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

Brain-protective Luteolin treatment for brain dysfunction: The autism model

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Luteolin is a naturally occurring flavonoid abundant in fruits and vegetables and has received increasing attention for its neuroprotective properties.

 

Foods with high concentrations of luteolin

• Fruits like apples, apricots, raspberries, blueberries, strawberries, and oranges.
• Herbs and vegetables like Chamomile, sage, thyme, artichoke leaves, lemon, parsley, celery, carrots, cabbage, onions, tomatoes, green pepper.
• Olive oil.  

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Pharmacological actions of luteolin

·        Antiinflammatory

·        antioxidant

·        Immunomodulation

·        Strengthening blood-brain barrier

 

Rationale for use in brain dysfunction

• Neuro-inflammation plays a crucial part in neuro-behavioral dysfunction
• Immune system abnormalities are involve in many brain dysfunction like autism
• Allergies are common in many patients especially those with autism
• Mast cells are involved in allergic phenomenon, inflammation and immune modulation
• Mast cell activation is seen in autism
• Luteolin acts on mast cells inhibiting release of inflammatory chemical mediators thus suppressing inflammation. 

Potential actions of luteolin in brain

1.      Protect susceptible brain cells

2.      Potentiate actions of existing brain cells

3.      Stimulate regeneration of more brain cells especially to replace dead or dysfunctional brain cells or neurons.

 

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Animal data on luteolin

• Luteolin decreases death of brain cells as a result of neuroinflammation.
• Luteolin diminishes diabetes induced cognitive dysfunction, decreased memory and mental speed. These changes in diabetes occur due to increased oxidative stress and inflammation.
• Luteolin decreases pro-inflammatory cytokine (interleukin-6) induced behavioral problems of social interaction in mice. 

Human studies of luteolin in autism spectrum disorders

A study of 37 children with autism showed that parents of subjects who took a dietary supplement containing luteolin and quercetin for 4 months reported significant improvements of eye contact, attention and social interaction in many of the patients. However, no objective measures were used in that study.

 

Luteolin in autism study

Dr. Taliou and colleagues  from the Second Department of Psychiatry, Athens University Medical School, Attikon General Hospital, Athens, Greece conducted a trail of dietary supplement containing luteolin in subjects with autism spectrum disorders and reported their findings in the journal Clinical Therapeutics. 

 

Design of Luteolin-autism study

• Open labeled trial
• 50 kids (4-10 years of age) with autism
• Symptom list confirmed by using the Autism Diagnostic Observation Schedule
• ASD diagnosis relying on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. 

Luteolin-autism study intervention and follow up

• Each capsule of flavonoid formulation contained100 mg of luteolin 100mg derived from chamomile plus 70 mg of quercetin 70 mg and 30 mg of quercetin glycoside rutin.
• Dose: 1 capsule per 10 kg body weight per day for 26 weeks
• Baseline evaluation followed by follow-up at 18 weeks and 26 weeks. 

Outcome measures of Luteolin-autism study

•  Primary outcome was based on Vineland Adaptive Behavior Scales domains which include communication, daily living skills and socialization.
•  Secondary outcomes comprised of Aberrant Behavior Checklist, the Autism Treatment Evaluation Checklist, and the Clinical Global Impression-Improvement score.

Results of Luteolin-autism study

• 40 subjects completed the study. Six withdrew due to increased irritability due to intervention, one due to noncompliance and one withdrew after completing baseline evaluation.
•  VABS composite score improved significantly suggesting an improved adaptive functioning.
•  Of VABS subsets, there was a significant improvement in daily living skills as well as social domains, whereas the improvement in communication demonstrated a trend towards significant improvement.
•  ABI scores were significantly higher for all domains.
• ABC scores demonstrated a significant improvement on hyperactivity, irritability, lethargy as well as stereotypic behavior (p<0.01) whereas improvement in inappropriate speech showed trend towards improvement.
•  ATEC scores improved only for health/physical/behavior. 

Adverse effects in luteolin-autism study

The most frequent side effect was escalation of irritability which caused a withdrawal from study in 6 patients.

 

Conclusions/comments on luteolin-autism study

• Multiple pathogenic mechanisms are involved in neurobehavioral dysfunction. Mast cells are involved in inflammation, immune modulation, allergic phenomenon etc. These cells may one of the key pathways of behavioral dysfunction characterized by neuroinflammation and autoimmune dysregulation.
• Since multiple pathways may be involved in such disorders, multi-therapeutic strategy has the best prospect of outcome.
• The results of this study suggest that suppression of this important mast cell pathway may potentially enhance the effect of other therapeutic modalities. Large randomized controlled trials are needed however to confirm above findings.

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Does acupuncture heal fibromyalgia?

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Good effective treatment for fibromyalgia continues to evade medical science. Acupuncture is one of the many treatment modalities that has been used over the years. In fact, about 20% of fibromyalgia sufferers use it.

Dr. Deare and colleagues from the Compmed Health Institute, Southport in Queensland, Australia performed an expert meta-analysis of the clinical trials available to date on the role of acupuncture in fibromyalgia and reported their findings in the Cochrane Database Systematic Reviews, May 2013.

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Findings of acupuncture-fibromyalgia study
The investigators identified nine trials with 395 participants subjects meeting the inclusion criteria. Three of these studies used electroacupuncture.

• Acupuncture decreases pain and stiffness as compared to no treatment or standard treatment.
• Effect of acupuncture is similar to sham acupuncture in improving pain, fatigue and sleep or overall feeling of well-being.
• Electroacupuncture is better than manual acupuncture.
• Acupuncture is safe.
• Electro-acupuncture alone in combination with exercise and medications may be an option for patients fibromyalgia.

Dr. Minocha’s comments

• Treatment guidelines from various professional societies continue to be divided on role of fibromyalgia .
• German guidelines offer acupuncture a treatment option. Canadian guidelines while declining to endorse it as a therapy did acknowledge short term beneficial effects.
• Lack of ideal sham needle hinders performance of high quality blinded trials. Patients should consider above findings in the context of how much benefit they are getting from the current therapies they may be undertaking.

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Is Unhealthy Gut Linked to Rosacea?

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Cause of rosacea continues to defy science. These patients tend to have a higher prevalence of GI problems. In addition, rosacea is associated with GI diseases with manifestations beyond the gut, e.g. inflammatory bowel disease and celiac disease. Stomach infection with Helicobacter pylori bacteria has also been observed. 

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The gut is the largest immune organ in the body and the gut bacteria are involved in education of the body’s immune system. Based on such data, gut has been implicated in the causation of rosacea via the gut-immune-skin-brain axis. 

Study: Dr. Parody and colleagues from the University of Genoa, Italy wanted to examine the role of small intestinal bacterial overgrowth in the causation of rosacea. They also studied the effect of eradication of such abnormal bacterial patterns on clinical manifestations of rosacea.

Methods of rosacea-gut study:

• 113 patients and 60 healthy age-sex matched controls
• Presence of small intestinal bacterial overgrowth (SIBO) was diagnosed by lactulose breath test and glucose breath test.
• Patients with SIBO were given the rifaximin antibiotic that is not absorbed into the body and as such acts only in the gut.
• Patients without SIBO were also treated with the same gut-selective antibiotic.

Results of rosacea-gut study:

• 46 percent of rosacea patients had SIBO as compared to only 5% among healthy controls.
• Of the patients in whom SIBO was effectively eradicated, 71% of the patients totally cleared the rosacea lesions whereas 21% were greatly improved.
• In contrast, rosacea skin lesions in 90% of the patients in placebo group remained unchanged while the skin lesions worsened in the remaining 10 percent.
• Subsequently, patients in placebo group were also treated with the same gut-selective antibiotic. This resulted in complete clearing of rosacea lesions in 7% of these patients.

Conclusion of rosacea-gut study

The prevalence of SIBO is higher among rosacea patients as compared to healthy controls.

Healing of intestinal bacterial overgrowth results in complete or almost complete healing of rosacea skin lesions. These beneficial effects are maintained for at least 9 months.

Treatment with antibiotic was of no effect in patients who did not have SIBO.

Dr. Minocha’s comments

Abnormal stimulation of the immune system appears to be involved in rosacea. Such a stimulation may be due to a bacteria whether in the gut or on the skin. Results of this study using a gut selective antibiotic strongly link the gut and skin together in causation.  

Antibiotics are part of our armamentarium to treat rosacea. Perhaps these act by healing the abnormal bacterial patterns in the gut. However, many of these broad spectrum antibiotics have risk for significant adverse events. 

Stretching the argument further, probiotics have been used to effectively treat SIBO. Perhaps, we should use probiotics to treat rosacea. However, all probiotics are not created equal and the benefits in different disease states are strain specific. 

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Limited data suggest that Lactobacillus casei Shirota as well as a blend of Lactobacillus casei, Lactobacillus plantarum, Streptococcus faecalis and Bifidobacterium brevis are effective in eradicating SIBO. 

Some dermatologists are already following using probiotics as adjunct treatment of skin disorders like acne and rosacea.

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