8 vs. 6.9±1.1 µmol/g Hb, p=0.02) and after supplementation (5.9±0.6 vs. 6.9±0.8, p=0.003) (Fig. 2).



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  		Fig. 2. Error barplots showing the effect of oral Mg supplementation in Mg deficient patients. Values shown are mean and 95% CI before (visit 1) and after (visit 2) supplementation. Closed squares and interrupted line denote patients not improving Mg stores after supplementation (non-responders, n=11), closed circles and closed line denote the responders (n=10). *p<0.05 and **p<0.005 in the paired comparison before versus after supplementation. §p<0.05 and §§p<0.005 in the between-groups comparison responders versus non-responders.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
CONCLUSION
 REFERENCES
 
In the present group of patients with chronic fatigue, with satisfactory Mg dietary intakes and blood concentrations, there were very few cases of severe Mg deficiency (% retention >50%) or hypomagnesemia. No association was found between Mg deficiency on the one side and Mg dietary intakes, blood concentrations and the presence of CFS on the other [33]. The situation therefore concerns a "subclinical" or moderate state of Mg deficiency, which is not directly related to severe dietary deficiencies. This moderate Mg deficiency is more frequently encountered in daily clinical practice than the severe deficiencies seen in experimental animal models. Therefore it should be stressed that the conclusions from the present study cannot be extrapolated to the effects of severe Mg deficiency on oxidant-antioxidant balance or to the possible modulatory role of Mg in clinical situations in which oxidative stress is already established by the presence of dyslipidaemias, hyperglycemia or severe vitamin and/or trace element deficiencies.

Higher Mg body stores were associated with a higher total antioxidant capacity but only of the component which was dependent on serum albumin. However, the lack of effect on these parameters of an acute increase in plasma Mg during the intravenous test and even of long-term oral supplementation with Mg suggests that the lower serum albumin and antioxidant capacity evidenced in the Mg deficient patients is not directly caused by the low Mg stores. Possible causes of this impaired antioxidant capacity are an overall impaired nutritional status [34] or elevated concentrations of inflammatory cytokines, which inhibit albumin transcription in the liver [35]. Indeed, severe Mg deficiency has been shown to lead to increases in inflammatory cytokines as well as to changes in circulating leucocyte subpopulations [36] and in leucocyte adhesive function [37]. In view of these findings, it has even been proposed that the causal link between Mg deficiency, oxidative stress and the resulting disease (in this case chronic fatigue) might be the inflammatory state.

Although erythrocyte GSH was not lower in the Mg deficient patients and was not affected by Mg supplementation, the subgroup ("non-responders"), whose Mg body stores did not improve after supplementation, had persistently lower blood GSH concentrations, suggesting a relationship between intractable Mg deficiency and low GSH. This observation is consistent with animal models of severe deficiency, where Mg deficient diets cause a decrease of erythrocyte GSH which can be reversed by Mg supplementation and which is related to a decrease in intraerythrocytic ATP rather than to any changes in activity of GSH-synthesising enzymes [38,39,12]. This GSH loss has recently also been attributed to NO overproduction and oxidation of GSH by the resulting peroxinitrite [40].

The relationship between Mg dietary intakes and blood concentrations of antioxidants and lipids suggests that eating foodstuffs rich in Mg, which are also the foodstuffs rich in fibers, is accompanied by higher serum vitamin E and HDL-cholesterol concentrations and with lower concentrations of uric acid, transferrin and triglycerides. Some of these are factors which have been associated with the incidence of atherosclerosis [41], and, in this respect, higher dietary intakes of Mg can be considered to protect against cardiovascular disease as already demonstrated by epidemiological studies [42]. However, the observation that concentrations of total Mg in body stores or in blood are not related to dietary Mg intakes suggests that higher intakes are not necessarily followed by higher total amounts of Mg being taken up in the intestine. Nevertheless, we cannot preclude any changes in the biologically active Mg because the ionised Mg concentrations were not measured in these patients. Altura et al. [43] have shown that even short-term dietary elevations in Mg intake can result in a significant elevation of serum ionised Mg, even though total serum Mg is unaffected. Thus, the beneficial effects of dietary Mg might be mediated by higher concentrations of ionised Mg.

In our Mg deficient patients, oral Mg supplementation was only accompanied by an increase in serum concentrations of vitamin E. This improvement could be explained by either a concomitant increase in both Mg and vitamin E intakes (both being predominantly determined by the fiber intake) or by a sparing effect of Mg on vitamin E by preventing its in vivo oxidation. Several lines of evidence support the latter mechanism. Intravenous Mg has been shown to attenuate the production of ascorbate free radical in an in vivo ischemia-reperfusion dog model [44]. Short-term Mg deficiency in rats is followed by increased lipoprotein and tissue susceptibility to in vitro peroxidation, but this is not immediately accompanied by a significant decrease in vitamin E content [45]. However, long-term Mg deficiency in rats does result in a lowering of tissue vitamin E content, and supplementation with vitamin E prevents some free radical-associated deleterious effects of severe dietary Mg deficiency [46–48]. This evidence suggests the following sequence of events: Mg deficiency leads to a chronic state of increased free radical production, which in the long run depletes antioxidants such as vitamin E. The alternative hypothesis is that Mg deficiency leads to a decrease in the synthesis of antioxidants, with the resulting imbalance in favor of the pro-oxidants leading to increased oxidative stress [49].

The susceptibility of lipoproteins to peroxidation was assessed by incubating non-HDL lipoproteins with copper in vitro and measuring the velocity and total production of two end-products: TBARS and fluorescent products formed from the interaction of TBARS and other products with macromolecules such as apoB. Mg affected this process at several stages and in divergent ways. On the one hand, Mg dietary intake, serum vitamin E and slope (or velocity of formation) of fluorescence were seen to be strongly interrelated even before supplementation. The improvement in serum vitamin E after Mg supplementation was only accompanied by a decrease in the slope of fluorescence. In contrast, the other parameters of lipid susceptibility to in vitro peroxidation, such as the propagation and saturation phases of TBARS production and the lagtime for the appearance of fluorescent products, were predominantly determined by serum cholesterol rather than by concentrations of antioxidants and Mg. Lipid profiles, and these parameters of susceptibility to in vitro peroxidation actually remained remarkably unaffected by Mg supplementation. These observations contrast with some results reported in experimental animals. In rabbits fed a non-atherogenic diet, oral Mg supplementation (a three-fold increase over normal intakes), which led to a 15% increase in serum Mg, was accompanied by a 24% decrease in serum cholesterol and a 33% decrease in serum triglycerides [50]. In rats suffering from pronounced dietary Mg deficiency, the resulting decrease in plasma Mg was accompanied by significant increases in serum triglycerides and phospholipids, as well as in TBARS formation in LDL and VLDL in vivo and in vitro [51]. These differences might be explained by species-differences in LDL/VLDL proportions [52] and in vitamin E distribution or by dose-differences. In the present study, we were only able to document the effect of Mg supplementation in moderately Mg deficient patients who had lipid profiles within the normal ranges. Moreover, the Mg supplements given corresponded to less than a two-fold increase over the usual intakes, and they were extended over a period of three months or more. Although body Mg stores improved substantially, Mg supplementation did not result in any change in total blood Mg concentrations. Any pharmacological effect of Mg on lipid profiles and peroxidation could therefore be ruled out.

The influence of the dietary fatty acid composition should also be taken into account when comparing such studies. In a study conducted in swine, the higher cholesterol and LDL-cholesterol concentrations found in the animals fed butter instead of margarine or basal diet and receiving a satisfactory basal Mg intake were no longer found when dietary Mg was increased two-fold, although this was not accompanied by any significant increase in plasma Mg. Being a cofactor for the enzymes involved in the desaturation of saturated fatty acids and of linoleic to arachidonic acid, Mg could play an important role in the polyunsaturated fat/cholesterol composition of the LDL particle and thus in its fluidity and uptake, which will ultimately also regulate plasma cholesterol concentrations [53]. Furthermore, the important role of Mg in cellular lipid metabolism is illustrated by the effects of Mg deficiency on decreasing both phospholipid synthesis [54] and fatty acid chain length and double bond content [55].


   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
REFERENCES
 
These results highlight the need to distinguish between the effects of Mg body stores, blood concentrations and Mg dietary intakes. These three compartments appear to influence antioxidants and lipid susceptibility to in vitro peroxidation in an independent manner. Mg body stores are associated with total antioxidant capacity of blood, dependent on albumin and GSH concentrations, but do not influence lipid susceptibility to in vitro peroxidation. Mg dietary intakes and supplements only have a beneficial influence on serum concentrations of vitamin E and on the stage of lipid peroxidation dependent on it (slope of fluorescence). Further investigations on the role of ionised Mg in these effects should help in clarifying these findings.


   ACKNOWLEDGMENTS
 
We are grateful to S. Schrans, P. Aerts and I. Fiers for skillful technical assistance, to A. Mazur and N. Fogh-Andersen for helpful suggestions and to the Danone Institute for partly financing this project.


   FOOTNOTES
 
Abbreviations: CFS=chronic fatigue syndrome, TEAC=Trolox equivalents antioxidant capacity, ABTS=2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid), TBARS=thiobarbituric acid reactive substances, non-HDL=low density and very low density lipoproteins.

Received July 1, 1999. Revised April 1, 2000. Accepted April 1, 2000.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 

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