Studies of High Dosage Vitamin B6 (and often with Magnesium) in Autistic Children and Adults
1965 - 2005
(Twenty-one of twenty-two
studies yielded positive results, including 13 double-blind placebo-controlled trials; even minor adverse effects rarely were seen)
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AUTHOR/YEAR
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SUBJECT/DOSAGE
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DESIGN/OUTCOME
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1. Heeley & Roberts (1965)
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16 autistic children
30 mg, B6 one time
(one child continued)
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Tryptophan load test. 11 of 16
Children normalized urine.
(Child who continued showed
"remarkable" progress)
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2. Bonisch (1968)
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16 autistic children
100 mg - 600 mg B6
(mostly 300-400 mg)
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Open trial 12 of 16 improved,
3 spoke for the first time
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3. Rimland (1973)
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190 autistic children
4 megavitamins; 150 mg
to 450 mg B6
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Compared B6 effect in computer-
selected subgroups; computer "blind"
to treatment effects.
45% "definite improvement" (p<.02)
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4. Rimland, Callaway,
Dreyfus (1978)
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16 autistic children
75 mg to 3,000 mg B6
(mostly 300-500 mg)
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Double-blind placebo crossover,
11 of 15 better on B6 (p<.05)
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5. Gualtieri et al. (1981)
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15 autistic children
300 mg to 900 mg B6
plus other vitamins & minerals
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Open trial 12 weeks, then
No-treatment period. 6
Children showed "substantial"
improvement. Basal serum
Prolactin levels (PRL) were
lower in responders. (p<.05)
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6. Ellman (1981)
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16 autistic adults and
adolescents.
1 gram/day B6
500 mg/day magnesium
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Double-blind placebo
Crossover. Four showed
Global improvement, five
showed partial improvement.
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7. Barthelemy et al. (1981)
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52 autistic children
11 normal controls
30 mg/kg/day B6 (up to
1 gram) 10-15 mg/kg/day
magnesium
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Three double-blind crossovers,
comparing B6 alone,
magnesium alone, and B6 +
magnesium with placebo.
B6 + magnesium was best.
Highly significant (p<.01-p<.001)
Decreases in autistic behaviors;
Significant (p<.02) decrease in urinary HVA.
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8. LeLord et al. (1981)
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Study 1: 44 children
With autistic symptoms.
Study 2: 21 children
selected from above 44.
600 mg-1,125 mg/day B6
400 mg-500 mg/day
magnesium
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Study 1: open trial to identify
responders.
Study 2: double-blind placebo
crossover comparing responders
and non-responders.
15 of 44 improved. In 14 of
15, improvement disappeared
3 weeks after cessation of
treatment. Double-blind study
confirmed behavior improvement
(p<.01). HVA levels levels (n=37)
also improved (p<.01).
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9. Martineau et al. (1982)
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24 autistic children
30 mg/kg/day B6
15 mg/kg/day magnesium
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Compared electrophysiological
effects of magnesium given
alone or with B6. In
conditioning experiment, B6 +
magnesium significantly
improved brain response
latencies and amplitudes (p<.05).
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10. Jonas et al. (1984)
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8 autistic adults
1 gram/day B6
380 mg/day magnesium
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Double-blind crossover
Behavior improved significantly;
non-significant improvement in
HVA excretion.
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11. Martineau et al. (1985)
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60 autistic children
30 mg/kg/day B6 (up to
1 gram/day)
10 mg-15 mg/kg/day
magnesium
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4 crossed-sequential double-blind
trials, comparing B6 alone,
magnesium alone, and
B6 + magnesium with placebo.
B6 + magnesium was
best. Significant improvement
in behavior, HVA excretion,
and evoked potentials.
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12. Martineau et al. (1986)
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One 4-year-old child
30 mg/kg/day B6
15 mg/kg/day magnesium
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Long term (8 mo.) study.
Clear improvement in behavior,
HVA levels, and evoked
potentials over the 8 months;
deterioration six weeks after
cessation resulted I reinstating
B6 + magnesium treatment.
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13. Martineau et al. (1988)
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11 autistic children
30 mg/kg/day B6
10 mg/kg/day magnesium
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Controlled study; eight weeks
of treatment followed by no-
treatment period. B6 group showed
significant behavioral improvement,
normalization of evoked
potentials, drop in dopamine
levels. Behaviors returned to
baseline when treatment
was discontinued.
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14. Martineau et al. (1989)
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6 autistic children
30 mg/kg B6,
10 mg/kg magnesium 8 weeks,
6 autistic children given
1.5 mg/kg fenfluramine 12 weeks.
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Comparisons made in
electrophysiological (AER)
effects of the two treatments.
B6, but not fenfluramine,
"resulted in the appearance of
a conditioning phenomenon and the
demonstration of auditory-visual and
auditory-tactile cross-modal
associations during treatment."
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15. Rossi et al. (1990)
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Open trial on 30 autistic
patients
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40% of patients improved "in the
most typical behavioral features of
autism." HVA, VMA and 5HIAA
levels did not correlate with clinical
improvement.
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16. Moreno et al. (1992)
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60 families with
autistic children
studied with battery
of clinical and
biochemical tests
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"Three out of eight probands who
received megadoses of pyridoxine
(vitamin B6), subjectively gained in
language abilities, affectivity, and
response to conductial modification
therapy."
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17. Menage et al. (1992)
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10 autistic children
7 control children
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5 boys on megadose B6/magnesium
for 8 weeks: "overall improvement
of their disorders …. Particularly,
improvement was observed for certain
autistic symptoms (lack of interest in
people, abnormal eye contact,
impairment in verbal and nonverbal
communication)." Improved T-cell
deficits.
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18. Findling et al. (1997)
(See critique by Rimland, 1998)
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10 autistic children
420-1000 mg B6
140-350 mg magnesium
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Double-blind placebo crossover, 4-week trials, no washout
period, no test of compliance. Authors claim no benefit was seen, but were
unable to produce data.
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19. Hopkins (1999)
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13 autistic children
14 mg/kg/day of B6
(maximum 1 gm/day)
magnesium=1/2 dosage of B6
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Double-blind placebo controlled study.
One month washout period between B6-placebo phases.
Eight of 13 subjects (61%) showed benefit, using
behavioral and electrophysiological data (increased amplitude and decreased
latency of P300 responses).
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20. Audhya (2002)
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184 autistic children on increasing doses of B6 and
magnesium, not to exceed 20 mg/kg/day of B6
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89 children (48%) improved significantly, 86 (47%)
improved marginally, and 9 (5%) showed worse behavior. (Main thrust of
research was to study laboratory indices of metabolic status of the
children.)
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21. Kuriyama (2002)
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16 "PDD" children, ages 6-16, 200 mg/day B6 (far below
usual megadose range, and no magnesium was used)
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4-week randomized double blind placebo-controlled study,
subjects on B6 showed 11.2 IQ point increase compared to 6 points for placebo
group (statistically significant)
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22. Rimland & Edelson (2005)
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5780 autistic children and adults. B6 and magnesium dosages decided by
parents and physicians
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Parents rated 85 biomedical interventions as to safety and
efficacy. B6 and magnesium were rated "Helpful" in 47%, "No effect" in 49%,
and "Made worse" in 4%.
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References
Audhya, T. (2002, October).
Laboratory indices of vitamin and mineral deficiency in autism. Paper presented at the Defeat Autism Now!
Conference, San Diego, California.
Barthelemy, C., Garreau, B., Leddet, I., Ernouf, D., Muh,
J.P., & LeLord, G. (1981).Behavioral
and biological effects of oral magnesium, vitamin B6, and combined magnesium-B6
administration in autistic children.Magnesium
Bulletin, 3, 150-153.
Bonisch, V.E. (1984).
Erfahrungen mit pyrithioxin bei hirngeschadigten kindern mit autistischem
syndrom.Praxis der
Kinderpsychologie, 8, 308-310.
Ellman, G. (1981, November). Pyridoxine effectiveness on autistic patients at Sonoma State
Hospital.Paper presented at Research
Conference on Autism, San Diego, CA.
Findling, R.L., Maxwell, K., Scotese-Wojtila, L., Huang, J.,
Yamashita, T., & Wiznitzer M. (1997).
High-dose pyridoxine and
magnesium administration in children with autistic disorder: an absence of
salutary effects in a double-blind, placebo-controlled study. Journal of
Autism and Developmental Disorders, 27, 467-478.
Gualtieri, C.T., Von Bourgondien, M.E., Hartz, C., Schopler,
E., & Marcus, L. (1981, May). Pilot study of pyridoxine treatment in
autistic children.Paper presented at
American Psychiatric Association meeting, New Orleans, LA.
Heeley, A.G., & Roberts, G.E. (1966). A study of tryptophan metabolism in
psychotic children.Developmental
Medicine and Child Neurology, 3, 708-718.
Hopkins, J.N. (1999).
The effects of vitamin B6 supplements on the behaviour and brain
activity of subjects with autism.
Unpublished master’s thesis, Swinburne University of Technology,
Victoria, Australia.
Jonas, C., Etienne, T., Barthelemy, C., Jouve, J., &
Mariotte, N. (1984).Interet clinique
et biochimique de l’association vitamine B6 + magnesium dans le traitement de
l’autisme residuel a l’age adulte.Therapie,
39, 661-669.
Kuriyama, S., Kamiyama, M., Watanabe, M., & Tamahashi,
S. (2002).Pyridoxine treatment in a
subgroup of children with pervasive developmental disorders. Developmental Medicine & Child
Neurology, 44, 284-286.
LeLord, G., Muh, J.P., Barthelemy, C., Martineau, J.,
Garreau, B., & Callaway, E. (1981).
Effects of pyridoxine and magnesium on autistic symptoms: initial
observations.Journal of Autism and
Developmental Disorders, 11, 219-230.
Martineau, J., Garreau, B., Barthelemy, C., & LeLord, G.
(1982).Comparative effects of oral B6,
B6-Mg, and Mg administration on evoked potentials conditioning in autistic
children.In A. Rothenberger (Ed.), Proceedings:
Symposium on Event-Related Potentials in Children (pp.411-416). Essen, F.R.G. 11-13 June, 1982. Elsevier
Biomedical Press, Amsterdam.
Martineau, J., Barthelemy, C., Garreau, B., & LeLord, G.
(1985).Vitamin B6, magnesium and
combined B6-Mg: therapeutic effects in childhood autism. Biological Psychiatry, 20,
467-468.
Martineau, J., Bathelemy, C., & LeLord, G. (1986). Long-term effects of combined vitamin
B6-magnesium administration in an autistic child. Biological Psychiatry, 21, 511-518.
Martineau, J., Barthelemy, C., Cheliakine, C., & LeLord,
G. (1988).Brief report: an open
middle-term study of combined vitamin B6-magnesium in a subgroup of autistic
children selected on their sensitivity to this treatment. Journal of Autism and Developmental Disorders,
18, 435-447.
Martineau, J., Barthelemy, C., Roux, S., Garreau, B., &
LeLord, G. (1989).Electrophysiological
effects of fenfluramine or combined vitamin B6 and magnesium on children with
autistic behavior.Developmental Medicine
and Child Neurology, 31, 728-736.
Menage, P., Thibault, G., Barthelemy, C., LeLord, G., &
Bardos, P. (1992).CD4+ CD45RA+ T
lymphocyte deficiency in autistic children: effect of a pyridoxine-magnesium
treatment.Brain Dysfunct., 5,
326-333.
Moreno, H., Borjas, L., Arriela, A., Saez, L., Prassad, A.,
Estevez, J., & Bonilla, E. (1992).
Heterogeneidad clinica del syndrome autista: un estudio en sesenta
familias.Invest Clin, 33,
13-31.
Rimland, B. (1973).
High dosage levels of certain vitamins in the treatment of children with
severe mental disorders.In D. Hawkins
& L. Pauling (Eds.), Orthomolecular Psychiatry (pp. 513-538). New York: W.H. Freeman.
Rimland, B. (1988).
Controversies in the treatment of autistic children: vitamin and drug
therapy.Journal of Child Neurology,
3 (suppl.), S68-S72. (The data
reported in this paper are augmented by a greatly increased number of cases in:
Rimland, B. and Edelson, S.M., 2005, cited in present review).
Rimland, B. (1998).
High dose vitamin B6 and magnesium in treating autism: Response to study
by Findling et al.Journal of Autism
and Developmental Disorders, 28, 581-582.
Rimland, B., Callaway, E., & Dreyfus, P. (1978). The effects of high doses of vitamin B6 on
autistic children: a double-blind crossover study. American Journal of Psychiatry, 135, 472-475.
Rimland, B., & Edelson, S.M. (2005). Parent ratings of behavior effects of
biomedical interventions (Pub. 34, Rev. March 2005). San Diego: Autism Research Institute.
Rossi, P., Visconti, P., Bergossi, A., & Balcatra, V.
(1990, November).Effects of vitamin B6
and magnesium therapy in autism.Paper
presented at the Neurobiology of Infantile Autism Conference, Tokyo, Japan.
© copyright 2005, 2006 Autism Research Institute
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