-An overview of multiple treatment interventions that can be of use in treating autism
                                                                                              John F. Coombs, M.D.- 2015.5

It is rare that a single problem/single remedy approach will solve complex medical problems. Almost always, there are many different contributing factors, all of which interact and affect each other, in a ‘web’-like manner. And so it usually happens that in order to see improvement in children with autism, many different factors have to be considered during the healing process. At the same time, families can only make so many changes at one time, and so the process of biological healing is usually slow and gradual, but progressive, taking a period of many months to years. The rate of healing depends on the severity of the autism, the age of the child, the presence of complicating medical conditions, and a family’s ability to afford & carry out treatments that can be suggested. Following is an outline of some of the factors that can be addressed in a biological approach to autism spectrum disorder. Bear in mind that this is not a complete list, and this list is more like a ‘web’ than a list; in that any one category will affect and be affected by all the others. Therefore this list of categories should be considered both as different parts and as a unified whole. Almost always many of these factors have to be addressed simultaneously to reverse autism spectrum disorder (ASD). An analogy for a systems approach to treating ASD is that of driving off the road in a snowstorm. You need a whole gang of men, pushing all at once, to get your car out of the ditch.  If they took turns pushing on your car one at a time, your car wouldn't budge. So it is with treating ASD.

 Parents of ASD children reading this should be advised that the list is long and daunting. It is meant only as a reference, to provide a brief orientation to some of the many different therapies that can be used in treating autism. In reality, it is Impossible to try to apply all of these at one time. For each child the goal is to select from this list those treatments most likely to benefit a child and that can be reasonably carried out by the family.

• Many children with autism develop unusual eating patterns that can be hard to change. Nevertheless it is important to work towards a diet that will help healing. Autistic children will do better with a diet that is free of processed foods, food additives, hidden sugars, GMO foods, hydrogenated oils, and trans fatty acids, as well as foods to which they have become sensitive.
• Adequate protein intake is essential to good health (especially brain & muscle), and protein powder may be necessary to boost a child’s protein intake.  
• Be careful to avoid hidden sugars! Remember that North Americans are eating over 20 times more sugar that they did 170 years ago, and that is one of the reasons for the dramatic increase in all forms of chronic disease. Rarely do ASD children make progress if they are eating even average amounts of sugar.
• Good fats are essential to health, especially brain health. But some fats heal (e.g.-top quality vegetable oils & fish oils) and some fats kill (processed, rancid, or heated oils). Learn the difference!

• Autistic children all have gastrointestinal imbalances to some degree, and most are sensitive to at least some of the more common ‘problem’ foods: gluten, dairy (casein), yeast, soy, or some of the other common food sensitivities. Almost all ASD children do better on the Gluten/Casein free diet. Documentation of gluten/casein sensitivity can be confirmed with fecal antibody testing (Enterolab in Texas-expensive, but the most sensitive testing). Many children are helped by additionally excluding foods which show a significant reaction on standard food sensitivity testing (IgG ELISA blood testing). Yeast, soy, corn are common additional food sensitivities.
• All children should be avoiding the toxic effects of junk food, commercially processed carbohydrates, commercially processed fats, and GMO foods. All of these contribute to immune activation and inflammation.

• Food additives, such as MSG, hydrolyzed vegetable protein, and aspartame are neurotoxic, and should be avoided. Foods which are high in glutamic or aspartic acid may trigger a reaction, and should be either avoided, or tested with an elimination/challenge diet test. (See list of potentially neuro-excitatory foods.)
• Other food components that may cause reactions in susceptible children are: phenols, salicylates, solanines (nightshade family), histamines, or oxalates.
• In children with severe bowel flora disturbances (especially Clostridia overgrowth), it is necessary to restrict intake of both simple and complex carbohydrates, using some modification of the SCD/GAPS/FODMAPS/paleo spectrum of diets. The dietary modifications have to be tailored to each individual child’s tolerances.

• Most of food is grown on impoverished soil, and we live in a polluted environment, and contend with various forms of stress. All ASD children will benefit from at least a basic level of supplemental vitamins, minerals, essential fatty acids, and antioxidants.  A very basic list would include:
• A good quality vitamin/mineral: For children-a quality children’s chewable vitamin/mineral (Natural Factors-Big Friends, or Douglas Labs-Vita-Kids) or contents of Selekta Multi (small capsules), 1-3/day.
• Vitamin C: 500- 4000 mg./ day, in divided doses, depending on weight; less if the Vitamin C causes intestinal distress.) For children in the midst of viral infections the dose can be increased, sometimes as high as 1000 mg per year of age, to a maximum of 10,000 mg spread over a 24 hour period.
• Vitamin D: Vitamin D plays an important role in brain development, and its deficiency may contribute to the development of autism. Almost all ASD children in northern latitudes are low in vitamin D except when they are getting daily sun exposure during the summer months. Vitamin D supplementation should follow the recommendations of posted on the Vitamin D Council website, and winter levels should be checked to confirm adequate dosing.
• Essential fatty acids: most ASD children are significantly deficient in Omega 3, and adequate EPA/DHA supplementation is important to reduce inflammation throughout the body. Only some children will need supplemental omega 6. Typical Omega 3 doses are: low dose, but easy to administer: Nordic Naturals- DHA Jr.- contents of 4 caps daily, more adequate dosing: Nordic Naturals Cod Liver oil ½-1 tsp. daily, or Nordic Naturals- Pro-Omega-2 capsules daily for adolescents.
• Antioxidants: Proanthocyanidins (grape seed, bilberry) or Astaxanthins are very good in conjunction with Vitamin C for reducing inflammation and treating colds & allergy.

The need for such intense supplementation is determined by a child's symptoms, and metabolic &/or genomic testing.
• Methylation Support: most ASD children are undermethylators, and derive significant benefit from adequate support with methylcobalamin. Children do best with subcutaneous injections (tiny: 0.05 ml.) given 2-3 times per week. The only oral form that I have found almost as effective as injections is the nano particulate methylcobalamin spray sold on Dr. Mercola's website. Adult dosing for this is six sprays sublingually once daily; for children the average dose ranges from 1-6 sprays daily, depending upon response.
-Some children who benefit from methylcobalamin have further improvement with addition of oral folinic acid (200-1000 mcg daily, depending upon weight and tolerance). Some will benefit from further addition of TMG or DMG.
-In providing methylation support, there may be an initial ‘detox’ reaction including hyperactivity and other adverse symptoms. It takes clinical skill to be able to differentiate between these children (for whom the doses should be lowered in dose and/or frequency, and only gradually increased) and those who are hypermethylators (who may do better with hydroxycobalamin, often in smaller doses).
• Higher doses of vitamin/minerals/antioxidants:
i) to compensate for poor absorption,
ii) to compensate for inefficient cellular enzyme activity resulting from genetic variations (‘cofactor loading’ of enzyme systems); in particular enzyme pathways related to methylation and neurotransmitter control
iii) to compensate for abnormally high levels of oxidative stress.
• High dose supplements such as Klaire Labs Vitaspectrum, though often helpful, can sometimes trigger adverse reactions, presumably because of inadvertently supporting abnormal bacterial overgrowth. It is best to start this supplement with fractional doses, and to increase the dose only as tolerated.
• Specific amino acid supplementation, especially to balance neurotransmitter levels (serotonin, dopamine, noradrenaline). This can be particularly important for children with poor protein absorption, as indicated by low serum prealbumin levels, or low levels on plasma amino acid analysis

Recent research suggests that mitochondrial dysfunction is more commonly present in ASD children than previously thought. About 5% of ASD children have true mitochondrial disease, which is genetically caused, and can have quite severe effects. However, a much larger proportion of ASD children have some degree of acquired mitochondrial dysfunction, caused by some of the other factors described in this outline (such as high body burden of environmental toxins, toxic effects of severely imbalanced bowel flora, side effect of certain drugs, physiological stress, increased oxidative stress). This form of mitochondrial dysfunction is typically milder that full-blown mitochondrial disease. Provision of broad-spectrum nutritional 'mitochondrial cocktails' can be given in an attempt to improve mitochondrial function. Better recovery with acquired mitochondrial dysfunction may be obtained by addressing the underlying contributing factors mentioned above.

Because of our climate and northern latitude, most Canadians are low in Vitamin D, especially in winter. Adequate exposure to the sun is virtually impossible in winter, though full spectrum lighting can help this. For some children, adequate ultraviolet light is a requirement over and above adequate supplementation with Vitamin D.

• Rational use of drug medication -Keep drug use to a minimum- Care is needed in administering general anesthetics and in prescribing pharmaceuticals, watching carefully for adverse reactions. Mitochondrial dysfunction and impaired methylation are two factors that lead to this vulnerability. 
• Avoid foods to which one is sensitive (As noted in section 2 above). 
• Reduce exposure to environmental toxins (especially mould, tobacco, chemicals, and heavy metals).
• Reduce overall exposure to mycotoxins (fungal toxins): both from within the body (intestinal yeasts) and from outside the body (from yeast & mould in the diet and moulds in the air). Fungal toxin is a contributing factor in many chronic diseases, according to WHO research conducted by Dr. Costantini.
• Reduce total body burden of heavy metals
-Many ASD children benefit from lowering their body burden of heavy metals, even though their blood levels do not meet official standards for toxicity. Though many autism doctors try to document heavy metal overburden using challenges with oral or IV chelators, I prefer not to do this because of the risk of significant detoxification reactions. It is safer to test hair (to detect ongoing environmental exposure) and blood (to distinguish between true toxicity as opposed to merely a measurable body burden), and where appropriate, observe the clinical response to gradual reduction of the body burden of heavy metals. 
-Thiol-based pharmaceuticals (DMSA, DMPS) need to be used with care, and should be reserved for those with true heavy metal toxicity. EDTA (in oral and suppository forms) is the safest and least expensive pharmaceutical chelating agent. 
-I often see good long term clinical response using oral thiolized silica (an ingenious combination of two GRAS food additives developed by Dr. Christopher Shade). This is a compound is not absorbed systemically, and acts only within the bowel. Thiolized silica is sometimes used in combination with oral liposomal EDTA. These two oral chelators are safe enough to warrant a careful clinical trial of their use in children in whom heavy metal overburden is suspected. Transdermal chelators usually are ineffective.

ASD is as much a disorder of the gut as of the nervous system. Most children with ASD have a severely imbalanced bowel flora, and correcting this can be a major challenge. (The technical term for this is called balancing the microbiome.) Toxic chemicals (produced by abnormal microbes in the intestine and by the rotting of undigested food) are absorbed through the bowel wall and slowly cause widespread damaging effects throughout the body, including the nervous system.
• Normalise digestive activity (Digestive enzymes, especially those that assist in breakdown of complex carbohydrates can often help absorption and balance of bowel flora.)
• Adequate dietary fibre and control of constipation
Constipation is a common problem in ASD, contributing to increased dysbiosis and neurotoxicity. Constipation usually responds to appropriate changes in diet, addition of fibre, adequate probiotics, and supplemental flax oil and/or magnesium. If this is not sufficient, temporary use of PEG 3350 (Lax-A-Day) may be warranted to break a vicious cycle leading to constipation
• Eliminate pathogens (bad bowel bugs) and restore a healthy balance to the bowel flora (microbiome)
Abnormal bowel bacteria (e.g.- Clostridia, strep, and probably other species) play a prominent role in causing autistic symptoms, but overgrowth of yeast (Candida), parasites (worms & amoebae) also can have a role. Their elimination is usually a slow, gradual process requiring a combination of careful adherence to diet combined with antimicrobials and probiotics.
• Research lags behind clinical experience with regards to overgrowth of bowel yeast (fungal dysbiosis), but it has long been observed by autism docs that antifungal drugs (such as nystatin or fluconazole) can give significant improvement in many ASD children. Fortunately, research is underway at the University of Guelph to document overgrowth of intestinal yeasts in these children.
• Antimicrobial biological compounds (Biocidin, grapefruit seed extract, olive leaf extract, garlic, Lauricidin, pau d’arco, etc.) can also be helpful in normalizing gut flora, particularly when multiple agents are given in rotation.
• Probiotics (Bacterial: in order of potency: Bio-K, Genestra HMF Neuro, Custom Probiotic D-Lactate free; Yeast: Saccaromyces boulardii). Other adjunctive probiotics include AOR Probiotic #3, Thorne FloraMend, Mutaflor, Prescript-Assist. Probiotics are often much more effective given in very high doses to show clinical benefit, but some children can tolerate only limited doses because of Herxheimer-like (‘die-off’) reactions.
• A more recent development in normalizing the microbiome is the use of therapeutic microscopic helminths in children who have been raised in super-hygienic environments. These agents would be called 'probiomics'.
• Normalization of the microbiome typically requires the combined use of antimicrobials, antifungals, probiotics, and sometimes probiomics. A word of caution however: Though most ASD children respond to the use of these therapies very well, others have severe nasty die-off reactions (Herxheimer-like reactions) that prevent aggressive use of such medications. It is therefore best to start with low doses and increase doses only as tolerated. For long-term use, antifungals and antimicrobials are best used as multiple agents, given sequentially in 5-7 day rotations to avoid the development of antimicrobial resistance by the pathogenic bacteria or yeast. If abnormal bowel flora persists in spite of treatment, there is likely some other factor that has not been adequately addressed: Inadequate attention to diet, ongoing allergy, toxic overburden, immune deficiency, chronic ‘stealth’ infection, etc.

We are living in an increasingly toxic world, and ASD children generally have an impaired ability to remove foreign chemicals and heavy metals that have accumulated in body tissues. The detoxification methods described below can be of use in the proper clinical setting, but can be harmful if misused. Detoxification must be undertaken slowly & gradually!
• Enhance hepatic (liver) detoxification: Almost all ASD children show evidence of reduced glutathione levels, which profoundly impairs their ability to detoxify toxic environmental chemicals. A number of nutritional and biological supplements have been shown to promote production of glutathione, and these can benefit ASD children.
• Most spectrum children have an impaired  sulfation (phenol sulfotransferase) enzyme system, an important liver detoxification pathway. Epsom salts baths can help restore this function.
• Enhance detoxification through the skin: Far-infrared sauna therapy, if used consistently and frequently can help detoxify ASD children, and will remove toxic chemicals, such as pesticide residues, PCB’s, etc. This has to be done cautiously, and combined with mineral repletion. 

• Bentonite clay baths can also be effective for slow, gradual detoxification, and they are easier to administer than saunas.

• Hidden, chronic ‘stealth’ infections can lower immunity without causing acute symptoms. This typically involves multiple chronic opportunistic infective agents: viral (measles, mumps, rubella, HHV6, herpes virus), bacterial (especially streptococcus and increasingly in certain areas of the country, Lyme and its co-infections), fungal (especially Candida), and helminthic (intestinal worms). This chronic infective load on the body is now termed ‘total pathogenic burden’. This burden impairs immune function and also impairs the ability to detoxify foreign chemicals and heavy metals. Therefore reducing the total pathogenic burden is often necessary to enable ASD children to progress in their recovery. Though short-term treatment with pharmaceuticals may be appropriate, it is better in the long-term to work with milder and slower biological antimicrobials or immune-stimulating biological treatments, in combination with other treatment approaches mentioned in this outline.

• Various therapies can be used to help normalize an imbalanced immune system. This includes various biological compounds (including colostrum derivatives), as well as desensitization treatments for environmental sensitivities (best done with oral desensitization, as opposed to standard allergy shots). More aggressive therapy such as intravenous gamma globulin is done in the US, but seldom available in Canada. 
• Some children respond well to homeopathic treatments, which can be used to modulate the immune system. (However, in my experience severely affected children rarely respond well to homeopathy as a stand-alone therapy for autism.)

• Subtle ('subclinical') imbalances in thyroid, adrenal, male/female or pituitary hormone (oxytocin, melatonin) levels can complicate some cases of ASD; more likely to be found in severely affected older children and adults than young children. Treatment requires detailed testing and careful management.

• Though lack of physical activity is seldom a problem for younger children with ASD, if illness prevents physical activity, then other means of maintaining health and muscle tone need to be considered (massage, rebounder/mini-trampoline). The rebounder also helps increase lymphatic flow and is quite therapeutic for some children.

• This is more a concern for children with associated cerebral palsy or who have had injuries. Poor posture, chronic muscle tension, pelvic and spinal imbalances can lead to areas with impaired blood flow, low oxygenation, and subsequent accumulation of metabolic toxic residues. Various forms of postural, structural, and massage therapy can help reverse these conditions. Cranial therapy does help with improving circulation of cerebrospinal fluid in selected cases, usually younger children with previous head injuries or forceps delivery.

• Though this form of therapy is still in its infancy, in certain applications the use of magnetic and electrical fields has proven useful. Electromagnetic therapy can help restore compromised circulation, improve intracellular communication and signaling, and help with lowering the body burden of environmental toxins. Both fixed field and pulsed field therapy has its application in restoring balance.

• Prolonged sleep deprivation can have an increasing debilitating effect upon physical and emotional health of both ASD children and parents. Using some of the known biological sleep aids (e.g., melatonin, magnesium, 5-HTP) in combination with diet and dysbiosis therapy can help avoid having to resort to drug medication to break a sleep deprivation cycle.

• Behaviour therapy is considered standard in the management of ASD, but can be very expensive if paid for privately. Biological treatment works synergistically with behavioural therapy and improves its response rate. Children with severe autism are neurotoxic, and in these children behavioural therapy alone is not likely to meet with success: underlying biological Imbalances need to be addressed at the same time. (Analogy: Behaviour therapy would not work with someone who has just imbibed a quart of whiskey: only after the person’s nervous system had been detoxified would such therapy have a chance to work.)

These may include, where appropriate, use of hyperbaric oxygen, or brain training therapies. Dr. Norman Doidge, author of The Brain’s Way of Healing, has done much to increase awareness of the potential benefits of neuroplasticity science.

• Brain training therapies include neurofeedback training, music therapy, and physical therapies such as Brain Gym and Brain Balance programs.

• Neurofeedback is a form of brain wave entrainment (harmonization) using EEG biofeedback. The technique can be used with children as young as 6 years old, provided that they can sit and watch a computer screen.

My sense of brain training therapies is that success will depend upon a good match between the child and the therapy/therapist, and best combined with biomedical treatment to reduce underlying neurotoxicity and neuroimmune dysregulation.