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Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6


Magnesium Research. Volume 19, Number 1, 53-62, March 2006, Original article


Summary  

Author(s) : M Mousain-Bosc, M Roche, A Polge, D Pradal-Prat, J Rapin, JP Bali , Explorations Fonctionnelles du Système Nerveux, Centre Hospitalier Universitaire Carémeau, Nîmes, Laboratoire de Biochimie, Centre Hospitalier Universitaire Carémeau, Nîmes, Département de Pharmacologie, Université de Bourgogne, Dijon, Laboratoire de Biochimie, Faculté de Pharmacie, Montpellier (France).

Summary : Previous studies reported positive results with the use of Mg-vitamin B6 in autism. Despite these reports, this intervention remains controversial. In order to study relationships between changes in clinical symtoms and biological parameters, 33 children (mean age: 4 [1-10] years old) with clinical symptoms of pervasive developmental disorder or autism (PDD, as defined in DSM-IV) were followed for at least 6 months; another group of 36 children (same age) devoided of any known pathology was used as control. All PDD children received a magnesium-vit B6 (Mg-B6) regimen (6 mg/kg/d Mg and 0.6 mg/kg/d vit B6). Intraerythrocyte Mg 2+ (Erc-Mg), serum Mg 2+ (s-Mg) and blood ionized Ca 2+ (i-Ca) were measured before and after treatment. Clinical symptoms of PDD were scored (0 to 4). In contrast to s-Mg or i-Ca, PDD children exhibited significantly lower Erc-Mg values than controls (2.17 ± 0.4 versus 2.73 ± 0.23 mmol/L; 16/33). The Mg-B6 regimen led to an increase in Erc-Mg values (2.42 ± 0.41 (after) versus 2.17 ± 0.4 mmol/l (before), 11/17) and this supplementation improved PDD symptoms in 23/33 children (p < 0.0001) with no adverse effects: social interactions (23/33), communication (24/33), stereotyped restricted behavior (18/33), and abnormal/delayed functioning (17/33); 15/33 children were improved in the first three groups of symptoms. When the Mg-B6 treatment was stopped, PDD symtoms reappeared in few weeks. A statistically significant relationship was found in Erc-Mg values from children before treatment and their mothers. In conclusion, this study suggests that the behavioral improvement observed with the combination vitamin B6-magnesium in PDD/autism is associated with concomitant modifications of Erc-Mg values.

Keywords : pervasive developmental disorders, autism, magnesium-vitamin B6 diet, intraerythrocyte magnesium, ionized Ca 2+

Pictures

ARTICLE

Auteur(s) : M Mousain-Bosc1, M Roche2, A Polge2, D Pradal-Prat1, J Rapin3, JP Bali4

1Explorations Fonctionnelles du Système Nerveux, Centre Hospitalier Universitaire Carémeau, Nîmes
2Laboratoire de Biochimie, Centre Hospitalier Universitaire Carémeau, Nîmes
3Département de Pharmacologie, Université de Bourgogne, Dijon
4Laboratoire de Biochimie, Faculté de Pharmacie, Montpellier (France)

For over 30 years, parents have given high doses of pyridoxine and Mg2+ to their children and have observed improved social responsiveness. B6 and Mg2+ have received more scientific support than any other biological intervention for behavioural disorders (for review, see [1]). There are studies from 18 different research groups showing that B6 and Mg2+ are beneficial to about half of autistic individuals, with no significant adverse effects. Eleven of these studies involved a double-blind placebo design which documented decreases in behavioral problems, improvements in appropriate behavior, and normalization of brain wave activity and urine biochemistry. There is also evidence that B6 and Mg2+ may reduce seizure activity. Parent reports confirm improvement in attention, learning, speech/language, and visual contact [2-5]. More recently, in a pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder, Adams et al. [6] found significant improvements in sleep and gastrointestinal problems compared to the placebo group. Despite all these data, the intervention of Mg-B6 remains controversial and contradictory studies have been published [7, 8]. In a recent meta-analysis of all studies published from 1960s, Nye et al. [9] concluded that, “Due to the small number of studies, the methodological quality of studies, no recommendation can be advanced regarding the use of B6-Mg as a treatment for autism”. Together with the fact that both the American Psychiatric Association and the American Academy of Pediatrics have stated that megavitamin treatment for learning disabilities and autism is not justified, these findings explain the lack of clinical studies about the use of magnesium and vitamin B6 (Mg-B6) in the treatment of autism.However, recently, new data concerning a possible association between Mg-B6 supplementation, neurobehavioural symptoms, and the Mg2+ status of children have been published, opening a new way of research in this domain: the first one from Liebscher et al. [10] suggested that patients with attention deficit hyperactivity disorders should be considered as potentially Mg-deficient as regards to a wrong interpretation of the serum Mg test (tetanic patients have lower Mg values than normals). The second one from Kozielec et al. [11, 12] reported for the first time an intraerythrocyte magnesium depletion in hyperactive children; we recently published similar data [13]. In order to study the effect of Mg-B6 for treating social, communication and behavioural responses of children with pervasive developmental disorders or autism in connection with the magnesium/calcium status of the child, we designed an open study on 33 children with PDD syndrome. Our results showed a statistically significant improvement of the symptoms after Mg-B6 supplementation together with a rise in Erc-Mg values.

Patients and methods

Patients and treatment

Thirty-three children (1-10 year-old, mean: 4 ± 2, 21 boys, 12 girls) were followed over a period of about 24 months. All children presented clinical symptoms of pervasive developmental disorders (signs of autism), as described in DSM-IV [14] (at least 3 from the 4 groups) :
  • group “loss of social interactions”: visual contact, connection with equals, delight partition, social reciprocity,
  • group “loss of communication”: delayed communication, no communication, stereotyped language, social mimicking,
  • group “stereotyped restricted behaviour”: stereotyped interests, customs, motor affectation, handling things,
  • group “abnormal or delayed functioning”: social interactions, language, symbolic games.

Each symptom, evaluated at the same time, was scored from 0 to 4 by the physician, after discussion with parents and teachers, and the values for each symptom were statistically compared before and after Mg-B6 treatment either individually or within each group of symptoms. As defined in DSM-IV, an improvement in PDD under treatment is observed when scored values of at least 3 of the four groups of symptoms decreased (improvement was defined as a difference in cumulated scored value under treatment higher than 5).

The control group contained 36 children (mean age: 4.37 ± 2 y.o., 14 girls and 22 boys) somatically and behavioury healthy, devoided of any sign of neuropathology or of a pathology known to influence magnesium homeostasis. These children did not receive any Mg-B6 therapy; they were selected as regard to their normal behavior at school with parental agreement.

A Mg-B6 regimen (6 mg/kg/d Mg, 0.6 mg/kg/d vit. B6) was established in all PDD children (mean duration: 8 ± 5 months). No other medical treatment was given before and during the Mg-B6 treatment period.

Serum Mg2+ (S-Mg) and intra-erythrocyte Mg2+ (Erc-Mg) were measured by a colorimetric assay (chlorophosphonazo III) [9] (Erc-Mg) in an INTEGRA automate (Roche Diagnostics) and blood ionized Ca2+ concentrations by electrometric assay (i-Ca) (Bayer Diagnostics). To perform Erc-Mg measurements, red blood cells (RBC) were washed 3 times in 0.9% NaCl, centrifuged, and RBC (1 mL pellet) were lysed in 2 mL water for 15 min at + 4°C. Then, 1 mL 20% trichloracetic acid was added, the mix was stirred on vortex and centrifuged. The supernatant (1/4 dilution) was used to measure Erc-Mg. When repeated four times in healthy children at one month periods, Erc-Mg values varied by 12% around initial values. This method was adapted on an INTEGRA automate after calibration with the atomic absorption assay. Biological parameters, including s-Mg, Erc-Mg, and i-Ca, were measured at the first clinical visit of the child; then, after two months treatment. The following evaluations depended on the frequency of the visits (every six months, for instance). Of course, the control group, only containing healthy children, was not treated by Mg-B6.

Statistics

All statistical analyses were done after testing all variables of interest to determine whether they are approximately normally distributed: two different types of tests for normality were used; Shapiro-Wilk and Shapiro-Francia. Since the majority of the variables are not normally distributed, the non-parametric paired Wilcoxon signed-rank test was used to compare values between before and after treatment. For the comparison of Erc-Mg values for PDD children, and their parents versus control children, the non-parametric Mann & Whitney test was applied. Significance at p < 0.05.

Results

Tables 1 and 3( Table 1 )( Table 2 )( Table 3 ) report mean ± SD values for biological (table 1) and clinical (table 3) data of the patients before and after Mg-B6 supplementation.

Erc-Mg values are lower in PDD children and their parents as compared to controls

In PDD children, while s-Mg and i-Ca did not statistically differ from control children, Erc-Mg values were significantly lower as compared to those from control group (2.17 ± 0.4 mmol/L, n = 33, versus 2.73 ± 0.23 mmol/L, n = 36) (p < 0.05) (( figure 1 ) and table 1). Sixteen on thirty-three (48%) of PDD children showed Erc-Mg values less than 2.27 mmol/L (mean-2SD of control children). In addition, mothers and fathers of PDD children, together (n = 7) or separately (n = 16) showed statistically significant lower Erc-Mg values than control children (2.16 ± 0.38 mmol/L, n = 23, and 2.19 ± 0.33 mmol/L, n = 12) (p < 0.05, respectively) (table 2). When we tried to correlate Erc-Mg values from PDD children to those of their mothers, a statistically significant correlation appeared (r2= 0.2243, p < 0.05) (( figure 2 )).
Table 1 Biological characteristics of PDD children under treatment: Mean ± SD values of Erc-Mg, i-Ca, and s-Mg (mmol/L) are reported.

Age (years)

4.03 ± 1.93

Duration of Mg-B6 treatment (months)

8 ± 5.8

Erc-Mg (mmol/L)

Control children

2.73 ± 0.23

Children before treatment

2.17 ± 0.4

Children after treatment

2.42 ± 0.41

Ratio after/before

1.18 ± 0.34

Mothers

2.16 ± 0.38

Fathers

2.19 ± 0.33

i-Ca (mmol/L)

Before treatment

1.21 ± 0.08

After treatment

1.20 ± 0.05

Ratio after/before

1.00 ± 0.1

s-Mg before treatment (mmol/L)

0.89 ± 0.06


Table 2 Comparison between Erc-Mg values from PDD children and their parents. Mean ± SD Erc-Mg values (mmol/L) in control and in PDD children, their mothers and fathers are reported. Erc-Mg was measured as indicated in figure 1. Statistical comparison was done using Mann & Whitney non parametric test. Statistical significance at p = 0.05.

Control

PDD Children

Mothers

Fathers

Children (36)

(29)

(23)

(12)

Erc-Mg values (mmol/L)

2.73 ± 0.23

2.17 ± 0.40

2.16 ± 0.38

2.19 ± 0.33

Significance versus controls (p)

-

0.001

0.001

0.001

Significance versus PDD children (p)

0.001

-

NS

NS

Number of cases of patients with Erc-Mg < 2,27 mmol/L (-2 s.d.)

0

18 (62%)

14 (61%)

9 (75%)


Table 3 Clinical characteristics of PDD children under treatment: Mean ± SD scored values for each symptom in the PDD children’s group, as described in DSM-IV, are reported.

PDD symptom

N

Mean ± SD score value before

Number of children with score > 3

Mean ± SD score value after

Number of children with score > 3

Social interactions

Visual contact

33

3.33 ± 0.89

26

1.36 ± 1.19

6

Connection with equals

33

3.12 ± 0.74

28

1.51 ± 1.00

6

Delight partition

33

3.03 ± 0.81

25

1.54 ± 1.06

6

Social reciprocity

33

3.30 ± 0.68

29

1.51 ± 1.06

6

Cumulated score values

33

12.61 ± 3.01

-

5.94 ± 4.10

-

Loss of communication

Delayed communication

33

3.39 ± 0.50

33

2.00 ± 1.00

9

No communication

33

3.09 ± 0.72

26

1.54 ± 0.87

4

Stereotyped language

33

2.85 ± 0.71

24

1.54 ± 1.09

6

Social mimicking

33

3.27 ± 0.75

29

1.39 ± 1.05

5

Cumulated score values

12.61 ± 2.16

-

6.48 ± 3.77

-

Stereotyped restricted behavior

Stereotyped interest

33

3.03 ± 1.16

24

1.27 ± 0.91

3

Customs

33

1.88 ± 1.36

12

0.64 ± 0.82

1

Motor affectation

33

2.36 ± 1.14

17

1.00 ± 0.90

3

Things handling

33

1.88 ± 1.17

10

1.03 ± 1.04

3

Cumulated score values

12.61 ± 2.16

-

6.48 ± 3.77

-

Abnormal or delayed functioning

Social interactions

33

3.26 ± 0.89

28

1.80 ± 1.22

10

Language

33

3.39 ± 0.62

29

1.90 ± 1.22

10

Symbolic games

33

3.13 ± 0.88

27

1.66 ± 1.15

9

Cumulated score values

12.61 ± 2.16

-

6.48 ± 3.77

-

ERC-Mg values increased under Mg-B6 supplementation

In PDD children who received a Mg-B6 supplementation for at least two months, a statistically significant rise in Erc-Mg values was observed (2.42 ± 0.41 (after) versus 2.17 ± 0.4 mmol/l (before), Wilcoxon test p = 0.0198) (table 4( Table 4 ))), but these values were still lower than for controls (2.73 ± 0.23 mmol/L) (( figure 1 ) and table 1). 11/17 (65%) of children showed increased Erc-Mg values after treatment. No statistically significant variation under Mg-B6 treatment has been observed either in s-Mg (Wilcoxon test p = 0.14) or in i-Ca (Wilcoxon test p = 0.088). When the Mg supply was stopped, Erc-Mg values return to low levels in about 2 months.
Table 4 Effect of Mg-B6 treatment in PDD childrenStatistical comparisons of biological parameters between after versus before treatment. Since majority of the variables are not normally distributed, the non-parametric paired Wilcoxon signed-rank test was used to compare values between before and after treatment. Statistical significance at p = 0.05.

Comparison after versus before Mg-B6 treatment

Wilcoxon test

Erc-Mg

z = -2.330

Prob > z = 0.0198

i-Ca(2+)

z = 1.706

Prob > z = 0.0880, NS

Social interactions

z = 5.074

Prob > z = 0.0000

Loss of communication

z = 5.061

Prob > z = 0.0000

Stereotyped restricted behavior

z = 5.119

Prob > z = 0.0000

Abnormal/delayed functioning

z = 4.726

Prob > z = 0.0000

Evolution of PDD clinical symptoms under Mg-B6 supplementation

In PDD children, Mg-B6 treatment for at least 2 months modified the clinical symptoms of the disease (( figure 3 ) and table 3): namely, social interactions (mean cumulated score values: 5.94 ± 4.10 versus 12.61 ± 3.01 before treatment, p < 0.0001) and communication (mean cumulated score values: 6.48 ± 3.77 versus 12.61 ± 2.16 before treatment, p < 0.0001), stereotyped behavior (mean cumulated score values: 6.48 ± 3.77 versus 12.61 ± 2.16 before treatment, p < 0.0001) and abnormal functioning (mean cumulated score values: 6.48 ± 3.77 versus 12.61 ± 2.16 before treatment, p < 0.0001) were statistically reduced (table 3). For each of the analyses above, the paired t-test gave similar values to that found with the Wilcoxon signed rank test, although the non parametric tests are prefered due to the clearly non-normal data. 23/33 (social interactions), 24/33 (communication), 18/33 (stereotyped behavior) and 17/33 (abnormal functioning) of PDD children showed a difference in cumulated scored value under treatment higher than 5, value defined to consider an improvement in the symptoms. Twenty on thirty-three (60%) of PDD children improved under Mg-B6 treatment (improvement for 3 of the four groups of symptoms). Among these 20 children who improved under treatment, 8/12 exhibited increased Erc-Mg levels. The main clinical observation in all patients was the improvement in social behaviour.

Duration of treatment

Children were treated with Mg-B6 from 2 to 40 months. Two months Mg-B6 supplementation did not induce a statistically significant rise in Erc-Mg values, and only small changes in children’s behaviour. These changes became significant after 6 months treatment. When the magnesium treatment was stopped, clinical symtoms of the disease reappeared in few weeks.

Discussion

Magnesium is known to be essential for number of physiological and biochemical central and peripheral processes. Associated to vitamin B6, it has been proposed for many years as a nutritional factor which could be used in the treatment of autism. The neurobiological basis of such a treatment supposes the existence of an impairment in the neuronal Mg2+ pathway which could be reversed under Mg-B6 therapy. Mg2+ acts as an ionic membrane regulator and modulator of ion transfer through membrane channels. In the brain, it has been shown that traumatic injury causes a decline in Mg2+ concentrations, focally as well as in blood circulation, and contributes to the development of neurologic deficit [15]. Similarly, brain ischemia caused a decline in intracellular free Mg2+ concentrations [16] and magnesium salt administration improved motor outcome in this situation [17]. One of its most important modes of action is to inhibit the glutamate N-methyl-D-aspartate (NMDA) channel [18]. The activity of this channel generates an influx of calcium and, in turn, leads to an excitotoxic cell death and apoptosis [15]. In the same way, abnormal dietary deficiency of Mg2+ as well as abnormalities in Mg2+ metabolism play important roles in different types of heart diseases and Mg2+ influences catecholamine signaling in such diseases [19].

Recently, in primary autistic children, using positive emission tomography (PET), Zilbovicius et al. [20, 21] observed in 16/21 of children a significant decrease in cerebral blood flow localized at the temporal lobes level. Taken together with the fact that Mg2+ was shown to increase blood pressure [22] and that brain from rats fed with low Mg2+ diets are more susceptible to permanent brain focal ischemia [23], we can hypothesize that intracellular Mg2+ depletion could be responsible, at least in part, for some central activity disorders observed in PDD/autistic children.

In our study, an intra-erythrocyte Mg2+ depletion was evidenced in almost half of the PDD children. To explain such a phenomenon, two hypotheses can be proposed:

  • a metabolic inhibition of membrane Na+/K+ ATPase (observed in autism [24]) with a concomitant rise in intracellular Ca2+ and decrease in intracellular Mg2+;
  • a genetic defect in magnesium transport through the plasma membrane (Na+-Mg2+ exchanger [25, 26] or TRPM chanzymes [27]).

As Erc-Mg can be considered as representative of some intracellular Mg concentrations, a decrease in Erc-Mg without changes in serum Mg concentrations could be interpreted as an alteration of Mg2+ transport through plasma membrane. The demonstration that TRPM7 is critical for Mg2+ homeostasis evoked the possibility that mutation of TRPM channels may cause disease in humans as a result of reduced intracellular Mg2+ levels: mutations were found in the case of hypomagnesemia with secondary hypocalcemia disease [28], and, in this case, symptoms associated with TRPM6 mutations were improved by supplementation with high Mg2+ doses, in agreement with increased Mg2+ entry through the passive mode of Mg2+ influx. This genetic hypothesis was also supported by our data showing a positive correlation between low Erc-Mg values in PDD children and their mothers. Similarly, Feillet-Coudray et al. have found that, in mice genetically selected for low magnesium levels, Mg efflux from erythrocytes was significantly increased; the genetic regulation of erythrocyte Mg2+ content depends on the modifications of Mg2+ influx [29, 30]. To confirm such an hypothesis, a genetic study of PDD children’s families clearly has to be developed.

When PDD children were supplemented with Mg-B6 treatment, Erc-Mg values increased more or less and only in 65% of children. The failure to get normal Erc-Mg values under Mg-B6 treatment supports the hypothesis of a defect in Mg2+ transport in erythrocytes: in sickle cell disease, Mg pidolate supplementation was found to decrease Na+/Mg2+ exchanger activity with a partial rise in Mg2+ and K+ contents of erythrocytes [31]. Doses of Mg-B6 and duration of the treatment, which have not been taken into account in our study, could also be involved in explaining such an observation. Concerning the respective roles of pyridoxine and Mg2+ in these observations, it was classically admitted that Mg2+ is associated to pyridoxine to decrease the irritable side-effects of the B6 therapy and that B6 is the main factor involved in the improvement of clinical symptoms in autistic patients. Following Erc-Mg values during Mg-B6 treatment, we bring here evidence of the role of Mg2+ itself in this therapy. In addition, in mothers of PDD children who had pregnancy disturbances, a preventive Mg-B6 therapy seems to be required.

Mg-B6 treatment of PDD children was shown to ameliorate symptoms of the disease: three of the four main groups of clinical signs described in DSM-IV were significantly reduced and we found for the first time that 8/12 of children who improved under treatment showed higher Erc-Mg values. Persons only slightly deficient in magnesium become irritable, high-strung, sensitive to noise, hyperexcitable, apprehensive, and belligerent. If the deficiency is more severe, or prolonged, they may develop twitching, tremors, irregular pulse, insomnia, muscle weakness, jerkiness, and leg and foot cramps. These symptoms can also been found in some cases of PDD/autism. Although this study was an opened non-controlled study, we found a relationship between clinical signs of PDD/autism and a biological parameter Erc-Mg. However, we were unable to establish any correlation between improvement of symptoms and increase in Erc-Mg. Various possibilities can explain this lack of correlation:

  • Erc-Mg is probably not the best biological parameter to follow the relationship between magnesium homeostasis and neurological dysfunctions of PDD/autism; contradictory reports have been published on the use of Erc-Mg as index of Mg2+ status [32, 33]. New biological tests which could help to study genetic alterations of magnesium transport (lymphocytes…) have to be tested;
  • Other neurofunctional disorders may be involved in autism, such as a decrease in temporal blood flow. Even if low Erc-Mg levels have been shown to be related to decrease in blood pressure, there is no evidence to associate in all cases blood pressure and cerebral blood flow.

Conclusion

This study brings new information about the therapeutic role of a Mg-B6 regimen in children with PDD syndrome. This effect seems to be associated, at least in part, to a cellular Mg2+ depletion, as evidenced by intra-erythrocyte Mg2+ measurements. Children with pervasive developmental disorders (including autism) exhibit low Erc-Mg levels. Parents frequently showed similar low Erc-Mg values suggesting a genetic defect in Mg2+ transport. Installing a Mg-B6 supplementation for some weeks restored higher intra-erythrocyte Mg2+ values and significantly reduced the clinical symptoms of these diseases.

Acknowledgements

The authors would like to express their thanks to parents and teachers of the children included in this study for their permanent support. They are grateful to all the staff of Centre Hospitalier Universitaire of Nîmes and to Dr Jean Durlach (Association pour le Développement des Recherches sur le Magnesium, Paris) for his interest to our work. They would like to acknowledge Sanofi-Aventis for its interest and financial support. They also would express their thanks to Dr Joan Ryan (Melbourne, Australia) for her help in statistical determinations.

References

1 Kidd PM. Autism, an extreme challenge to integrative medecine. Altern Med Rev 2002; 7: 472-94.

2 Rimland B, Callaway E, Dreyfus P. The effect of high doses of vitamine B6 on autistic children: a double-blind crossover study. Am J Psychiatry 1978; 135: 472-5.

3 Lelord G, Callaway E, Muh JP. Clinical and biological effects of high doses of vitamine B6 and magnesium on autistic children. Acta Vitaminol Enzymol 1982; 4: 27-44.

4 Martineau J, Barthelemy C, Cheliakine C, Lelord G. Brief report: an open middle-term study of combined vitamine B6-Mg(2+) in a subgroup of autistic children selected on their sensitivity to this treatment. J Autism Dev Disord 1988; 18: 435-47.

5 Kuriyama S, Kamiyama M, Watanabe M, Tamahashi S, Muraguchi I, Watanabe T, Hozawa A, Ohkubo T, Nishino Y, Tsubono Y, Tsuji I, Hisamichi S. Pyridoxine treatment in a subgroup of children with pervasive developmental disorders. Dev Med Child Neurol 2002; 44: 284-6.

6 Adams JB, Holloway C. Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder. J Altern Complement Med 2004; 10: 1033-9.

7 Tolbert L, Haigler T, Waits MM, Dennis T. Brief report: Lack of response in an autistic population to a low dose clinical trial of pyridoxine and magnesium. J Autism Dev Disord 1993; 23: 193-9.

8 Findling RL, Maxwell K, Scotese-Wojtila L, Huang J, Yamashita T. Wisnitzer M. High-dose pyridoxine and magnesium administration in children with autistic disorder: an absence of salutary effects in a double-blind, placebo-controlled study. J Autism Dev Disord 1997; 27: 467-78.

9 Nye C, Brice A, Nye C. Combined vitamin B6-magnesium treatment in autism spectrum disorder. Cochrane Database Syst Rev 2005; 4; (CD003497).

10 Liebscher DH, Liebscher DE. About the misdiagnostics of magnesium deficiency. J Am Coll Nutr 2004; 23: 730S-731S.

11 Kozielec T, Starobrat-Hermelin B. Assessment of magnesium levels in children with attention deficit hyperactivity disorders (ADHD). Magnes Res 1997; 10: 143-8.

12 Starobrat-Hermelin B, Kozielec T. The effect of magnesium physiological supplementation on hyperactivity in children with attention deficit hyparactivity disorder (ADHD). Positive response to magnesium oral loading test. Magnes Res 1997; 10: 149-56.

13 Mousain-Bosc M, Roche M, Rapin J, Bali JP. Magnesium-VitB6 intake reduces central nervous system hyperexcitability in children. J Am Coll Nutr 2004; 23: 545S-548S.

14 American Psychiatric Association. Diagnostic and statistic manual of mental disorders.. IVth edition text revision. Washington: APA, 1994.

15 Vink R. Magnesium in traumatic brain injury: past findings and future directions. In: Rayssiguier Y, Mazur A, Durlach J, eds. Advances in Magnesium Research: Nutrition and Health. 2001: 405-12.

16 Helpern JA, Van de Linde AM, Welch KM, Levine SR, Schultz L, Ordidge RJ, Halvorson H, Hugg JW. Acute elevation and recovery of intracellular [Mg2+] following focal cerebral ischemia. Neurology 1993; 43: 1577-81.

17 Health DL, Vink R. Neuroprotective effects of MgSO4 and MgCl2 in closed head injury: a comparative phosphorus NMR study. J Neurotrauma 1998; 15: 183-9.

18 Schmidt CJ, Taylor VL. Release of [3H]norepinephrine from rat hippocampal slices by N-methyl-D-aspartate: comparison of the inhibitory effects of Mg2+ and MK-801. Eur J Pharmacol 1988; 156: 111-20.

19 Chakraborti S, Chakraborti T, Mandal M, Mandal A, Das S, Ghosh S. Protective role of magnesium in cardiovascular diseases: a review. Mol Cell Biochem 2002; 238: 163-79.

20 Zilbovicius M, Boddaert N, Belin P. Temporal lobe dysfunction in childhood autism: a PET study (positron emission tomography). Am J Psychiatry 2000; 157: 1988-93.

21 Gervais H, Belin P, Boddaert N, Leboyer M, Coez A, Sfaello I, Barthelemy C, Brunelle F, Samson Y, Zilbovicius M. Abnormal cortical voice processing in autism. Nat Neurosci 2004; 7: 801-2.

22 Macdonald RL, Curry DJ, Aihara Y, Zhang ZD, Jahromi BS, Yassari R. Magnesium and experimental vasospasm. Neurosurgery 2004; 100: 106-10.

23 Demougeot C, Bobillier-Chaumont S, Mossiat C, Marie C, Berthelot A. Effect of diets with different magnesium content in ischemic stroke rats. Neuroscience Let 2004; 362: 17-20.

24 Kurup RP, Kurup PA. A hypothalamic digoxin-mediated model for autism. Intern J Neuroscience 2003; 113: 1537-59.

25 Ebel H, Kreis R, Gunther T. Regulation of Na+/Mg2+ antiport in rat erythrocytes. Biochim Biophys Acta 2004; 1664(2): 150-60.

26 Ebel H, Gunther T. Na+/Mg2+ antiport in erythrocytes of spontaneously hypertensive rats: role of Mg2+ in the pathogenesis of hypertension. Magnes Res 2005; 18: 175-85.

27 Montell C. The TRP superfamily of cation channels. Sci STKE 2005; 272: re3.

28 Schlingmann K, Weber S, Peters M, Niemann Nejsum L, Vitzthum H, Klingel K, Kratz M, Haddad E, Ristoff E, Dinour D, Syrrou M, Nielsen S, Sassen M, Waldegger S, Seyberth HW, Konrad M. Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nat Genet 2002; 31: 166-70.

29 Feillet-Coudray C, Coudray C, Wolf FI, Henrotte JG, Rayssiguier Y, Mazur A. Magnesium metabolism in mice selected for high and low erythrocyte magnesium levels. Metabolism 2004; 53: 660-5.

30 Feillet-Coudray C, Trzeciakiewicz A, Coudray C, Rambeau M, Chanson A, Rayssiguier Y, Opolski A, Wolf FI, Mazur A. Erythrocyte magnesium fluxes in mice with nutritionally and genetically low magnesium status. Eur J Nutr 2005; (sept):15 (E-pub ahead of print).

31 De Franceschi L, Bachir D, Galacteros F, Tchernia G, Cynober T, Neuberg D, Beuzard Y, Brugnara C. Oral magnesium pidolate: effects of long-term administration in patients with sickle cell disease. Br J Haematol 2000; 108: 284-9.

32 Borella P, Ambrosini G, Concari M, Bargenelli A. Is magnesium content in erythrocytes suitable for evaluating cation retention after oral physiological supplementation in marginally-deficient subjects? Magnes Res 1993; 3: 149-53.

33 Basso LE, Ubbink JB, Delport R. Erythrocyte magnesium concentration as an index of magnesium status: a perspective from a magnesium supplementation study. Clin Chim Acta 2000; 291: 1-8.


 

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