Treatments of Autism Justified in Scientific Publication |
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TreatmentThis section does not include psychological, teaching, or social treatment but rather the techniques of modifying the chemistry of the body generally using pharmacological methods. To a large degree the
treatment of autism is organised in three therapeutic directions: 1. Prevention of the disease (e.g. genetics,
maternal exposure, vaccination problems), 2. Treatment of the progress of the
disease i.e. as if damage to the brain may take place early but continues to
take place unless action is taken (leaky gut syndrome, immunotherapy, diets,
vitamins, heavy metals, hormones, pioglitazone, oxidative stress). 3.
Treatment of the symptoms of the condition (naltrexone, melatonin,
risperidone etc). Symptomatic autism represents a range of disease and parents want to see any improvement that they can and so their report may well not be adequate. As such cases may well not respond in the same way as each other, and many findings may be oddly optimistic.
There have been some reviews (see Neurochemistry modifiers) but some wider ones: Theoharides TC, Doyle R, Francis K, Conti P, Kalogeromitros D. Novel therapeutic targets for autism. Trends Pharmacol Sci. 2008 Aug;29(8):375-382. Epub 2008 Jul 6. |
Various attempts
at treatment assessment are carried out by parents through international
organisations. This is a very
important factor simply because of the difficulty of carrying these out by
medical and psychological professions. |
Reviews
You should always remember that some reviews are aimed mainly at the subject that the author is particularly knowledge about and tends to avoid other aspects. Because of this I would recommend reading several reviews if possible.
Autism: an emerging 'neuroimmune disorder'
in search of therapy. Theoharides
TC, Kempuraj
D, Redwood
L. Expert
Opin Pharmacother. 2009
Sep;10(13):2127-43 Increased
oxidative stress and immune dysregulation are present in ASDs. Mast-cell activation
may contribute to gut-blood-brain barrier disruption and brain inflammation. No
effective treatments have emerged. Well-designed clinical trials with
nonpsychotropic drugs were few and ASD characteristics varied considerably,
making conclusions difficult. Psychotropic drugs are often used for stereotypic
and aggressive behaviours. Unique combinations with antioxidant and
anti-inflammatory flavonoids hold promise.
Anti-oxidants
The aim is to avoid the damage that takes place to brain
tissue as a result of the inadequacy of anti-oxidants that are present (either
because they are used up or they are inadequately produced).
Vitamin C
Dolske MC, Spollen J,
McKay S,
Dolske
MC, Spollen J, McKay S, Lancashire E, Tolbert L. A preliminary trial of
ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol
Biol Psychiatry. 1993 Sep;17(5):765-74. (they felt that they were going to be acting
directly on the brain with a dopaminergic action).
Modifiers of glutathione production: see below. The factors that may be involved in
maintaining glutathione are B12, and
tetrahydrofolate see below. To understand
its method see the oxidative stress page of the web
site.
Also anti-oxidants: carnosine, polyunsaturated fatty acids, hyperbaric oxygen
(you must read the articles to understand the mechanism of this as it seem
odd),
Sulphate uptake: see Feingold diet
Coenzyme Q (known as Q10, Ubiquinone). No data is available in autistic patients but can be shown to have a major action in mitochondrial disease and presumably in mitochondrial dysfunction, which may be more common than is realised. However, see Young AJ, Johnson S, Steffens DC, Doraiswamy PM. Coenzyme Q10: a review of its promise as a neuroprotectant. CNS Spectr. 2007 Jan;12(1):62-8. Review
Idebenone or Ginko Biloba. Most of the data is from other conditions in
which oxidative stress in known to have a major effect (Parkinsonism) and in
animal models. In those conditions
there has been statistical advantage from both this and Vitamin E to some
degree.
First preliminary results of an observation of Ginkgo Biloba treating
patients with autistic disorder .Phytother Res.
Niederhofer H.
2009 Mar 9. They tried giving three patients
received 2 x 100 mg Ginkgo Biloba EGb 761 for 4 weeks and claim an
advantage. Clearly there can be no statistics
from this but it suggests that research should be carried out.
Vitamin E, selenium, co enzyme Q10, grape seed extract (pycnogynol).
No published clinical data for advantage.
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Carnosine supplementation
It is supposed to act as a
neuroprotective compound that could be absorbed from the gut. It has an anti-oxidant activity
Chez
MG, Buchanan CP, Aimonovitch MC, Becker M, Schaefer K, Black C, Komen J.
Double-blind, placebo-controlled study of L-carnosine supplementation in
children with autistic spectrum disorders. J Child Neurol. 2002 Nov;17(11):833-7. (L-Carnosine, a dipeptide, can enhance frontal
lobe function or be neuroprotective. It can also correlate with
gamma-aminobutyric acid (GABA)-homocarnosine interaction, with possible
anticonvulsive effects.They decided that they found a statistically significant
improvement in the children involved and that this was without problems. The exact reason for the improvement was
unclear but has been claimed to be associated with an anti-oxidant activity)
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Hyperbaric
Oxygen
Hyperbaric oxygen therapy
(HBOT). The known data is that autistic children appear to have a lower
blood flow to the brain and presumably a lower supply of oxygen. The idea is that hypoxia causes a decrease in
mitochondrial activity unless a high level of oxygen is present in the blood
and increase mitochondrial activity. For
a full explanation see: Rossignol DA, Bradstreet JJ. Evidence of mitochondrial dysfunction in
autism and implications for treatment.
Am J Biochem and Biotechnol 2008;4:208-17.
Rossignol
DA, Rossignol LW, James SJ, Melnyk S, Mumper E. The effects of hyperbaric
oxygen therapy on oxidative stress, inflammation, and symptoms in children with
autism: an open-label pilot study. BMC Pediatr. 2007 Nov 16;7 (all is shows is that there doesn’t appear to
be a toxicity problem with starting the study).
Rossignol appears to be going to produce useful data in the future.
Weiss
HR, Liu X, Zhang Q, Chi OZ. Increased cerebral oxygen consumption in Eker
rats and effects of N-methyl-D-aspartate blockade: Implications for autism. J
Neurosci Res. 2007 Aug 15;85(11):2512-7. (the Eker rat is the model for tuberous sclerosis
and they did not find any useful advantage except in that the brain of the rat
had a higher oxygen consumption)
Rossignol DA. Hyperbaric oxygen therapy might improve certain pathophysiological findings in autism.
Med Hypotheses. 2007;68(6):1208-27. Epub 2006 Dec 4.
Hyperbaric oxygen therapy in Thai autistic children. Chungpaibulpatana J, Sumpatanarax T, Thadakul N, Chantharatreerat C, Konkaew M, Aroonlimsawas M. J Med Assoc Thai. 2008 Aug;91(8):1232-8 Improvement was shown in five domains with a significant level. Seventy-five percent of children shown improvement while 25% did not seem to respond to the treatment.
Hyperbaric oxygen therapy in autism: is there evidence?
Yildiz S, Aktas S, Uzun G. Undersea Hyperb Med. 2008 Nov-Dec;35(6):453-5.
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Modifiers
of neurochemistry: (Methyl phenidate, Memantine, Galantamine, Lamotragine, Risperidone, Atomexetine, Antipsychotics,
SSRIs, Melatonin, Guanfacine, cycloserine, mirtizapine, naltrexone)
This involves the consideration that the damage in autism has already been done and that all we can now is to modify the symptoms that we see. Attempts have been made with many chemical drugs, which are available and exceptionally active. They have created as anti-psycholtics, anti-depressives, anti-anxiety drugs, etc. Their main activities are through the modification of the activities of the neurones themselves There are not enough controlled trials with specific drugs and some of them are difficult to compare with each other simply because they use assessments differently. One good review: Hazell P. Drug therapy for attention-deficit/hyperactivity disorder-like symptoms in autistic disorder. J Paediatr Child Health. 2007 Jan-Feb;43(1-2):19-24. Review. Also another review indicates that at this time we really should have enough data to have a good guess as to which direction to go in to look for neurochemical modifier drugs: Walker MA. Treatment of autism spectrum disorders: neurotransmitter signaling pathways involved in motivation and reward as therapeutic targets. Expert Opin Ther Targets. 2008 Aug;12(8):949-67. There are some reviews Pharmacologic treatment for the core deficits and associated symptoms of autism in children. West L, Waldrop J, Brunssen S. J Pediatr Health Care. 2009 Mar-Apr;23(2):75-89
Methylphenidate (MPH) is a prescription stimulant commonly used to treat
Attention-deficit hyperactivity disorder, or ADHD. A lot of parents claim
that there is little advantage to the drug, but others disagree. It is
not clear that it makes any long term advance but rather the attempt is
to calm specific patients.
Coleman M, Steinberg G, Tippett J, Bhagavan HN, Coursin DB, Gross M, Lewis C, DeVeau L. A preliminary study of the effect of pyridoxine administration in a subgroup of hyperkinetic children: a double-blind crossover comparison with methylphenidate. Biol Psychiatry. 1979 Oct;14(5):741-51. (interesting in terms of the way in which they interpreted the response of the patient with serotonin chemistry)
Posey DJ, Aman MG, McCracken JT, Scahill L, Tierney E, Arnold LE, Vitiello B, Chuang SZ, Davies M, Ramadan Y, Witwer AN, Swiezy NB, Cronin P, Shah B, Carroll DH, Young C, Wheeler C, McDougle CJ. Positive effects of methylphenidate on inattention and hyperactivity in pervasive developmental disorders: an analysis of secondary measures. Biol Psychiatry. 2007 Feb 15;61(4):538-44.
Research
Units on Pediatric Psychopharmacology Autism Network. Randomized, controlled, crossover trial of
methylphenidate in pervasive developmental disorders with hyperactivity. Arch
Gen Psychiatry. 2005 Nov;62(11):1266-74.
(Methylphenidate was superior to placebo on the primary outcome measure,
with effect sizes ranging from 0.20 to 0.54 depending on dose and rater.
Thirty-five (49%) of 72 enrolled subjects were classified as methylphenidate
responders. However there were side effects, and the advantages were not only
not present but also were often not great).
This article has a plenty of references to the drug as it has been used
since the 1970s.
Positive effects of methylphenidate on social communication and self-regulation in children with pervasive developmental disorders and hyperactivity. Jahromi LB, Kasari CL, McCracken JT, Lee LS, Aman MG, McDougle CJ, Scahill L, Tierney E, Arnold LE, Vitiello B, Ritz L, Witwer A, Kustan E, Ghuman J, Posey DJ. J Autism Dev Disord. 2009 Mar;39(3):395-404.
Memantine: an NMDA inhibitor:
Chez
MG, Burton Q, Dowling T, Chang M, Khanna P, Kramer C.Memantine as
adjunctive therapy in children diagnosed with autistic spectrum disorders: an
observation of initial clinical response and maintenance tolerability.J Child
Neurol. 2007 May;22(5):574-9. (They claim
advances in speech, personality, and interaction..and few side effects: effectively
acting as a glutamate inhibitor)
Niederhofer
H. Glutamate antagonists seem to be slightly effective in
psychopharmacologic treatment of autism. J Clin Psychopharmacol. 2007 Jun;27(3):317-8.
Erickson
CA, Posey DJ, Stigler KA, Mullett J, Katschke AR, McDougle CJ.A
retrospective study of memantine in children and adolescents with pervasive
developmental disorders. Psychopharmacology (Berl). 2007 Mar;191(1):141-7.
Epub 2006 Oct (Eighteen patients (15 male, 3 female; mean age=11.4 years, range
6-19 years) received memantine (mean dosage=10.1 mg/day, range 2.5-20 mg/day)
over a mean duration of 19.3 weeks (range 1.5-56 weeks). Eleven of 18 (61%)
patients were judged responders to memantine based on a rating of "much
improved" or "very much improved" on the CGI-I. Significant
improvement was also seen on the CGI-S. Improvement was primarily seen
clinically in social withdrawal and inattention. Adverse effects occurred in 7
of 18 (39%) patients and led to drug discontinuation in 4 of 18 (22%) patients.
This suggests a controlled trial would be a good idea)
Treating autism pharmacologically: also tacrine might
improve symptomatology in some cases.Niederhofer H. J Child Neurol. 2007 Aug;22(8):1054; author reply 1054-5.
Cycloserine (a partial antagonist of the NMDA
glutamate receptor subtype)
Posey DJ, Kem DL, Swiezy NB, Sweeten TL, Wiegand RE, McDougle CJ. A pilot study of D-cycloserine in subjects with autistic disorder. Am J Psychiatry. 2004 Nov;161(11):2115-7 (cycloserine is an agonist for N-methyl-d-alanine and they claim that it caused a major improvement in the clinical condition of autistic children even when compared with controls. This was single blind and so it may need to be done again but is an interesting finding).
Niederhofer
H, Staffen W, Mair A. Galantamine may be
effective in treating autistic disorder. BMJ. 2002 Dec 14;325(7377):1422. No specific drugs seem to
improve autism significantly. Desipramine, dextroamphetamine, clonidine,
neuroleptics, and methylphenidate are reported to be only slightly effective
but also to have possible severe adverse effects.2–4
We conducted a placebo controlled, double blind crossover randomised controlled
trial investigating the efficacy of galantamine in autistic disorders. They
found a marginal advantage in irritability with galantamine.
A prospective, open-label trial of galantamine in
autistic disorder. Nicolson R, Craven-Thuss B, Smith J. J Child Adolesc Psychopharmacol. 2006 Oct;16(5):621-9
Eight of 13 participants were rated as responders on the basis of their
improvement scores on the Clinical Global Impressions scale. Overall,
galantamine was well-tolerated, with no significant adverse effects apart from
headaches in one patient. CONCLUSION: In this open trial, galantamine was
well-tolerated and appeared to be beneficial for the treatment of interfering
behaviors in children with autism, particularly aggression, behavioral
dyscontrol, and inattention. This is
interesting in that it is a acetylcholine esterase inhibitor that specific
finds its way to act in the CNS. It
works to slow the clinical symptomatic progress of Alzheimer’s disease, and
through this we can say that it is a safe drug.
Galantamine in the treatment of adult autism: a report of three clinical cases. Hertzman M. Int J Psychiatry Med. 2003;33(4):395-8
Galantamine and donepezil attenuate pharmacologically induced deficits in prepulse inhibition in rats. Hohnadel E, Bouchard K, Terry AV Jr. Neuropharmacology. 2007 Feb;52(2):542-51.
Lamotrigine (a modifier of
glutamate release, used as an antiepileptic drug. Epilepsy is commonly found in
autism, particularly young teens)
Belsito
KM, Law PA, Kirk KS, Landa RJ, Zimmerman AW. Lamotrigine therapy for
autistic disorder: a randomized, double-blind, placebo-controlled trial. J
Autism Dev Disord. 2001 Apr;31(2):175-81. (they did not feel that any advantage was seen)
Enalapril (ACE inhibitor)
Understanding co-morbidities affecting children with epilepsy. Pellock JM. Neurology. 2004 Mar 9;62(5 Suppl 2):S17-23.
[Antiepileptic drugs in the treatment of autistic regression syndromes] García-Peñas JJ. Rev Neurol. 2005 Jan 15;40 Suppl 1:S173-6. Spanish
Nagaraj
R, Singhi
P, Malhi
P. Risperidone in children with autism: randomized, placebo-controlled,
double-blind study. J Child
Neurol. 2006 Jun;21(6):450-5. Risperidone was associated with increased appetite
and a mild weight gain, mild sedation in 20%, and transient dyskinesias in three children.
Risperidone improved global functioning and social responsiveness while
reducing hyperactivity and aggression in children with autism and was well
tolerated.
West
L, Waldrop J. Risperidone use in the
treatment of behavioral symptoms in children with autism. Pediatr Nurs. 2006
Nov-Dec;32(6):545-9. Review
Chavez
B, Chavez-Brown M, Rey JA. Role of risperidone in children with autism
spectrum disorder. Ann Pharmacother. 2006 May;40(5):909-16.
Miral
S, Gencer O, Inal-Emiroglu FN, Baykara B, Baykara A, Dirik E. Risperidone
versus haloperidol in children and adolescents with AD : A randomized,
controlled, double-blind trial. Eur Child Adolesc Psychiatry. 2008 Feb;17(1):1-8.
Epub 2007 (they claim that risperidone is better, with both having low side
effect, at keeping AD patient calmer)
Jesner
OS, Aref-Adib
M, Coren
E. Risperidone for autism spectrum disorder. Cochrane Database Syst Rev. 2007
Jan 24;(1):CD005040. As in many
other Cochrane studies, they decide that the assessment of value in autism is
exceptionally difficult and with relatively small numbers. As such they cannot state the specific value
for the treatment.
Aman
MG, Hollway JA, McDougle CJ, Scahill L, Tierney E, McCracken JT, Arnold LE,
Vitiello B, Ritz L, Gavaletz A, Cronin P, Swiezy N, Wheeler C, Koenig K, Ghuman
JK, Posey DJ. Cognitive
effects of risperidone in children with autism and irritable behavior. J Child
Adolesc Psychopharmacol. 2008 Jun;18(3):227-36 (all they could say really was
that there was no detrimental effects of the drug on 38 children being tested.
)
Atypical antipsychotics in children and adolescents with
autistic and other pervasive developmental disorders. McDougle CJ,
Stigler KA,
Abnormal movements with the addition of clindamycin to risperidone
in a girl with autism. Malone RP,
Risperidone in the treatment of behavioral disorders
associated with autism in children and adolescents. Canitano R,
Scandurra V. Neuropsychiatr Dis Treat. 2008
Aug;4(4):723-30
Risperidone for attention-deficit hyperactivity disorder
in people with intellectual disabilities. Thomson A, Maltezos S,
Paliokosta E, Xenitidis K. Cochrane Database Syst Rev. 2009 Apr
15;(2):CD007011. This takes many of the
assessments at treatment of symptoms and tried to find whether they were
successful statistically and reliably. CONCLUSIONS:
There is no evidence from RCTs that risperidone is effective for the treatment
of ADHD in people with ID. Prescribing in this population can only be based on
open-label studies or extrapolation from research in people with autism and
disruptive behaviour disorders; however these studies have not investigated
people with ID separately so there are reservations regarding the applicability
of these findings.
Does risperidone improve hyperacusia in children with
autism? Ghanizadeh A. Psychopharmacol Bull.
2009;42(1):108-10. This was a
fascinating study in 5 patients. Hyperacusia was improved after initiation of
risperidone and disappeared after
discontinuation of risperidone. It re-happened in the re-challenge
test.
Atomexetine is an
antidepressant, mainly used for treating attention deficit hyperactivedisorder
(ADHD) in 2005 has been tried out on individual patients since then.
Arnold
LE, Aman MG, Cook AM, Witwer AN, Hall KL, Thompson S, Ramadan Y.
Atomoxetine for hyperactivity in autism spectrum disorders: placebo-controlled
crossover pilot trial. J Am Acad Child Adolesc Psychiatry. 2006 Oct;45(10):1196-205.
Niederhofer
H, Damodharan SK, Joji R, Corfield A. Atomoxetine treating patients with
Autistic disorder. Autism. 2006 Nov;10(6):647-9.
Olanzapine (an
antipsychotic, aimed against anxiety)
Posey
DJ, Stigler KA, Erickson CA, McDougle CJ. Antipsychotics in the treatment
of autism. J Clin Invest. 2008 Jan;118(1):6-14. They are frequently used to treat
irritability and associated behaviours including aggression and self injury.
They may also be efficacious for hyperactivity and stereotyped behavior.
Hollander
E, Wasserman S, Swanson EN, Chaplin W, Schapiro ML, Zagursky K, Novotny S.
A double-blind placebo-controlled pilot study of olanzapine in
childhood/adolescent pervasive developmental disorder. J Child Adolesc
Psychopharmacol. 2006 Oct;16(5):541-8. Basically showing that they could alleviate some
symptoms.
The role of antipsychotics in the management of
behavioural symptoms in children and adolescents with autism. Malone
RP, Waheed A. Drugs. 2009;69(5):535-48. It
admits that the major use for these can
only be for severe tantrums. The most
studied antipsychotic drugs include haloperidol and risperidone, although studies
of other antipsychotic drugs are underway. Safety concerns associated with
treatment include the risk of drug-related dyskinesias, which is greater with
the first-generation drugs, and the risk of weight gain and associated
metabolic problems (i.e. increases in glucose and lipids), which is greater
with second-generation agents. Prescription of antipsychotic drugs requires
careful monitoring because of these safety risks and the likelihood of
long-term use. Drug administration should be initiated at low dosages and
subsequent dosage changes should be based on tolerability and clinical response
Ziprasidone in adolescents with autism: an open-label
pilot study. Malone RP, Delaney MA, Hyman SB, Cater JR. J Child Adolesc Psychopharmacol. 2007
Dec;17(6):779-90. (A very
small pilot study)
The effect of a switch to ziprasidone in an adult population with autistic disorder: chart review of naturalistic, open-label treatment. Cohen SA, Fitzgerald BJ, Khan SR, Khan A. J Clin Psychiatry. 2004 Jan;65(1):110-3. This was mainly a trying of a new antipsychotic because older ones made the recipient obese etc. The mean +/- SD daily dose of ziprasidone was 128 +/- 41 mg, and all 10 patients continued with this same treatment after completion of the 6-month trial. Seven patients were found to have an improvement or no change in their maladaptive behavior. Eight patients (80%) lost weight (mean change = -13.1 +/- 7.0 lb [-5.9 +/- 3.2 kg]), 4 (80%) of 5 patients had a decrease in total cholesterol level, and 3 (60%) of 5 had a decrease in triglyceride levels. Data on lipid levels were available for 5 of the 10 patients. Behavioral activation was not noted in this population. There were no significant adverse effects associated with ziprasidone.
Selective serotonin reuptake inhibitors (also see SSRI in Serotonin)
These were considered
because of the high levels of serotonin uptake that is seen in cells of
autistics (again the reason is unclear).
Kolevzon
A, Mathewson KA, Hollander E. Selective serotonin reuptake inhibitors in
autism: a review of efficacy and tolerability. J Clin Psychiatry. 2006 Mar;67(3):407-14.
(a review including the use of fluoxetine, the commonest in the
Fatemi SH, Realmuto GM, Khan L, Thuras P. Fluoxetine in treatment
of adolescent patients with autism: a longitudinal open trial. J
Autism Dev Disord. 1998 Aug;28(4):303-7. Improvement from baseline
was seen in four subscales: irritability (21%), lethargy (37%), stereotype (27%),
and inappropriate speech (21%). Hyperactivity subscale improved by 14%
but did not attain statistical significance. Fluoxetine appears to have
important behavioral effects in treatment of clinic-referred autistic children.
Garstang
J, Wallis M. Randomized controlled trial of melatonin for children with
autistic spectrum disorders and sleep problems. Child Care Health Dev. 2006
Sep;32(5):585-9.
(Although the study was small owing to recruitment difficulties, it still
provides evidence of effectiveness of melatonin in children with sleep
difficulties and ASD, which we predict a larger study would confirm)
Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder.Tordjman S, Anderson GM, Pichard N, Charbuy H, Touitou Y. Biol Psychiatry. 2005 Jan 15;57(2):134-8.
Giannotti
F, Cortesi F, Cerquiglini A, Bernabei P. An open-label study of
controlled-release melatonin in treatment of sleep disorders in children with
autism. J Autism Dev Disord. 2006 Aug;36(6):741-52
(During treatment sleep patterns of all children improved. After
discontinuation 16 children returned to pre-treatment score, readministration
of melatonin was again effective. Treatment gains were maintained at 12 and
24-month follow-ups. No adverse side effects were reported. In conclusion,
controlled-release melatonin may provide an effective and well-tolerated
treatment for autistic children with chronic sleep disorders.)
Gupta
R, Hutchins J. Melatonin: a panacea for desperate parents? (Hype or truth).
Arch Dis Child. 2005 Sep;90(9):986-7.
Abnormal melatonin synthesis in autism spectrum
disorders. Melke J, Goubran Botros H, Chaste P, Betancur C, Nygren
G, Anckarsäter H, Rastam M, Ståhlberg O, Gillberg IC, Delorme R, Chabane N,
Mouren-Simeoni MC, Fauchereau F, Durand CM, Chevalier F, Drouot X, Collet C,
Launay JM, Leboyer M, Gillberg C, Bourgeron T.
Mol Psychiatry. 2008 Jan;13(1):90-8. A low melatonin level has been reported in
individuals with autism spectrum disorders (ASD), but the underlying cause of
this deficit was unknown. They are
saying that there is a poor connection between daytime and night time vs the
production of melanin in autistic children.
Also they follow the gene that produces it and suggest that this may be
involved.
Assessment and pharmacologic treatment of sleep
disturbance in autism. Johnson KP, Malow BA. Child Adolesc Psychiatr Clin N Am. 2008
Oct;17(4):773-85, viii. Review.
Melatonin for insomnia in children with autism spectrum
disorders. Andersen IM, Kaczmarska J, McGrew SG, Malow BA. J Child Neurol.
2008 May;23(5):482-5.
A randomized, placebo-controlled trial of controlled
release melatonin treatment of delayed sleep phase syndrome and impaired sleep
maintenance in children with neurodevelopmental disabilities.
Wasdell MB, Jan JE, Bomben MM, Freeman RD, Rietveld WJ, Tai J, Hamilton D,
Weiss MD. J Pineal Res. 2008 Jan;44(1):57-64.
Overall, the therapy improved the sleep of 47 children and was effective in
reducing family stress. Children with neurodevelopmental disabilities, who had
treatment resistant chronic delayed sleep phase syndrome and impaired sleep
maintenance, showed improvement in melatonin therapy
Melatonin in treatment of chronic sleep disorders in adults
with autism: a retrospective study. Galli-Carminati G, Deriaz N,
Bertschy G. Swiss Med Wkly. 2009 May
16;139(19-20):293-6
Posey
DJ, McDougle CJ. Guanfacine and
guanfacine extended release: treatment for ADHD and related disorders.
CNS
Drug Rev. 2007 Winter;13(4):465-74 (Small placebo-controlled trials support the use of
guanfacine for the treatment of ADHD. There is more limited research on the use
of guanfacine in treating hyperactivity occurring in children diagnosed with
PDD)
Handen BL, Sahl R, Hardan AY. Guanfacine in Children with Autism and/or Intellectual Disabilities. J Dev Behav Pediatr. 2008 Jun 12. Guanfacine, an alpha2-adrenergic receptor agonist, has shown some promise as an alternative to psychostimulants. Significant benefits were observed on the Hyperactivity subscale of the parent and teacher Aberrant Behavior Checklist (ABC) and Global Improvement Ratings. No gains were noted on other ABC subscales. Five of the 11 subjects (45%) were judged to be responders based on a 50% decrease in the ABC Hyperactivity subscale score between the placebo and guanfacine conditions. Several side effects were reported, including drowsiness and irritability.
Coskun M, Mukaddes NM. Mirtazapine treatment in a subject with autistic disorder and fetishism. J Child Adolesc Psychopharmacol. 2008 Apr;18(2):206-9. (this is basically in the treatment for sexual fetishism)
St John's Wort treating patients with autistic disorder.
Niederhofer H. Phytother Res. 2009 Mar 9.
Subjects were included in the study if their eye contact and expressive
language was inadaequate for their developmental level and if they had not
tolerated or responded to other psychopharmacologic treatments
(methylphenidate, clonidine or desipramine). Parent and mentor ratings on the
Aberrant Behavior Checklist, irritability, stereotypy, and inappropriate speech
factors improved slightly during treatment with
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Anti-infective
Agents
The aim being to change
the number and type of bacteria and yeast present in the gut: See site concerning gut flora. Notably see the section concerning probiotics (i.e. taking
in low pathogenicity bacteria and yeasts in the diet) as the section goes into
the use of these in other inflammatory conditions of the gut.
Anti-fungals: aimed at stopping the overgrowth of yeasts in the
gut flora. E.g. fluconazole. No useful
scientific data available.
Anti-bacterials aimed at
the anaerobes: e.g. metronidazole. No useful
scientific data although this has been stated at conferences with Finegold.
Vancomycin (active against all Gram-positive bacteria). Shown to have a notable activity in improving
autism. See Sandler in the gut
flora section of the web site. The reason for this is currently uncertain and the
drug is only available by medical prescription. The drug is very expensive and
effect appears to go after it is stopped.
Monolaurin, a small chain fatty acid type antibiotic that is
given orally. There is no scientific
published evidence that it is of any advantage but many individual parents
claiming its activity. Available over
the internet.
Acyclovir (an inhibitor of the ability of herpes viruses to
infect cells) . Now there is
suggestions that this has no significant
value.
Antibiotics: a possible treatment for regressive-onset
autism. Whelan J. Drug Discov Today. 2000 Nov 1;5(11):487-488. (this is
a review of what has been found as this point).
Short-term benefit from oral vancomycin treatment of
regressive-onset autism. Sandler RH, Finegold SM, Bolte ER, Buchanan
CP, Maxwell AP, Väisänen ML, Nelson MN, Wexler HM. J Child Neurol.
2000 Jul;15(7):429-35. This doesn’t say
a lot but it is clearly an important result in which autistic children were
treated with vancomycin and there was improvement. When the drug was stopped the effect
disappeared. This suggested that gut
bacterial things will alter the psyche of the child.
Explanation is complex:
partly because we simply don’t know why in a large proportion of autistic cases
there is an change in serotonin distribution in the blood. See serotonin
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Immunotherapy (Pioglitazone, Transfer
Factor, Phosphodiesterase inhibitor, Steroids/ACTH, Thalidomide,
Pentosan, Gamma-globulin)
The aim being to decrease
the inflammation seen in the gut wall and to some degree in the brain. As a result several drugs have been tested
but with only minor reports for some.
Sperner-Unterweger
B. Immunological
aetiology of major psychiatric disorders: evidence and therapeutic
implications.
Drugs. 2005;65(11):1493-520. Review. (a wide review)
Gupta
S. Immunological treatments for
autism. J Autism Dev Disord. 2000 Oct;30(5):475-9. review e.g. Steroids. The idea is to decrease the immune response
to external factors and to internal autoimmunes.
In fact this is a drug
used in diabetes that for some reason appeared to have some advantage in
Alzheimer’s disease, in which a specific form of damage takes place in the
brain.
Boris
M, Kaiser
CC, Goldblatt
A, Elice
MW, Edelson
SM, Adams
JB, Feinstein
DL. Effect of pioglitazone treatment on symptoms in autistic children. J
Neuroinflammation. 2007 Jan 5;4:3 (small numbers, anti-inflammatory effect
in brain etc). Feinstein
DL Therapeutic potential of peroxisome proliferator-activated receptor
agonists for neurological disease. Diabetes
Technol Ther. 2003;5(1):67-73. They
did work in vitro on cell cultures looking at the PPAR activation, which
can have additional effects upon cellular physiology, including
anti-proliferative and anti-inflammatory. These effects are observed in many
cell types, including brain glial cells and blood lymphocytes, cells whose
activation contributes to the initiation and progression of damage occurring in
neurological diseases such as Alzheimer's disease (AD) and multiple sclerosis
(MS). In view of the need for development of additional therapeutic options,
several recent studies have tested the possibility that PPAR agonists would be
neuroprotective in these diseases.
Notably the effect is probably also seen in autism. (don’t forget other PPARs like rosiglitazone
and others e.g. Pershadsingh
HA.
Peroxisome proliferator-activated
receptor-gamma: therapeutic target for diseases beyond diabetes: quo vadis?
Expert Opin Investig Drugs. 2004 Mar;13(3):215-28. The reasons behind it all are to do with
decreasing the action of microglia and astrocytes: Storer
PD, Xu J, Chavis J, Drew PD. Peroxisome proliferator-activated receptor-gamma agonists inhibit the
activation of microglia and astrocytes: implications for multiple sclerosis. J
Neuroimmunol. 2005 Apr;161(1-2):113-22. and that may make sense when you see this paper: Vargas
DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the
brain of patients with autism. Ann Neurol. 2005 Jan;57(1):67-81. Erratum in: Ann Neurol.
2005 Feb;57(2):304
Pioglitazone as a therapeutic agent in autistic spectrum
disorder. Emanuele E, Lossano C, Politi P, Barale F. Med Hypotheses.
2007;69(3):699. (this explains how the immune effects of pioglitazone may
actually be therapeutic. )
Gamma globulin
This was
tried out in the idea of the transfer factor being simply a gamma globulin and
the reports from elsewhere being that there would be some advantage. See immunology.
This is a
fairly non-specific affair in which a compound (protein, chemical but not a
cell) can be transferred from the blood of a well animal and cause the
alleviation of disease in humans.
Because it is not a specific serum-derived injection it cannot be a
pharmaceutical as such and very difficult to demonstrate as safe. However, simply finding it as being effective
in any way would be an insight into the pathology of the disease: see
Fudenberg.
Lawrence
HS, Borkowsky
W. Transfer factor--current status and future prospects. Biotherapy.
1996;9(1-3):1-5.
Fudenberg HH, Fudenberg HH. Transfer factor: past, present and future. Annu Rev Pharmacol Toxicol. 1989;29:475-516. Review.
Fudenberg
HH.. Dialysable lymphocyte extract (DLyE) in infantile onset autism: a pilot
study. Biotherapy. 1996;9(1-3):143-7. (They found that a high proportion of the
children improved dramatically and the effect went away when the treatment was
stopped) (I’m quite surprised that it got the OK for the research on what was
clearly such a baseline piece of study! It is mentioned in Phillis Kidd’s
review: Kidd
PM. Autism, an extreme challenge to integrative medicine. Part 2: medical
management. Altern Med Rev. 2002 Dec;7(6):472-99. and review: Sperner-Unterweger
B. Immunological aetiology of major psychiatric disorders: evidence and
therapeutic implications. Drugs. 2005;65(11):1493-520.
Immunoglobulins: see under
immunology above
Schneider
CK, Melmed RD, Barstow LE, Enriquez FJ, Ranger-Moore J, Ostrem JA. Oral
human immunoglobulin for children with autism and gastrointestinal dysfunction:
a prospective, open-label study. J Autism Dev Disord. 2006 Nov;36(8):1053-64.
(They carried out twelve male subjects diagnosed with AD were evaluated using a
GI severity index (GSI) while receiving daily dosing with encapsulated human
immunoglobulin. Following eight weeks of treatment, 50% of the subjects met
prespecified criteria for response in GI signs and symptoms and showed
significant behavioral improvement as assessed by the Autism Behavior Checklist)
However this was not a controlled trial and the data was not present for
stopping the drug.
A phosphodiesterase inhibitor, which
acts against the action of TNF-alpha.
Plioplys G. Intravenous immunoglobulin treatment of
children with autism. J Child Neurol
1998;13:79-82.
Pentoxifylline: A
selective phosphdiesterase inhibitor that acts against allergies partly by
inhibiting TNF-alpha. It also increases
the blood flow to the brain by allowing an increase in the deformability of the
red cell membranes. This must be one of
the many drugs that are now useful for use in the treatment of inflammatory
bowel disease..showing that many further ones have not yet been considered in
autism.
Steroids and ACTH
Geier
MR, Geier DA. The potential importance of steroids in the treatment of
autistic spectrum disorders and other disorders involving mercury toxicity. Med
Hypotheses. 2005;64(5):946-54. (This is the
hepothesis that if you can do something about the immunity against the mercury
of the vaccines etc then improvement may be seen)
Matarazzo
EB. Treatment of late onset autism
as a consequence of probable autommune processes related to chronic bacterial
infection. World
J Biol Psychiatry. 2002 Jul;3(3):162-6. Adrenocorticotrophic hormone
(ACTH), prescribed in the first months of the disease, cured one case. The
other patient, who was two years old when autistic symptoms appeared and was
treated only six years later, showed a partial but definitive improvement with
the immunosuppressive treatment.
Spironolactone
This is an inhibitor of
aldosterone, a steroid hormone produced by the adrenal gland, and its job is to
modify the sodium and potassium levels in the blood by altering the absorption
by the kidney tubeules. It does claim
potent immune modifying properties that might make it an excellent medical
intervention in autism (hence the hypothesis below)
Bradstreet JJ, Smith S, Granpeesheh D, El-Dahr JM, Rossignol D.Spironolactone might be a desirable immunologic and hormonal intervention in autism spectrum disorders. Med Hypotheses. 2007;68(5):979-87. Epub 2006 Dec 5 (they also tried it out on a single patient, who appeared to improve)
I can find no data on its
use in autism but it would seem reasonable to have tried. The drug, apart from awful effect on the
foetus, and it effect in calming and inducing sleep, was noticed in
Pentosan polysulphate.
Acts against cytokines by interacting
with heparan binding sites on cell surfaces.
Given orally the attempt is to decrease the inflammatory nature of the
gut without steroids. No published data.
Gamma-globulins from other people:
this is taken as a serum fragment from a normal person and injected into
the autistic one. See inflammation.
Bacteria flora for the gut: the idea
being that prevent any other infection getting in.
Saccharomyces boulardii: potential adjunctive treatment
for children with autism and diarrhea.
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This is suggesting that
the thyroid releasing hormone changes and autoimmunity against thyroid factors
may be involved. No good data concerning
treatment using thyroid hormones.
Cook EH. Autism: review of neurochemical investigation. Synapse 1990;6:292-308. Showed a high rate of abnormal response to TRH challenge
Adams
JB, Holloway CE, George F, Quig D. Analyses of toxic metals and essential minerals in
the hair of
Román
GC. Autism: transient in utero hypothyroxinemia related to maternal
flavonoid ingestion during pregnancy and to other environmental antithyroid
agents. J Neurol Sci. 2007 Nov 15;262(1-2):15-26. Epub 2007 Jul 24. (they
have tried giving a thyroid hormone decrease to animals for a short period
during pregnancy. This caused
neurological illness in the offspring.
The association between autoimmunity in autism is seen above (see Singh-K)
and how immunity against the thyroid has been seen.
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Nutrient Therapy. Also
see folate, B12, tetrahyrobiopterin, fatty acids
One reason why this can be at least
tried easily by parents is that commonly it does not involve pharmaceuticals
and because vitamins are easily available from local pharmacies or on the
internet. However filled with good
ideas, the data for many of the claims is missing.
Isaacson et al., “Autism:
A Retrospective Outcome Study of Nutrient Therapy,” Journal of Applied
Nutrition, vol. 48, No. 4, 1996.
Kidd
PM. Autism, an extreme challenge to integrative medicine. Part 2: medical
management. Altern Med Rev. 2002 Dec;7(6):472-99.
Johnson
S. Micronutrient accumulation and depletion in schizophrenia, epilepsy,
autism and Parkinson's disease? Med Hypotheses. 2001
May;56(5):641-5 (Johnson goes into why there may
be significance in diet)
Raiten
DJ, Massaro
T Perspectives
on the nutritional ecology of autistic children. Autism Dev Disord. 1986
Jun;16(2):133-43.
Rimland B. Controversies in the treatment of autistic children: vitamin and drug therapy. J Child Neurol. 1988;3 Suppl:S68-72.
Vitamins of various kinds as mixtures
Adams
JB, Holloway C.Pilot study of a moderate dose multivitamin/mineral
supplement for children with autistic spectrum disorder. J Altern Complement
Med. 2004 Dec;10(6):1033-9. (see fatty
acids above)
Lonsdale
D, Shamberger RJ, Audhya T. Treatment of autism spectrum children with
thiamine tetrahydrofurfuryl disulfide: a pilot study. Neuro Endocrinol Lett.
2002 Aug;23(4):303-8. Thiamine tetrahydrofurfuryl disulfide appears to have
a beneficial clinical effect on some autistic children, since 8 of the 10
children improved clinically. We obtained evidence of an association of this
increasingly occurring disease with presence of urinary SH-reactive metals,
arsenic in particular.
Niacin and B6: Kleijnen J, Knipschild P. Niacin and vitamin B6 in mental functioning: a review of controlled trials in humans.Biol Psychiatry. 1991 May 1;29(9):931-41 ‘(Fifty-three controlled trials of the effects of niacin, vitamin B6, and multivitamins on mental functions are reviewed. The results are interpreted with emphasis on the methodological quality of the trials. It turns out that virtually all trials show serious short-comings: in the number of participants, the presentation of baseline characteristics and outcomes, and the description of changes in concomitant treatments. Only in autistic children are some positive results are found with very high dosages of vitamin B6 combined with magnesium, but further evidence is needed before more definitive conclusions can be drawn.’)
Rimland B, Callaway E, Dreyfus P. The effect of high doses of vitamin B6 on autistic children: a double-blind crossover study. Am J Psychiatry. 1978 Apr;135(4):472-5. (they felt there was an advantage)
Vitamin D3: No useful scientific data available.
High
dose Vitamin A (very high doses for short period suggested to clear the body of
measles virus). No scientific data
available in terms of treatment. There is
an hypothesis that autism is associated with a G-protein modification, which is
brought back to normal using Vit A see Megson-M. in 2000.
Activated B6. (see the
literature on magnesium and activated B6)
This is considered because
pyridoxal (B6) seems to be in high concentrations and this suggests that it is
not being turned into pyrodoxal-5-phosphate (activated B6) in the body
adequately.
Adams
JB, George F, Audhya T. Abnormally high plasma levels of vitamin B6 in
children with autism not taking supplements compared to controls not taking
supplements. J Altern Complement Med. 2006 Jan-Feb;12(1):59-63. (indicating that the body
has difficulty in changing the B6 to the phosphated form).
Coleman
M, Steinberg G, Tippett J, Bhagavan HN, Coursin DB, Gross M, Lewis C, DeVeau L. A preliminary study of the
effect of pyridoxine administration in a subgroup of hyperkinetic children: a
double-blind crossover comparison with methylphenidate.
Biol Psychiatry. 1979 Oct;14(5):741-51. (The children had had low whole blood serotonin levels – which is a bit odd in itself - and a history of previous responsiveness to methylphenidate. The results of the double-blind clinical evaluation showed trends suggesting that both pyridoxine and methylphenidate were more effective than placebo in suppressing the symptoms of hyperkinesis. Pyridoxine elevated whole-blood serotonin levels, methylphenidate did not. Clinical and laboratory evidence indicated that the pyridoxine effects persisted after the 3-week period when the vitamin had been given in this experimental design. Inadequate statistics were put with the data)
Taurine:
Gaull GE. Taurine in pediatric nutrition: review and update. Pediatrics. 1989 Mar;83(3):433-42. Review
No evidence of significance in autism. Moreno-Fuenmayor H, Borjas L, Arrieta A, Valera V, Socorro-Candanoza L. Plasma excitatory amino acids in autism. Invest Clin. 1996 Jun;37(2):113-28. (they showed no particular oddity for the levels of taurine in the blood of autistic children but eleven children had increased aspartic acid and eight children had high levels of glutamate; seven of these children had a concomitant increment of taurine.)
Terahydrobiopterin: clinical advantage but complex study: see below.
Folate: no advantage found: see below
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Enzymes as part of the diet.
The suggestion is that the
inflammation that appears to take place in the upper bowel may give rise to a
lack of disaccharidases and other similar enzymes that are generally present in
the gut wall. The problem with the theorising
is that there is no clinical study published that assesses the value of giving
oral enzymes (generally derived gut and pancreas of cattle at slaughter).
Horvath K et al,
Gastrointestinal abnormalities in children with autistic disorder,” J. Pediatrics
135;no. 5 (1999) 559-563.
Horvath K and Perman
JA “Autistic disorder and
gastrointestinal disease,” Curr. Opinion in Pediatrics, 14 (2002) 583.
Kushak R and Buie T
“Disaccharidase deficiencies in patients with autistic spectrum disorders,” presented
at DAN!
Kushak R, Winter W, Farber
N, Buie T. Gastrointestinal symptoms and
intestinal disaccharidase activities in children with autism. J Pediatri Gastroenterol Nutr. 2005;41:508.
Larazotide: Modifier of gut membrane tight junctions
The data that the gut of
an autistic child will absorb larger compounds to a much greater degree than a
control, and the possibility that it will permit the penetration of compounds
from the gut (e.g. bacteria associated peptides or poorly digested food) that
would not otherwise enter the portal system to the liver both suggest that
tight junctions may be involved. These
are the attachments of one cell to the next between all the cells of the
surface membranes of the gut wall. With
tight junctions being active it is found that many compounds cannot bypass the
cells and enter the blood, but must pass through the cells themselves to get
into the body. However, if the tight
junctions are inadequate what happens is that the blockage of many compounds does
not take place.
An epithelial cell on the gut wall that is
joined to the one next to it by tight junctions (pink) and various other
complex systems that allow compounds to pass from within one cell to the next. The most important factor about the tight
junction is that it prevents compounds bypassing the cell to get into the
body. As a result, absorbed compounds
are much more decided by the cellular action than if the tight junctions were
not active.
The claim is that larazotide (AT 1001) is able to cause tight junction to act more efficiently or appear again whereas previously they no longer acted.
Tight junctions, leaky intestines, and pediatric
diseases. Liu Z, Li N, Neu J. Acta Paediatr.
2005 Apr;94(4):386-93. This review provides an overview of evidence for the
role of tight junctions breakdown in diseases such as systemic inflammatory
response syndrome (SIRS), inflammatory bowel disease, type 1 diabetes,
allergies, asthma, and autism.
The safety, tolerance, pharmacokinetic and
pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects:
a proof of concept study.
Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse. Arrieta MC, Madsen K, Doyle J, Meddings J. Gut. 2009 Jan;58(1):41-8.
Larazotide
(image from ChemBlink) = AT1001
As you can see, Larazotide
is an octapeptide. To some degree it is
not surprising that it penetrates the gut in order to carry out its action on
tight junctions in that this type of penetration is carried out by many small
peptides. However, in ASD we may well
find that it has exceptionally good penetration.
At the moment the research
is going towards the most obvious usage; the treatment of patients with celiac
disease and they claim that the drug appears to work in that condition but with
relatively low case numbers. A major
trial with the disease is imminent.
However the researcher, Alessio Fasano is quite clear in his ability to
look into many other aspects of its usage and included autism in this.
Gluten-free, casein-free
diets (and some with low sugars
and low additives)
This follows the
suggestion that opioid peptides present in diet penetrate into the brain and
cause a change in its activity. The data
is varying according to the researcher but there does appear to be some
evidence that it has some ability.
Claims by parents that the return of even minute amounts of the food to
the diet by mistake may cause a clear
affect on the autism is interesting (simply because there is a tendency
for neurones to produce more receptors when there is a lack of stimulating
compound), but there is no scientific data currently. Also see naltrexone.
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A simple compound that is
involved in the it is required for the transport of fatty acids from the cytosol into the
mitochondria during the breakdown of lipids (or fats) for the generation of
metabolic energy. The carnitines exert a
substantial antioxidant action, thereby providing a protective effect against
lipoperoxidation of phospholipid membranes and against oxidative stress induced
at the myocardial and endothelial cell level.
Filipek PA, Juranek J, Nguyen MT, Cummings C, Gargus JJ. Relative
carnitine deficiency in autism. J Autism Dev Disord. 2004;34:615-623. A random retrospective chart review was conducted to
document serum carnitine levels on 100 children with autism. Concurrently drawn
serum pyruvate, lactate, ammonia, and alanine levels were also available in
many of these children. Values of free and total carnitine (p < 0.001), and
pyruvate (p = 0.006) were significantly reduced while ammonia and alanine
levels were considerably elevated (p < 0.001) in our autistic subjects. The
relative carnitine deficiency in these patients, accompanied by slight
elevations in lactate. There does not
appear to be clinical evaluation of giving carnitine as a therapeutic measure
currently.
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Used as an antioxidant
supply of SH (may use other liver herbs with it). The problem is that it should not be given as
an oral drug in that it will not reach most tissues in the body. Because of this it seems extremely difficult
to carry out studies concerning the treatment using glutathione.
The formation of
glutathione, in order to act as an antioxidant.. Large amounts of work (involving Aw-T) has
been to see the changes in gut wall oxidation and glutathione in inflammatory
bowel diseases.
Aw
TY. Intestinal glutathione: determinant of mucosal peroxide transport,
metabolism, and oxidative susceptibility. Toxicol Appl Pharmacol. 2005 May 1;204(3):320-8.
(summarizes our current understanding of the determinants of intestinal
absorption and metabolism of peroxidized lipids. Supporting the pivotal role
that glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate
(NADPH) play in mucosal transport and metabolism of lipid hydroperoxides and
how reductant availability can be compromised under chronic stress such as
hypoxia)
Aw
TY, Wierzbicka G, Jones DP. Oral glutathione increases tissue glutathione
in vivo. Chem Biol Interact. 1991;80(1):89-97. (it probably means in the
gut wall)
Favilli
F, Marraccini P, Iantomasi T, Vincenzini MT.Effect of orally administered
glutathione on glutathione levels in some organs of rats: role of specific
transporters. Br J Nutr. 1997 Aug;78(2):293-300 (GSH levels were
measured simultaneously in various organs after oral GSH administration to
untreated rats. However levels were not
increased in the liver where it interacted with gammaGT)
Williams
TA, Mars AE, Buyske SG, Stenroos ES, Wang R, Factura-Santiago MF, Lambert GH,
Johnson WG. Risk of autistic disorder in affected offspring of mothers with
a glutathione S-transferase P1 haplotype. Arch Pediatr Adolesc Med. 2007 Apr;161(4):356-61.
(They felt that the mother’s inability to deal with toxic factors permitted the
damage to the foetus that had been seen)
Aw TY, Wierzbicka G, Jones DP. Oral glutathione increases tissue glutathione in vivo. Chem Biol Interact. 1991;80(1):89-97. (In a way it is surprising to find this as a pharmacokinetics for the oral product. The reason being that is might be expected to excreted or broken down very easily. As a result of this it may turn out to be very useful)
Golse
B, Debray-Ritzen P, Durosay P, Puget K, Michelson AM. [Alterations in two enzymes: superoxide
dismutase and glutathion peroxidase in developmental infantile psychosis
(infantile autism) (author's transl)] Rev Neurol (
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Slippery elm and gut
supporting herbs e.g. aloe vera, glutamine, peppermint and ginger: No data is available.
Metal
modification in the diet
The data concerning the
use of many of these must be difficult to interpret in that there is argument
concerning whether the patient has (or does not) and excess.
Hypocalcinurics Improve
with Calcium Supplementation Lower Hair Calcium in Autistics Reported (Dev
Brain Dysfunct 1994; 7: 63-70)
Gamma amino butyric
acid. Cohen
BI. Use of a GABA-transaminase agonist for treatment of infantile
autism. Med Hypotheses. 2002 Jul;59(1):115-6. (so far there is no data that GABA is an
advantage)
Magnesium sulphate
salts. Epsom salts in the bath as an attempt to cause
a greater uptake of sulphate. The reason
for this is that there is poor penetration and absorption of magnesium from the
gut or sulphate in adequate amounts.
However it has been suggested that this is not through the skin. See Magnesium
Ferritin: No
scientific data is available.
Zinc. No
scientific data is available.
Pentoxifylline: blood flow increase
This, and it metabolites appear
to increase the amount of oxygen present in tissues by improving
microcirculation. This may be by
altering the deformability of red cells as they pass through. Note that oxypentofylline as an action
against the production of TNF-alpha.
Gupta
S, Rimland B, Shilling PD. Pentoxifylline: brief review and rationale for
its possible use in the treatment of autism. J Child Neurol. 1996 Nov;11(6):501-4.
Review. (Little data)
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Heavy metals: See metals for the systems used
to modify the levels of mercury and others found in the body.
This is involved in the
sulphation and cycle: see the page concerning oxidation.
Messahel S, Pheasant AE, Pall H, et al. Urinary levels of neopterin
and biopterin in autism. Neurosci Lett 1998:241:17-20.
Fernell E, Watanabe Y, Adolfsson I, et al. Possible effects of
tetrahydrobiopterin treatment in six children with autism--clinical and
positron emission tomography data: a pilot study. Dev Med Child Neurol
1997;39:313-318. (During the treatment
period, all parents reported improvements in the child's social
functioning-mainly eye contact and desire to interact-and in the number of
words or sounds which the child used. Small positive changes were noted on the
Griffiths Developmental Scales between the two testing occasions. THBPt levels
in CSF increased significantly after treatment.
Danfors
T, von
Knorring AL, Hartvig
P, Langstrom
B, Moulder
R, Stromberg
B, Torstenson
R, Wester
U, Watanabe
Y, Eeg-Olofsson
O. Tetrahydrobiopterin in the treatment of children with autistic disorder:
a double-blind placebo-controlled crossover study. J
Clin Psychopharmacol. 2005 Oct;25(5):485-9. (Small nonsignificant
changes in the total scores of Childhood Autism Rating Scale after 3- and
6-month treatment. In addition, a high positive
correlation was found between response of the social interaction score and IQ.)
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(there is some data
concerning folate receptor auto immunity – see Pub Med).
Eto
I, Bandy MD, Butterworth CE Jr.
Plasma and urinary levels of biopterin, neopterin, and related pterins
and plasma levels of folate in infantile autism. J Autism Dev Disord. 1992 Jun;22(2):295-308. (they found no difference in the plasma
folate of 13 controls with autistics)
N,N,dimethylglycine. This can be given as a treatment to autism
but there is now evidence that there is no advantage
Kern
JK, Miller
VS, Cauller
PL, Kendall
PR, Mehta
PJ, Dodd
M. Effectiveness of N,N-dimethylglycine in autism and pervasive
developmental disorder. J Child
Neurol. 2001 Mar;16(3):169-73. “there
was a smaller proportion of negative changes in the dimethylglycine group, but
the quantitative changes in the dimethylglycine behavioral assessments were not
significantly different from what was observed among children who received
placebo”
There has been some data
showing that there is a possibility of the body replacing damaged cells in the
brain using injected stem cells. The
best data is from prion infections models in animals and the effect is quite
remarkable.
Ichim
TE, Solano
F, Glenn
E, Morales
F, Smith
L, Zabrecky
G, Riordan
NH. Stem cell therapy for
autism J Transl Med. 2007 Jun 27;5:30. (they data the theory from the idea that cord
blood CD34+ cells taken from cord blood improves blood supply to the
brain. They propose that mesenchymal
stem cells and cord blood CD34 cells may be useful in the treatment of
autism. At this point there is no data
to show that they are right)
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