Digestion, health and nutrition: Dr. Anil Minocha, a gastroenterologist and nutritionist

Carnitine supplements as treatment of autism?

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Abnormalities of mitochondria are widely prevalent in patients with autistic spectrum disorders. Prevalence of abnormal biomarker values of mitochondrial dysfunction is higher in patients with autism. Biomarkers of mitochondrial dysfunction include carnitine and lactate.

 

Filipek from the University of California in Irvine, Ca have demonstrated that patients with autistic spectrum disorders have higher prevalence of carnitine deficiency. Carnitine deficiency has been attributed to the mitochondrial defects. Such alterations could in turn play in role in pathogenesis of effects on brain as manifested by various behavioral effects.

 

Literature suggests potential role for carnitine supplementation for treatment of autism; however, thus far, there has been lack of good randomized controlled trials to examine the effect of carnitine.

Is It Leaky Gut or Leaky Gut Syndrome?

 

Hypothesis: L-carnitine supplementation ameliorates the effects of mitochondrial dysfunction in patients with autistic spectrum disorders.

 

Study: Geier and colleagues from the Institute of Chronic Illness in Silver Springs, MD conducted a double blind, randomized placebo controlled trial to evaluate the effect of levocarnitine in 30 patients with autism spectrum disorders.

 

Intervention: Liquid L-carnitine 50 mg/kg bodyweight per day or placebo for 3 months.

Outcome measures:

• Childhood Autism Rating Scale (CARS)
• Hand muscle testing
• Modified clinical global impression (CGI)
• Autism Treatment Evaluation Checklist (ATEC)
• Treatment adherence measurement (TAM)
• Frequency and intensity of side effect rating (FISER)
• Global rating of side effect burden (GRSEB)
• Patient report of incidence of side effects (PRISE)

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Results: L-carnitine treatment led to significant improvement in: Childhood Autism Rating Scale, hand muscle testing, modified clinical global impression, and Autism Treatment Evaluation Checklist.

Changes in carnitine levels in serum were positively associated with improvements in associated with hand muscle strength, cognitive scores, and Childhood Autism Rating Scale scores.

 

Conclusions: L-carnitine supplementation results in clinical improvement in several clinical parameters in patients with autistic spectrum disorders.

 

Is It Leaky Gut or Leaky Gut Syndrome?

 

Dr. Minocha’s opinion: The results of the study are dramatic and provocative; however, further substantiation may be in order.

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Autism, leaky gut and elimination diets

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Autism: Is it linked to leaky gut syndrome? Do elimination diets help?

There has been a lot of “buzz” about the role of increased intestinal permeability (intestinal hyperpermeability) or leaky gut syndrome in the pathogenesis of autism and autistic spectrum disorders or ASD. A leaky gut may allow absorption of larger molecules especially peptides etc. derived from food which then in turn could potentially affect the neurological function manifesting as behavioral problems.

Is It Leaky Gut or Leaky Gut Syndrome?

Let’s look at some of the facts:

• Celiac disease that is related to gluten may present with clinical picture of autism.   
• D’Eufemia et al from La Sapienza University in Italy performed a lactulose-mannitol test to evaluate the intestinal permeability in 21 autistic and 40 control kids. The investigators reported that abnormal permeability through a damaged or dysfunctional gut (i.e.leaky gut) was present in 43% of the autistic kids and none of the control children. 
• De Magistris and colleagues from the Second University of Naples, Italy studied alterations in intestinal permeability in kids with autism and their first degree relatives. Abnormal permeability or leaky gut was seen in 37% of kids with autism, as compared to 21% in first degree relatives and only 5% in healthy controls. Faecal calprotectin was increased in 24% of autistic kids, 12% of first degree relatives and none in controls. The investigators concluded that the results support the “leaky gut” hypothesis and measurement of intestinal permeability may identify those kids with autism that  may benefit from elimination diet. In addition, the high prevalence of abnormalities in the relatives indicates that genetic factors involving tight junctions may play a role in the pathogenesis. 
• American Academy of Pediatrics feels that the literature supporting the role of leaky gut in autism is “limited” and that more studies are needed.

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If leaky gut plays a role in autism, exclusion of certain foods like gluten and casein with potentially noxious products may help the patients.

• Knivsberg et al. from the Stavanger University College, Norway conducted a randomized controlled trial of effect of gluten free, casein-free diet in kids with autism and found that development of children at the end of 12-months who underwent dietary intervention with gluten-free, casein-free diet was superior to the controls who were on their usual diet. 
• Elder eta l from the University of Florida conducted a double blind cross over trial of casein free, gluten free diet in kids with autistic spectrum disorder. Outcome parameters include autistic symptoms and urinary peptide levels. Overall, there were no differences between the two groups. However, parents of 9 of the 15 kids wanted to continue the diet and reported subjective clinical improvement. 
• A Cochrane database review by Millward and colleagues from the Derbyshire Children’s Hospital in Derby, UK and Literature and Evidence Research Unit at Nottinghamshire Healthcare Trust in Woodbeck, UK conducted a systematic review and meta-analysis of literature on the role of elimination diets in autistic spectrum disorder. The authors identified two randomized controlled trials albeit small. Elimination diet showed benefit in overall autistic traits, social isolation and overall ability to interact. 
• Rossingnol from the International Child Development Resource Center, Melbourne, FL in 2009 gave a grade C recommendation for the use of elimination diets in autistic kids. 
• Since the publication of the above reports, opinions as well as the position statement of American Academy of Pediatrics, another randomized controlled trial has been published. Whiteley et al. from the University of Sutherland in the United Kingdom conducted a 2-stage single blinded randomized controlled trial of gluten free and casein free diet in kids with ASD. Outcome measures included Autism Diagnostic Observation Schedule (ADOS) and the Gilliam Autism Rating Scale (GARS) as markers for  core autism behaviours, Vineland Adaptive Behaviour Scales (VABS) to evaluate the developmental level, along with nd Attention-Deficit Hyperactivity Disorder - IV scale (ADHD-IV) for assessment of  inattention and hyperactivity. Results at 12-months demonstrated a significant improvement in the intervention group on the  ADOS, GARS and ADHD-IV. Results at 24 months showed benefit was sustained at 24 months although the clinical impact showed a plateau.

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Bottom-line: While there is controversy, my "belief" is consistent with Reichelt and Knivsberg from the Rikshospitalet Medical Centre, University of Oslo in Norway who conclude in Annals of Clinical Psychiatry that a gut-to-brain axis connection in autism is both possible and probable based on the effect of diet on excreted compounds and behavior in conjunction with the clinical data available. Obviously, large studies over time will be needed to resolve the controversy.

More topics below.... or click to Home page      

Other topics of interest:

1. Can probiotics strengthen selective intestinal barrier? 
2. Autism related to gut bacteria? 

 Is It Leaky Gut or Leaky Gut Syndrome?

Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health

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Are abnormal Intestinal bacteria linked to autism?

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Can antibiotics cure some cases of autism? 

By A. Minocha MD

Intestinal bacteria provide numerous health benefits and disruption of this milieu has been associated with many diseases not just inside the gut but in rest of body as well. There is some evidence suggesting autism is associated with impaired gastrointestinal health especially alterations in gut bacteria.

Is It Leaky Gut or Leaky Gut Syndrome?

In addition to the fact that some kids provide history of antibiotic use and diarrheal illness prior to onset of the disease, a subset of children develop normally initially before manifesting illness. The spores of the Clostridium bacteria have received special attention in this regard.

Evidence mostly consists of data points, the question is, is it reasonable to conclude that there is a link based on connecting these data points. Some say YES, critics say NO. The proponents frequently cite the following study as one of the pieces of evidence implicating alterations gut bacteria especially clostridia in the pathogenesis of autism.

Sandler and colleagues from the Rush Children’s Hospital at the Rush Medical College in Chicago Illinois performed a study on use of the antibiotic vancomycin patients with autism and published their findings in the study titled ,”Short-term benefit from oral vancomycin treatment of regressive-onset autism” in the Journal of Child Neurology.

Vancomycin is an antibiotic which when given by mouth is works only in the gut since it is not absorbed though the gut into the blood stream.

Hypothesis: Changes in the bacterial flora of the gut may promote increased growth of neurotoxin producing bacteria in the gut with potential to cause manifestations of autism.

Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health

Study: Children with antecedent broad-spectrum antibiotic treatment followed by chronic diarrhea along a decline of previously acquired skills, and then frank manifestations of autism were included. 11 children with regressive-onset autism met the inclusion criteria and participated in the study.

Results: Analysis of multiple coded pre- and post-vancomycin assesments including paired videotapes scored by a clinical psychologist blinded to treatment revealed an improvement in 80% of the children. However, the improvement was short-lived and declined post-treatment.

Authors conclusions: While the investigators did not suggest  vancomycin protocol used in the study as an effective therapeutic modality for autism, they concluded that the findings do implicate a possible gut bacteria-brain axis connection.

Dr. Minocha's comment: The literature on role of gut bacteria in autism is controversial and scientific community is divided into two camps. You make the call in consultation with your physician.

Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health

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Leaky gut syndrome	Is mangosteen good for health
Autism and leaky gut	Autism and gut bacteria
Intestinal bacteria for health and disease	Gut bacteria genes and gut at interphase in autism
L-carnitine treatment for autism	Vitamin D and autism
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Autism and gut bacteria: Do antibiotics work?	Chronic abdominal pain in kids
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Black raspberries and cancer risk	Diet for Crohn’s disease patients
Irritable bowel syndrome or IBS	Cancer risk of artificial sweeteners

Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health   

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Is VitaminD deficiency a growing epidemic. maybe?	Mangosteen is not the same as mango

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