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Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health
Originally believed to be a disorder primarily affecting central nervous system, neurobehavioral and neurodevelopmental disorders like autism spectrum disorders and ADHD are currently viewed by many as part of a multi-system disorder with heterogeneous presentations. Many risk factors have been identified, but there is a lack of agreed upon unified framework and/or inability to precisely identify what is primary and what is secondary problem.
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While at macro-level, it is my hypothesis that altered gastrointestinal system is at the core of the chronic problems in autism and attention deficit disorders (ADHD), in this article, I am discussing mitochondrial dysfunction as a unifying factor at cellular level.
According to Palmieri and Persico, post-mortem studies of brains of autism patients indicate that abnormalities in mitochondrial function occur as a result of dysfunctional immune system and altered calcium signaling processes.
Implications of lack of identified core problem
- The comorbidities affecting various body-systems including peripheral nervous system, gastrointestinal , musculoskeletal, endocrine, immune and metabolic systems lends credibility to the use of a variety of diverse therapies each affecting one or more comorbidities, rather than addressing what might be a hitherto undefined core problem.
- Most of the therapies prescribed by different specialists address only specific symptoms as seen by a particular specialist, and sometimes right hand does not know what left hand is doing.
Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health
Potential for mitochondrial dysfunction in autism
- Abnormal mitochondrial function has been implicated in diverse neuro-degenerative as well as psychiatric disorders like schizophrenia, Alzheimer's dementia, bipolar disorder, autism and ADHD.
- Cellular dysfunction as manifested by mitochondrial dysfunction appears to be an excellent candidate that can connect all the dots as seen in the pathophysiology and diverse clinical manifestations of ASD .
- There is a region-specific deficits in mitochondrial function in autism system disorders, suggesting the role of oxidative stress and mitochondrial dysfunction in the pathophysiology of autism.
- Mitochondrial dysfunction contributes to oxidative stress, immune dysfunction and cell death in the brain and may lead to neuro-developmental abnormalities in autism.
- Since mitochondria perform a lot of basic yet critical functions including cellular respiration, a mitochondrial dysfunction can have an impact across the various organ systems. In fact, genetic disorders with autism-like characteristics may also be attributed to mitochondrial dysfunction.
- L-carnitine which protects against mitochondrial dysfunction provides therapeutic benefit in autism.
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A few words about mitochondrion
- Specific organelles in the cell
- Number of mitochondria in any cell varies depending on its energy activity. Low energy requiring cells like skin have fewer mitochondria as compared to high energy cells in brain, gut etc.
- Have their own genome/DNA
- Involved in cellular respiration
- Metabolize glucose and fatty acids to generate energy in the form of ATP
- Involved in critical metabolic and physiologic processes including neurotransmitter release
- Thought to be critical mediators of neuron loss in diverse neurodegenerative disorders
Is It Leaky Gut or Leaky Gut Syndrome?
Mitochondrial dysfunction and gut dysfunction are not mutually exclusive
- Mitochondrial dysfunction does not explain all of pathophysiology of autism spectrum disorders. From the organ specificity standpoint, it is my hypothesis that impaired gut and its milieu including intestinal bacteria, digestive processes and micronutrient deficiencies play a critical role in modifying the brain physiology manifesting as behavioral and other cognitive problems.
- At the end of this article, I outline some evidence that mitochondrial dysfunction of autism is actually consistent with my hypothesis of gastrointestinal dysfunction as the key.
Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health
Prevalence of mitochondrial disease v dysfunction in autism spectrum disorders
- Evidence for mitochondrial dysfunction in autism has been mounting over the years and it may be present in as many as 80% of kids with autism leading some to argue for a “mitochondrial autism” category.
- Most mitochondrial dysfunction is not accompanied by genetic alterations suggesting that this is a secondary and not primary phenomenon.
- GI symptoms may precede other manifestations of mitochondrial dysfunction.
Diagnosis of mitochondrial disease
Diagnosis can be difficult and relies on scoring systems based on a number of discreet criteria and point system ascribed to different features based on assessment of and then scoring of clinical features, biochemical and molecular tests, brain imaging, and metabolic enzymes tests. Muscle biopsy is needed for confirming evidence of mitochondrial disease but is missing from many patients in many studies.
Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health
Typical clinical features of mitochondrial disease also seen in autism
- Developmental delays
- Developmental regression or loss of previously acquired skills in 1/3rd of cases
- Seizure disorder in 25% of patients
- Muscular weakness
- Gastrointestinal problems in 10-90% patients depending upon the study
- Accelerated growth of head circumference, height and length during infancy
- Growth problems
- Laboratory features like elevated lactate in 17-77%
- Elevated alanine in 36%
- High lactate, protein and alanine in cerebrospinal fluid
- Abnormal mitochondria on electron microscopy
Features of mitochondrial disease uncommonly seen in autism
- Exercise intolerance
- Peripheral neuropathy
- Pyramidal and extrapyramidal signs
- Cardiac and kidney problems
- Abnormal white matter on brain imaging
- EMG abnormalities
In contrast to above, many of the mitochondrial dysfunction features that are not associated with autism include migraine, stroke, eye and hearing problems etc.
Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health
Metabolic dysfunction versus metabolic disease as the key to autism
- A large population based study after examining muscle biopsy estimated the prevalence of mitochondrial disease in autism population to be only 7.2% in general ASD population. However, this might be an underestimate since mitochondrial dysfunction may occur in presence of lab abnormalities (serum lactate) used to screen for mitochondrial disease. In addition, mitochondrial dysfunction may be present despite patients not meeting strict criteria for mitochondrial disease.
- A controlled study by Giulivi et al. and published in the Journal of American Medical Association estimated mitochondrial dysfunction to occur in as many as 80% kids with autism.
Linking gastrointestinal dysfunction and mitochondrial dysfunction
- Intestinal wall is susceptible to mitochondrial damage during stress like sepsis. Dr. Julian from the Ohio State University reported in the International Journal of Experimental Pathology that these changes are then followed by epithelial barrier dysfunction or increased intestinal permeability or leaky gut.
- Patients with chronic fatigue syndrome (CFS) suffer from neurological impairment similar to seen in patients with D-lactic acidosis. A comparison of intestinal bacteria in patients with CFS and controls showed a higher number of Enterococcus and Streptococcus bacteria that produce more D-lactic acid from glucose metabolism indicating mitochondrial dysfunction. The investigators concluded that the presence of these bacteria explains not only the clinical features of CFS but also mitochondrial dysfunction seen in patients.
- Low-molecular-weight phenolic acids are produced as a result of metabolism of aromatic amino acids and polyphenols by the intestinal bacteria. Fedotcheva and colleagues from the Russian Academy of Sciences reported in the journal Toxicology Letters that these bacterial metabolic products are increased during sickness and cause increased mitochondrial dysfunction as manifested by alterations in production of reactive oxygen species etc.
- An altered intestinal bacterial flora is evident within hours of development of acute pancreatitis. This is accompanied by increased intestinal permeability or leaky gut along with an early organ-selective mitochondrial dysfunction in the lung and jejunum.
Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health
Enteric nervous system or second brain is more susceptible to mitochondrial dysfunction than brain
- Nervous system of the gut also known as enteric nervous system is susceptible to mitochondrial dysfunction even more than the brain and is consistent with increased prevalence of gastrointestinal symptoms in patients with primary inherited mitochondrial disorders.
- Not all regions of the gut and enteric nervous system or the "Second Brain" are equally affected during illness, a phenomenon seen in the central nervous system as well.
Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health
Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health
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