Paediatrica Indonesiana

VOLUME 54 May ‡ NUMBER 3

Case Report

Evidence based case report: Pyridoxine

supplementation in children with
pervasive developmental disorders
Sekarpramita Darmaputri1, Tjhin Wiguna2

3
HUYDVLYH GHYHORSPHQWDO GLVRUGHUV 3''
is defined as a neurodevelopmental disor-
der, characterized by social withdrawal,
communication deficits, and repetitive
EHKDYLRUV 3'' LQFOXGH DXWLVWLF GLVRUGHU 5HWW·V
syndrome, childhood disintegrative disorder, Asperger’s
syndrome, and pervasive developmental disorder not
otherwise specified or atypical autism. Update of
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VKRZUHSRUWVRIHVWLPDWHGSUHYDOHQFHIRUDXWLVP
KDVYDULHGEHWZHHQDQGFKLOGUHQSHU
and predominantly occurs in males than females
participants showed improvement in speech and
language.4 Since then, the study of vitamin B6 use for
3''WUHDWPHQWVKDVEHHQH[WHQVLYHO\FRQGXFWHGDQG
some clinicians administered it empirically, but none
has been able to produce a conclusive result.
It was found that in autistic children the enzyme
S\ULGR[DO NLQDVH ZKLFK ZRUNV WR SKRVSKRU\ODWH
YLWDPLQ % LQWR WKH DFWLYH IRUP S\ULGR[DO
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E\ S\ULGR[DO NLQDVH UHVXOWV LQ KLJK SODVPD OHYHOV RI
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SKRVSKDWH LV D FRIDFWRU IRU  HQ]\PH LQFOXGLQJ
PDOHIHPDOHUDWLR 3
There is a hypothesis that behavioral problems
in children with pervasive developmental disorder
are highly associated with the neurotransmitter
imbalances. Therefore, psychotropic medications (eg.
atypical antipsychotics, selective serotonin reuptake
inhibitors, and psychostimulants), which work on
dopamine and serotonin receptors, are the FDA-
neurotransmitters serotonin, dopamine, gamma
aminobutyric acid (GABA), and the catecholamines.6,
77KHUHIRUHORZOHYHOVRI3/3FRXOGKDYHZLGHUDQJLQJ
effects on human metabolism, including those on
PHQWDOIXQFWLRQ+RZHYHUVXSSOHPHQWDWLRQRI3/3
as a therapy is implausible as the phosphate group is
UHPRYHGGXULQJGLJHVWLRQVR3/3ZRXOGOLNHO\KDYH
no additional benefit.6 Ames et al then postulated
DSSURYHGPHGLFDWLRQVIRU3''4 On the other hands, WKDW KLJK GRVHV  PJGD\7 of vitamin B6
WKH XVH RI QRYHO XQFRQYHQWLRQDO DQGRU RIIODEHO
treatments associated with the neurotransmitters
SDWKZD\ IRU FKLOGUHQ ZLWK 3'' LV LQFUHDVLQJ DQG
From the International Class and Division of Child and Adolescent
more common. 3V\FKLDWU\'HSDUWPHQWRI3V\FKLDWU\8QLYHUVLW\RI,QGRQHVLD0HGLFDO
3\ULGR[LQH YLWDPLQ % DV D FRPSOHPHQWDU\ School, Jakarta, Indonesia.
therapy was first reported to improve speech and
Reprint requests to: Sekarpramita Darmaputri, University of Indonesia
ODQJXDJH LQ VRPH FKLOGUHQ GLDJQRVHG ZLWK ´DXWLVP 0HGLFDO 6FKRRO -DODQ 6DOHPED 5D\D  -DNDUWD  ,QGRQHVLD 7HO
V\QGURPHµZKHQ%RQLVKREVHUYHGWKDWVRPH (PDLOd.sekarpramita@yahoo.com.

186‡Paediatr Indones, Vol. 54, No. 3, May 2014

 Sekarpramita Darmaputri et al: 3\ULGR[LQHVXSSOHPHQWDWLRQLQSHUYDVLYHGHYHORSPHQWDOGLVRUGHUV

“Autis*” OR “child pervasive development A “vitamin B6” OR “pyridoxine” OR

disorders” OR “speech disorders” OR “vitamin B complex” OR “vitamin B”
“language delay” OR “PDD”
N
D
Limits to: Humans

Cochrane EMBASE PubMed PsycINFO

643 368 241 209

Inclusion criteria: Exclusion criteria:

Ǧ Full text is available Ǧ Inappropriate topic
Ǧ Age: 0 to 18 year old Ǧ Non-data based papers (eg. reviews,
Ǧ Diagnosed as PDD or ASD topic discussions, etc)
Ǧ Randomized controlled trial design

Screening title / abstract, useful articles:

Cochrane EMBASE PubMed PsycINFO

12 10 5 8

Excluding doubles, useful articles:

Cochrane EMBASE PubMed PsycINFO

2 1 2 0

Reading full-text, useful articles:

Cochrane EMBASE PubMed PsycINFO

1 1 1 0

Figure 1. Flowchart of the searching and selection strategy

increased intracellular substrate concentrations and
thus activated the defective enzymes to phosphorylate
LQWR3/38
In our center, vitamin B6 is often empirically pre-
scribed in low-dose (not in accordance with standard
operational procedure), although no prior assessment
to its efficacy ever studied before. Hence this review
is conducted to increase the awareness of and to
LQYHVWLJDWH ZKHWKHU S\ULGR[LQH VXSSOHPHQWDWLRQ LV
superior to placebo as a therapeutic management in
FKLOGUHQZLWK3''
Case illustration
A 7-year old boy with autistic specturm disorder
accompanied by her mother came for a routine control
DW WKH &KLOG DQG $GROHVFHQW 3V\FKLDWU\ 3ROLFOLQLF
Two years ago, his mother realized that he could
not behave calmly, frequently got temper tantrum,
and easily got upset and uneasy. He also could not
communicate verbally or non-verbally. The was no
significant eye contact, and he did not follow simple
LQVWUXFWLRQV +H UHSHDWHGO\ WDONHG ´WLWLµ RU ´ELELµ
without any meanings. However, there was not any
self-destructive behavior nor any attempt to harm
other people. He was taken to hospital to have speech
and occupational therapy.
Two months ago, a therapist told his mother
that the patient is diagnosed as autistic spectrum
disorder and could not be helped only with the speech
and occupational therapy only. He also needed a
medication for reducing his autistic behavior.
&XUUHQWO\KHFDQQRWH[SUHVVKLVFRPPXQLFDWLRQ

Paediatr Indones, Vol. 54, No. 3, May 2014‡187

 Sekarpramita Darmaputri et al: 3\ULGR[LQHVXSSOHPHQWDWLRQLQSHUYDVLYHGHYHORSPHQWDOGLVRUGHUV

YHUEDOO\ DQG LV TXLWH GLIILFXOW LQ H[SUHVVLQJ KLV in a systematic review, only 3 studies included into this
needs by using a non-verbal behavior. Although review. No meta-analysis is identified.
he is getting better at maintaining his eye contact, 1\H %ULFHLQCochrane Review reported
but he is still reported to have few friends at his only 3 out of 85 studies met the inclusion criteria
school, have no social reciprocity and lack of social are relevant to the study. 1\H  %ULFH VWDWHG
MXGJPHQW$GGLWLRQDOO\KHDOVRVKRZVDVWHUHRW\SHG it is impossible to produce a meta-analysis due to
repetitive, or idiosyncratic language. He did not show
any response when another child asked him to play
WRJHWKHU'XULQJH[DPLQDWLRQKHNHSWRQLQWHUHVWHG
LQWKHZDVKLQJELQZDONHGDURXQGWKHH[DPLQDWLRQ
room, and even climbed up the chair. According to
his mother, he likes to flap his fingers every time he
IHHOVH[WUHPHO\KDSS\RUH[WUHPHO\XSVHW+HZDVJLYHQ
5LVSHULGRQH[PJDQGS\ULGR[LQH[PJ
ODFNRIQHFHVVDU\GDWDIRUDQDO\VLV7ROEHUW
and differences in both clinical populations and
outcome measures between another two remaining
VWXGLHV )LQGOLQJ  DQG .XUL\DPD ).
1HYHUWKHOHVV WKH UHYLHZ E\ 1\H  %ULFH LV DEOH
to produce a systematic review which concluded a
finding that current studies are unable to provide
sufficient data to warrant the effectiveness and
HIILFDF\RIYLWDPLQ%DVDWKHUDS\IRU3'' This
FRQFOXVLRQLVVXSSRUWHGE\5RVVLJQROHWDO
Methods ZKRDOVRUHYLHZHGWKHH[DFWVDPHVWXGLHVDV1\H 
%ULFH
The The Cochrane, EMBASE, PubMed, PsycINFO An updated systematic review is conducted by
GDWDEDVH ZHUH VHDUFKHG XVLQJ NH\ZRUGV ´$XWLV
µ 0XU]DHWDO who reviewed one study by Adams
25 ´FKLOG SHUYDVLYH GHYHORSPHQW GLVRUGHUVµ 25 +ROORZD\5+RZHYHU$GDPV +ROORZD\
´VSHHFKGLVRUGHUVµ25´ODQJXDJHGHOD\µ25´3''µ GLGQRWH[FOXVLYHO\DGPLQLVWHUYLWDPLQ%0JDVWKHLU
$1'´YLWDPLQ%µ25´S\ULGR[LQHµ25´YLWDPLQ therapy, but instead a moderate dose of multivitamin
%FRPSOH[µ25´YLWDPLQ%µRQ$SULO$OO
MRXUQDODUWLFOHVUHODWHGZLWKWKHFRPSDULVRQRIYLWDPLQ
B6 and placebo in improving social, communication,
DQGEHKDYLRUDOUHVSRQVHVIRUFKLOGUHQZLWK3''ZHUH
collected.
Searches were limited to randomized controlled
trials (RCTs), systematic review, or meta-analysis as
WKHLUGHVLJQV5&7VDUHH[FOXGHGLIWKH\KDYHEHHQ
UHYLHZHGLQDV\VWHPDWLFUHYLHZDQGRUPHWDDQDO\VLV
and mineral supplement. Hence, result of the study
might be erroneously interpreted. Considering the
shortcomings of the study, Murza et al concluded they
VXSSRUWHG1\H %ULFH·VUHYLHZ
Critical appraisal of Tolbert et al.10
We assessed the Tolbert et al. study as valid. They
described and randomized their treatment assignments
2WKHU LQFOXVLRQ FULWHULD LQFOXGH FKLOGUHQ  FRQWUROJURXSJURXSDQGJURXSFOHDUO\+RZHYHU
\HDUVGLDJQRVHGZLWK3''DQGIXOOWH[WDYDLODELOLW\
([FOXVLRQFULWHULDLQFOXGHGLUUHOHYDQWWRSLFVDQGVWXG\
is not written in English or Indonesian language. The
flowchart of searching and selection strategy can be
seen in Figure 1.
Results
A total of 35 studies were retrived after screening
no details of the randomizing process were given in
their report. Characteristics of participants in the
JURXSV ZHUH QRW VLJQLILFDQWO\ GLIIHUHQW 3DUWLFLSDQWV
were followed up for a sufficient duration and
completely (35 weeks), analyzed in the groups to
which they belonged, and were treated similarly,
H[FHSWIRUWKHH[SHULPHQWDOWUHDWPHQW3DUWLFLSDQWV
and clinicians were blinded to treatment.
1RQHWKHOHVV WKH LPSRUWDQFH RI WKLV MRXUQDO
article could not be assessed, as the data was
IRUSRVVLEOHUHOHYDQWWLWOHVDEVWUDFWDQGHYDOXDWHGIRU
potential inclusion, of which 7 studies remained after
H[FOXGLQJLUUHOHYDQWWRSLFDQGGRXEOHVUHODWHGWRVDPH
WLWOHH[WUDFWHGIURPGLIIHUHQWGDWDEDVHV$IWHUUHDGLQJ
IXOOWH[WDQGH[FOXGHGVRPH5&7VKDYHEHHQUHYLHZHG
188‡Paediatr Indones, Vol. 54, No. 3, May 2014
LQVXIILFLHQWIRUDQDO\VLVRIUHODWLYHULVN55DGMXVWHG
relative risk (ARR), relative risk reduction (RRR), and
number needed to treat (NNT).8 Nor did the authors
use pooled SD and effect size. Applicability analysis
of this article revealed that it could not be applied to
 Sekarpramita Darmaputri et al: 3\ULGR[LQHVXSSOHPHQWDWLRQLQSHUYDVLYHGHYHORSPHQWDOGLVRUGHUV
Table 1. Description of the eligibile RCTs reviewed by Nye & Brice (2009)10 and Rossignol (2009)11
Tolbert et al. (1993)10
To assess the safety and
Research questions of the
GHſECE[QHNQYFQUGXKVCOKP
study
B6/Mg
Randomized, double-blind,
Study design con-trolled, asymmetric cross-
over trial
20 participants; aged 6–18
Participants
years
B6 (20 wks) Æ placebo
(10 wks)
Interventions B6 (10 wks) Æplacebo
(10 wks)Æ B6/Mg (10 wks)
Control Æreceived nothing.
Vitamin B6 dose 200 mg/70 kg/day
Magnesium dose 100 mg/70 kg/day
Scores on Rivto-Freeman
Outcome measurements Real-Life Rating Scale for
Autism
Low dose vitamin B6/Mg was
Results ineffective for PDD; safety
unclear
Length of follow up 35 weeks
Lost to follow up None
Unclear; reported data not
Risk of bias: Allocation in useable form for analysis;
concealment control group not randomly
assigned.
CARS: Childhood Autism Rating Scale, CGI: Clinical Global Impression, CPRS:
RCT: Randomized Controlled Trial, IQ: Intelligent Quotient, SQ: Social Quotient
our patient, despite the similarity of the study sample
Findling et al. (1997)11 Kuriyama et al. (2002)12
To assess the short-term To assess the effectiveness of vitamin B6
UCHGV[CPFGHſECE[QH in improving IQ and social quotient (SQ)
vitamin B6/Mg scores in children with PDD
Randomized, double-blind, Randomized, double-blind, controlled,
controlled, cross-over trial; outcome assessor and
cross-over trial statistician also blinded
12 participants; aged 3–12.9
years 8 PDD participants; aged 6–17 years
- 10 completed the program
B6 1x100 mg (2 wks) Æ B6 2x100 mg (2
B6 (4 wks)Æ placebo (4
wks)
wks)
Placebo 1x1 (2 wks) Æplacebo 2x1 (2
Placebo (4 wks) Æ B6/Mg
wks)
(4 wks)
Parent’s diary
30 mg/kg/day (max: 1 gram/ 1x100 mg/day followed with 2x100 mg/
day) day
10 mg/kg/day (max: 350 mg/
-----
day)
Performance on CARS,
IQ (Wechsler Intelligence Scales for
CGI, CPRS, OCS, Conners
Children-III) test 9
teacher, and Conners
SQ scores (Social Maturity Scale test)
parent scale
Vitamin B6/Mg was
ineffective for autism 0QUKIPKſECPVKPETGCUGQHVQVCN+3XGTDCN
disorder treatment; safe for IQ, performance IQ and SQ scores.
short-term.
10 weeks 4 weeks
16.67% did not complete the
None
program
Unclear Unclear
Children’s Psychiatric Rating Scale, OCS: Obsessive-Compulsive Symptoms,
3DUWLFLSDQWVZHUHIROORZHGXSIRUDVXIILFLHQWGXUDWLRQ
characteristics to our patient’s condition and the
clinical question asked. Additionally, Tolbert et al.
reported no benefit and no harm from administering
ORZ GRVHV RI S\ULGR[LQH0J WKHUDS\ Values and
preferences of the patient were not assessed. Hence,
applicability to our patient remains questionable.
Critical appraisal of Findling et al.11
DQG FRPSOHWHO\  ZHHNV DQDO\]HG LQ WKH JURXSV
to which they belonged, and were treated similarly,
H[FHSWIRUWKHH[SHULPHQWDOWUHDWPHQW3DUWLFLSDQWV
and clinicians were blinded to treatment.
7KH LPSRUWDQFH RI WKLV MRXUQDO DUWLFOH ZDV
assessed using the Critical Appraisal Worksheet from
Dartmouth College: Therapy study with continuous
outcome calculations. An intervention review by Nye
et alSURYLGHGWKHQHFHVVDU\PHDQGLIIHUHQFH
Findling et alGHVFULEHGDQGUDQGRPL]HGWKHLU DQG &, RI WKH VWXG\7 3\ULGR[LQH VKRZHG QR
treatment assignment (control group and vitamin significantly beneficial effect for improving behavioral
%0J +RZHYHU WKH\ GLG QRW UHSRUW WKH GHWDLOV deficits in autistic spectrum disorder in children. A
of their randomization process. Characteristics of disadvantage of the Findling et alVWXG\ZDVWKDW
participants were not significantly different between RI &RQQHUV WHDFKHU DQG  RI &RQQHUV SDUHQW
groups. Two participants withdrew from the study. questionnaires were not completed.

Paediatr Indones, Vol. 54, No. 3, May 2014‡189

 Sekarpramita Darmaputri et al: 3\ULGR[LQHVXSSOHPHQWDWLRQLQSHUYDVLYHGHYHORSPHQWDOGLVRUGHUV

Applicability analysis of this article revealed established yet.8 Most commonly clinical sign of
that it could be applied to our patient, however, no autism is an elevation of whole-blood serotonin
beneficial effect was shown in the study. The study
sample characteristics were similar to that of our
patient and they asked similar clinical questions.
However, the study reported no beneficial effect bsed
on the performance scales assessed as well as mild
adverse effects of treatment. As such, there was no
clear indication for us to start treating our patient
with the combination. Additionally, patient’s value
and preferences had not yet been assessed.
K\GUR[\WU\SWDPLQHZKLFKLVIRXQGLQ!RIWKH
patients. Increased concentrations of homovanillic
acid, a breakdown product of dopamine, have also
been found in several autistic patients.
3\ULGR[LQH WKHUDS\ KDV EHHQ UHSRUWHG WR EH
successful in autism,7 UDLVLQJ WKH SRVVLELOLW\ D 3/3
requiring enzyme might be defective in those patients
UHVSRQVLYH WR YLWDPLQ % 7KH RQO\ 3/3UHTXLULQJ
enzyme directly involved with the synthesis or
degradation of dopamine and serotonin is AADC
Critical appraisal of Kuriyama et al.12 GLK\GUR[\SKHQ\ODODQLQH GHFDUER[\ODVH8 However,
elevated homovanillic acid, which is at least partially
.XUL\DPD et al  GHVFULEHG DQG UDQGRPL]HG
WKHLUWUHDWPHQWDVVLJQPHQWFRQWURODQGS\ULGR[LQH
groups). However, they did not report the details
of their randomization process. Characteristics of
participants were not significantly different between
JURXSV 3DUWLFLSDQWV ZHUH IROORZHG XS LQ WKH VKRUW
term (4 weeks), analyzed in the groups to which they
EHORQJHGDQGZHUHWUHDWHGVLPLODUO\H[FHSWIRUWKH
H[SHULPHQWDO WUHDWPHQW 3DUWLFLSDQWV DQG FOLQLFLDQV
were blinded to treatment.
7KH LPSRUWDQFH RI WKLV MRXUQDO DUWLFOH ZDV
assessed using the Critical Appraisal Worksheet from
Dartmouth College: Therapy study with continuous
UHYHUVLEOH ZLWK S\ULGR[LQH WKHUDS\ LQ VRPH YLWDPLQ
%²UHVSRQVLYH SDWLHQWV GRHV QRW VXJJHVW D GHIHFW
in this enzyme. 8 Additionally, cases of AADC
deficiency have been reported in the literature and
result only in a very severe inborn metabolic disorder
involving deficient concentrations of dopamine and
serotonin.8
It remains to be a question whether other
enzymes in the metabolic pathways of these neu-
rotransmitters may be responsible for the various
forms of autism that involve altered neurotransmitter
PHWDEROLVP,QDGGLWLRQWR3/3WKHFRHQ]\PHV)$'
NAD, S-adenosylmethionine, tetrahydrobiopterin,
outcome calculations..XUL\DPDet alGLGQRW and ascorbate are also used by enzymes in serotonin
report the details on their research, however, an and dopamine metabolism.8 Therefore, it is hypoth-
intervention review by Nye et al.7SURYLGHGWKH
VWXG\GDWDIURP.XUL\DPDet al. The study showed no
significant results for total IQ, verbal IQ, performance
,4 RU VRFLDO TXRWLHQW VFRUHV +HQFH S\ULGR[LQH
showed no significant beneficial effect on IQ or SQ
compared to placebo.
Applicability analysis of this article revealed
that it could not be applied to our patient as it did
not match his characteristics, was not feasible, and
the values and preferences of the patient had not yet
been assessed.
Discussion
esized if different autistic patients harbor mutations
in different metabolic enzymes, it may be possible to
reverse the effects of autism by targeting a treatment
to each individual patient. However, what should
be taken into consideration is autism is diagnosed
E\ FOLQLFDO QRW ELRFKHPLFDO LQGH[HV )XUWKHUPRUH
so little is known about the biochemical basis of this
condition, hence it is difficult to associate a treatment
response with a particular biochemical or physiologic
pathway.8
7KHFRQFOXVLRQWKDWS\ULGR[LQHLVDQHIIHFWLYH
treatment of autism remains as a challenge due to
methodological shortcomings inherent in the studies.7
0RUHRYHUQHZHUV\VWHPDWLFUHYLHZVE\1\H %ULFH
Autism PD\ EH GXH WR GHIHFWV LQ D 3/3UHTXLULQJ
enzyme or enzymes involved in the metabolism of
serotonin and dopamine, although a genetic link
WR D YLWDPLQ %²UHTXLULQJ HQ]\PH KDV QRW EHHQ
190‡Paediatr Indones, Vol. 54, No. 3, May 2014
 and Murza et al consistently stated
that vitamin B6 may not be effective in improving
clinical manifestations of autism in comparison with
placebo. Although vitamin B6 is relatively safe to
administer due to its water-solubility characteristic,
 Sekarpramita Darmaputri et al: 3\ULGR[LQHVXSSOHPHQWDWLRQLQSHUYDVLYHGHYHORSPHQWDOGLVRUGHUV

however possible adverse effects as a result of high- IRU3''

dose vitamin B6 and magnesium should be taken
into account when prescribing vitamin B6 in patients
ZLWK3'',WKDVEHHQGRFXPHQWHGWKDWKLJKGRVH
of vitamin B6 is associated with dorsal root ganglia
impairment, painful and neurological problems,
peripheral neuropathy (eg. numbness or tingling,
weakness, feelings of burning, tickling, or pricking in
In conclusion, there is insufficient evidence
to warrant the advocacy of vitamin B6 whether in
monotherapy or in combination with magnesium as
therapeutic approach to improve individuals with
3'' PDLQ GRPDLQV Vocial, communication, and
behavioral responses) when compared to placebo.
Furthermore, administration of high-dose vitamin B6
WKH GLVWDO H[WUHPLWLHV XQFRRUGLQDWHG PRYHPHQWV may lead to several adverse effects.
breathing difficulties, fatigue, and vomiting. 
 Another adverse effects, which are commonly

reported are enuresis, irritability, and sensitivity to References

sound. &RPELQLQJ S\ULGR[LQH ZLWK PDJQHVLXP
lessened some of the adverse effects when only  &XUUHQWL68QGHUVWDQGLQJDQGGHWHUPLQLQJWKHHWLRORJ\RIDXWLVP
S\ULGR[LQHLVJLYHQ &HOO0RO1HXURELRO
Rossignol et al   JUDGHG S\ULGR[LQH  +XJKHV-8SGDWHRQDXWLVP$UHYLHZRIUHSRUWVSXEOLVKHGLQ
magnesium as grade C treatment in their review. They (SLOHSV\ %HKDYLRU
DOVRGHVFULEHWKHUHFRPPHQGHGDGMXQFWLYHWUHDWPHQW  /HY\60DQGHOO'6FKXOW]5$XWLVP/DQFHW
for autism spectrum disorders as follows:  %RQLVK9([SHULHQFHVZLWKYLWDPLQ%ZLWKEUDLQGDPDJHGFKLOGUHQ
‡ *UDGH $ PHODWRQLQ DFHW\OFKROLQHVWHUDVH ZLWKDXWLVWLFV\QGURPH3UR[LVGHU.LQGHUSV\FKRORJLH
LQKLELWRUVQDOWUH[RQHDQGPXVLFWKHUDS\ 7.
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& DOSKD DGUHQHUJLF DJRQLVWV K\SHUEDULF Mineral Supplement for Children with Autistic Spectrum Disorder.
R[\JHQWUHDWPHQWLPPXQRPRGXODWLRQDQGDQWL The Journal of Alternative and Complementary Medicine.
LQIODPPDWRU\ WUHDWPHQWV R[\WRFLQ DQG YLVLRQ 
therapy; and 6. Adams J, George F, Audhya T. Abnormally high plasma levels of
‡ *UDGH & FDUQRVLQH PXOWLYLWDPLQPLQHUDO vitamin B6 in children with autism not taking supplements compared
FRPSOH[SLUDFHWDPSRO\XQVDWXUDWHGIDWW\DFLGV to controls not taking supplements. J Altern Complement Med.
S\ULGR[LQH0J HOLPLQDWLRQ GLHWV FKHODWLRQ
cyroheptadine, famotidine, glutamate antagonists,
acupuncture, auditory integration training,
massage, and neurofeedback.
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 3IHLIIHU61RUWRQ-1HOVRQ/6KRWW6(IILFDF\RI9LWDPLQ%DQG
Magnesium in the Treatment of Autism: A Methodology Review and
6XPPDU\RI2XWFRPHV-$XWLVP'HY'LVRUG
8. Ames B, Elson-Schwab I, Silver E. High-dose vitamin therapy
stimulates variant enzymes with decreased coenzymes binding affinity
systematic review conducted by Rossignol et al, LQFUHDVHG.P5HOHYDQFHWRJHQHWLFGLVHDVHDQGSRO\PRUSKLVPV
and availability, feasibility, and cost-effectiveness of the $P-&OLQ1XWU
supplementations reviewed, vitamin C may be a better  0XU]D . 3DYHONR 6 0DODQL 0 1\H & 9LWDPLQ %PDJQHVLXP
DGMXQFWLYHWUHDWPHQWIRU3''FKLOGUHQFRPSDUHGWR treatment for autism: the current status of the research. Magnesium
S\ULGR[LQH0J VXSSOHPHQWDWLRQ 'ROVNH et al  5HVHDUFK
carried out a randomized double-blinded placebo-  1\H & %ULFH $ &RPELQHG YLWDPLQ %PDJQHVLXP WUHDWPHQW LQ
FRQWUROOHGFURVVRYHUVWXG\RIYLWDPLQ&JNJERG\ DXWLVPVSHFWUXPGLVRUGHU7KH&RFKDQH&ROODERUDWLRQ
ZHLJKWGD\LQPJWDEOHVGLYLGHGLQWRVHSDUDWH
GRVHV LQ  FKLOGUHQ ZLWK $6' 7KH VWXG\ UHSRUWHG
significant improvements in stereotypical behaviors,
including rocking, pacing, and whirling without any
adverse effect were noted. No study is found regarding
the drug interaction between vitamin B6 and vitamin
C with risperidone, as the FDA-approved medication
 5RVVLJQRO ' 1RYHO DQG HPHUJLQJ WUHDWPHQW IRU DXWLVP VSHFWUXP
GLVRUGHUV D V\VWHPDWLF UHYLHZ $QQDOV RI &OLQLFDO 3V\FKLDWU\

 )LQGOLQJ50D[ZHOO.6FRWHVH:RMWLOD/+XVDQJ-<DPDVKLWD7
:L]QLW]HU0+LJKGRVHS\ULGR[LQHDQGPDJQHVLXPDGPLQLVWUDWLRQ
in children with autistic disorder: an absence of salutary effects in
a double-blind, placebo-controlled study. J Autism Dev Disord.
Paediatr Indones, Vol. 54, No. 3, May 2014‡191
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