Pyroluria

Pyrrole Disorder

Omega 3s can worsen mental symptoms in bipolar or schizophrenic patients.... if they have a pyrrole disorder. This phenotype is dramatically short of arachidonic acid & giving omega 3 oils aggravates the situation since omega 3 and omega 6 EFA's are in competition for delta 5,6 desaturases. We use red blood cell membrane analysis for EFA's if we suspect this problem. Pyroluric mental patients will usually get worse if given fish oils, DHA, EPA, etc. They thrive on Primrose Oil, a good source of AA and other omega 6s. (June 23, 2003)

Most persons with pyroluria respond very quickly to the B-6, Zn, C, E therapy..... Major improvements are often seen by the 2nd day, and almost always by the end of the first week. The exceptions are: (1) persons with severe mental illness (schizophrenia or bipolar), (2) persons with other significant chemical imbalances, and (3) patients with a major malabsorptive condition. When pyroluria is diagnosed along with another chemical imbalance, I like to track a patient during the first 6-8 weeks to determine which is the dominant imbalance. If major improvement occurs immediately, it's because pyroluria has been corrected. Some patients report a nice early improvement followed by a plateau, and then another advance. Schizophrenic and bipolar pyrolurics usually report some progress after a few weeks, but it may take 3-6 months to get to steady state. The biggest problem with the Kp analysis is getting a proper sample to the lab. The kryptopyrrole molecule is unstable and will disappear rapidly at room temperature or if exposed to bright light. The urine sample must be placed in a freezer immediately after acquisition. Kp can be lost in the freezer if the temperature isn't well below 32 degrees F. We've also learned that exposure to bright light results in breakdown of the Kp molecule. Finally, the sample must be maintained in a frozen condition during shipment. I would greatly suspect any Kp value below 3.0. Usually this means the sample didn't get to the lab in proper condition. With respect to reference levels: We consider a healthy level to be between 4-8 mcg/dL. We consider persons between 10 and 20 to have mild pyroluria, and a good response to treatment is usually reported. Persons exhibiting 20 to 50 mcg/dL have moderate pyroluria, which can be a devastating condition. Persons above 50 mcg/dL have severe pyroluria. Longitudinal testing of pyrolurics has shown that major variations can occur during a day. For example, Arthur Shawcross (famous NY serial killer) had levels ranging from 35 to 203, with higher levels observed during stressful periods in prison. However, he always tested as pyroluric in multiple tests. Stresses, illnesses, injury, etc can be expected to elevate Kp levels. Medical history and review of symptoms are vital to this diagnosis. The major challenge in differential diagnosis of pyroluria is the similarity in symptoms between pyroluria and overmethylation (low blood histamine). Another problem is that symptoms of pyroluria are greatly muted in undermethylated, obsessive/compulsive persons. These persons may be high achievers, with great internal tension..... Persons with pyroluria alone tend to underachieve, partly because of a poor short term memory and associated reading problems. (Nov 10, 2003)

We've obtained hair Zn and plasma Zn levels (simultaneously) about 40,000 times. Low hair zinc correlates beautifully with low plasma levels. However, very elevated Zn in hair nearly always means Zn deficiency and loss plasma Zn levels. Most of the time this involves a Pyrrole disorder which results in very high Zn excretion in urine (and hair). In a healthy person without metal-metabolism problem, only about 4 percent of excreted Zn leaves through the kidneys. [28 Nov 03] Symptoms of pyroluria include (1) stunting of growth, (2) unpleasant body odor, (3) delayed puberty, and (4) skin stretch marks. This family's symptoms are certainly consistent with pyroluria. Pyroluria definitely runs in families. We have a mother in Kane County, IL who has 15 children & all of them tested pyroluric. The mother had a Kp level of over 150 herself

Can vitamins, omega fats improve behavior?

Study links diet to mental health San Francisco Chronicle Carol Ness Wednesday, January 15, 2003 Nutritional Epidemic?: Studies on animal and human brains... When your parents told you to take your vitamins, they wanted you to grow up big and strong. They weren't thinking it might keep you out of trouble. But listen to this: In a recent study from England, inmates given daily vitamins, minerals and omega fatty acids drastically reduced their bad behavior. Compared to inmates who didn't get the nutritional supplements, they didn't fight as often, break as many rules, mouth off or act out as much. The study, done at an Aylesbury juvenile jail by Oxford University physiology researcher Bernard Gesch, is far from conclusive. But it suggests that the connection between what we eat and how we behave goes much deeper than "too much sugar makes my kids crazy." The logical extension of its findings could reach far beyond prison walls. If good nutrition can keep an inmate in line, think what it could do for road rage and violent crime. "This data is very interesting, although it raises as many questions as it answers," says James Gilligan, an expert on violence at New York University and consultant to the San Francisco jail's anti-violence education program. He adds that the Gesch study, along with a couple of other recent studies of omega 3 fatty acids' effects on mental illness, "at least suggest the possibility that ordinary foodstuffs like fatty fish may decrease impulsive behavior -- which includes a variety of antisocial behaviors." The study isn't the first to connect nutrition and behavior. Small studies have shown that vitamin supplements may raise kids' grades and improve their behavior at school. But Gilligan says the protocol for the new studies is far more rigorous. Most nutrition research looks at the body. We all know how saturated fats strangle our hearts, and studiously track the ways substances like lycopene in tomatoes might prevent cancer. But when it comes to behavior and mental health, the role of nutrition in general and fatty acids in particular is just emerging. Gesch, a former probation officer, runs a nonprofit called Natural Justice, which researches the causes of criminal behavior. His study involved 231 juvenile offenders. Half got a daily multivitamin and four pills containing essential fatty acids. The other half got five pills containing only vegetable oil. Their diets and behavior were monitored both before and during the study, which ranged from weeks up to 9 months. Results appeared in the British Journal of Psychiatry last year. Antisocial incidents -- everything from assault and hostage taking to insolence and rule- breaking -- dropped at least one-third among prisoners who got the supplements, but insignificantly among the ones taking the placebo. Gesch says he's not saying nutrition is the only cause of antisocial behavior, but that the results "could not be explained by ethnic or social factors." He cautions that the results need to be replicated -- and then more studies done to explain them. But they show the potential for reducing violence in prisons, and in the community, he says. His study stirred up enough interest that Gesch will present his work at the American Psychiatric Association's annual conference in San Francisco in May. The study drew the interest of Dr. Joseph Hibbeln, a researcher on nutrition and behavior at the U.S. National Institute on Alcohol Abuse and Alcoholism. For Hibbeln, who has labored in relative obscurity for 15 years on the effects of omega fatty acids on humans, Gesch's study is like gold. The human brain is made up largely of fat, Hibbeln says. And his theory is that American brains have changed over the last century as Americans have eaten less seafood and vastly more soybean oil, the ubiquitous "vegetable oil" that's in most processed foods. The shift means Americans now consume far more omega 6 fatty acids (present in the oil) than omega 3s (present in seafood) -- and the two affect the brain very differently, Hibbeln says. Omega 6 fats compete with omega 3s, and omega 3s are losing the battle in the American diet, Hibbeln said. And studies on animal and human brains have shown that without enough omega 3s, serotonin levels plummet. Low serotonin can lead to depression and impulsive behavior, and Hibbeln is convinced that our dietary changes are one reason American levels of depression and violence have risen. Gesch's study and new ones underway build on ongoing work by California State University at Turlock researcher Stephen Schoenthaler, who also has run tests on both offenders and schoolchildren that suggest improving nutrition affects behavior. In some of the new studies just coming out, omega 3 supplements helped reverse depression and bipolar disorder. Gesch says his study doesn't prove anything about why the inmates who got supplements acted better -- and much more research is needed. Gilligan cautions against thinking that finding one biological key to bad behavior is the answer to violence, which has deeply complicated social, psychological and cultural causes. And, he says, making sweeping policy changes would be wrong until more is known. But at the same time, adding a nutritional component to RSVP, the San Francisco jail's successful anti-violence program, might make sense. "It's hard to see where it would do any harm," he says. In California, however, the new research is unlikely to affect what prisoners are fed, let alone get them daily vitamins. State law says prisoners' meals must meet government nutrition guidelines, but in fact the regulations only address protein and a couple of the major vitamins like C and A. In San Francisco jails, inmates get 2,900 calories a day, at 99 cents per meal -- which means a lot of starch. Jan Wyatt-Lucha, food director in the Marin County Jail and consultant to the state Board of Corrections, says inmates' minimum diets are updated every few years. But vitamin supplements? "They are not going to do it because it costs too much," she says. Money aside, improving the diet of a captive population is one thing. People in jail already eat better than a lot of people on the street, Wyatt- Lucha says. "Getting the nutrients into people is matter for social policy," says Gesch. And parents. Carol Ness is a Chronicle staff writer. E-mail her at cness@sfchronicle.com. http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2003/01/15/FD182842.DTL This article appeared on page FD - 1 of the San Francisco Chronicle

Mercury and ADD/Autism/Allergies/Immune System

Get your coffee before sitting don to read this one. It's long, but it's full of information! ~L Immune Reactive Conditions: The mercury connection to autism, schizophrenia, ADD, eczema, lupus, asthma, and allergies (snipped from larger study) Bernard Windham- Chemical Engineer The incidence of neurotoxic, allergic, and immune reactive conditions such as autism, scizophrenia, ADD, dyslexia, allergies, asthma, eczema, lupus, psoriasis, childhood diabetes, etc. have been increasing rapidly in recent years(1,2,3,5,23). A recent report by the National Research Council found that 50% of all pregnancies in the U.S. are now resulting in prenatal or postnatal mortality, significant birth defects, or otherwise chronically unhealthy babies(3). Exposure to toxic chemcials or environmental factors appear to be a factor in as much as 28 percent of the 4 million children born each year(3), with 1 in 6 having one of the neurological conditions previously listed.. According to the U.S. FDA, at least 26 million have allergies and at least 17 million have asthma. The largest increase has been in infants (1,2,,5-7,23), with an increase in autism cases to over 500,000 (1,2,23,22), an over 500% increase to a level of almost 1 per 250 infants in the last decade(2), making it the 3rd most common childhood condition, along with similar increases in ADD, and over 10 % of infants- approximately 15 million in the U.S. with such conditions or systemic eczema(1). Studies researching the reason for these rapid increases in infant reactive conditions seem to implicate earlier and higher usage of vaccines containing mercury(thimerosal) as a likely connection(2,2b,23,30,40). A recent study comparing pre- and post-vaccination mercury levels, found a significant increase in both preterm and term infants after vaccination(42), with post-vaccination mercury levels approximately 3 times higher in the preterm infants as compared with term infants. The study found mercury blood levels up to 23.6 ug/L and received an average dose of 16.7 ug/kg. Just this one vaccination gave an exposure to mercury that is many times the U.S. ATSDR adult minimum risk level(MRL) for mercury of .3/ug/kg body weight per day(41). It has been estimated that if all of the vaccines recommended by the American Assoc. of Pediatrics are given and contain thimerosal, then by age 6 months an infant would have received 187 micrograms of ethyl mercury which is more than the EPA/ATSDR health standard for organic mercury(33,41) and by age 3 the typical child has received over 235 micrograms of mercury thimerosal from vaccinations which is considerably more than Federal mercury safety guidelines (41), in addition to significant levels from other sources for many(23). Infants during this period have undeveloped blood brain barriers and much of the mercury goes to the brain, resulting in significant adverse neurological effects in those that are most susceptible(43,3). Because of the evidence the FDA has completed a study and written a letter to vaccine manufacturers asking that mercury be removed from vaccines. The updated letter stated, "The Center for Biologics Evaluation and Research (CBER) has completed its evaluation of the use of thimerosal in vaccines...Our review concluded that reducing or eliminating thimerosal from vaccines is merited(44). The letter pointed to a joint statement by the American Academy of Pediatrics and the United States Public Health Service in 1999, which "called for the removal of thimerosal from vaccines as soon as possible." Many thousands of parents have reported that their child got such conditions after vaccination, and tests have confirmed high levels of mercury in Many of those tested, along with other toxic exposures. An additional source of thimerosal to the fetus of women who are RH negative is the 30 micrograms in the RhoGAM shot they receive. Underweight infants that get the same dose of thimerosal as other infants have also been found to be at special risk. Many of those diagnosed with high mercury levels have also been found to have significant improvement after mercury detoxification(23,30,40,11,35). Thimerosal had been previously removed from similar preservative uses in eye drops and eye medications after evidence of a connection to chronic degenerative eye conditions. After over 15,000 law suits were filed in France over adverse effects of the Hepatitis B vaccine, the French Minister of Health ended the mandatory hepatitis B vaccination program for all school children. Adverse effects included neurological disorders and autoimmune disorders such as multiple sclerosis and lupus. Some hospitals in the U.S. also quit recommending certain vaccinations. Although vaccinations appear to be the largest source of mercury in infants, mercury has been found to be transmitted from the mother to the fetus through the placenta and accumulate in the fetus to higher levels than in the mother’s blood(22). Breast milk of women who have amalgam fillings or eat a lot of fish has also been found to be a significant source of mercury in infants and young children(22,45). A direct mechanism involving mercury’s inhibition of cellular enzymatic processes by binding with the hydroxyl radical(SH) in amino acids appears to be a major part of the connection to these allergic/immune reactive conditions (15-23,36,46). For example mercury has been found to strongly inhibit the activity of xanthine oxidase and dipeptyl peptidase (DPP IV) which are required in the digestion of the milk protein casein(15,16,17,19,20,22), and the same protein that is cluster differentiation antigen 26 (CD26) which helps T lymphocyte activation. CD26 or DPPIV is a cell surfact glycoprotein that is very susceptible to inactivation by mercury binding to its cysteinyl domain. Mercury and other toxic metals also inhibit binding of opioid receptor agonists to opioid receptors, while magnesium stimulates binding to opioid receptors (15). Studies involving a large sample of patients with autism, scizophrenia, or mania found that over 90 % of those tested had high levels of the milk protein beta-casomorphin-7 in their blood and urine and defective enzymatic processes for digesting milk protein(24,25,27), and similarly for the corresponding enzyme needed to digest wheat gluten(24,26).The studies found high levels of Ig A antigen specific antibodies for casein, lactalbumin and beta-lactoglovulin and IgG and IgM for casein. Beta-casomorphine-7 is a morphine like compound that results in neural dysfunction (24,25), as well as being a direct histamine releaser in humans and inducing skin reactions (14,21,25c). Similarly many also had a corresponding form of gluten protein (26). Elimination of milk and wheat products and sulfur foods from the diet has been found to improve the condition. A double blind study using a potent opiate antagonist, naltrexone(NAL), produced significant reduction in autistic symptomology among the 56% most responsive to opioid effects(28). The behavioral improvements was accompanied by alterations in the distribution of the major lymphocyte subsets, with a significant increase in the T-helper- inducers and a significant reduction of the T-cytotoxic-suppressors and a normalization of the CD4/CD8 ratio. Studies have found mercury causes increased levels of the CD8 T-cytotoxic-suppressors(29). As noted previously, such populations of patients have also been found to have high levels of mercury and to recover after mercury detox(23,11,22,30,40). As mercury levels are reduced the protein binding is reduced and improvement in the enzymatic process occurs(22,11). Additional cellular level enzymatic effects of mercury’s binding with proteins include blockage of sulfur oxidation processes and neurotransmitter amino acids which have been found to be significant factors in many autistics(18,36,46,17), plus enzymatic processes involving vitamins B6 and B12, with effects on the cytochrome-C energy processes as well. Epson salts(magnesium sulfate)baths, supplementation with the p5p form of Vit B6 and vit B12 shots are methods of dealing with these enzymatic blockages that have been found effective by those treating such conditions. Mercury has also been found to have adverse effects on cellular mineral levels of calcium, magnesium, zinc, and lithium(39,22,46). Supplementing with these minerals has also been found to be effective in the majority of cases(39) Another of the results of these toxic exposures and enzymatic blockages is the effect on the liver and disfunction of the liver detoxification processes which autistic children have been found to have (30,36,22). All of the autistic cases tested were found to have high toxic exposures/effects and liver detoxification profiles outside of normal(30). Along with these blockages of cellular enzymatic processes, mercury has been found to cause additional neurological and immune system effects in many through immune/autoimmune reactions(11,12,35). Mercury(22) as well as thimerosal (31,32) also have direct neurotoxic effects on brain nucleotid binding proteins through their effect on Ca2+ATPase and Na+/K+ATPase activity. But the effects on the neurological and immune systems of exposure to various toxic substances such as toxic metals and environmental pollutants has also been found to have additive or synergistic effects and to be a factor in increasing eczema, allergies, asthma, delayed food allergies, and sensitivity to other lesser allergens(14-22,35). Most of the children tested for toxic exposures have found high or reactive levels of other toxic metals, and organochlorine compounds (30,40,11,12,35,4). Other than the organochlorines or toxic metals which are discussed later, three common pollutants that have been documented to have effects on such conditions are traffic and industrial pollutants nitrogen oxide, power plant residual oil fly ash, and organochlorine pollutants(4). Another effect of mercury and toxic metals is a reduction in B- lymphocytes (37,38,22). One of these studies(37) dealing with autistic patients and further work with such patients has found this causes a tendency to be more seriously affected by viruses and to develop intestinal disorders including leaky gut, lymphoid modular hyperplasia, and a high incidence of parasites. Allergic contact eczema is the most frequent occupational disease(1,22), and the most common cause of contact eczema is exposure to toxic metals(1, 6- 12,22). The metals most commonly causing allergic immune reactivity are nickel, mercury, chromium, cobalt, and palladium(1,6-14,22). The highest level of sensitization is to Infants, who are most reactive to thimerosal, a form of mercury that has been used as a preservative in vaccines and eye drops(6,7). There is strong suggestive and clinical evidence for a connection between toxic metals and autism(2b,15-40).

Digestive/metabolic problems in ADHD/Autism

From: Holistic Primary Care – online article Digestive, Metabolic Problems Abound In Patients with ADHD, Autism By Erik L. Goldman Editor in Chief PORTLAND, OR- Attention Deficit Hyperactivity Disorder and autism are multifactorial biological disorders requiring a multimodal therapeutic approach that addresses the gastrointestinal, immunologic and metabolic problems usually associated with the behavioral abnormalities, said Jeff Bradstreet, MD, at the annual meeting of the American Holistic Medical Association. "Conventional allopathic concepts define ADHD and autism as 'psychiatric' disorders. I think that's bunk. I look at ADHD and autism biologically," said Dr. Bradstreet, founder of the International Child Development Resource Center (ICDRC), a clinic and foundation that has treated over 2,000 children with ADHD or autism. "As an MD, I had to move toward naturopathic principles to learn how to treat these disorders." Over the years, Dr. Bradstreet has developed sophisticated therapeutic protocols centered on correcting digestive problems, eliminating allergens and environmental toxins, and improving nutrition. Whenever possible, he prefers to treat these kids without pharmaceuticals. "I only use drugs as a rescue modality." While ADHD and autism are related in many ways, and sometimes overlap, Dr. Bradstreet believes they are distinct conditions. He rejects the notion that autism is simply an extreme form of ADHD. However, he contends that both reflect altered brain and CNS function, which are the net result of environmental toxin overload, abnormal immunologic reactions, impaired hepatic detoxification, and GI dysfunction which can sometimes be extreme. There is still plenty of debate over how to define these conditions and even more regarding their etiologies. But there is little argument regarding the sharply increasing incidence and prevalence. The most recent estimate is that one in every five school aged boys in the US must take a stimulant to go to school. There are over 350 million doses of methylphenidate given to US schoolchildren every year. Federal registries suggest there are between 9 and 12 million children with ADHD. Data from California indicate one in 160 school age children have some form of autism; the figures have doubled over the last four years. "Some of this may be overdiagnosis, but I think that most of it is not. It is very, very real." Dr. Bradstreet and his colleagues believe ADHD arises from a combination of immunologic, allergic and digestive dysfunction that begins with damage to the child's immune system early in development. The injury may be due to environmental toxin exposure, but in the majority of cases, he believes mercury-containing vaccines do play a role. Thimerosal and aluminum in vaccines are intrinsically neurotoxic, and they can also modulate immune function. Live viral vaccines contain as much as 25 mcg of mercury (as thimerosal) per dose. Young children receiving serial live viral vaccines get quantities of mercury that, on a body weight basis, exceed safe levels for US adult fish consumption. Dr. Bradstreet and his colleagues recently completed a case control study showing a statistically significant correlation between mercury exposure at an early age and autism. Those who had the highest levels of mercury exposure had a 6.4-fold increased prevalence of autism than those at the lowest levels. There was no correlation between autism and lead or cadmium exposure. "It is not just vaccine mercury, but environmental mercury as well." The vaccine etiology, though still highly controversial, has been gaining credence in recent years. A CDC-funded study recently showed a statistically significant difference in the prevalence of ADHD, autism, and tick disorders between individuals who received mercury-containing vaccines at 3 months, and those who did not. Analysis of data from the federal Vaccine Adverse Events Reporting System (VAERS) and the US Department of Education do show a linear correlation between the odds ratio for neurodevelopmental disorders and thimerosal exposure (Geier DA, Geier MR. Pediatr Rehab. 2003. 6 (2): 97-102). However, two recent Danish population-based studies comparing rates of these disorders between hundreds of thousands of individuals vaccinated with thimerosal-containing versus thimerosal-free vaccines, failed to show any correlation (Hviid A, et al. JAMA. 2003; 290 (13): 1763-6, Madsen KM, et al. Pediatrics. 2003; 112 (3 pt. 1): 604-6). Most conventionally-trained pediatricians hold that there is little risk of autism from vaccines, especially thimerosal-free vaccines. They argue that if there is any risk, it is probably very small, and that the benefits of vaccination far outweigh any potential risks. Dr. Bradstreet, the father of an autistic child, strongly disagrees. "There are still no truly mercury-free vaccines," he said, suggesting that this may explain the absence of a correlation in the Danish studies. "We are making progress and they are getting better. But there's still a lot of mercury out there." Live virus vaccines, such as the one for measles are particularly problematic, said Dr. Bradstreet. "The way it is injected, the virus gets immediate access to the tissues in which it prefers to proliferate the lymph nodes and CNS-and escapes immune system clearance. As a result, residual virus can become a problem. In one recent study, 50% of a cohort of children with autism had cerebrospinal fluid antibodies to measles virus proteins found in the MMR vaccine. Many ADHD/autism children also have a unique form of irritable bowel disease in which proteins traceable to vaccine strains of measles are found. While there is still much room for debate about the connection between vaccines and neurodevelopmental disorders, there is a growing consensus that children with ADHD and autism typically have gastrointestinal problems, and that the two are related. The GI tract in most of these patients is, to put it bluntly, a total mess, said Dr. Bradstreet. He insisted that without cleaning up the gut problems, it is impossible to make headway in resolving ADHD and autism. Lower GI dysfunction, enzyme deficiencies and impairments of hepatic detoxification pathways are very common. Patients typically excrete large amounts of sulfate in their urine, sometimes as much as 10 times more than normal children. The cause is yet not known, but it results in impairment of sulfate-dependent hepatic detoxification pathways. These patients also excrete cysteine, a key amino acid for glutathione production. Cysteine wasting is a characteristic of residual viral infection, and it results in compromise of glutathione-dependent detoxification pathways. The net result is that these individuals can't break down and excrete toxins. Pancreatic enzyme deficiency is very common; Dr. Bradstreet noted that approximately 75% of the children he treats have significant deficiencies of key pancreatic enzymes. As a result, they do not digest proteins properly, setting the stage for both upper and lower GI problems. Researchers at the department of pediatric gastroenterology, University of Maryland studied 36 autistic children via endoscopy, biopsy, and intestinal and pancreatic enzyme analysis. They found that 69% had grade I or II esophageal reflux and inflammation, 42% had chronic gastritis, 67% had duodenitis, and 58% had low carbohydrate digestive enzyme levels (Horvath K, et al. J Pediatr. 1999; 135 (5): 559-63). Diarrhea and constipation are common in these patients. Some kids tend to have more diarrhea, while others have constipation so extreme they develop impactions. "You can sometimes feel these huge fecal masses if you palpate their abdomens," said Dr. Bradstreet. This can be particularly problematic because in essence, they are storing large loads of toxins, further burdening their already compromised hepatic detoxification pathways. Many ADHD/autism patients have "leaky gut" syndrome, characterized by a breakdown of the tight junctions between endothelial cells in the gut lumen. This is evidenced by the presence of lactulose in their fecal material (D'Eufemia P, et al. Acta Pediatr. 1996; 85 (9): 1076-9). A highly permeable gut wall allows passage of all sorts of antigenic proteins, toxins, and pathogens into the circulation. Dr. Bradstreet is particularly concerned about "exorphins," protein fragments from the incomplete digestion of grain gluten and casein. Some of these protein fragments, like beta-casomorphins and gluteomorphins, are neuroactive and able to bind to opioid receptors in the brain. In a child with a leaky gut, these exorphins easily pass into circulation, and since hepatic clearance of opioid neurotransmitters is already compromised, the exorphins hang around for a long time. He believes they are driving factors in the cognitive symptoms and abnormal behaviors of ADHD and autism (Wakefield AJ, et al. Aliment Pharmacol Ther. 2002; 16 (4): 663-74). Some of the most compelling work linking digestive system problems with neurobehavioral disorders like ADHD and autism comes from the work of Andrew J. Wakefield and his Inflammatory Bowel Disease Study Group at the Royal Free and University College Medical School, London. His team performed ileocolonoscopy with biopsies on 60 children with developmental disorders including autism, ADHD and Asperger's syndrome, as well as 50 unaffected control subjects. They found ileal lymph node hyperplasia in 93% of the affected children, but in only 14% of the controls, and colonic node hyperplasia in 30% of the affected kids, but 5% of the controls. Close to 90% of the kids with developmental disorders had chronic colitis, versus only 4% of the controls (Wakefield AJ, et al. Am J Gastroenterol. 2000; 95 (9): 2285-95). This builds on an earlier study of 12 children, all of whom showed nodular hyperplasia and colitis (Wakefield AJ, et al. Lancet. 1998; 351 (9103): 637-41). Clostridium, which can secrete a number of neuroactive toxins, also plays a role in some patients. Patients with late onset autism sometimes have increased numbers of clostridial species in the gut. Dr. Bradstreet described the bizarre case of a dog that inadvertently ate feces from an autistic child: the dog went into a coma for 7 days. "Researchers at the University of Michigan are studying feces from this child to see what might have caused this extreme reaction. We think it might be clostridial toxins." Management of the complex multi-system problems characteristic of ADHD, autism and other developmental problems is a major challenge for physicians and families of these children. Dr. Bradstreet centers his approach on the following goals: improvement of GI function, restoration of normal immune function, elimination of heavy metals and other toxins, and supplementation to optimize hepatic, immunologic, neurologic, and cognitive function. He does use DMSA chelation to eliminate mercury and other heavy metals, and said that over 70% of these children will show major improvements in behavioral symptoms just from this alone. "It is the number one treatment as rated by the parents; no drug even comes close." Other treatments that help with detoxification include: Selenium: At a dose of 25 mcg/day, this mineral facilitates detoxification by binding to mercury by forming selenium-mercury complexes that can be safely excreted in the urine. It is also an essential cofactor for synthesis of glutathione peroxidase, a key antioxidant enzyme. Milk Thistle (Silybum marianum): Standardized preparations of 70-80% silymarin, an important bioactive component of this plant, were shown to improve liver function in patients with solvent-induced liver damage. There is also a study of 166 children with chronic liver disorders, 70% of whom showed liver function improvements while taking silymarin. N-Acetyl Cysteine (NAC): Since most patients with ADHD or autism are cysteine deficient, this is a cornerstone of treatment. NAC is a precursor of glutathione, an essential player in hepatic detox pathways. Dr. Bradstreet recommends starting with a low dose of 25 mg/day and gradually increasing up to 200 mg daily. Calcium-D-glucarate (as Betaine): This salt of D-glucaric acid inhibits beta-glucuronidase, and increases net elimination of toxins and steroid hormones via glucuronidation, a critical step in Phase II hepatic detoxification. Begin with 150 mg, and increase to 1,000 mg per day. Alpha Ketoglutarate (AKA): These patients often show elevated ammonia levels, derived from abnormal GI flora. AKA helps detoxify ammonia. It is also a precursor of glutamine which helps heal the gut mucosa. The dose range is 250-750 mg/day. Taurine: This sulfonic amino acid is involved in formation of bile salts, which are essential for toxin elimination. Taurine also plays a role in neuromodulation, and tends to have a calming effect on ADHD patients. Begin with 100 mg and build up to 1,000 mg/day. Methionine: This amino acid binds heavy metals, and adds methyl groups to xenobiotics, aiding in their excretion. Supplemental methionine increases production of several cytochrome P450 enzymes. The dose range is 100-400 mg. Given that many of these patients have enzyme deficiencies, enzyme replacement using fixed combinations of plant-based enzymes is a cornerstone of therapy. A recent clinical trial in which 29 children with autism spectrum disorders were given an enzyme formula containing exo- and endo-peptidases, showed measurable improvements on 13 cognitive and behavioral parameters. Dr. Bradstreet strongly recommends a gluten and casein-free diet. While not a "cure," this can certainly have a big impact (Knivsberg AM, et al. Nutrit Neurosci. 2002; 5 (4): 251-261). He also advised eliminating as many common allergenic foods as possible. This includes corn, wheat, soy and nuts. Other important nutrients and supplements that can improve digestive, immunologic and neurologic function in these patients include: Omega-3 Fatty Acids: "This is a must. These patients are almost always deficient." Omega-3s are critical components of neuronal membranes and they are essential for normal neurologic development. 1,000 mg per day is a reasonable starting dose, but don't hesitate to go as high as 3,000 mg. Probiotics: Once the severe GI abnormalities are cleared, it is important to re-seed the gut with healthy flora. Probiotic supplements are the easiest way to accomplish this. Vitamins A, C, and E: These "letter" vitamins, as well as beta-carotene are all important antioxidants, and patients with ADHD/autism are usually deficient. While a good multivitamin will probably provide most of what these patients need, it doesn't hurt to add additional vitamin C, which supports glutathione-mediated detoxification pathways. B Vitamins: B6 is probably the most well-studied vitamin in management of ADHD/autism. It is essential for healthy brain function, and patients are typically deficient. Since 1965, there have been 18 trials of high-dose B6. Overall, the data suggest that this will help 50%, while the other 50% show no benefit. Some studies suggest that B6 should be taken with magnesium. Zinc and other mineralsk: Both serotonin and melatonin are synthesized via zinc-dependent enzymes. Zinc-deficient children are often irritable, sullen and difficult to soothe. ADHD/autistic patients are usually deficient in zinc, as well as magnesium, iron and calcium. Dr. Bradstreet has also found pycnogenol, a derivative of French maritime pine trees, and L-theanine, derived from green tea, to be effective in improving cognitive function and helping to produce a calm but focused attention in these patients. Co-enzyme Q10, L-carnitine, L-carnosine and dimethyl aminoethanol (DMAE) are also helpful in improving cognitive function. Recently, Dr. Bradstreet formulated a line of products called Learner's Edge , that brings together many of these diverse nutrients and botanicals in an easy-to-use system. The line is manufactured by Integrative Therapeutics (www.learners-edge.com), and is the subject of a longitudinal clinical trial jointly sponsored by Arizona State University, Southwest College of Naturopathic Medicine, and Dr. Bradstreet's ICDRC.