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

Vitamin E for fatty liver or NAFLD or NASH

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Sanyal from Virginaia commonwealth University studied the effect of vitamin E and pioglitazone in nonalcoholic fatty liver diease (NAFLD). They randomly assigned  patients with NAFLD to pioglitazone medication, vitamin E (800 IU/d) or placebo for 96 weeks. Patients with diabetes were excluded.

Is It Leaky Gut or Leaky Gut Syndrome?

 The results were published in New England Journal of Medicine.

Results

Vitamin E group demonstrated a significantly greater rate of improvement as compared to placebo (43% vs. 19%, P=0.001). Both vitamin E and pioglitazone reduced inflammatory pathological chnages in liver accompanied by reductions in abnormally high liver enzymes as compared with placebo. 

Conclusions

Vitamin E maybetter than placebo for the patients with fatty liver disease or nonalcoholic steatohepatitis or NASH without diabetes.  Be sure to talk to your doctor before taking it for NASH. Some studies have linked vitamin E to adverse outcomes. 

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Does Cyproheptadine Help in Autism?

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Are mast cells involved in autism?

Increasing evidence albeit indirect and circumstantial suggest that neurochemicals released by mast cells as a result of a variety of triggers like infection, intestinal bacteria, food allergies and toxins may be responsible for autism spectrum disorders in at least a subset of the patients.

Is It Leaky Gut or Leaky Gut Syndrome?

The involvement of mast cells is supported by the fact that there are alterations in 5HT or serotonin in patients with ASD. High 5HT or serotonin levels have bidirectional impact on not just the brain but also the gut.

What do mast cells do?

Mast cells are postulated to play a key role in immune system, allergies including eczema, autoimmune disorders like multiple sclerosis, rheumatoid arthritis etc. Clinical manifestations are varied including headache/migraine, abdominal migraine , skin allergies and eczema, respiratory allergies, and food allergies, asthma, urticaria, gastrointestinal disturbances, many of which appear to be more common in autism.

One way to prove if the hypothesis is correct is by using agents that inhibit mast cell activation  and/or some of the neurochemicals released by mast cells.

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Autism-mast cell hypothesis:

Increased serotonin levels or hyperserotonaemia may be a pathologic factor in autism and cyproheptadine, a histamine-1 as well as 5-HT2 antagonist as well as a inhibitor of mast cell activation is of benefit for treatment.

What is cyproheptadine used for?

According to the NIH/NCBI publications in the US National Library of Medicine, "Cyproheptadine relieves red, irritated, itchy, watery eyes; sneezing; and runny nose caused by allergies, irritants in the air, and hay fever. It may also be used to relieve the itching of allergic skin conditions, and to treat hives, including hives caused by exposure to cold temperatures and by rubbing the skin."

Autism-cyproheptadine study

Dr. Akhondzadeh and colleagues from the Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, conducted the study and published their results in the Journal of Clinical Pharmacy and Therapeutics.

• Randomized, double-blind, placebo-controlled trial
• 40 kids between 3 and 11 years and with diagnosis of autism
• Outpatients specialty clinic at University Psychiatric Teaching Hospital
• Chief clinical manifestation: severely disruptive symptoms
• Comparison of cyproheptadine + haloperidol versus haloperidol alone (+ placebo)
• Patients assessed at baseline and after 2, 4, 6 and 8 weeks
• Dose: haloperidol titrated to maximum 0.05 mg/kg/d and cyproheptadine titrated up to maximum 0.2 mg/kg/day

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Autism-cyproheptadine study outcome measures

• Aberrant Behaviour Checklist-Community (ABC-C)
• Childhood Autism Rating Scale (relating to people and verbal communication
• Side effects and extrapyramidal symptoms recorded using a checklist and the Extrapyramidal Symptoms Rating Scale

Autism-cyproheptadine study results showed improvement in cyproheptadine group

• ABC-C scores improved with cyproheptadine plus haloperidol as compared to haloperidol alone. Patients in cyproheptadine demonstrated a significant mean decrease in ABC score of −10.9 compared to a mean decrease of −3.7 in patients receiving placebo
• Childhood Autism Rating Scale scores improved with cyproheptadine + haloperidol as compared to haloperidol alone
• No significant difference in extrapyramidal symptoms side-effects

Autism-cyproheptadine study conclusions

Is It Leaky Gut or Leaky Gut Syndrome?

Cyproheptadine combines with a conventional antipsychotic may be superior to conventional antipsychotic alone for patients with autistic spectrum disorder. Results of the study lend support to the hypothesis that mast cells may be involved in the pathogenesis of autism spectrum disorders.

 Elbe and Lalani recently concluded in the Journal of  Canadian Acad Child Adolescent Psychiatry that it may be considered for use on an off-label basis when FDA approved medications are not effective or cause significant undesirable effects.  

Is It Leaky Gut or Leaky Gut Syndrome?

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Treating swallowing problem eosinophilic esophagitis with 6-food elimination diet SFED Elimination Diet

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Swallowing problems are common among children as well as adults. Eosinophilic esophagitis is being increasing recognized as a prominent cause.

Overview of eosinophilic esophagitis

• Allergy mechanism is involved.
• Food allergies have been implicated.
• Optimal treatment has thus far been less than satisfactory.
• Elemental diet as well as six food elimination diet (SFED) has shown promise in children with a symptomatic response rate of 97% .

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Symptoms of Eosinophilic esophagitsis

• Dysphagia or swallowing problems
• Food impaction
• Heartburn
• Noncardiac chest pain

What is Six-Food Elimination Diet or SFED?

SFED diet  involves exclusion of following from diet:

• Cow’s milk
• Soy
• Eggs
• Wheat
• Peanuts
• Tree nuts
• Fish especially shell fish

Six-food elimination diet plan  is not a classic food allergy dietary approach in which food targets are based on food sensitization patterns .

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Design of SFED elimination diet study

• Prospective clinical study at Northwestern University School of Medicine.

Initial testing of subjects

• Patients underwent skin prick testing to identify any specific known allergies.
• Potential allergens in air that were tested included tree, grass, ragweed, house-dust and mold etc.
• Testing for food allergans included peanuts, tree nuts, eggs, wheat, milk, soy.

Methods of SFED elimination diet study

• Patients underwent a baseline upper GI endoscopy, then 6-weeks of six food elimination diet and then again an upper GI endoscopy with biopsies.
• Those patients whose biopsies showed normalization then were introduced to specific foods one at a time ( for 2-weeks each)
• Repeat endoscopy and biopsy of esophagus in order to identify the food trigger in that particular subject.

Patients studied in  SFED elimination diet study

• 50 subjects participated in the initial component
• 20 subjects completed the reintroduction diet plan

Effect on dysphagia or swallowing problem

• 94% of subjects dervied benefit
•  Dysphagia frequency scores declined from a median 3.5 to 2.0
• Dysphagia duration score decreased from 2.2 to 1
• Dysphagia intensity score decreased from 3.4 to 1.8.
• Endsocopic scores improved in 78% percent of patients.
• SFED also resulted in improved quality of life as measured by SF-36 scores.

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Are all foods equally to blame?

• No!
• Wheat was involved in 60%
• Milk contributed to the disease in 50% of the cases.
• Symptom recurrence occurred in all 20 subjects upon reintroduction of elimination diet components along with abnormalities on upper GI endoscopy and biopsy.

Elimination diet trial versus skin prick testing

•  Skin prick testing was able to identify specific allergen in only 13% of the cases.

Limitations  of SFED elimination diet study

• Uncontrolled study
• The “normalization” of the biopsy specimens did notocur in 36% of patients despite symptomatic improvement

Conclusions of SFED elimination diet study

• The normalization of biopsies on histology is less than that is seen in response to elemental diet in children.
• Other dietary allergans, cross-allegans and/or involvement of aero-allergens may be involved.
• SFED provides a reliable and practical means of identifying food triggers and tailor the dietary regimen accordingly.
• Diet may not be able to cure.
• Finding of the eggs and wheat being the commonest offending agent is consistent with data from other studies.

A thought to ponder and link

• Gluten free, casein free diet has been shown to be of benefit in autism.
• Wheat is source of gluten while cow's milk is source of casein!

Dr. Minocha's comments

Rather than going for expensive allergy testing, it might be more prudent to adopt a diagnostic/therapeutic trial of elimination diet, SFED plan being one of them.

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Effect of Stress on Gut: Leaky Gut?

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  Stress/anxiety and intestinal barrier function

Mechanisms on effect of stress

• Stress, whether  physiological, pathological, psychological or  pharmacological affects  fluid, electrolyte, and mucus secretion and absorption, gastrointestinal motility, as well as visceral sensitivity along with structural and functional alterations of gastrointestinal barrier. All this can the intestinal barrier leaky. 
• The translocation of toxins/pathogens initiates an inflammatory reaction which then leads to a dominos effect and promotes more dysfunction due to the effect of absorbed toxins/pathogens which make the barrier even more permeable via inflammatory reaction.

• An emerging paradigm suggests that stress responses or dysfunctions in the endoplasmic reticulum and in mitochondria contribute to the loss of tissue homeostasis and to the development of chronic intestinal inflammation and disruption of intestinal barrier. 

Alterations in intestinal barrier function are seen in animal models of acute as well as chronic stress.

Is It Leaky Gut or Leaky Gut Syndrome?

 Acute stress on barrier function in animals

• Acute, cold-restraint and/or immobilization stress causes an increase in intestinal permeability across the transcellular and paracellular pathways.

• Stress induced changes occur via temporary redistribution of Tight Junction proteins along with alterations in mast cells, autonomic nervous system and corticotropin-releasing hormone. Many of the alterations are attenuated in animal models deficient of with mast cell–deficient animals.
• Stress  worsens colitis in animal models of Inflammatory Bowel Disease associated with  decrease in colon mucus production, along with  increase in colon permeability.

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Animal data on stress and bowel function

• Stress and anxiety have been implicated in causing as well as exacerbating  functional bowel disorders.
• Rats separated from their mothers show visceral hypersensitivity and increased stress-induced defecation along with  increased mucus secretion, mucosal damage and  increased number of  goblet cells suggesting disrupted intestinal barrier.

Stress in humans and barrier function

Stress induced increase in permeability has been implicated in a variety of functional, allergic and inflammatory disorders Thus psychological stress offers anther target for intervention in such disorders.

• Psychologic stress modulates  the clinical activity in inflammatory bowel disease as well as  irritable bowel syndrome.

Stressed patients are more likely to suffer relapses of functional and inflammatory disorders.

Is It Leaky Gut or Leaky Gut Syndrome?

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