(Author's note - Further discussions with Dr. Kane have allowed me to significantly improve and deepen the science of this article. Worth reading again!)
Let me be clear. I hate the expression “autism puzzle.” The only time I’ll have the slightest affection for it is when it’s used in a sentence such as “The autism puzzle has been solved.”
This article delves into theories which will hopefully bring that day closer. I don’t say the theory expressed here is true. But it's interesting. And I believe it’s worth discussion.
In the recently published book, “Food and Nutrients in Disease Management”, ($133 on Amazon) edited by Ingrid Kohlstadt is a chapter entitled “Autistic Spectrum Disorder: Dynamic Intervention for Neuronal Membrane Stabilization” by Patricia Kane, Ph.D, Annette Cartaxo, M.D., and Richard Deth, Ph.D. In the chapter a number of interesting claims are made. I believe they’re consistent with the experiences of many people with autism, and if verified, provide a clear picture of what has gone wrong with the disease, and more importantly, the road out of autism and other neurological disorders.
The discussion begins with evidence of neuroinflammation discovered by Dr. Andrew Zimmerman and his colleagues at Johns Hopkins in 2005. This neuroinflammation upsets the balance between excitatory and calming neuro-transmitters, causing the glutamate system to become overexcited and GABA production to be curtailed. This results in the development of autistic symptoms and other neurological disturbances such as seizures.
Two biomarkers of this glutatmate excitotoxicity are mitochondrial dysfunction involving 1) viral exposures which damages the mitochondrial membrane resulting in formation of swellings (dendritic beading) along the nerve dendrites and 2) the formation of lipid rafts, ceramides within the cells impairing mebrane function. The authors assert that the appearance of dendritic beading is indicative of a damaged mitochondrial membrane, made up of fatty acids called cardiolipin, after exposure to a virus. They have also observed that calcium disregulation is also an accompaniment to mitochondrial dysfunction, leading inevitably to oxidative stress.
The authors have examined red cell fatty acid analysis for the past 12 years through a biomedical analysis at BodyBio (Dr. Kane's company) on thousands of children with autism and other disorders with testing by the Peroxisomal Disease Laboratory of the Kennedy-Krieger Institute at Johns Hopkins University. They have hypothesized that autism is the result of a disturbance in cellular function due to toxic insult. Specifically, there’s a build-up of very long chain fatty acids (VLCFAs) which causes impairment in the functioning of the peroxisome. The peroxisome is a cellular organelle responsible for critical cellular functions such as detoxification, creating cellular fatty acid structures (phospholipids), generating bile acids necessary for digestion, and breaking down very long chain fatty acids.
In discussing autism with me, Dr. Kane suggested I imagine the very long chain fatty acids as prison bars, imprisoning the cell so that these rigid structures form lipid rafts not allowing the organelles (organs within the cell like the mitochondria andperoxisome) and the cell membrane to perform its fluid, vibrating function, but rather leave it static, like a couch potato. The cell membrane is composed of 50% phospholipids, which are critical for the health and vitality of cellular function.
The cellular membrane should be viewed as something akin to a port, the skin of the cell from which the cell receives nutritents from the outside world. If the docks aren’t in good shape then the cell can’t get the material it needs to function properly and cannot expel what it does not need. Because of the disruption in the cell membrane, the formation of lipid rafts due to toxic insult, receptors such as the dopamine receptor that Dr. Richard Deth has written so much about relating to autism, is not embraced properly by the phospholipids, leading to distortion of the cell and the ability of the receptors like dopamine to sit properly in the membrane. Phosphatidylcholine makes up 50% of the outer lipid membrane and is the most powerful tool we have in our arsenal to heal the mebrane, heal the brain.
The authors write, "Peroxisomal disorders are characterizes by an accumulation in tissue and body fluids of renegade fatty acids: saturated and mono-unsaturated VLCFAs (very long chain fatty acids), odd chain fatty acids, and branched chain fatty acids, pristanic and phytanic, which are normally degraded within the peroxisome, but instead can accumulate and form lipid rafts, or ceramides, which derange cell membrane structure. The accumulation of renegade or VLCFAs reflects blocked detoxification and methylation pathways, and may be characteristic in autism, PDD, seizure disorders, stroke, neurological disease and states of neurotoxicity." In essence, the buildup of very long chains causes swelling or edema of the cell from the buildup of very long chain fatty acids. Harvard autism neurologist Dr. Margaret Bauman originally found that children with autism had "big, fat neurons" while Dr. Kane discovered that children with autism had "big, fat peroxisomes" after examining the levels of very long chain fatty acids in red cell studies from Johns Hopkins.
In 1996 Dr. Kane had proposed that autism may be the aftermath of a toxic insult, a viral infection which evoked hepatic encepahlopathy, resulting in hyperammonenemia and suppression of several key enzymes, such as carbamylphosphate synthesase, glutamine synthesase and ornithine transcarbamylase. The high levels of ammonia would cause an "increase in brain edema (water) and a deterioration in neuropsychological function."
The ammonia would also cause abnormalities in neurotransmitters and induce injury to astrocytes which are already under oxidative stress. For this and a number of other reasons, Kane believes the oxidative stress should be viewed as the result of a toxic event, rather than the cause of autism. Kane asserts that because of this, treating a patient with anti-oxidants is a little like pouring water on a house after it's already burned to the ground. She suggests "treatment should be centered on re-building membrane structure and thereby stabilizing membrane function." This involves clearing the body of ammonia, very long chain fatty acids, and giving the cells those building blocks which they've long been denied.
Another problem which has attracted the authors’ attention is her finding of increase in the white matter in the brains of children with autism after observing the buildup of DMAs in the red cell fatty acid test from Johns Hopkins. Normally these markers are low, showing demyelination in children with pervasive developmental delay and seizures. In autism, there is instead a state of overmyelination. Dr. Bauman notes in her recently updated book on autism that the most likely explanation for the increase in brain size is "the presence of abnormal myelin production."
In their work Drs. Kane and Cartaxo (a developmental pediatrician)have also noted that about one-third of the autistic children tested have low cholesterol. Low cholesterol is yet another indicator of poor cell membrane integrity. Because of my complete dedication to you readers I had my daughter’s blood tested by the Peroxisomal Disease Laboratory of the Kennedy-Krieger Institute of Johns Hopkins University through BodyBio for the presence of abnormal fatty acids. (Yes, you may address me by my Native American name, “Don’t-have-a-buck” for my propensity to test all of these various theories!)
My daughter tested high for levels of very long chain fatty acids which form these lipid rafts (indicating neuroinflammation) high levels of DMAs (myelin markers, also showing neuroinflammation), and low in essential fatty acids. In resolving these issues it’s Kane’s approach to “burn” off the very long chain fatty acids, “build” by supplementing the essential chain fatty acids necessary for proper neuron development, and “balance” the other fatty acids. This usually involves the “intravenous administration of phosphatidylcholine (Lipostabil), folinic acid, (Leucovrin) reduced glutathione (Wellness Pharmacy) and phenylbutyrate, appropriate co-enzymes, such as vitamins and minerals, and balanced essential fatty acids (including oral supplementation with evening primrose oil, egg yolk, meat fat, sunflower oil, flax oil, high EPA fish oil, wild salmon, sardines) targeted to the patient’s individual results.”
In my discussions with Dr. Kane she was also able to relate these theories to many other therapies which have been used in autism. Hyper-baric oxygen therapy (HBOT) for example is quite good for burning off the very long chain fatty acids she’s seen in many autistic children. However, it will also burn off the essential fatty acids as well and can destabilize the neurons. Therefore, as a result, those children most likely to benefit are those who already have a good balance of essential fatty acids so that they can handle the decrease.
Dr. Kane has been using the short chain fatty acid, phenylbutarate for the past 14 years for children with seizure disorders, post stroke, brain injury, and autism. She found that phenylbutyrate as a prescription or over the counter, burned off very long chain fatty acids, but without the complications of HBOT. Phenylbutyrate though must be used with balanced essential fatty acids and phosphatidylcholine to keep the cells healthy.
Children with seizures are more likely to have a buildup of very long chain fatty acids, but an exceptionally low amount of total lipid content within their cells, and thus HBOT treatment may increase their seizure activity. The high level of myelin marker DMAs (indicating brain inflammation), elevation of very long chain fatty acids (also from brain and liver inflammation) with low essential fatty acid levels from my daughter’s test also explains the failure of her stem cell treatments last year. Her body didn’t have enough short chain fatty acids to provide the raw materials necessary for the stem cells to flourish.
In a similar vein, the ketogenic diet, which involves eating a great deal of fat, causes the body to burn off very long chain fatty acids forming lipid rafts or ceramides, but may not fully resolve the problem unless the essential fatty acids, phosphatidylcholine and butyrate are given. This may be why approximately one-third of the children who have success on the diet have their seizures reappear after stopping the diet. There is no need to use the severe restrictions of the ketogenic diet as Kane describes in another chapter of the book, "Food and Nutrients in Disease Management" on seizures. Kane has a diet called the Membrane Stabilizing Diet and can be found in the Detox Book for Patients.
The question of susceptibility genes for autism has also drawn a great deal of attention from Dr. Kane, although she notes there has been a lack of consistent findings. She observes that certain genes can lead to an increased immune reactivity that may be turned on during fetal development due to the mother's exposure to toxins or after the child is born in relation to heavy metals, chemicals, virus, toxic mold, or pesticides. She has had several patients with gross exposure to heavey metals such as arsenic from the city’s water supply, as well as methylmercury during fetal development from the mother’s daily consumption of white albacore tuna, and massive metallic mercury exposure from a spill at the mother's dental clinic.
One point that is often misunderstood is that heavy metals are liquid soluble and reside in cells. It is impossible to detoxify heavy metals bound to proteins like metallothionen or within the nervous system with chemical chelators like DMSA or DMPS. These children had gross developmental abnormalities from heavy metal posioning which were resolved through the intravenous administration of Lipostabil (phosphatidylcholine), Leucovorin (folinic acid), glutathione, and phenylbutyrate. It is Kane's opinion that “in-born” errors of metabolism don’t present any greater challenges than those errors of metabolism which are acquired later in life.
Dr. Kane’s lipid therapy treatment has also impacted her own life. When her son was 18 months old he had a severe stroke which left him in such a debilitated state the doctors told her she should place him in an institution. She believes this happened as a result of her dentist putting pure mercury into a filling and covering it with amalgam. She believes this mercury went straight into her child during her pregnancy as well as while she was breast-feeding. She states the only medical reason a child can have a stroke before the age of 3 is due to an ornithine transcarbamylase deficiency (this enzyme detoxifies ammonia). As the enzyme ornithine transcarbamylase is suppressed with exposure to mercury, ammonia levels rise, and the child has repeated strokes. She was able to save her son's life by using lipid therapy and within a few months had completely recovered. Dr. Kane went on to work with children whom everybody else had given up on, children with brain injury, intractable seizures, global development delay, and autism.
Although Dr. Kane's son completely recovered from the stroke, unfortunately, when he went away to college he was exposed to an array of neurotoxins. He worked in an enclosed space with acrylic paint (arsenic, lead, cadmium), soldering lead/copper in his art work, and also received a meningitis vaccination required by the university (he had never been vaccinated previously). He had not one stroke, but a series of strokes, and began exhibiting autistic symptoms.
In a panic Dr. Kane called her long-time friend Dr. Bernie Rimland and asked if he'd ever heard of adult-onset autism. After receiving a negative answer from Dr. Rimland she went to the library desparate to find an answer. She found a case of a brother and sister with adult-onset autism from the cluster of cases from the mercury exposure at Minamata Bay, Japan in the 1950s. The exposure of mercury had suppressed the enzyme ornithine transcarbamylase causing an increase in ammonia and autistic symptoms. (There's also a report in Medline of adult-onset autism in a 31 year-old man from infection by the herpes virus and Dr. Kane told me she had seen a case of West Nile dementia in a 70 year-old man that presented with autistic symptoms.) For the second time in his life, Dr. Kane’s son started on lipid therapy and he again recovered.
In Dr. Kane’s view autism is best described as a disruption of cellular lipid metabolism. She believes the starting point for this discussion is viral in nature, and complicated by heavy metals such as lead, mercury, or cadmium, pesticides, toxic mold exposure, chemicals, Lyme disease and other infections. Each one of these environmental insults on its own, or in combination, can disrupt lipid metabolism.
Personally, I believe Dr. Kane’s work to be an important contribution to addressing autism. She has presented her work at Columbia University, the NIH, Johns Hopkins, as well as many other medical institutions. This work seems to be well-known, as I had no difficulty in getting my regular pediatrician to sign off on these tests. After having so many tests done at labs of unknown quality it was refreshing to see this last set being sent off to Johns Hopkins.
I’ll keep you posted as to what happens next.
Kent Heckenlively is Legal Editor of Age of Autism