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

Brain Dysfunction? Learn about glial cells & dual protection by antioxidants

By A. Minocha MD, author: Guide to Alternative Medicine and the Digestive System

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Antioxidants also protect against inflammation in brain

It is well known that the antioxidants protect brain against oxidative stress and thus ameliorate brain dysfunction due to myriad causes. Little known fact is that antioxidants also protect nervous tissue indirectly by inhibiting inflammation of glial cells in the brain.

Glial cells have also been called the Forgotten Brain Cell. Glial cells actually vastly outnumber the classic nerve cells or  neurons. While much of research related to brain disorders has focussed on neurons, increasing attention is now being drawn to functioning of glial cells

What are glial cells

Glial cells are a group of complex supporting cells and unlike the nerve cells or neurons are not involved in neural conduction.  

• What are the functions of glial cells
• Glial cells insulate the adjoining neurons from one another. Glial cells also perform the housekeeping cleaning function of the brain. In fact they are critical for optimal function
  of neurons and thus the brain.
• According to Andrew Koob, author of the book, “The Root of Thought”, glial cells are involved in the brain processing and the imagination function.
• Dr. Hughes calls microglia the “constant gardeners”

Glial cells and inflammation in brain

• Brain inflammation is typical for many neurodegenerative diseases.
• While optimal mmune response to any insult or injury in brain is critical for a healthy brain, an inappropriate response or an over-reaction damges the normal brain tissue.
• Glial cells get activated by the slightest of the insults in brain including infection, trauma, toxins, nutritional deficiency, or decreased blood supply etc. that may occur as a result of confluence of  genetic and environmental elements.
• Activated glial cells produce mediators of inflammation. 

Glial cell related neuroinflammation in neurodegenerative diseases

• Typically, immune system is protective, however, overactivation causes damage
  to the brain.
• Inflammation-immune reaction are seen in many neurodegenerative disorders like Alzheimer's, Parkinsons disease etc.
• Multiple studies have documented abnormalities of glial cells especially microglia.
• In addition to typical inflammatory cells, activated microglia are also evident along with pro-inflammatory neurochemicals.

Glial cell involvement in neurobehavioral dysfunction like autism

• Studies of PET Scans of subjects with autism show an enhanced activation of microglia as compared to controls.
• Dr. Maezawa and colleagues  from the University of California in Davis, CA argue that microglia respond to environmental provocation during pregnancy as well as early childhood by altering the expression of genes (epigenetics) resulting in abnormal activity of neuronal synapses based on the
  experiences/exposures.
• Glial dysfunction related to genetic and epigenetic factors can adversely affect the growth and developmental trajectory with or without inducing  evoking inflammation.
• There appears to be a decreased glial density in brain of subjects with ADHD on imaging studies and suboptimal supply of energy from glial cells  has been implicated in the variability in behaviour and the underlying neuronal activity of children with ADHD.

Above factors suggest that glial cell dysfunction may be involved in neurobehavioral disorders like autism and ADHD/ADD.

Dual role for antioxidants in neuroprotection inlcuding antiinflammatory action

Antioxidants may thus not only protect brain against oxidative stress but also indirectly by inhibiting oxidant/antioxidant imbalance induced neuroinflammation. Beause of multiple redundant metabolic pathways involved in neuroinflammation, a cocktail of antioxidants rather than a single antioxidant may offer the best chance for neuroprotection.

Learn about 12-point autism treatment program OR more topoics of interest below

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Use of elimination diet in autism	Food allergies and intolerance are not the same
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What is Rumination Syndrome? How to Treat?

By A. Minocha MD, author: Guide to Alternative Medicine and the Digestive System

Rumination syndrome is effortless and persistent or repetitive, regurgitation of recently consumed food back from the stomach into mouth.  It is considered among one of the functional gastrointestinal disorders and is defined by Rome III  criteria. 

Who may suffer from rumination syndrome?

It was initially described in mentally and developmentally challenged children. Although normal in cows and other animals, rumination is not a part of healthy digestion process in humans. It may be seen in healthy subjects of all ages including adults irrespective of cognitive function. 

What causes rumination syndrome?

Causation is poorly understood. Basically, it is a learned behavior/disorder, a reflex response, and not an intentional action.  There is a voluntary although unintentional contraction of abdominal muscles raising the pressure in stomach and regurgitating the food upstream up the esophagus and into the mouth.  

Clinical manifestations of rumination syndrome

The rumination or regurgitation episode typically occurs 1-2 hours after meals. The food arriving into the mouth is either spitted out or reswallowed.  The event is not preceded by retching or nausea. The regurgitated food is easily recognized and tastes just fine. The event stops once the regurgitate tastes acidic.  

Diagnosis of rumination syndrome

 Diagnosis is mainly clinical. A good history is the cornerstone of diagnosis.  Manometry may aid diagnosis but is not esential and is performed in specialized centers only.

Difference between vomiting and rumination syndrome

 Rumination  different from vomiting. The process is volatile. The food regurgitated into mouth cannot be retained in a vomiting episode. In contrast,  the food can be retained the mouth in a rumination episode, and is subsequently spitted or reswallows.

Treatment of rumination syndrome

1. Reassurance plus behavioral therapy is succesful in as many as 90% of patients

2. Behavioral therapy includes habit reversal techniques involving unlearning of the learned behaviors. Since rumination cannot occur during relaxed diaphragm, patients are given diaphragmatic rebreathing training wherein patients relax their diaphragm during and after meals. This is easily learnt, performed and is highly effective. 

3. Chewing gum helps.

4, Medications: Prokinetic agents, baclofen may be tried, however, there is lack of studies

5. Surgery: Antireflux surgery

Efficacy of medicinal and surgical treatments has not been well studied and likely not effective not of value.

Long term consequences of rumination

• Mostly nuisance value
• No long term health consequences in most cases
• Few patients develop esophagitis
• Weight loss is uncommon

Read contents/reviews of Dr. Minocha's book at Guide to Alternative Medicine and the Digestive System

 Facebook AutismItsGutStupid group page 

Leaky gut syndrome	Quinoa, a complete food even NASA likes
Inflammation: The good, the bad and the ugly	Paleolithic or stone-age diet overview
Day care infections: Try probiotics	Whole fruit versus fruit juice
Effects of gut bacteria starts during pregnancy	Honey and cough
Breast milk benefits and alternatives	Implications of FODMAP diet health and sickness
Cranberry juice versus antibiotics for urinary tract infections	ADHD: Causes, role of diet, gut and treatment
Mangosteen benefits: myths or reality	Food allergies and intolerances
Does Vegetarian diet reduce mortality	Nutritional supplements for liver disease
Aquatic therapy for chronic pain	CT (CAT) scans and risk of cancer

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Role of Gut Bacteria in Infantile Colic

By A. Minocha MD, author: Guide to Alternative Medicine and the Digestive System

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Colic is seen in about 25% of the infants especially in neurobehavioral disorders like autism and involves excessive crying. Parents are too familiar with abdominal colic in kids and the frustration it causes. It is a poorly understood entity and the parent’s  frustration is further compounded by inadequate prevention and treatment options.

Recent data implicates alterations of gut bacteria in causing the disease. A corollary to this would be that readjusting the balance of gut bacteria can help heal these kids of what sometimes seem like never ending crying spells.

Dr. de Weerth from the Behavioral Science Institute, Radboud University,  Netherlands wished to examine if there are differences in the early on intestinal bacteria in kids with colic problems. There article titled, “Intestinal Microbiota of Infants With Colic: Development and Specific Signatures” was published in the journal Pediatrics.

Methods of colic-bacteria study

The investigators  studied the the bacterial DNA from 12 colicky infants. The data was compared to similar age-matched infants without colic. More than 200 stool samples were taken from study subject and controls.

Results of colic-bacteria study

• Significant patterns of intestinal bacteria were found in colicky subjects
• There was increase in bacterial biodiversity after birth in healthy subjects and not in colicky infants
• Bacterial groups responsible for colic-related differences in bacteria were evident in colicky subjects as early as 1-2 weeks after birth.
• Unhealthy bacteria of Proteobacteria type were increased more than 2-fold in colicky infants
• Healthy Bacteroidetes and Firmicutes  including bifidobacteria and lactobacilli bacteria were decreased in infants with colic. Many of these are known to anti-inflammatory effects including increased  production of butyrate in the colon which ahs been shown to affect pain in several studies. Dr. Banasiewicz have shown that administration of microencapsulated sodium butyrate reduces the frequency of abdominal pain in patients with irritable bowel syndrome. 

Conclusions and Dr. Minocha's comments

• Specific/unique intestinal bacterial fingerprint is evident early on within first couple of weeks in babies who later on develop colic.
• The dysbiosis likely results in chronic low grade inflammation, large amounts of intestinal gas and pain resulting in crying for extended periods at a time.  
• Maternal diet during pregnancy and breast-feeding  period may also play a role.
• The greater levels of bacteria that are big producers of butyrate among babies who do not develop colic later on provides clues to targeting therapies for crying seen in such babies, an obvious example would be the use of probiotics and prebiotics in the baby’s formula.

Read contents & reviews of Dr. Minocha's  Guide to Alternative Medicine and the Digestive System 

More topoics of interest below

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Blog: Digestion, Health and Nutrition

Meat animals: Perils of using antibiotics and others drugs

By A. Minocha MD, author: Guide to Alternative Medicine and the Digestive System

The meat you buy at the grocery store comes from a variety of sources which in turn have an eclectic plethora of strategies on growing these animals.

One big factor is the use of antibiotics in animals. This is important that alterations in meat from the bacteria as well as the residual antibiotic in the meat consumed has led to an exponential rise of antibiotic resistant organisms that we may at times suffer from as a disease.

Statement of the problem

An astonishing amount of antibiotic, 300 mg of antibiotics is used in production of every kilogram of meat and eggs. Estimation of the seriousness of the role of animal reservoir in emerging antibiotic resistant bacteria in humans is no easy task.

Emerging evidence suggests that while the main culprit is the indiscriminate antibiotic use by us, the antibiotic use in animals continues to play increasing role.

Historical perspective

Originally the antibiotics were used to treat or stave off infections. However, little known fact from recent times is that antibiotics are frequently used to promote growth in these animals, thus bigger the animal, the greater the pay off!

Stokestad and Jukes reported very low sub-therapeutic doses of antibiotics (1/10 to 1/100 of the therapeutic dose) administered animals in feed improves feed-to-weight ratio for poultry, swine, and beef cattle. This allowed the practice to become widespread while ignoring the potential for deleterious consequences on human health.

Effect of antibiotic use in animals on farm dwellers/workers

Subsequent studies found that animal growth promotants (AGPs) resulted in more resistant bacteria in the gut of not just the farm animals but also the farm workers as compared to when AGPs were not used.

A landmark study reported in 1976 by Levy and colleagues and published in the New England Journal of Medicine examined the impact of low-dose oxytetracycline as an AGP on the intestinal bacteria of chickens and farm workers.

Amazingly, investigators found not only the chickens with antibiotic resistant bacteria but also in the gut of the family living on the farm. 

Consequences of antibiotic use in animals

According to Price and colleagues from the Translational Genomics Research Institute (TGen), Pathogen Genomics Division, Flagstaff, Arizona, methicillin-resistant Staphylococcus aureus clonal complex 398 (CC398) since its discovery in the early 2000s,has become a rapidly emerging cause of human infections, most often associated with livestock exposure.

Their findings suggest a bidirectional exchange between animals and humans and highlight underscore the public health risks of antibiotic used meat animals. 

According to World Health organization, “A crisis has been building up over decades, meaning that today common yet life-threatening infections are becoming difficult or even impossible to treat. It is time to take much stronger action worldwide to avert an ever-increasing health and economic burden.” 

How do altered bacteria contaminate the food chain?

Contamination resulting in animal to human transmission occurs not just via food but also directly by contact and indirectly via the food chain, water, air, and use of manure in food farm soil. Bacteria continue to survive to some extent in skin as well as feces and then make their way into not just the meat but also people as well as equipment involved in handling or cooking the meat.

Antibiotic use in fish farming is also booming. Water borne bacterial transfer to humans may be a much larger problem as compared to one from terrestrial animal to humans.

Above cobweb of transmissions results in an ecological imbalance leading to more and more resistant and pathogenic bacteria.

Are there any more problems beyond resistant bacteria?

Beyond the obvious increased prevalence of antibiotic resistant bacteria, the altered meat and or the antibiotic may affect down the food chain, including but not limited to our intestinal milieu, especially our intestinal bacteria and our internal ecological balance.

Effect on human health

The antibiotic use in animals affects not just the health of people on the farm but distant people along the food chain who consume it.

Factors affecting health consequences:

• Type of antibiotic
• Dose of antibiotic
• Any other drugs used
• Number of animals treated

 Relationship between diet, intestinal bacteria and health status has been clearly established, and suggests that diet-driven changes in intestinal bacteria correlate with health decline. 

Just one example of Clostridium difficile—a potential next big killer

C. difficile is seen as bacteria in the gastrointestinal tract most mammals and birds. In addition to the increasing resistance, its infection early in life has been linked to diverse disorders. Although there is no direct evidence proving transmission of Clostridium difficile from animals to humans, strong circumstantial evidence suggests that it might be a zoonotic disease. 

Effect of reduced antibiotic use on antibiotic resistance in meat animals

Agers from the National Food Institute, Technical University of Denmark, writing in the Antimicrobial Agents and Chemotherapy demonstrated that discontinuation of an already low use of cephalosporin antibiotics in pig production has significantly reduces the occurrence of resistant E. coli bacteria. 

Why farmers don’t want to stop using antibiotics in farm animals?

• Antibiotics promote growth resulting in more meat per feed of financial benefit.
• However, the argument that stopping antibiotic use would lower the meat production may not be credible based on experience in Denmark.
• Diminishing antibiotic use in animals has actualy resulted in increase in pork production, This has been termed--The “Bacon Boost” Similar lack of adverse effects has been documented in poultry as well.

Beware of the many vested interests

In addition to purported benefit of growth of animals and hence more money for farmers:

• Veterinarians who sell antibiotics to farmers
• Pharmaceutical companies who manufacture antibiotics/drugs
• Lobbyists who lobby against regulation of antibiotic use in animals
• Politicians who get campaign donations from lobbyists

Are there alternatives to antibiotic use to promote animal growth?

Use of probiotics and synbiotics (probiotic plus prebiotic) has been advocated for containing this antibiotic resistance and bacterial contamination.

Santini and colleagues suggest that an alternative and effective approach to antibiotic administration to livestock to reduce bacterial contamination is the use of probiotics. Just as in humans, this would help augment the animal’s natural defense mechanism against infections.

Baffoni and colleagues from the Department of Agro environmental Sciences and Technologies, University of Bologna, Bologna, Italy, have shown that a Bifidobacterium-based synbiotic product can reduce the transmission of C. jejuni bacteria in broiler chickens along the poultry food chain which is of course important for poultry consumers. 

Role of healthy additive cocktails in animals

Rodriguez and colleagues from Spain have shown that cereal diets like Wheat- and barley-based diets with or without additives like enzymes (xylanase plus β-glucanase), prebiotic, probiotics affect broiler chicken performance, digestibility of the meat as well as intestinal bacteria of the chicken. 

Can the alternate options make up for the growth promoting effects of AGPs

Improve farming practices and breeding programs:

• Reduced animal density
• Improved hygienic conditions
• Judicious use of antibiotics
• Use of additives like enzymes, prebiotics, probiotics, and vaccines

Above factors can more than make up for growth promoting effects of AGPs.

Graveland et al from the Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands studied MRSA bacterial colonization in veal calves and humans working and living on the MRSA in farm workers/dweller humans was 1% when less than 20% of the calves were carriers. In contrast, humans had greater than 10% prevalence in farms with higher carrier prevalence in calves. 

Benefits of manipulating bacteria in meat animals

The modulation of intestinal microflora in food animals without using any antibiotics would serve two purposes:

1) modulation of number and type of bacteria in animal’s gut would contribute to health and superior growth in the animal 

2) Decrease transmission of pathogenic bacteria to humans reducing the possibility of foodborne disease,

The latter in turn would reduce disruption of normal healthy pattern of the human microbiota thus also reduce potential for chronic ailments associated with dysbiosis, e.g. allergic and inflammatory diseases etc.

Are there any other drugs in meat besides antibiotics

A Consumer Report study found small amounts of drug ractopamine used to promote growth. While it is legal in the U.S. America, it has been banned in many countries including China, European Union. Side-effects of this drug include anxiety and restlessness. 

Are their actual antibiotics in meat you eat?

Yes indeed. Even though most meat is proclaimed to be antibiotic free, most of it does contain small amounts of a variety of antibiotics fed to the animals. The USDA is now using more sensitive tests for antibiotic detection after the USDA inspector general's report said, "the effects of these residues on human beings who consume such meat are a growing concern." Obviously, this issue has not been studied over long term but may be contributing to dysbiosis related diseases, 

What are out regulatory agencies doing?

The European Union banned the use of antibiotics in food animals for growth. In Denmark, farmers suspected of inappropriately using antibiotics for non-infection reasons are issued a “Yellow card” akin to football games in the U.S.

Food and Drug Administration in the United States only asks voluntary cessation of antiotic and drug use and encourages judicious use. FDA works collaboratively with veterinary and animal producer organizations to develop and distribute information to support the judicious use of antimicrobial drugs in food-producing animals.

 The Government Accountability Project (GAP) The Washington, D.C.-based non-profit advocacy organization has sued the FDA for declining request for information withheld data pertaining to the sale of antibiotics for use in food animals under the Freedom of Information Act.

Implications for us in nutshell

While there is no direct evidence of benefit, a prudent exercise may be:

• Infants and children in early life when their intestinal bacterial fingerprint is being established should not consumed antibiotic treated meat
• Kids/adults with psychological issues pursue organic meat in order to avoid effects of antibiotics as well as other drugs that affect brain.
• Patients with chronic disorders associated with dysbiosis, intestinal permeability or leaky gut and chronic low grade inflammatory state may best be served by avoiding antibiotic meats as well.

What is your opinion of organic meat versus non-organic meat? Is it worth the extra cost?  Dr. Minocha would appreciate your thoughts/comments.

Read reviews of  Guide to Alternative Medicine and the Digestive System 

More topoics of interest below

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Oral health in autism: dental caries and gums gingivitis	FODMAP diet: one type of elimination diet to try
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Use of elimination diet in autism	Food allergies and intolerance are not the same
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Home AutismItsGutStupid Page                    Facebook AutismItsGutStupid group page 

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Autism and ADHD: Role of Gut & Maternal-Fetal Immune Dysfunction

By A. Minocha MD, author: Guide to Alternative Medicine and the Digestive System

The problem

Studies indicate increasing incidence of autism spectrum disorders and ADHD.  Lack of a specific laboratory abnormality and reliance on symptom complex makes diagnosis unclear/controversial  in many cases. Likewise, one cannot distinguish whether the clinical manifestations are as a result of different diagnosis or  symbolize diverse manifestations of a similar various genetic and/or environmental factors underlying the diagnosis of neurodevelopmental and neuropsychiatric disorders like autism spectrum disorders and ADHD.

Genetics versus environment

While a strong genetic predisposition is suspected, less than half of the variance can be explained by genetic influences. The role of environmental influences is being increasingly appreciated although the specific factors involved may be very diverse and not yet clearly identified. Prenatal injury like an infection interacts with other environmental and genetic factors in shaping the risk of postnatal brain dysfunction.

 Increased prevealnce of allergic disorders in autism/ADHD along with streptococcus-mediated neuropsychiatric disorders suggest that critical tole of the immune system in causing and/or perpetuating such disorders.

Perhaps, autism and ADHD occur as a result of “perfect storm” when genetic or environmental  imbalances conspire together at any/many of the crucial steps involved in the development of nervous system.

Gut at the cross-roads on interplay between immune and nervous system

One  factor of “perfect storm” that may be involved is the immune system which develops as a result of not just the genetic make-up but also the environmental factors especially during its maturation.  The gut and its trillions of bacteria as they move from neonatal pattern to the adult bacterial pattern play a critical role in the final make-up of the immune system.

Any disturbances along in later life can still upset the proverbial apple-cart making things worse. Conversely, modulation of gut bacteria has the potential to module the immune system, the neuro-immune interactions along with multiple diverse clinical manifestations of diseases like autism. Immune activation caused by bacterial components that may enter across leaky gut are known to impair attention.

Evidence that exclusion diets as well as use of probiotics is of benefit in many patients with autism and ADHD lends further support to the the hypothesis of critical role of gut.

Immune alterations in neuropsychiatric disorders like autism/ADHD

 Evidence suggests ongoing inflammation in brain specimens, elevated pro-inflammatory cytokine profiles in brain and blood, increased presence of brain-specific auto-antibodies and abnormal immune cell function in neurodevelpopmental disorders.  There is increased incidence of allergic sensitization and allergic rhinitis in ADHD.

According to Careaga and Ashwood, of University of California, Davis, CA, changes have been documented  in immune cell number, cytokines,  cellular function at rest and in response to immunological challenge in autism. The worse the immune dysfunction,, the greater the  impairment in behaviors that are core features of autism especially impaired social interactions and communication.

Maternal versus fetus immune system

Pregnancy contributes to an exponential increase in complexity of immune interactions since mother's immune system has to be tolerant of both the fetus and its antigens while at the same time maintaining a  healthy immuneresponsive system  that can mount an effective defensive responses to real pathogens. 

Conversely, the fetus is constantly exposed to “environmental aliens” made up of maternal components including maternal immune system e.g. antibodies, cytokines and immune complexes.

Maternal IgG antibodies during pregnancy and early infancy

Just like the semi-permeable or exclusionary intestinal barrier, the placenta is also a selective barrier  allowing nutrition as well as neuro-endocrine-immune signals to go through to the growing fetus while blocking potentially harmful pathogens.

Among the factors allowed passage to the fetus are protective maternal IgG antibodies such that their levels in new born fetus are higher than even in the mother. This allows the new born baby ready-made means of immunity while its own immune system is immature and not up to speed.

Maternal autoantibodies

Unanticipated chaos may in fetus when mother has autoantibodies which are acting already against her own tissues. These antibodies can also cross the placenta into the growing fetus. Usually such harmful antibodies disappear by about 6 months after birth.

However, their presence in the fetus in-utero and early infancy which is a critical period for neuro-immune developmental and gene expression processes has potential to affect the growth and development of different organs including brain and as such impact the life over short and long term.

Examples of such dysfunction include transient myasthenia gravis (short term) and neonatal lupus causing cardiac defects (long term).

Maternal antibodies,  blood-brain barrier and central nervous system

While IgG antibodies cannot usually cross blood brain barrier and gain access to the brain in adults, such is not the case in fetus because of immature barrier structure and function. Genetic predisposition to delayed or dysfunctional or nonselective barrier function may be involved in pathogenesis of autism.

Maternal  antibodies and/or immune complexes mimicking targets in fetal brain may sometimes occur as a result of a toxin or infectious exposure leading to inflammation in the brain and long term damage.

Maternal IgG and neurodevelopmental disorders

Comparison of kids with autism and controls has shown the presence of fetal brain specific antibodies targeting fetal brain proteins are found in kids with autism. Some of these aberrant antibodies correlate with poor expressive language scores, other antibodies appear to  be involved with increased irritability on the Aberrant Behavioral Checklist. Thus diverse patterns of abnormal antibodies may be found leading to diverse manifestations.

Conclusion of Immune dysfunction and neurodevelopmental disorders

Patients with autism and their families display many  immune abnormalities including cytokines that are mediators of immune activities but are also  critical to development and function of the nervous system.  

There is a dramatic change in immune cell pathways as well cytokines during an infectious episode as well as during toxic exposures and as such may be at crossroads between the interplay of genetic and immune factors underlying autism. Potentially damaging pro-Inflammatory cytokines with potential to interact with brain have  been documented in autism

Alterations in immune function are associated with increased behavioral problems in patients with autism. Whether these changes represent a cause-effect relationship or a mere association remains to be clearly established.

Potential significance of research on immune system and autism

Greater specificity of Identification of immune interactions with nervous system during its early development would allow for development of specific targets for therapeutic interventions. 

References: 1. Careaga M and Ashwood P. Autism spectrum disorders: from immunity to behavior. Methods Mol Biol. 2012.  2. Braunschweig et al. Behavioral correlates of maternal antibody status among children with autism. J Autism Dev Disord. 2012. 3. Onore  et al. The role of immune dysfunction in the pathophysiology of autism. Brain Behav Immun. 2012. 

Read reviews of  A. Minocha MD,'s  book Guide to Alternative Medicine and the Digestive System

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Effects of gut bacteria starts during pregnancy	Honey and cough
Breast milk benefits and alternatives	Implications of FODMAP diet health and sickness
Cranberry juice versus antibiotics for urinary tract infections	ADHD: Causes, role of diet, gut and treatment
Mangosteen benefits: myths or reality	Food allergies and intolerances
Does Vegetarian diet reduce mortality	Nutritional supplements for liver disease
Aquatic therapy for chronic pain	CT (CAT) scans and risk of cancer

Home AutismItsGutStupid Page                    Facebook AutismItsGutStupid group page 

Digestion, Health & Nutrition                          Facebook Dr. Anil

Digestion, Health & Nutrition                          Facebook Dr. Anil

Diagnosis of mitochondrial dysfunction and role of muscle biopsy

Brief overview of  mitochondrial disorders and dysfunction

By A. Minocha MD, author: Guide to Alternative Medicine and the Digestive System

• Multi-system disorders affecting in varying proportions the nervous system, heart, muscles, vision, hearing and kidneys etc.
• Symptoms may wax and wane.
• Manifest in a variety of ways and neurodevelopmental problems like mental or growth retardation and seizures occur only in some but not all cases. Likewise the severity of symptoms varies.
• Even family members with the same disorder can experience vastly different symptoms.
• Usually seen during childhood although they may in some cases manifest during adult life. 
• Patients partially fulfilling criteria for mitochondrial disorders are frequently termed as mitochondrial dysfunction.

Are mothers to blame for mitochondrial disorders/dysfunction

• Contrary to popular misconception mitochondrial diseases are inherited not just from the mother; rather they represent complex inheritance patterns including mutations, most of which are not in the mitochondrial DNA.
• Disorders occurring as a results of mutations in mitochondrial DNA are of course derived from mother only.
• Mitochondrial disorders may also occur as a result of environmental factors like infections and toxins that may “poison” the mitochondrial functional processes. 

Outcome and prognosis of mitochondrial disorders

• Not curable
• Therapy is aimed at control of symptoms and disabilities 

Therapeutic options/strategies

• Avoiding  trigger like stress etc.
• Medications
• Nutritional supplements tend to help in many cases. 

Diagnosis of mitochondrial disorders/dysfunctiom

According to Dr. Rodenburg  from the Nijmegen Center for Mitochondrial Disorders (NCMD),  Department of Pediatrics, Department of Laboratory Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. as reported in the journal Journal of Inherit and Metabolic diseases, “The diagnostic examination of patients requires a multi-disciplinary clinical and laboratory evaluation in which the biochemical examination of the mitochondrial functional state often plays a central role. In most cases, a muscle biopsy provides the best opportunity to examine mitochondrial function". 

Diagnostic strategies for mitochondrial disorders/dysfunction

• One should not oversimplify the diagnosis of a mitochondrial disorder. Broadly, the diagnostic criteria may be classified into  Clinical, Biochemical and Genetic. Presence of more than two abnormal tests makes the diagnosis more likely.
• There is no single test to diagnose mitochondrial disease. There is dearth of less invasive, specific and sensitive diagnostic tools based on serum biomarkers.
• An experienced integrated approach is necessary for accurate diagnosis and relies on a combination of clinical observations, laboratory evaluation, brain imaging, and muscle biopsies
• Blood levels of lactate are frequently used as a screening tool. An abnormal test invariably calls for further investigation. , however, a normal test does not exclude the diagnosis.
• A battery of tests that can be performed include analysis of on blood, urine and spinal fluid to look for presence of mitochondrial dysfunction.
• For example, an abnormal genetic test on a blood sample may not be adequate for diagnosis of mitochondrial disorder and may require muscle biopsy for confirmation in many cases.
• A comprehensive portrait of mitochondrial energy-generating system can be obtained by tests performed on  of muscle biopsy including evaluation of  individual oxidative phosphorylation enzymes,  mitochondrial respiration, substrate oxidation and rate of ATP synthesis. 

Role of muscle biopsy for diagnosis

• Muscle tissue is subjected to comprehensive analysis including histology, genetic and  enzyme testing.
• Although a muscle biopsy is frequently touted as the "gold standard" for diagnosis of mitochondrial disorders, it is fraught with its own shortcomings.
• The enzyme testing on a tissue sample is especially difficult and has not been standardized making interpretations subject to interpretation.
• Muscle biopsy makes results of research studies on mitochondrial disorders more trustworthy. 

What is muscle biopsy

• Muscle biopsy is a simple, low risk surgical procedure involving skeletal muscle.  The analysis on the on other hand tends to be complex and varies with laboratories.
• Muscle biopsy is usually performed under local anesthetic.
• All muscle biopsy are not the same.
• May be Open versus Needle Biopsy. The open biopsy involves use of sharp scissors/scalples. An open biopsy, a  2-to-3-inch incision is made and  tissue is taken and sutures may be used to close the incision.  In a needle biopsy, tissue is collected with a large bore needle.
• Typically two to three pieces are taken. One is analyzed as fresh specimen, while other is analyzed as fixed tissue. Still another piece is used for analysis of enzyme and genetic testing. Analysis may be undertaken on fresh or frozen samples. 

Tests done on muscle biopsy

Tests performed on muscle biospy include but are not limited to:

• H&E stain for routine histology
• Nicotinamide adenine dinucleotide tetrazolium reductase (NADH) staining for assessment of NADH enzymes seen in mitochondria and endoplasmic reticulum.
• Staining for myofibers
• Modified Gomori trichrome stain
• Fat stains to assess for presence of fat in muscle
• Human leukocyte antigen class by immunohistochemistry
• The lab may also use electron microscopy to get very high magnification views of the cellular structure, which can confirm structural abnormalities.
• Enzyme testing may be undertaken on the ground up muscle tissue or from the mitochondria extracted from the muscle. Although controversial, analysis of fresh tissue sample may have advantages over frozen tissue analysis.
• Although mutations can be detected by blood sample, DNA analysis may be needed on a muscle sample to test for mitochondrial DNA mutations. 

Contraindications of muscle biopsy

• High risk of intractable bleeding or presence of infection at the biopsy site. 

Caution about muscle biopsy for mitochondrlal disorders/dysfunction

Undertaking a muscle biopsy and it’s comprehensive analysis  should not be undertaken lightly.

• A diagnosis of mitochondrial disorder/dysfunction has limited impact on long-term outcome. The benefits and its limitations of muscle biopsy  should also be weighed with the surgical risks although small.
• The cost associated with it which can easily be north of $10,000 should be a matter for serious consideration for most people.
• Because of limited impact on outcome, many physicians do not insist on muscle biopsy for a diagnosis.
• A muscle biopsy may not always be necessary in cases where diagnosis can be made based on identification of a genetic mutation associated with mitochondrial function along with clinical manifestations consistent with it. 

Learn about 12-point autism treatment program OR more topoics of interest below

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Quinoa: one complete high protein food	Health benefits of probiotics and prebiotics
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Use of elimination diet in autism	Food allergies and intolerance are not the same
Do cranberry and/or mannose protect against urinary tract infections or UTI	Coconut oil repairs unhealthy skin

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ADHD, Diet and Artificial Food Colors Additives

ADHD and Diet, Food Color Controversy

By A. Minocha MD, author: Guide to Alternative Medicine and the Digestive System

ADHD, a common neurodevelopmental disorders presents with diverse clinical manifestations. The etiology/pathogenesis of this disorder continues to remain an enigma. A variety of hypothesis have been put forth in this context.

While genetic predisposition has been implicated, this does not explain the entire variance and as such the role of environment has been highlighted. Neurobehavioral toxicity may occur due to a wide variety of chemicals/toxins widely spread across the environment.

Potential environmental injury/toxic factors

• Toxin exposure (prenatal and perinatal)
• Birth injury
• Low birth weight
• Social conflicts and stress
• Diet
• Intestinal milieu including bacteria
• Food additives/preservatives

Role of diet in historical context

Of the factors outlined above, the role of gut and diet has received increasing attention in recent years. These include the role of food allergies as well as exposure to food additives (colors and flavors) and preservatives.

1920s    Food allergies were implicated in causing learning and behavioral problems.

1972      Food additive hypothesis was proposed by Feingold who proposed a Feingold diet which excluded any natural salicylates in food as well as food additives

1982    National Institute of Health (NIH) consensus development conference recommended further studies

1983     Kavale  meta-analysis concluded that clinical impact of diet is too small to be meaningful

2004    Schab and Trinh meta-analysis concluded that artificial food colorings contribute to behavioral symptoms in hyperactive syndromes like ADHD.

2007   McCann population based study concluded that food colors and/or sodium benzoate preservative in diet is linked to hyperactivity in children.

2008 European Union Parliament imposed requirement for warning labels on foods containing six colors. Overall, the FDA approves 9 colors for use in foods of which Orange B is not approved in Europe.  The synthetic colors requiring warning labels in Europe include Allra Red AC, tartrazine, sunset yellow, quinoline yellow, carmoisine and ponceau. The latter three are not approved in the U.S.

2008 Center for Science in the Public Interest (CSPI) filed a petition asking the FDA to regulate the use of food colorings.

2011 FDA concluded that scientific evidence did not support cause-effect relationship between food colorings and ADHD manifestations

2011 Food and Drug Administeration (FDA) approved synthetic colors include Brilliant blue, indigotine, green S or fast green, orange B, citrus, amaranth, erythrosine, allura red, tartrazine and sunset yellow.

2011 Stevens qualitative review of 35 years of research concluded that food additives play a role in a subset of ADHD patients and exclusion diets may be helpful in such cases.

The Stevens review also concluded that in kids with suspected senstitivies to synthetic food coloring additives, up to 89% improve when exposed to greater than 100 mg of artificial food coloring. 

State of current literature on role of diet, food color additives and ADHD

The issue of role of food additives and ADHD continues to be mired in debate. The European and US authorities have taken different policy approaches to this issue.

Dr. Nigg and colleagues from the Oregon Health and Science University, Portland, OR,conducted a systematic review and meta-analysis in an attempt to review the up to date literature and hopefully resolve the controversy.

Their findings were published in an article titled, “ Meta-analysis of attention-deficit/hyperactivity disorder or attention-deficit/hyperactivity disorder symptoms, restriction diet, and synthetic food color additives” in the Journal of American Academy Child Adolescent Psychiatry (2012).

Methods of ADHD and diet, food coloring study:

• An extensive search of medical literature was conducted including Medline/PubMed.
• The 53 human studies published between 1976 to Feb 2011 were graded for relevance
• Overall 35 publications met the inclusion criteria.
• Rational grouping of parent/observer data
• Rational grouping of psychometric laboratory test data
• Meta-analytic computations were conducted using appropriate software.

Results of ADHD and diet, food coloring meta-analysis:

Effects of exclusion of food additives/colors as part of overall elimination diet:

• The results from open-labelled trials yielded a 47% response rate.
• The six controlled trials found that elimination diet that included eliminations of food colorings and additives result in a response rate of 41.5 percent.
• These results indicate that dietary restriction results in a reliable and clinically meaningful impact.

Role of synthetic food additives:

• The studies generally included subjects who had followed some kind of modified version of Feingold restricted diet and then were challenged with food additives in some fashion like cookies, capsules etc.
• For studies based on parental reports, the estimated size effect was 0.18 and was highly significant. Parents reported higher greater effects with higher doses without any impact of duration of exposure.
• For the 10 studies utilizing teacher/observer reports comprising a total of 323 subjects, the results on impact of food coloring showed a trend towards statistical significance (p=0.07).
• Six studies comprising 154 kids utilized psychometric tests of attention for analysis. The results revealed a reliable significant effect of food coloring on the psychometric tests in ADHD. The results were significant when studies included colors only or FDA approved colors only.

Proportion of kids reacting to colors:

• 14 studies comprising of 241 pre-seleccted kids responsive to elimination diets, studied proportion of kids reacting to colors.
• While the overall the event rate was 18 percent, it was 24% when only the studies utilizing well-defined criteria were analyzed.
• Using these results from preselected kids were diet responsive, it was estimated that 8% of kids with ADHD have symptoms related to food colors.

Conclusion of the ADHD, diet, food coloring study:

1. Some kids with ADHD react to food additives as assessed by the parents; however it is unclear if this is due to FDA approved colors
2. The results of studies utrilizing parent assessment versus teacher assessment are inconsitant
3. Most studies examined effect of variety of combinations of colors thus rendering analysis of any specific color difficult.
4. Inconsistency in parent-teacher observation studies notwithstanding, the studies utiliziing objective psychometric tests of attention showed reliable and significant effect of food colors with an effect size of 0.27. These affects could not be explained by publication bias.
5. The adverse effect of food additives appears to be 1/3^rd to 1/6^th the size of effect of drugs used to treat the disorder.
6. As many as 33% 9of kids with ADHD may respond to dietary exclusions. Since 8% have symptoms related to food colors, the precise mechanism for response to elimination diet remains obscure.
7. There is paucity of studies dealing exclusively with FDA approved food colors or unselected study samples.

Note:

1. Some of the kids sensitive to food color additives also display sensitivity to onsalicylate foods like milk, chocolate, soy, eggs, wheat, corn, legumes/lentils in addition to salicylate-rich foods like grapes, tomatoes, and citrus.
2. Many experts argue that "cosensitivity" is more of a rule rather than an exception.

Other topics of interest:

1. Autism, leaky gut and elimination diets
2. Can probiotics strengthen selective intestinal barrier or leaky gut?
3. Autism related to gut bacteria?
4. Melatonin is not just for sleep. It helps gut too
5. Toileting posture: Taking care of business well!

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Learn about 12-point autism treatment program OR more topoics of interest below

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Use of elimination diet in autism	Food allergies and intolerance are not the same
Do cranberry and/or mannose protect against urinary tract infections or UTI	Coconut oil repairs unhealthy skin

 

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ADHD Treatment: Chinese Compound Herbal Preparation Helps Attention, Impulse Control

Role of Compound Herbal Prepapration for Attention Deficit Hyperactivity Disorder (ADHD)

By A. Minocha MD, author: Guide to Alternative Medicine and the Digestive System

Treatment of ADHD or ADD poses numerous challanges. A wide variety of drugs including CNS stimulants, antidepressand and bupropion are frequently used. The response to these medications is variable; besides they are beset with adverse undesirable effects. Parents are frequently looking for alternate herbal, natural and nutrition remedies. 

Background of CHP-ADHD Study:

Compund herbal preparations or CHP derived from Chinese Herbal Medicine  is one such potential strategy. One of the hypothesis underlying ADHD causes is deficiency of essential micronutrients and compound herbal preparations are believe to have coginition enhancing properties by replenishing essential fatty acids, phospholipids, vitamins and minerals.

Dr. Katz and colleagues  from the Sheba Medical Center in Israel examined the efficacy of Nur­ture & Clar­ity in ADHD and published their findings in the paper, "A compound herbal preparation (CHP) in the treatment of children with ADHD: a randomized controlled trial" in the Journal of Attention Disorders 2010.

Composition of compound herbal prepapation (CHP brand name Nur­ture & Clar­ity)

• Paeo­niae Alba
• With­a­nia Som­nifera
• Cen­tella Asi­at­ica
• Spir­ulina Platen­sis
• Bacopa Monieri
• Mel­lissa Offic­i­nalis

Design of CHP-ADHD Study:

• Double blind, randomized, placebo controlled
• Tertiarry care university  medical center
• N=120 kids with a new diagnosis of ADHD based on DSM-IV codes
• Intervention: Compound herbal preparation (n=80) versus placebo (n=40)

Results of CHP-ADHD Study:

1. 91% of kids in treatment and 48% in the control group completed the study
2. Treatment group demonstarted a significant improvement in total TOVA scores as well as 4 subscales
3. The significance of the improved difference between the Chinese  compound herbal preparation (CHP)  treatment versus  placebo group was seen even when using the higher standard of comparison i.e. Intent to treat analysis

Conclusions of Compound Chinese Herbal Prepartion-ADHD Study:

Compound herbal preparation treatment is benficial in treatment of ADHD or ADD and improves the following symptoms:

• Attention
• Cognition
• Impulse control 

Learn about 12-point autism treatment program OR more topoics of interest below

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Quinoa: one complete high protein food	Health benefits of probiotics and prebiotics
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Zinc supplements boost immune sytem and reduce respiratory infections	Turmeric: A must-have healthy spice in kitchen.
Use of elimination diet in autism	Food allergies and intolerance are not the same
Do cranberry and/or mannose protect against urinary tract infections or UTI	Coconut oil repairs unhealthy skin

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Good Teeth, Gums Reduce Risk of Diseases In Distant Organs

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Why is oral-dental health so important?

By A. Minocha MD, author: Guide to Alternative Medicine and the Digestive System

Oral cavity is involved in first encounter for foreign bodies and pathogens to the respiratory and gastrointestinal tract.

• Orodental space represents the tip of the spear for most things good and bad (food, drugs, toxins, pathogens) that enter the body especially the gastrointestinal tract.
• Ironically, the status of orodental cavity may reflect the overall health including nutritional and immunological status.
• Orodental changes may be cause of effect or what is happening in the body. 

Orodental flora

Oral cavity is  “dirty”. A variety of bacteria are present including pathogens that have potential for local and body-wide repercussions.

• As many as 500 species are encountered and most of them are not pathogenic.
• In the presence of immune dysfunction, the pathogenic bacteria can become pathogenic manifesting in chronic inflammatory periodontal disease and can then affect the entire body.
• Orodental activities, as simple as chewing, flossing brushing and minor procedures like  scaling result in release of bacteria into blood circulation, although the  bacteremia is usually transient.
• However, the release of bacteria or their toxic product into the circulation have potential to seed another nidus of infection/inflammation setting off a deleterious chain reaction.

 Is localized focus of infection anywhere significant

Poor oral-dental health implies a localized focus of infection.

• The word “localized” may be a misnomer since a localized focus of infection need not have localized effects only.
• Not unlike cancer, metastasis of bacterial infection may occur in the form of bacteremia, release of bacterial toxin into the circulation.
• Metastatic inflammation describes the phenomenon wherein bacterial antigen released into circulation interacts with an antibody resulting in immune complexes that can have their own disease processes. 

Localized focus of infection: A historical perspective

Concept of localized focus of infection is not new; in fact it is rooted in history of medicine since ancient times

• Hippocrates successfully treated a case of arthritis by performing tooth extraction.
• Dr. C.H. Mayo in 1914 declared in Journal of American Medical Association that “root abscesses and pus pockets connecting them are often the source of acute and  chronic rheumatism”. 

Localized orodental infection foci

• Much of  the research has focused on periodontal lesions and their systemic effects beyond oral cavity
• Caries is also increasingly attracting attention in recent times
• WHO considers caries a global health problem 

How does focus of infection including orodental affect body

Diffusion or metastasis of bacteria, toxins and antigens into the body can initiate or worsen a distant and/or generalized illness. Affects can be far away including heart and brain

• Administration of components of normal mouth bacteria (commensal) Porphyromonus gingivalis exacerbates encephalomyelitis in mice.
• An additional concept gaining traction is involvement of RAGE. 

The emerging RAGE concept (Anger at cellular level)

RAGE (Receptor for Advanced Glycation End Products ) has been implicated in multiple disorders.

• Signaling through RAGE has been implicated as a nemesis for diverse pathologies including periodontal disease, cardiovascular diseases, complications of diabetes mellitus including diabetic vasculopathy, Alzheimer disease, cancer, and neurologic conditions.
• An excess of AGEs (Advanced Glycation End Products) has been documented  in numerous organ systems including brain of patients with autism.
• RAGE are plentiful in gums and are  released into circulation when gums are inflamed.
• AGE-RAGE axis has been postulated as the mechanism of a variety of associations of orodental diseases and increased diseases beyond oral cavity including heart, blood vessels and nervous system [Katz et al 2010].

Oral-dental lesions in GI diseases

• Concept of oral-dental lesions in gastrointestinal diseases with far-reaching effects in various parts of the body  is well established.
• Examples include inflammatory bowel disease, Behcet’s disease, celiac disease etc. 

Effects of poor health on oral cavity

In addition to gastrointestinal disorders, aphthous lesions may occur due to immune dysfunction related to infections, malnutrition, allergies, stress and hematological and malignant disorders. More details in upcoming post.

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FODMAP diet and foods: Implications in health and disease

By A. Minocha MD, author: Guide to Alternative Medicine and the Digestive System

FODMAP DIET: ROLE IN IRRITABLE BOWEL, LEAKY GUT AND ALTERATION IN INTESTINAL BACTERIA

What is FODMAP and FODMAP Diet (Gibson and Shepherd 2010)

FODMAP is an acronym applied to group of short chain carbohydrates and sugar alcohols comprised of Fermentable Oligo- Di and Monosaccharides And Polyols

Disease associations: High FODMAP diet have been implicated in the rising tide of a variety of disorders.

• Crohn’s disease
• Celiac disease
• Irritable bowel syndrome
• Chronic fatigue syndrome
• Autism

FODMAPs share thee physiological properties:

• Poor absorption in small intestine
• Osmotically active small molecules
• Rapid fermentation by gut flora: the smaller the length of carbohydrate, faster the fermentation

High luminal FODMAP foods undergo rapid fermentation and create metabolic products that predispose to enhanced intestinal permeability, altered intestinal flora, intestinal gases and predispose to small bowel bacterial overgrowth (SIBO).

Examples of high FODMAP foods/diet include:

• Fructose (fruits, honey, high fructose corn syrup)
• Lactose (diary products)
• Fructo-oligosaccharides or fructans (wheat, onions)
• Galacto-oligosaccharides or galactans ( raffinose and stachyose) contained in legumes, beans, cabbage, onions etc.
• Polyols (sorbitol, mannitol, xylitol, maltitol) contained in apples, pears, plums etc. and low calorie sweeteners. Polydextrose and isomalt are frequently used as artificial sweeteners, are poorly absorbed.

What happens when you ingest high FODMAP diet

• Excess intake and delivery of undigested carbohydrates to the colon renders them subject to bacterial fermentation.
• The metabolic fermentation products including increased organic acids (short chain fatty acids), increased surfactant activity, increased gases (hydrogen, carbon dioxide, methane and hydrogen sulfide) and gut distension injure intestinal barrier by in part causing apoptosis.
• Short chain fatty acids (SCAFAs) excess excess has been shown to increase intestinal permeability in animal models.
• The gas content of gut plays an important role in gastrointestinal symptoms.

Problems occur especially when high FODMAP diet is consumed fast:

The process if rapid, can be especially “explosive”. This occurs when large amounts of undigested carbohydrates are exposed to disproportionately high and potentially pathogenic bacteria in gut e.g. small bowel bacterial overgrowth.

Type of food versus speed

• Oligosaccharides (smaller chain length carbs) and sugars are metabolized at a much faster rate than the longer chain length molecules like dietary soluble fiber.
• The speed of bacterial fermentation and generation of metabolic products varies according to substrate (lactulose >inulin> resistant starch)
• FODMAP elimination diet plan requires global and not individual product restriction.

FOMAP drawbacks

• Low FODMAP diet diminishes access to benefits of prebiotics like fiber
• Effects of high fiber/prebiotics

1. Increased bowel fluid by osmotic effects

2. Increased motility

3. Increased generation of short chain fatty acids that serve as food for colonocytes

4. Increase in beneficial strains of bacteria like bifidobacteria.

FODMAP diet and vegetarians

• Legumes and milk products are a major source of nutrition for vegetarians.
• Since the goal of FODMAP strategy is overall reduction, greater cuts need to be made in other categories in order to accomplish the desired goals.  
• Eat good carbs!

Turning harmful effects of FODMAPs into benefits

• A lower proportion of rapidly fermentable carbohydrates along with greater amount of slowly fermentable carbohydrates have potential for ameliorating harmful effects of FODMAPs and shifting the balance towards benefits.
• For example, ingestion of raw potato starch, guar gum and arabinoxylan causes intestinal injury especially involving enzymatic activities. The deleterious effects of these foods do not occur if they are consumed along with slowly fermentable wheat bran.
• Considering the demonstrated potential health benefits of prebiotics, the harm versus benefits may be individual specific based on diet consumed, gastrointestinal flora, rapidity and amount of bacterial fermentation, and presence of comorbid conditions in the context of genetic susceptibility.

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Cranberry versus antibiotic TMP-SMX for preventing recurrent urinary tract infections or UTI

By A. Minocha MD, author: Guide to Alternative Medicine and the Digestive System

Is it better to take antibiotics rather than cranberry to prevent urinary tract infections?

Urinary tract infections including bladder infections are common amongst women. Literature supports the use of Cranberries and cranberry juice for preventing urinary tract infections (UTIs). Cranberry is popular because it is natural and devoid of puported side-effects related to antibiotics expecially over long term.

The study authored by Beerepoot and colleagues from the Academic Medical Center in Amsterdam was published in Archives of Internal Medicine. While the study showed antibiotics to be better at preventing UTI over 1 year, are they really supeior to Cranberry over longer term?

Not so fast! There is a subtext to the overall cost to one's health associated with antibiotic TMP-SMX use which I discuss after the author's conclusions.

Study methods: The study involved 221 premenopausal women with history of recurrent urinary tract infections (UTI). Subjects received either TMP-SMX 480 mg once a day or cranberry capsules 500 mg twice a day for 12 months.

Results

1. Mean number of UTIs Cranberry 4.0 vs TMP-SMX 1.8
2. Proportion of women with atleast 1 UTI Cranberry 78% vs TMP-SMX 71%
3. Median time to symptomatic UTI Cranberry 8 months vs TMP-SMX 4 months
4. Antibiotic resistence to E. coli (UTI bacteria) Cranberry 28% vs TMP-SMX 91%

Authors' conclusions: Use of TMP-SMX antibiotic is superior to cranberry for over a period of 12 months at the expense of antibiotic resistence.

My comments

1. The antibiotic group in this study likely had an inherent advantage since the bioavailabilty of active compound in the antibiotic greater than the cranberry capsule group (Clinical significance to be established).
2. The superiority of antibiotic TMP-SMX over 1 year not withstanding, the occurance of more than 90% antibiotic resistence gives me pause and makes me wonder if the results would have reversed if the study was extended over longer term, say 5 years.
3. The long term of use of broad spectrum antibiotic such as TMP-SMX is fraught with dangers, many not well understood including the effect on overall health due to disruption of the bacterial balance and homeostasis in the gut.
4. Many women have moved somewhat past cranberry alone and are using it in combination with mannose.

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Carnitine supplements as treatment of autism?

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Levo-carnitine treatment improves autistic spectrum disorders

By A. Minocha MD, author: Guide to Alternative Medicine and the Digestive System

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.

 

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)

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.

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?

By A. Minocha MD, author: Guide to Alternative Medicine and Digestive System

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.

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.

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.

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.

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Other topics of interest:

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

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

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Autism and Gut Bacteria: Are they linked?

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Can antibiotics cure some cases of autism? 

By A. Minocha MD, author: Guide to Alternative Medicine and Digestive System

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.

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.

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 th 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. 

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Aquatic water therapy for chronic pain: Myth or reality?

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AQUATIC THERAPY FOR PAIN: Fact or fiction 

By A. Minocha MD, author: Guide to Alternative Medicine and Digestive System

Aquatic therapy also known as Water aerobic therapy or pool therapy refers to the physical therapy and rehabilitation performed in water without the need for weights.

• Scientific data and expert opinions indicate that it provides therapeutic benefit in fibromyalgia. 
• Aquatic therapy has potential for benefit in patients with other types of chronic pain disorders and cancer and neuro-rehabilitation.
• Human trials suggest that aquatic therapy also provides short-term benefit in patients with osteoarthritis.

A variety of hydrofitness devices are available and can be individualized.

Principles of aquatic or water therapy

Water provides resistance and is believed to be healthier than the use of weights. The hydrostatic pressure produces forces perpendicular to the bodys surface Water buoyancy helps support the weight of the patient.

The combination of water resistance and  buoyancy reduces weight bearing and stress placed on the joints allowing low impact exercises with reduced joint stress as compared to exercises on land.

A decrease in stress on joints makes it easier for patients to get benefits of exercise with lesser pain/stress.

Types of aquatic therapy

Water enthusiasts have many options regarding not only depth of water, i.e.shallow versus deep water therapy but also the format of exercises that they may enjoy and find easy to perform consistent with their health. Various types of aquatic therapy are available:

Ai Chi: Developed by Jun Konno of Japan, it combined deep breathing associated with slow movements of limbs and torso. 

Ai Chi Ne: This is a partner requiring 2-person exercise program involving breathing and stretch exercises.

BackHab: This may be undertaken as an individual or a group. It is specially tailored for patients with physical impairments including back problems. It includes walking in water and a variety of limb movements tailored to the patient’s health problems.

Bad Ragaz: Initially developed in Germany, it is described as  the Bad Ragaz Ring Method targeting  muscle re-education via utilizing particular ways of resistance, endurance, and  range of motion.

The Burdenko Method: The Burdenko Method combines land and water exercise therapy for athletic training as well as physically challenged subjects.

Feldenkrais: Created by nuclear physicist Moshe Feldenkrais, it is based on principle that our movements etc depend upon the way we think and feel. Thus exercises of combining breathing and flexibility of movement are undertaken in context of awareness of old patterns and concerted effort to modify them to improve the overall other aspects of life. Touch and tissue manipulation by the therapist may be involved.

Halliwick: It is a 10-point program of motor learning and mental adjutments that specializes in teaching patients with a variety of physical or mental disabilities to get involved with water activities exercises with the goal of getting them to move about and swim in water independently in water, and to swim.

Wassertanzen: Wassertanzen means water dance. This type of aquatic therapy is a dynamic movement therapy that involves exercises below the water surface utilizing nose clips. This form of therapy is unique in the sense that it involves the patient surrendering control of his/her breath to go under water.

Water Yoga: Yoga exercises are performed with subject in waist- to chest-depth water. 

Watsu: Created by Harold Dull, watsu as the name suggests is a combination of water and shiatsu wherein the subject is held in warm water by the therapist and moved around using water resistance as the source of massage. Watsu aims to integrate massage, muscle stretching and dance. It has been described as especially suited for elderly and pregnant.

Yogalates: It uses a combination of yoga, Pilates, and Ai Chi. 

Miscellaneous aquatic therapies: Other modifications/styles include Lyu Ki Dou and Water Pilates

Contraindications to aquatic/water therapy

• Significant cardiac or respiratory disease
• Fever and active  infections
• Urinary or stool incontinence
• Consult your physician prior to any exercise program 

Significance in of aquatic therapy in health and sickness

• While there is lack of data on the role of aquatic therapy in digestive health, data on its beneficial effect in chronic pain disorders like fibromyalgia indicates that it may have potential for therapeutic benefit in chronic functional bowel disorders. 
• Randomized controlled trials indicate that an exercise program thrice a week in a warm pool improves symptoms of fibromyalgia.
• Thomas and Blotman conclude that aerobic-only exercise provides improves physical function and may be therapeutic for tender points and pain in fibromyalgia.

Bottomline: Aquatic therapy is well suited for healing as well as health maintenance for diverse patient populations. Besides wide margin of therapeutic safety, the therapist can easily develop a specifically targeted therapeutic program for diverse clinical conditions.

An interesting topic: Is fasting good or bad for health?

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Is kava kava bad or toxic for liver?

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Kava Kava and liver damage or toxicity (hepatotoxicity)

By A. Minocha MD, author: Guide to Alternative Medicine and Digestive System

Kava kava akso known as kava Kava (Piper methysticum) root is widely used for treatment of  anxiety, depression and insomnia. Several reports have implicated in several  severe and even fatal  cases of hepatotoxicity. Immune-allergic mechanisms are believed to be involved in hepatotoxicity.

The regulatory causality evaluation of the reported cases has been mired in debatein the scientific community.  The Food and Drug Adminstration or FDA issued a customer advisory regarding the dangers of this agent in 2002. Its use is banned in several European countries.

Many experts like Anke have challenged  the concept of hepatotoxicity being caused by kava kava in many of the reported cases.  In vitro data does not support a hepatotoxic potential. Many of the effected patients reported in literature were also taking other medications.

Teschke in a thorough review published in Annals of Hepatology (2010) concluded  that kava kava may be hepatotoxic in a few individuals due to overdose, prolonged treatment, co-medication, and probably triggered by an unacceptable quality of the kava raw material. A 6-point program to improve quality by standardization to prevent liver toxicity due to kava has been recommeded.

Citation: Teschke R: Kava hepatotoxicity--a clinical review. Ann Hepatol. 2010;9(3):251-65.

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Natural Cranberry mannose blend for recurrent UTI

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Natural cranberry plus mannose treatment for recurrent urinary tract infections

By A. Minocha MD, author: Guide to Alternative Medicine and Digestive System

Cranberry juice has been widely used by women for natural treatment for for prevention and treatment of urinary tract infections based on promising scientific evidence.

In recent years, D-mannose, a sugar has gained a lot of attention for fight against infections of urinary tract including urinary bladder. The use of a combination of these two potentially natural remedies presents an attractive option for those interested in holistic, non-medicinal preventative and therapeutic approach to UTIs especially recurrent UTI.

The cranberry, d-mannose and bromelain study

Efros and colleagues from the Winthrop University Hospital in New York examined the effect of concentrated proprietary cranberry blend, UTI-STAT with Proantinox, in women with recurrent urinary tract infections.

Contents of the cranberry-mannose-bromelain treatment blend

UTI-Stat^® with Proantinox^® contains concentrated cranberry proanthocyanidins, vitamin C, d-mannose, fructo-oligosaccharide and bromelain.

The study was reported in the journal Urology 2010.

Methods of cranberry plus d-mannose and bromelain trial

The women recruited to the study had history of an average of 2.78 recurrent UTIs in less than six months. The goal was to study the effect of the treatment on efficacy and quality of life of these women with recurrent UTI.

28 women with an average age of 46.5 years particiapted in the study.

Results of cranberry plus d-mannose and bromelain study

The recommended dose of blend was set at 60 ml per day.

Based on historical data, only 9% of the women with recurrent urinary tract infections had recurrence of UTI. By 12 weeks, there was a significant reduction of worry among women along with an improved American Urological Association Symptom Index.

Investigator's conclusions about cranberry plus mannose for UTI

The cranberry liquid blend is safe and well tolerated in both pre- and postmenopausal women with history of recurrent urinary tract infections. It is effective in decreasing the incidence of recurrent UTI.

This indicates that such cranberry-mannose supplement might be of benefit in reducing risk of recurrent urinary tract infections in females.

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Do Zinc supplements prevent pneumonia in kids

Digestion, Health & Nutrition                    Facebook Dr. Anil

Effect of zinc supplementation on risk of pneumonia in children

By A. Minocha MD, author: Guide to Alternative Medicine and Digestive System

Pneumonia is common in children younger than five years of age and may even be fatal especially in infants and low socio-economic status. Several studies have evaluated the effect of zinc on preventing respiratory tract infection and a pneumonia related decrease in childhood mortality.

Study:

Lassi and colleagues from AK University Hospital examined the literature and conducted a meta-analysis to study the  efficacy of zinc supplementation for reducing risk of pneumonia in kids. The results of the study were reported in the Cochrane Database Reviews (2010).

The investigators considered randomised controlled trials (RCTs) examining the efects of  supplementation of zinc on the risk of pneumonia in children aged 2 to 59 months of age. The database included six trials (n= 7850 children)

Result of zinc supplements on lower respiratory infections:

Zinc supplementation reduced the incidence of pneumonia by 13 percent  (risk ratio 0.87;  0.81 to 0.94).

Zinc supplementaion, based on one study reduced the prevalence of pneumonia by 41% (RR 0.59; 0.35 to 0.99).

Conclusions: Zinc supplementation reduces the incidence and prevalence of pneumonia in kids. By the way, here is a previous post on similar topic.

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Is complimentary and alternative medicine beneficial in fibromylagia

Digestion, Health & Nutrition             Facebook Dr. Anil

 Evidence for beneficial effect of alternative medicine in fibromylagia

By A. Minocha MD, author: Guide to Alternative Medicine and Digestive System

There is paucity of medications to relieve the suffering of chronic pain disorders like fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome etc. Patients continue to resort to therapeutic interventions for fibromyalgia that may or may not be effective. Complimentary and alternative medicines form a big part. But are they effective?

De Silva and colleagues from School of Medicine and Dentistry, University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK, critically examined  the evidence related to beneficial effects of regarding complementary and alternative medicines (CAMs) in fibromyalgia. The study was published in the journal Rheumatology.

Study

These investigators performed a systematic review of the randomized controlled trials of fibromyalgia comparing  complimentary and alternative medicine therapies with  treatments or placebo. Methodologic quality of all studies included in analysis was assessed as moderate. 

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 Results

Homeopathy

Three studies in this critical analysis involved the use of homeopathic care. All three studies demonstrated improvement in pain.

Nutritional supplements of benefit 

• Anthocyanidins
• Capsaicin
• S-adenosylmethionine 

Nutritional supplements lacking benefit

• Soy

Some data this yr since publication of above review

Yoga and exercise

A randomized controlled trial by Carson and colleagues from Oregan Health and Sciences University found a 8-week yoga program to be of benefit.

Another randomized controlled trial  reported that moderate to high intensity nordic walking improves functional acpacity of patients without improving pain.

A randomized controlled trial from Wang and colleagues and published in the New England Journal of Medicine concluded that Tai Chi results in improvements in Fibromylagia Impact Questionaire as well as quality of life.

                            Read about Dr. Minocha's book Natural Stomach Care

Traditional Chinese medicine (TCM)

A systemetic review examined 25 randomized controlled trials evaluating the role of traditional Chinese medicine including acupuncture for fibromyalgia. Overall 10 trials merited examination as part of meta-analysis. The investigators concluded that TCM therapies are of benefit for treatment of fibromylagia.

                            Click to read about acupuncture

Cognitive behavioral therapy

Bernardy and colleagues performed a systematic review and meta-analysis on role of cognitive behavioral therapy (CBT) in fibromyalgia and published their results in the Journal of Rheumatology. The investigators concluded that CBT improves coping with pain and reduces depressed mood and health care seeking behavior.

Do you or someone you know have chronic pain disorder like fibromyalgia? Have you tried any of the alternative medicines? Please share your experience.

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It's the vegetarian diet, stupid

Digestion, Health & Nutrition             Facebook Dr. Anil

Vegetarian diet linked to lower mortality

By A. Minocha MD, author: Guide to Alternative Medicine and Digestive System

The war over body weight control consumes billions of dollars with numerous books and pundits promoting their own versions of anti-obesity and weight loss . Atkins' low carb diet has been one of the most popular fad to hit the market in recent years.

Concerns:

Questions have been raised about benefits versus risks of low carbohydrate diet as promoted by diet, i.e. is the weight loss being achieved at the risk to overall health? The concerns got heightened when Dr. Atkins himself died at least in part related to heart related illness.

An authoritative answer:

The report of a study funded by the National Institute of Health and published in the prestigious Annals of Internal Medicine, the official publication of the American College of Physicians.

 Study title and authors/affiliations:

The authors of the report titled,"Low-carbohydrate diets and all-cause and cause-specific mortality: two cohort studies" are Fung and colleagues from the Simmons College, Harvard School of Public Health, Boston, Massachusetts, and National University of Singapore, Singapore.

Study goals and follow up:

The authors asessed the type of low-carbohydrate diets, either animal-based (primarly animal fat and protein) or vegetable-based (predominantly vegetable sources of fat and protein) of the subjects based on scientifically validated food-frequency questionnaires done during during follow-up of the study subjects.

Study sources:

Nurses' Health Study and Health Professionals' Follow-up Study

Study subjects:

85,168 women and 44, 548 men without heart disease, cancer, or diabetes at baseline formed the data base. Over follow up, there were 12,555 deaths.

Results:

• Low-carbohydrate diet was associated with a modest increase in overall mortality
• The animal low-carbohydrate diet score was linked to higher all-cause mortality, cardiovascular mortality and cancer mortality.
• Higher vegetable low-carbohydrate diet consumption was associated with lower all-cause mortality and  cardiovascular mortality.

Conclusions:

 A low-carbohydrate animal based diet is associated with higher all-cause mortality in both men and women. In contrast, a vegetable-based low-carbohydrate diet was associated with lower all-cause and cardiovascular disease mortality rates.

Not surprisingly Atkins; competitor Dean Ornish diet protagonists have jumped on these conclusuion as part of the weight control diet propaganda war.

Here is some more on vegetarianism

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