A subtype of people with classic autism have uric acid
excretion which is elevated (>2 Standard Deviations above the normal mean).
According
to the research these hyperuricosuric autistic individuals may comprise
approximately 20% of the autistic population.
There is nothing new in these
findings and the research goes back 15 years.
At that time nobody looked too deeply as why uric acid was elevated and
the role of the purine
metabolism in behaviour.
Dr Naviaux
at the University of California is the researcher who is developing antipurinergic
therapy. I suspect his research is
really at the root of what is going on and that high uric acid is just a
consequence of an upstream metabolic dysfunction.
It does
seem that in some people doing just that does produce tangible benefits and not
just in autism; there was even a study in bipolar disorder. In bipolar, verapamil can also sometimes be effective.
Uric acid
Uric acid is a
chemical created when the body breaks down substances called purines. Purines
are found in some foods and drinks. These include liver, anchovies, mackerel,
dried beans and peas, and beer.
Most uric acid
dissolves in blood and travels to the kidneys. From there, it passes out in
urine. A high level of uric acid in the
blood is called hyperuricemia, the standard test though is to measure uric acid in urine.
Purine metabolism and autism
To learn about the purine metabolism and autism, I suggest
you read the research by Naviaux, like the study below:
Autism spectrum disorders (ASDs) now affect 1–2% of the children born in the United States. Hundreds of genetic,
metabolic and environmental factors are known to increase the risk of ASD.
Similar factors are known to influence the risk of schizophrenia and bipolar
disorder; however, a unifying mechanistic explanation has remained elusive.
Here we used the maternal immune activation (MIA) mouse model of
neurodevelopmental and neuropsychiatric disorders to study the effects of a
single dose of the antipurinergic drug suramin on the behavior and metabolism of
adult animals. We found that disturbances in social behavior, novelty
preference and metabolism are not permanent but are treatable with
antipurinergic therapy (APT) in this model of ASD and schizophrenia. A single
dose of suramin (20 mg kg−1 intraperitoneally (i.p.)) given to 6-month-old adults
restored normal social behavior, novelty preference and metabolism.
Comprehensive metabolomic analysis identified purine metabolism as the key
regulatory pathway. Correction of purine metabolism normalized 17 of 18 metabolic
pathways that were disturbed in the MIA model. Two days after treatment, the
suramin concentration in the plasma and brainstem was 7.64 μM
pmol μl−1 (±0.50) and 5.15 pmol mg−1 (±0.49), respectively. These data show good uptake of
suramin into the central nervous system at the level of the brainstem. Most of
the improvements associated with APT were lost after 5 weeks of drug washout,
consistent with the 1-week plasma half-life of suramin in mice. Our results show that purine
metabolism is a master regulator of behavior and metabolism in the MIA model,
and that single-dose APT with suramin acutely reverses these abnormalities,
even in adults.
Hyperuricemia
Purine synthesis is increased approximately 4-fold in hyperuricosuric
autistic patients, so they have elevated levels in their blood and also excrete high levels.
Be aware that there is both Hyperuricemia and Hypouricemia.
It looks like things can easily
get mixed up.
Some people have low levels of uric acid in their blood, because the
excrete too much in their urine.
Causes of hyperuricemia can be classified into three functional types:
increased production of uric acid, decreased excretion of uric acid, and mixed
type. Causes of increased production include high levels of purine in the diet
and increased purine metabolism.
In the case study below where
hyperuricosuric autism was successfully
treated, they actually used a therapy which is claimed for Hypouricemia
You will see reference below to this:-
This is very odd and please let
me know if you think of a logical explanation.
It seems that the therapies for
hypouricemia may treat hyperuricemia in autism.
Here is a summary from Wikipedia:-
Treatment
Idiopathic
hypouricemia usually requires no treatment. In some cases, hypouricemia is a medical
sign of an underlying condition that does require treatment. For example, if
hypouricemia reflects high excretion of uric acid into the urine (hyperuricosuria) with its
risk of uric acid nephrolithiasis, the
hyperuricosuria may require treatment.
Drugs and
dietary supplements that may be helpful
Antiuricosurics
Antiuricosuric
drugs raise serum uric acid levels and lower urine uric acid levels. These
drugs include all diuretics, pyrazinoate, pyrazinamide, ethambutol, and aspirin.
Antiuricosuric
drugs are useful for treatment of hypouricemia and perhaps also hyperuricosuria, but are
contraindicated in persons with conditions including hyperuricemia and gout.
Dietary sources of uridine
Some foods that contain uridine in the form
of RNA are listed below. Although claimed that virtually none of the uridine in
this form is bioavailable "since - as shown by Handschumacher's Laboratory
at Yale Medical School in 1981 - it is destroyed in the liver and
gastrointestinal tract, and no food, when consumed, has ever been reliably
shown to elevate blood uridine levels', this is contradicted by Yamamoto et al,
plasma uridine levels rose 3.5 fold 30 minutes after beer ingestion,
suggesting, at the very least, conflicting data. On the other hand, ethanol on
its own (which is present in beer) increases uridine levels, which may explain
the raise of uridine levels in the study by Yamamoto et al. In infants
consuming mother's milk or commercial infant formulas, uridine is present as
its monophosphate, UMP, and this source of uridine is indeed bioavailable and
enters the blood.
·
Sugarcane extract
·
Tomatoes (0.5 to 1.0 g uridine per kilogram
dry weight)
·
Brewer’s yeast (1.7% uridine by dry weight)
·
Beer
·
Broccoli
·
Offal (liver, pancreas, etc.)
Consumption of RNA-rich foods may lead to
high levels of purines (adenosine and
guanosine) in blood. High levels of purines are known to increase uric acid production
and may aggravate or lead to conditions such as gout. Moderate
consumption of yeast, about 5 grams per day, should provide adequate
uridine for improved health with minimal side effects.
Hyperuricemia
Medications most often used to treat hyperuricemia are of two kinds: xanthine oxidase inhibitors
and uricosurics. Xanthine oxidase inhibitors decrease the
production of uric acid, by interfering with xanthine oxidase. Uricosurics increase the excretion of
uric acid, by reducing the reabsorption of uric acid once the kidneys have
filtered it out of the blood. Some of these medications are used as indicated, others are used off-label. Several
other kinds of medications have potential for use in treating hyperuricemia. In
people receiving hemodialysis, sevelamer can significantly reduce serum uric acid,
apparently by adsorbing urate in the gut
Non-medication treatments for hyperuricemia include a low purine diet (see Gout)
and a variety of dietary supplements. Treatment with lithium salts has been used as lithium improves uric
acid solubility.
Decreased
excretion
The principal drugs that contribute to
hyperuricemia by decreased excretion are the primary antiuricosurics.
Other drugs and agents
include diuretics,
salicylates,
pyrazinamide,
ethambutol,
nicotinic
acid, ciclosporin,
2-ethylamino-1,3,4-thiadiazole, and cytotoxic
agents.
A ketogenic
diet impairs the ability of the kidney to excrete uric acid, due to
competition for transport between uric acid and ketones
Hyperuricosuric
Autism
Abstract
A subclass of patients with
classic infantile autism have uric acid excretion which is >2 S.D.s above
the normal mean. These
hyperuricosuric autistic individuals may comprise approx. 20% of the autistic
population. In order to determine the metabolic basis for urate
overexcretion in these patients, de novo purine synthesis was measured in the
cultured skin fibroblasts of these patients by quantification of the
radiolabeled purine compounds produced by incubation with radiolabeled sodium
formate. For comparison, de novo purine synthesis in normal controls, in
normouricosuric autistic patients, and cells from patients with other disorders
in which excessive uric acid excretion is seen was also measured. These experiments showed that de
novo purine synthesis is increased approx. 4-fold in the hyperuricosuric
autistic patients. This increase was less than that found in other
hyperuricosuric disorders. No unusual radiolabeled compounds (such as
adenylosuccinate) were detected in these experiments, and no gross deficiencies
of radiolabeled nucleotides were seen. However, the ratio of adenine to guanine
nucleotides produced by de novo synthesis was found to be lower in the cells of
the hyperuricosuric autistic patients than in the normal controls or the cells
from patients with other disorders. These results indicate that the hyperuricosuric subclass of autistic
patients have increased de novo purine synthesis, and that the increase
is approximately that expected for the degree of urate overexcretion when
compared to other hyperuricosuric disorders. No particular enzyme defect was
suggested by either gross deficiency of a radiolabeled compound or the
appearance of an unusual radiolabeled compound, and no potentially neurotoxic
metabolites were seen. Although
an enzyme defect responsible for the accelerated purine synthesis was not
identified, the abnormal ratio of adenine to guanine nucleotides suggests a
defect in purine nucleotide interconversion.
Here is a case study regarding the successful treatment of
hyperuricosuric autism with uridine supplementation.
Abstract
A single male subject with
hyperuricosuric autism was treated for a period of 2 years with an oral dose of
uridine, which increased from 50 to 500 mg/kg/day. This patient experienced
dramatic social, cognitive, language, and motor improvements. These improvement
decreased within 72 h of the discontinuation of uridine, but reappeared when
uridine supplementation was resumed. Thus, it appears that patients with
hyperuricosuric autism benefit from metabolic therapy with oral uridine therapy
in a manner similar to that seen in other disorders of purine metabolism in
which there is autistic symptomatology.
Uridine as a therapy in Bipolar
Disorder
Here is a
small trial using uridine to treat bipolar disorder in depressed adolescents:-
Abstract
This report is an open-label case series of seven depressed adolescents
with bipolar disorder treated with uridine for 6 weeks. Treatment response was
measured with the Children's Depression Rating Scale-Revised and the Clinical
Global Impressions scale.
Uridine was associated with decreased depressive symptoms, and was well
tolerated by study participants. Further systematic studies of uridine
are warranted.
Conclusion
In people
with autism and high levels of uric acid in urine and blood, there are some
interesting avenues to pursue. Very
confusingly, they appear to be the therapies more commonly suggested for hypouricemia.
Uridine seems
a good choice worth investigating for children with high levels of uric acid.
Beer is
better reserved for adults with Asperger’s.
It may
indeed turn out that high uric acid is a biomarker for people who will respond
to Naviaux’s antipurinergic therapy.