The Doctor Is In - Issue 30 2009

BIOMEDICAL

Dr. Dan Rossignol

Dr. Irva Hertz-Picciotto

email: [email protected]

Julie Matthews, CNC

Dr. Amy Yasko

Dr. Kenneth Bock

Please email your questions to: [email protected] Question 1 We have a 47-year-old son who has recently been diagnosed with Parkinson’s disease and is being treated very successfully with the lowest dosage of Sinemet that is available. There is no Parkinson’s disease in either of our families. Has anyone with autism had this same affliction? If so, is there any reason? Could Risperdal be a factor? Look forward to your reply. Response from Dr. KenNETH A. Bock: Parkinson’s disease is a neurodegenerative disorder of unknown etiology (causation); however, a confluence of genetic and environmental factors is suspected. Similarly, autism is a neurodevelopmental disorder with a complex multifactorial causation, also believed to be due to genetic susceptibility coupled with environmental factors. In both disorders, toxins are believed to play a role, most likely coupled with an impaired ability to detoxify these toxins. In Parkinson’s disease, pesticides and herbicides are especially believed to play a role, whereas in autism, heavy metals and chemicals are suspected contributory factors.

Risperdal is an atypical antipsychotic medication that is a dopamine antagonist. It is used in autistic children to control certain types of severe adverse behaviors, such as agitation, rage, and aggression. Its side effects (especially at higher doses) do include Parkinson-like symptomatology, such as stiff, rigid muscles, tremor, abnormal movements, and impaired gait. Question 2 They say the chance of identical twins becoming autistic is 60%. Is this a genetic condition? Response from DR. Irva HertzPicciotto The statement is not accurate. The data show that if one of two identical twins has autism, then the chance that the other one also has autism is between 60% and 90% in studies conducted so far. This would be from twin pairs that are not pre-selected for other factors. For comparison, the figure for fraternal twins is lower: about 10% (if one has autism, then about 10% of the time, the other twin also will). In reality, even when two twins both have the condition, the severity often varies considerably, which supports the importance

of environment, even when genetics is a major factor. Note also that if one child in a sibling pair (two children with the same parents) has autism, then the chances that a second child also develops autism seems to be around 10% (7% to 15% in well-conducted studies). Of course, those statistics do not tell us “how much of autism is due to genetics” or “how much of autism is due to environmental factors.” Also, it is absolutely crucial to understand that the percentages of cases “caused by genetics” and “caused by environment” do not sum to 100%. This is because most cases of autism have multiple causes; i.e., not only are there multiple causes across the population, but also: for each person who develops autism, there is a set of factors, all of which were necessary, and together were sufficient to cause brain development to go awry resulting in the behavioral syndrome known as autism. This set of sufficient causes might be five genes and one environmental insult, or vice versa, one gene and five environmental exposures. Also critical will be the timing of those exposures: the same exposure at 10 months of age may do nothing, but at one week of age or at 3 months of gestation might be quite damaging.

Disclaimer Information is not provided as medical advice. Parents / patients should research all information given. Every person’s physiology is unique. All information provided as a reply should be discussed with the patient’s personal physician and / or autism or other specialist appropriate to the symptom(s) or body system(s) involved in their individual situation, who provides the patient with regular medical oversight, monitoring, and lab testing, and who keeps up-to-date on the most recent research and interventions. Beginning any significant biomedical or other interventions that may impact physiology or making changes to an established regimen should be discussed with the patient’s physician in advance. ISSUE 30 2009

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BIOMEDICAL Question 4 My daughter has elevated mercury and lead in her hair analysis report. I have heard that CaEDTA is better at pulling out lead and DMSA is better at pulling out mercury. Which one and do you feel I should go with and why?

Note that there will likely be not only risk factors but also protective factors in the environment. Once we get a better handle on those environmental factors, we will be able to intervene to lessen the severity and possibly even prevent autism from developing, in at least some children. I hope this is helpful to you. Question 3 My child has increased gut permeability. He is 4 years old and has suffered in the past with constipation and diarrhea. Is DMSA chelation therapy advisable? Response from Dr. Dan Rossignol: You did not list if your child has autism, but I am assuming that this is the case. Increased gut permeability has been described is a subset of children with autism [1] and is probably indicative of underlying gastrointestinal inflammation, which is also relatively common in autism [2, 3]. Therefore, I suggest you focus on treatments for the underlying gastrointestinal problems. Before even contemplating any form of chelation therapy, you need to perform some testing to determine if chelation is even necessary, such as measuring markers of heavy metal toxicity (e.g., blood lead level, perhaps urinary porphyrin levels). Furthermore, performing chelation without having gastrointestinal inflammation under control could worsen the inflammatory problems. Work with your physician to determine if chelation is even advisable, and, if so, make sure that gastrointestinal inflammation is first treated adequately. 144

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Response from Dr. Dan Rossignol: What you describe is concerning because elevated mercury and lead in the hair is consistent with recent exposure. Hair grows at about 1 cm per month, so it depends how long the hair was that you sent off for testing, but if it was several cm long, then there has been exposure to lead and mercury within the past several months. The MOST important step to take in this situation is to identify the source of the mercury and lead, which means testing for these metals around the house, and then performing remediation. You would also be wise to measure blood levels, as this is a marker of recent exposure as well. You also need to work with a physician who is experienced with chelation if you decide to pursue that route, as chelation is only advisable under certain situations, and if evidence of toxicity has been met. Calcium EDTA is more effective at removing lead, and DMSA is effective in removing both lead and mercury, but again, you need to work with your physician before planning on going forward with chelation. Question 5 Can all-natural products such as Goji and GoChi help alleviate some of the symptoms of autism? Response from Dr. Dan Rossignol: Multiple studies have demonstrated that oxidative stress is a problem in some individuals with autism [1, 2], and this has been associated with regression [3]. Antioxidants including vitamin C [4], L-carnosine [5], methylcobalamin [6], melatonin [7], carnitine [8], zinc [9], and pycnogenol [10] have been shown to improve symptoms in some individuals with autism and attention-deficit hyperactivity disorder in double-blind, placebo-controlled studies. Goji and GoChi appear to have antioxidant properties and, therefore, may be beneficial, although I am unaware of any studies published to date on the use of these in autism. Therefore, I would suggest first using antioxidants that have been proven to be effective in double-blind placebo-controlled studies.

Question 6 Is there a correlation between children having an MTHFR mutation and seizures? My son has one of the MTHFR polymorphisms and has started having seizures. Also, might it make a difference as to whether the seizures would have started if he hadn’t been subject to mercury toxicity? In other words, how many of these factors singly or combined would precipitate seizures? Understanding that every child is unique and medical attention is called for if a child begins having seizures,are there other factors such as nutrient deficiencies, testosterone levels, or anything else that might be considered? Response from Dr. Amy Yasko: In terms of seizure activity, there are a number of factors that I have found to increase the incidence of seizures. First, lack of B-12 can be a major factor. There are some longer posts on my chat group about this topic, but the bottom line is that when we have significant MTR and MTRR mutations and not enough B-12 support, we can see increased seizure activity. This gets me to the second point which creates a bit of a catch 22...When we have high level detox of metals, such as mercury, lead, and especially aluminum, that can also increase the incidence of seizures. Using B-12 support can trigger detox. So, this is why it is a bit of a catch 22. When we have MTR and MTRR mutations we look to support with B-12, and the B-12 can be helpful in lowering seizure activity. However, at the same time, the increased B-12 can trigger detox which can increase seizure activity. It is often not until the excretion of toxins has progressed to lower the body burden that we can see the positive effects of B-12 support on reducing seizure activity. Finally, the level of excitotoxins in the system can also contribute to seizure activity. So, we’re looking at eliminating any added glutamine, glutamate, aspartate, aspartame, including these derivatives as complexed with minerals, for instance, looking to eliminate magnesium aspartate or supplements as “amino acid chelates,” as those will also include glutamate and aspartate. I also look to reduce the amount of calcium, as calcium in conjunction with glutamate can increase excitotoxin activity and may increase seizure activity. Looking to balance the glutamate with GABA, theanine, low dose lithium, magnesium, and low dose zinc may be useful, as well as other supplements that I have talked about in the past.

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email: [email protected] In answer to your question about MTHFR mutations and seizure activity: I have not seen a direct relationship between the two. If the MTHFR mutation has allowed for decreased methylation cycle activity, and that decreased activity has allowed for increased toxin accumulation, then indirectly the MTHFR may be increasing seizure activity by virtue of the increased toxin burden on the system. If we are talking about MTHFR A1298C mutations, we will frequently see those individuals as having more issues with aluminum toxicity, which may indirectly contribute to increased seizure activity as compared to those who are MTHFR C677T. Also, MTR and MTRR mutations, particularly those that I consider more severe, and the attendant need for B-12 may also be indirectly related to seizure activity. Question 7 I hear that glutathione is commonly depleted in autism and is poorly absorbed as a supplement. How best can I, through foods consumed, elevate glutathione levels in my child? Response from Julie Matthews, CNC: Glutathione, an important antioxidant, is used for detoxification, immune function, and intestinal integrity. Vitamins A, C, and E, zinc, selenium, and carotenes enhance immune response and “spare” glutathione--look for foods rich in these antioxidants. Asparagus, watermelon, broccoli, garlic, onion, and, particularly, whey protein (however, it’s not

casein-free) are good sources of glutathione. Methionine, betaine, and choline enhance liver function and increase the levels of glutathione. Methionine is found in meat, fish, sesame seeds, Brazil nuts, spinach, and potatoes. Betaine is found in beets, spinach, and broccoli. Egg yolk and liver contain choline. Question 8 Can you help me with my son who is permanently constipated? He can go for five days without passing a stool. I need to keep sugar out of his diet because he has Candida. He also can’t have wheat or casein. Response from Julie Matthews, CNC: There are a couple aspects to constipation-avoid the things that can contribute to inflammation and microbial imbalance, and add substances that help with constipation. I’m assuming that he is avoiding gluten, as well as wheat -- if not, remove gluten, as well. As far as food goes, also consider other food sensitivities such as soy, corn, eggs or other possible intolerances that can create inflammation in the gut. Candida and dysbiosis can cause constipation, consider the Specific Carbohydrate Diet or other diet that avoids complex starches and/or sugars to starve out any harmful microbes. Make sure the simple steps are covered first -- consume fiber through fresh fruits and vegetables, and drink adequate water. Fermented foods such as yogurt and kefir (dairy or non-dairy), raw sauerkraut, and

kombucha supply good bacteria that help with peristalsis (keeps the bowels moving), reduce inflammation, and support a healthy intestinal tract. Additionally, simmer prunes in apple juice, and have your child eat the prunes and drink the juice. Consider magnesium or vitamin C supplementation, both “loosen” stool. Simmer or steep flax seeds (not SCD-compliant) in water, strain and consume the liquid. Be sure to work with a physician that can view this from a medical perspective to make sure there isn’t anything medical going on. Question 9 Can you recommend good foods to feed my son who has ADD, I really need to help his memory as he is suffering at school. Response from Julie Matthews, CNC: First, avoid all artificial colors, flavors and preservatives, as well as MSG (monosodium glutamate, autolyzed yeast, hydrolyzed vegetable protein)--this is crucial. Avoid trans-fats such as partially hydrogenated oil, and consume healthy fats such as cod liver oil, olive oil, coconut oil, animal fats, and nuts. Make sure your child has a wellbalanced breakfast including protein and fat before school, such as eggs or a sausage patty. Choline, the precursor to acetylcholine, which is important for memory, can be found in egg yolks, nuts and seeds (particularly peanuts), liver, meat, milk products (if not dairy-free), fresh fruit, and vegetables (especially broccoli, cabbage, cauliflower, beets, asparagus, and tomatoes).

References for Question 3:

References for Question 5:

1. D’Eufemia P, Celli M, Finocchiaro R, Pacifico L, Viozzi L, Zaccagnini M, Cardi E, Giardini O: Abnormal intestinal permeability in children with autism. Acta Paediatr 1996, 85(9):1076-1079.

1. James, SJ, et al., Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet, 2006. 141(8): p. 947-56.

2. Ashwood P, Anthony A, Pellicer AA, Torrente F, Walker-Smith JA, Wakefield AJ: Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. J Clin Immunol 2003, 23(6):504-517.

2. Chauhan, A and Chauhan, V, Oxidative stress in autism. Pathophysiology, 2006. 13(3): p. 171-81.

7. Garstang, J and Wallis, M, Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems. Child Care Health Dev, 2006. 32(5): p. 585-9.

3. Chauhan, A, et al., Oxidative stress in autism: increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferrin--the antioxidant proteins. Life Sci, 2004. 75(21): p. 2539-49.

8. Van Oudheusden, LJ and Scholte, HR, Efficacy of carnitine in the treatment of children with attention-deficit hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids, 2002. 67(1): p. 33-8.

4. Dolske, MC, et al., A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry, 1993. 17(5): p. 765-74.

9. Bilici, M, et al., Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry, 2004. 28(1): p. 181-90.

3. Torrente F, Anthony A, Heuschkel RB, Thomson MA, Ashwood P, Murch SH: Focal-enhanced gastritis in regressive autism with features distinct from Crohn’s and Helicobacter pylori gastritis. Am J Gastroenterol 2004, 99(4):598605.

5. Chez, MG, et al., Double-blind, placebocontrolled study of L-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol, 2002. 17(11): p. 833-7.

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6. James, SJ, et al., Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr, 2009. 89: p. 1-6.

10. Trebaticka, J, et al., Treatment of ADHD with French maritime pine bark extract, Pycnogenol. Eur Child Adolesc Psychiatry, 2006. 15(6): p. 329-35.

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