Autism: Its Gut Stupid

Effect of probiotics on brain dysfunction: Multiple sclerosis analogy

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Growing evidence indicates that there is an ongoing cross-talk between  intestinal bacteria and brain mediated in part by immune system. There is some evidence linking intestinal bacteria in pathogenesis of some disorders like autism including differences in type of gut bacteria and short term effect of antibiotics.

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Herein we will review the link between the intestinal bugs and another nervous system disorder, i.e. multiple sclerosis.

Animal model of multiple sclerosis

Certain type of mice, e.g. Relapsing-remitting (RR) mouse model spontaneously develop experimental autoimmune encephalomyelitis (EAE) which in analogous to human multiple sclerosis (MS). Thus these mice are genetically predisposed to the disease which I will refer to as EAE/MS

• However not all of these mice develop disease EAE/MS
• Interestingly, the risk for development of disease (35% to 90%) varies depending upon where they are located i.e.  institution where breeding center is located .

Is It Leaky Gut or Leaky Gut Syndrome?

Hypothesis underlying multiple sclerosis (MS)

• There are two schools of thoughts. The changes in central nervous system (CNS) are primary initiating events. Others suggest that disease is rooted in the immune system.
• Not unlike autism, diet has been implicated in pathogenesis of MS in order to explain the exponential rise of the prevalence in Japan attributed to Western Lifestyles.
• According to Ochoa-Raparaz and colleagues from the Dartmouth Medical School in Lebanon, NH, the reservoir for the immune cells involved in multiple sclerosis may lie within the Gut Associated Lymphoid Tissue (GALT).

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Gut bacteria Brain study

Berer and colleagues from the Department of Neuro-immunology, Max Planck Institute of Neurobiology, Germany conducted studies in RR mouse model to determine the role of gut bacteria in the developmental of experimental multiple sclerosis.

• Comparison of totally germ free animals (never exposed to bacteria) and specific pathogen free (SPF) animals showed that disease EAE/MS developed in SPF animals within 3 months, it did not develop in germ free animals.
• Since bacteria play a key role in immune development, absence of disease in germ free animals suggests that lack of immune activation by gut bacterial stimulation.
• When the germ free mice were colonized with conventional bacteria, the formerly germ free mice developed EAE/MS disease shortly thereafter further substantiating the critical role of gut bacteria in autoimmune disorders.
• The difference between the 2 similar animals but with or without gut bacteria  is not based upon capacity to produce anti-MOG antibodies upon immunization.
• A word about MOG: Myelin Oligodendrocyte Glycoprotein (MOG) is a protein which plays an important role in myelinization of nerves in CNS. It is critical as an adhesion molecule providing structural integrity to the myelin, a sheath that insulates the nerves. When damaged for example by antibodies, it causes demyelinating disorders like multiple sclerosis (MS).
• Administration of anti-MOG serum results in increased risk of MS relapse presumably because of antibody induced damage to the myelin sheath.
• In subjects at risk for developing multiple sclerosis, the presence of these antibodies increases the likelihood that the subjects develop the disease.
• Caution: Data thus far on MOG link studies do not necessarily establish cause-effect relationship.

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How may gut bacteria affect brain?

• The gut bacteria could interact with MOG-specific lymphocytes by probably mimicking MOG which is important for maintaining integrity of myelin sheath of nerves.
• This suggests that the disease process starts in the Gut Associated Lymphoid Tissue (GALT). A bacterial stimulus results in autoimmune lymphocytes which instigate the demyelinating encephalomyelitis.

Potential therapeutic strategies to treat multiple sclerosis and other neurological diseases like autism if Gut Bugs and Brain theory is confirmed

• Repopulation of gut bacteria
• Immunization against bacterial antigens
• Antibiotics targeted against specific pathogens
• Probiotics to alter gut bacteraia balance to modify immune system

Evidence for some of the above therapeutic options

• Treatment of RR animals with probiotics reduces MS like symptoms as well as inflamation.
• Treatment with probiotics reduces the severity of established EAE/MS in mice.
• Opposite is true as well. Administration of lipid derived from normal mouth bacteria (commensal) Porphyromonus gingivalis exacerbates EAE/MS in mice.

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Omega-3 Fatty Acids: Implications for autism

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• Patients with autism spectrum disorders tend to have greater prevalence of gastrointestinal disorders.
• Many autism patients have food aversion and are picky eaters.
• Most of the pharmacological treatments in vogue currently have strikingly little evidence to support their use.
• Many parents have undertaken complementary and alternative treatments (CAM) especially nutritional interventions.
• Omega-3 fatty acid (n-fatty acids) supplementation has been advocated by many experts.
• Omega-3 fatty acid supplements are part of 12-step autism treatment program.

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Essential fatty acids

• Polyunsaturated fatty acids (PUFAs)
• Play critical role in function of nervous system as well as immune system
• Not synthesized in human body.
• Hence need to be consumed in diet or as supplements.
• Some fatty acids are conditionally essential

Omega-3 versus Omega-6 fatty acids

Long chain omega -3 fatty acids

• Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) mainly from fish and sea food.
• Most of the DHA build up in the brain occurs during late pregnancy to the third trimester of pregnancy to the second year of life.
• Conversion from ALA to DHA is more efficient in the developing brain than in the well-developed brain.
• Exogenous sources as diet is an important source for maintaining adequate DHA levels in adult brain.

Is It Leaky Gut or Leaky Gut Syndrome?

Short chain omega-3 fatty acids

• Alphalinolenic acid (ALA) mainly derived from vegetarian sources such as flaxseed, grains, soya beans and olives
• ALA can be converted to EPA and DHA to a modest degree by the human body

Omega-6 fatty acids (example Linolenic acid (LA)

• Major sources include derived from vegetable oils and animal fat
• Target ratio of omega-3 versus omega-6 fatty acids has been suggested to be 1:1 to 4:1
• Modern diet frequently exceeds these ratios increasing potential for sickness.

Essential fatty acids and nervous system

• Play a critical role in brain functions and transmission across nerves
• Balance between various essential fatty acids is a major determinant in the maturation of brain function.
• Inadequate 3-PUFA during the perinatal period in animal models leasd to disordered learning, neurotransmission and visual processes
• Polyunsaturated fatty acids (PUFAs) can cross blood brain barrier and enter brain

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How Omega-3 fatty acids may be important in ASD

• Reduced omega-3 fatty acids with or without changges in omega-6 fatty acids (increased imbalance) has been linked to nervous system disorders like ADD, dyslexia and dyspraxia.
• Role in pathogenesis of depression and schizophrenia.
• Some studies suggest that omega-3 fatty acid supplementation is of benefit in cases of depression and Alzheimer’s disease

Is It Leaky Gut or Leaky Gut Syndrome?

Increasing Incidence of Autism and Traditional versus Modern diet

• Ancient diets contained higher amount of wild sea food and fats from grass fed animals
• Modern diet is deficient in omega-3 fatty acids
• Modern diet contains excess of omega-6 fatty acids
• Fat in modern diet is mainly derived from vegetable sources and rich in omega-6 fatty acids
• Modern food processes like hydrogenation used to extend shelf life result in decrease in omega-3 fatty acids thus increasing the imbalance

Omega-3 fatty acid deficits may be patient specific

• May have greater than average requirement especially in case of inefficient metabolic processes

Evidence for omega-3 supplementation in autism spectrum disorders

• Most data is uncontrolled studies/reports (Johnson 2003, Patrick 2005; Bell 2004)
• Two small randomized controlled trials (Amminger 2007 and Bent 2011) with conflicting results
• Amminger study from Medical University of Vienna, Vienna demonstrated that omega-3 fatty acids are superior to placebo for improving hyperactivity and stereotypy.
• Bent study from University of California, San Francisco, CA, showed no effect although authors offered a disclaimer that “small sample size does not exclude small to moderate beneficial effects".
• A metaanalysis (Montgomery and Williams 2011) combining the above two studies concluded that “effectiveness of omega-3 fatty acids for ASD cannot be determined” since there is “insufficient evidence” indicating that omega-3 fatty acids are effective in ASD. Authors recommended that high quality, large randomized controlled trials to resolve the issue.

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Dr. Minocha’s comments on implications of above

• Both the controlled trials enrolled too few subjects especially for a disorder as heterogeneous as autism.
• Only large randomized controlled trials can resolve the issue of potential benefits.
• Based on available clinical and preclinical data and our modern diet, it is my opinion that omega-3 fatty acid supplements have potential to be of benefit in at least a subset of patients with autism spectrum disorders.

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More treatment strategies at the 12-point treatment program for autism. 

PANDAS: Do you know about it?	Warning signs of autism
Overview of autism spectrum disorders	Unhealthy gut and digestion are at root of many chronic diseases
Desulfovibrio: The new bad actor on autism scene	Abnormal gluten gliadin antibodies in autism
Functioning brain MRI scan evidence probiotics affect brain changes	D-ribose reenergizes brain in autism,  ADHD
Autism is rising in developing countries too	Probiotics improve brain function, mood, memory
Intergenerational effects: Implications for chronic diseases like autism	Altered Fermentation of Undigested Food by Gut Bacteria in Autism: Clues to Treatment Strategies
Antibiotics in meat: A case for organic food	Does Influenza and Antibiotic Use During Pregnancy Increase  Autism
Does proximity to freeway traffic  increase risk of autism	Ketogenic diet and autism
Moms' Probiotic Use Reduces Eczema	Effect of Gut Bacteria on Ultimate Health Starts During Pregnancy

Is It Leaky Gut or Leaky Gut Syndrome?

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Gut dysfunction link to behavioral problems: The autism model

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Autism spectrum disorders (ASD) are a group of heterogenous disorders characterized by behavioral problems etc along with non-neurological co-morbidities.

Evidence suggests that there is increased prevalence of gastrointestinal symptoms (whether or organic or neurobehavioral) in autism. Based on gut-brain hypothesis, such symptoms could be the child's method of communicating his/her symptoms to the care-giver.

Is It Leaky Gut or Leaky Gut Syndrome?

Autism-GI study overview

• Dr. Maenner and colleagues from the Waisman Center and Department of Population Health Sciences at the University of Wisconsin-Madison conducted the study.
• The investigators wished to examine if the behavioral problems tend to occur more in patients with gastrointestinal (GI) problems.
• The results of the study were reported in the Journal of Autism Developmental  Disorders.

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Autism-GI study design

• An ADDM network methodology was used. Behavioral features were compared between autism patients with and without GI problems.
• Patients were classified as autism if they met the DSM IV-TR  (American Psychological Association 2000) criteria  for the disorders at any time prior to the age of 8 years.
• The demographic and clinical information including results of psychometric tests and concurrent medical problems were recorded
• Eight different behavioral manifestations that may reflect a gastrointestinal disturbance were analyzed and included sleep abnormalities, mood disturbances and temper tantrums.
• Six non-GI related behavioral features like fear, delayed motor milestones were also analyzed for comparison.

Results of Autism-Gut study

• 7.2% of ASD patients studied had documented GI problems. Constipation and encopresis were common
• Autism patients with GI problems were more likely to have cerebral palsy and seizure like activity as compared to those who did not.
• Occurrence of gastrointestinal (G)I problems positively correlated with behavioral problems such as sleep problems, mood, abnormal eating habits, oppositional and defiant/destructive behavior, tantrums and delayed motor milestones.
• There was no association of GI problems with stereotypic/repetitive and self-injurious behaviors.
• There was lack of association with most control behaviors studied except delayed milestones.

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Conclusions of Autism-Gut Study

• The association of GI problems with cerebral palsy, seizure like activity and delayed milestones suggests that a subset of patients suffers from multisystem disorder involving nervous, gastrointestinal and immune system.
• Behavioral problems thought to be an expression of GI problems are common in autism although not specific to those with GI problems.
• Example: sleep problems were seen in 11% of those with GI problems as compared to 4% in those without
• Prevalence of autism behaviors does not accurately identify autism patients requiring gastrointestinal evaluation.

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How to make healthy salad

Great healthy salad making tips from a dietician.  Most things from scratch including salad dressing. It has protein component options for vegans also e.g. quinoa, buckwheat etc.  This could be a full meal on its own! 

Is It Leaky Gut or Leaky Gut Syndrome?

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Does oral N-Acetylcysteine Improve Irritability in Autism

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N-acetylcysteine and autism

• Disordered gut and nutrition have been implicated in autism.
• Pathogenic mechanisms involved in autism include an imbalance of the oxidant stress, excitatory/inhibitory systems along with alterations in glutamatergic synapses and transmission of  neuro-signals in the nervous system.
• N-acetylcysteine (NAC) is an antioxidant and modulates glutamatergic excitatory neurogenic systems.

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Significance of glutamatergic neurotransmission system

• Glutamate is the most common neurotranmitter in brain. Glutamate and GABA (gamma-aminobutyric acid) are the brain's major "workhorse" neurotransmitters involved in transmission of signals between different parts of the brain. These two are involved in diametrically opposite actions.
• While GABA is involved in primarily inhibitory pathways, glutamate is excitatory. These two neutransmission pathways and the signals involved maintain a healthy level of excitation.
• A disruption of this excitatory-inhibitory homeostasis can result in aberrent behaviors including excessive irritability.

Investigation of N-acetylcysteine in autism

Dr. Hardan and colleagues from the Department of Psychiatry and Behavioral Sciences at Stanford University in Stanford, California conducted the study titled "A Randomized Controlled Pilot Trial of Oral N-Acetylcysteine in Children with Autism". The results were published in the journal of Biological Psychiatry.

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Hypothesis of the N-acetylcysteine and autism study

N-acetylcysteine has beneficial effect on behavioral dysfunction characterized by  irritability in subjects with autism.

Design of the N-acetylcysteine and autism study

• Double-blind, randomized, placebo-controlled
• Subjects with autism
• Conducted over a period of 12 weeks
• Intervention group received N-acetylcysteine initially at 900 mg daily for 4 weeks, then 900 mg twice daily for 4 weeks and 900 mg three times daily for 4 weeks.

Is It Leaky Gut or Leaky Gut Syndrome?

Behavioral measures examined

• Primary measures included Aberrant Behavior Checklist [ABC] irritability subscale and safety measures
• Secondary measures examined included ABC stereotypy subscale, Repetitive Behavior,  Social Responsiveness.

Results of the N-acetylcysteine and autism study

• Thirty-three subjects (31 males, 2 females)  with autism were recruited.
• Full data for analysis was available for 14 subjects in the NAC group and 15 on placebo.
• Subjects in the N-acetylcysteine group demonstrated a  in significant improvement on Aberrant Behavior Checklist irritability subscale.

Conclusions of the N-acetylcysteine and autism study

• Oral N-acetylcysteine appears to be useful for control of irritability in children with autism.
• Caveat: This is a small pilot studies and larger studies are needed to confirm these results.

Is It Leaky Gut or Leaky Gut Syndrome?

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Review Autism Treatment Strategies at the 12-point treatment program for autism.

PANDAS: Do you know about it?	Warning signs of autism
Overview of autism spectrum disorders	Unhealthy gut and digestion are at root of many chronic diseases
Desulfovibrio: The new bad actor on autism scene	Abnormal gluten gliadin antibodies in autism
Functioning brain MRI scan evidence probiotics affect brain changes	D-ribose reenergizes brain in autism,  ADHD
Autism is rising in developing countries too	Probiotics improve brain function, mood, memory
Intergenerational effects: Implications for chronic diseases like autism	Altered Fermentation of Undigested Food by Gut Bacteria in Autism: Clues to Treatment Strategies
Antibiotics in meat: A case for organic food	Does Influenza and Antibiotic Use During Pregnancy Increase  Autism
Does proximity to freeway traffic  increase risk of autism	Ketogenic diet and autism
Moms' Probiotic Use Reduces Eczema	Effect of Gut Bacteria on Ultimate Health Starts During Pregnancy

Is It Leaky Gut or Leaky Gut Syndrome?

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Omega6 Fatty Acid Arachidonic acid Link to Autism Spectrum Disorders

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Autism spectrum disorders are characterized by neuro-developmental dysfunction including disordered connections in brain and associated problematic social relationships and interactions.

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Autism Fatty Acids (PUFA)  Study

Dr. Yui and colleagues from the  Ashiya University Graduate School of Education, Ashiya; Japan. The study titled, "Effects of Large Doses of Arachidonic Acid Added to Docosahexaenoic Acid on Social Impairment in Individuals With Autism Spectrum Disorders: A Double-Blind, Placebo-Controlled, Randomized Trial" was published in the Journal of Clinical Psychopharmacology

Polyunsaturated fatty acids (PUFAs) arachidonic acid (ARA) and docosahexaenoic acid (DHA), an omega-3 fatty acid play a key role maturation of neural networks in brain. In fact DHA is critical for grey matter of brain and is associated with healthy cognitive and social functioning.

Is It Leaky Gut or Leaky Gut Syndrome?

Few words about arachidonic acid

Arachidonic acid  is a omega-6 polyunsaturated fatty acid stored in the cell membrane that surrounds cells in our body. It plays a key role in signal transduction especially  in brain.

Role of arachidonic acid in signal transduction

It is a two-step process involving activation of a specific receptor on cell membrane by a signaling molecule. This activation results in another molecule like arachidonic acid transmitting the signal into the cell leading to an actual physiological or in some cases pathological response.

Hypothesis of Autism PUFA study

Supplementation with high doses of arachidonic acid plus DHA ameliorates social impairment in patients with autism spectrum disorders.

Methods and Materials of Autism PUFA study

• Duration: 16-weeks
• Subjects: 13 (7 intervention group; 6 placebo); Mean age 14.6 years
• Design: double-blind, randomized, placebo-controlled trial

Biochemical parameters studied

• Markers of signal transduction: Plasma antioxidants transferrin and superoxide dismutase.
• Outcome measure: Social Responsiveness Scale and the Aberrant Behavior Checklist-Community.

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Results of Autism PUFA study

• Arachidonic acid supplementation regimen significantly improved Aberrant Behavior Checklist-Community-measured social withdrawal and Social Responsiveness Scale-measured communication.
• There was a significant difference in plasma transferrin levels and a trend toward a significant difference in superoxide dismutase levels.

Conclusions of Autism PUFA study

Supplementation with high doses of arachidonic acid, an omega-6 fatty acid to DHA, an omega-3 fatty acid  improves impaired social interaction in individuals with autism spectrum disorder by affecting connecting signaling system in the brain.

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Is It Leaky Gut or Leaky Gut Syndrome?

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Tricyclic Antidepressants Treatment for Autism: How good is the evidence?

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Clinicians frequently use drugs affecting brain function in order to manage the manifestations of autism. Here is further evidence how many of the medications prescribed for autism spectrum disorders (ASD) have little evidence to back their use.  This post pertains to the use of tricyclic antidepressants (TCAs), a class of antidepressants with potential for significant side-effects.

Is It Leaky Gut or Leaky Gut Syndrome?

How do tricyclic antidepressants work in autism

Tricyclic antidepressants increase the neurotransmitters like norepinephrine and serotonin in the our brain. Use of TCAs for autism is based on their effects mediated via serotonin.

Tricyclic antidepressants for autism

While the use of tricyclic antidepressants in autism is common, how sure are we that they are actually effective, or it merely a placebo effect with side-effects? How do side-effects square with the strength of evidence for their efficacy in autism?

TCA-Autism Spectrum Disorders Study

Dr. Hurwitz and colleagues from the Department of Community Pediatrics, Liverpool Hospital, in Liverpool BC, NSW, Australia, conducted a meta-analysis and systemetic review of efficacy of TCAs in patients with autism.

The results of the study titled, "Tricyclic antidepressants for autism spectrum disorders (ASD) in children and adolescents. " were published in the Cochrane Database Syst Rev. March 2012.

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Objectives of TCA Autism study

The investigators wished to examine if TCA treatment in autism improves:

• Social interaction and communication
• Stereotypic and repetitive behaviours
• Comorbid states, such as depression and anxiety

In addition, authors evaluated the potential for adverse effects of TCAs

Is It Leaky Gut or Leaky Gut Syndrome?

Methodology of TCA-Autism Study 

The investigators searched the medical literature using a variety of databases for studies related to autism spectrum disorders including Cochrane Central Register of Controlled rials, MEDLINE, EMBASE, PsycINFO and  CINAHL along with Dissertation Abstracts International via Dissertation Express, and the metaRegister of Controlled Trials.

• Only randomised controlled trials on use of tricyclic antidepressants as compared to placebo, in children and adolescents with autism spectrum disorders were included in data for analysis.

Results of TCA-Autism study

Despite the rigorous search outlined above, the investigators were able to find only three studies that met the inclusion criteria. Two of the studies used clomipramine and while one studied  tianeptine.

• All the trials comprised of few subjects (12 and 32 subjects).
• Meta-analysis was not possible because of heterogeneity in studies
• Only one of the three studies found any evidence for possible short term effectiveness of tianeptine
• The results of observation of clinicians versus parents/teachers were contradictory. While parents/teachers reported benefit from tianeptine, the clinicians did not.
• Tianeptine use was associated with significant side-effects like drowsiness and reduced activity levels in these individuals while being treated with tianeptine.
• Similarly theresults of two studies on use of  clomipramine were conflicting.

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Dr. Minocha's comments

• Be aware of the limited and conflicting evidence on efficacy of TCAs in autism.
• Be aware of that TCAs have potential for significant side-effects
• More studies are needed before tricyclic antidepressants can be prescribed with confidence for treatment of individuals with ASD.

Note: Results of studies pertaining to SSRI class of antidepressants are no more comforting. Williams et al in 2010 concluded that there is lack of evidence of efficacy of SSRIs in children. However, there is limited evidence favoring use of SSRIs in adults from small studies.

Is It Leaky Gut or Leaky Gut Syndrome?

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Autism: Celecoxib COX-2 nonsteroidal antiinflammatory agent improves symptoms

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Inflammation and dysfunctional immune system have been implicated in neuropsychiatric disorders like autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia. In fact, there is a significant overlap in pathogenic factors, structural and functional abnormalities of brain, and clinical manifestations.

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Evidence for role of inflammation and immune dysfunction

1. Increased pro-inflammatory cytokines
2. Altered levels of antibodies
3. Altered levels of natural killer cells
4. Altered white blood cell function
5. Presence of auto-antibodies against brain of patients with autism spectrum disorders
6. Altered genes due to gene-gene, gene-environment, and epigenetic interactions giving rise to wide spectrum of clinical manifestations

Is It Leaky Gut or Leaky Gut Syndrome?

Similarities between ASD and schizophrenia

1. Shared pro-inflammatory andf immune dysfunction markers
2. Shared immune related genetic abnormalities
3. Overlap of altered genetic architecture including  individual, rare mutations
4. Neurotoxic role of glutamatergic neurotransmitter system in brain
5. Excitotoxicity and brain inflammation related to neuro-toxicity of glutamatergic system
6. Increased excitatory receptor activity in brain
7. Increased pro-inflammatory cytokines
8. Enhanced cyclooxygenase-2 (COX2) activity

Role of nonsteroidal anti-inflammatory drugs especially COX-2 inhibitor celecoxib

1. COX-2 inhibitor effective against inflammatory conditions like arthritis
2. COX-2 inhibitors rebalance type-1 and type-2 immune dysfunction
3. COX-2 inhibitors prevent death of brain cells
4. Beneficial effects of celecoxib  in early schizophrenia (Muller 2011)
5. Beneficial effect of celecoxib as adjunct to risperidone in schizophrenia (Akhondzadeh 2007)
6. Beneficial effect Aspirin as adjuvant to usual antipsychotic treatment of schizophrenia (Laan et al 2010)
7. Beneficial effects in major depression

Is It Leaky Gut or Leaky Gut Syndrome?

Dr. Asadabadi and colleagues examined the effect of adjunctive treatment using celecoxib for treatment of autism. The results of the study were published in the journal Psychopharmacology (2012).

Hypothesis of celecoxib-autism study

• Celecoxib has beneficial effects on aberrant behavior in autism

Study design of celecoxib-autism study

• Tertiary care referral center
• Double-blind randomized controlled trial for 10 weeks
• 40 children with autism between 5 and 11 years of age

Intervention

• Celecoxib (Celebrrex®) or placebo in addition to risperidone (Risperdal®)
• Celecoxib dose: 100 mg for first week and then 200 mg/d if body weight less than 30 kg and 300 mg/d for patients with bodyweight greater than 30 kg

Outcome measures studied

• Autism Behavior Checklist ABC-C, a 58-item tool to study disruptive behaviors
• Sub-domains of ABC-C studied included lethargy/social withdrawal, stereotypic behavior, inappropriate speech, irritability and hyperactivity/noncompliance

Results design of celecoxib-autism study

1. Complete response was attained in 55% of treatment group as compared to only 20% in placebo
2. Partial resoonse  was attained in 100% of treatment group as compared to only 60% in placebo
3. Celecoxib addition to risperidone significantly improved autism as compared to placebo:

• Irritability
• Lethargy/social withdrawal
• Stereotypic behavior

4. Celecoxib treatment did not help hyperactivity/noncompliance or inappropriate speech

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Dr. Minocha's comments

Celecoxib adjunctive treatment is beneficial for stereotypic behavior, lethargy/social withdrawal, irritability in patients wit autism spectrum disorders.

Natural Compounds with biochemical effects similar to celecoxib Cox2 

Curcumin, quercetin, green tea and white tea catechins, balcalein, luteolin in celary and parsley, omega-3 fatty acids, resveratrol, naringenin, milk thistle (silymarin), chyrsin, apigenin, blueberry extract, butyrate, baicalein, wogonin, a component in the plant Scutellaria baicalensis, N-Acetyl-L-cysteine, amentoflavone which is a component in Ginkgo biloba and magnesium.

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Is It Leaky Gut or Leaky Gut Syndrome? 

Levels of pesticides and bacteria in organic versus conventional foods

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Hippocrates said, "All illness begins in gut." There is another age old saying, "You are what you eat."

There has been a great deal of hype about the recent Stanford study that found that there is not a substantial difference in essential nutrients between organic and conventional foods. More about the study published in the Annals of Internal Medicine and as reported in the New York Times and the confusion it has caused among people trying to make difficult choices.

Is It Leaky Gut or Leaky Gut Syndrome?

Methods and results of organic versus conventional food study: 17 studies in humans and 223 studies of nutrient and contaminant levels in foods were included in the analysis. Bacterial contamination of retail chicken and pork was common but did not vary by farming techniques.  However, bacteria resistant to 3 or more antibiotics were found more commonly in conventional than in organic meats.

Conclusion of organic versus conventional food study: While not much difference in essential nutrients, organic foods have lower levels of pesticides, fewer highly antibiotic resistant food borne disease causing bacteria and much more cancer fighting phenols than conventional foods.

Going beyond the headlines:

Unfortunately, most of the headlines have been grabbed by the part of study showing no difference in nutrients and not to the remaining results.

This has led a lot of people to jump to conclusions that people might as well have conventional foods in lieu of the more expensive organic.

The proponents of this arguments miss the point that the reason why many people prefer organic foods over conventional foods is because of potential pathogens and toxins in conventional foods that go into growing and processing.

Limitations of the study to put results in the context: 

Even the authors of this study conceded that studies were heterogeneous and limited in number, and publication bias may be present. Given these substantial limitations, one should be careful in drawing any far reaching conclusions. One conclusion however was a bit more definitive that "consumption of organic foods may reduce exposure to pesticide  and antibiotic-resistant bacteria".

Dr. Minocha's question for you: What do you think about the contradictory opinions that the study has created and what is your opinion?

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Autism is rising in developing countries too!

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Western studies indicate a continued dramatic rise in incidence and prevalence of autism spectrum disorders. Most of the Because of dearth of data from developing countries, the policy makers have been largely been adopting the Western data for formulation of their local policies.

Is It Leaky Gut or Leaky Gut Syndrome?

FREE at Barnes & Noble: Doctor's Guide to Milk and Your Health: The Good, The Bad or The Slow Poison

However, utilizing the U.S. data of 1 in 88 persons affected by autism is fraught with potential for errors since the genetic pool as well as the environmental influences are dramatically different.

Limited data about autism in developing countries:

Is the incidence of autism developing countries similar to the West? Is the incidence rising just as it is in the west? Dr. Feng and colleagues from the Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore seek to answer these and related questions in a review published in the  Asia Pacific Psychiatry. 

Autism-China study

• The investigators searched the literature for studies relating to autism in China.
• 7 studies were found in the English language literature.

Autism in mainland China

While one autism study from mainland China reported annual prevalence of 2.38/10,000 with the caveat that this might be an underestimation, another reported a much greater prevalence of 11/10,000 persons.

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Autism in Taiwan

Studies from Taiwan that has westernized at a much faster rate than mainland China, studies have reported a dramatic rise in autism in the last two decades.

• While one study by Dr. Chien and colleagues found that prevalence of autism spectrum disorders had surged from 1.79/10,000 in 1996 to  28.72/10,000 persons in 2005 with a corresponding of approximately 5-fold increase in incidence over the same period. 
• An even higher prevalence rate of 122.8/10,000 persons in Taiwan was reported for the year 2007 based on Taiwan national health insurance database.

Autism in Hongkong

Studies suggest an average of prevalence of autism 16.1/10,000 during the 1986-2005.

Dr. Minocha's comments

Is It Leaky Gut or Leaky Gut Syndrome?

It is unclear from the above studies if the recent increase in autism is an actual increase or an increased diagnosis. Considering the rapidly increasing autism rates in the U.S., it appears that at least a component of above increase in developing countries represents an actual increase along with globalization taking place all over.

Learn about 12-point autism treatment program        

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