PORTLAND, OR—Attention Deficit Hyperactivity Disorder and autism are associated with a complex of gastrointestinal, immunologic, and metabolic problems requiring a multimodal therapeutic approach, said Jeff Bradstreet, MD, at the annual meeting of the American Association of Naturopathic Physicians.

Dr. Bradstreet, is founder of the International Child Development Resource Center (ICDRC), a clinic and foundation that has treated over 2,000 children with ADHD or autism. He has developed sophisticated protocols centered on correcting digestive problems, eliminating allergens and environmental toxins, and improving nutrition. Whenever possible, he treats these kids without pharmaceuticals. "I only use drugs as a rescue modality."

ADHD and autism 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.

9 Million and Growing

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 data indicate 9–12 million children have ADHD. California data show one in 160 school 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 very, very real."

Dr. Bradstreet believes ADHD has its roots in damage to a child's immune system. The injury may be due to environmental toxin exposure, but he believes mercury-containing vaccines play a major role. Thimerosal and aluminum in vaccines are intrinsically neurotoxic, and can also modulate immune function.

The Vaccine Debate

Live viral vaccines contain as much as 25 mcg of 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 led a case control study showing children with highest levels of mercury exposure had a 6.4-fold increase in autism compared with those at the lowest levels. A CDC study recently showed a significant difference in prevalence of ADHD, autism, and tick disorders between individuals who got mercury-containing vaccines at 3 months, and those who did not. Data from the federal Vaccine Adverse Events Reporting System (VAERS) and the US Department of Education show a linear correlation between neurodevelopmental disorders and thimerosal (Geier DA, Geier MR. Pediatr Rehab. 2003. 6 (2): 97–102).

However, two Danish population studies of hundreds of thousands of people given 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 pediatricians hold that there is little risk of autism from vaccines, especially thimerosal-free vaccines. Dr. Bradstreet, the father of an autistic child, strongly disagrees. "There are still no truly mercury-free vaccines," he said. 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."

GI Dysfunction Common

While there is still room for debate over the vaccine issue, it is clear that children with ADHD or autism have GI 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. Lower GI dysfunction, enzyme deficiencies and impairment of hepatic detoxification are common. Without clearing up the gut, it is impossible to resolve the behavioral and cognitive problems.

Patients typically excrete large amounts of sulfate in their urine, sometimes as much as 10 times more than normal children. This results in impairment of sulfate-dependent hepatic detoxification pathways. They also excrete cysteine, a key amino acid for glutathione production, thus compromising glutathione-dependent pathways. The net result is that they can't break down toxins.

Pancreatic enzyme deficiency is also common; Dr. Bradstreet said roughly 75% of the children he treats have deficiencies of key pancreatic enzymes and do not digest proteins properly, resulting in upper and lower GI problems.

University of Maryland researchers studied 36 autistic children via endoscopy, biopsy, and enzyme analysis. They found 69% had grade I or II esophageal reflux, 42% had gastritis, 67% had duodenitis, and 58% had low carbohydrate enzyme levels (Horvath K, et al. J Pediatr. 1999; 135 (5): 559–63).

Diarrhea and constipation are common. Some 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 toxin loads, further burdening their livers.

Many patients have "leaky gut," 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 feces (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 incomplete digestion of grain gluten and casein. Some of these, like beta-casomorphins and gluteomorphins, are neuroactive and bind to opioid receptors. In a child with a leaky gut, exorphins easily pass into circulation. Since hepatic clearance of opioid neurotransmitters is already compromised, they hang around for a long time. He believes they contribute to cognitive and behavioral symptoms (Wakefield AJ, et al. Aliment Pharmacol Ther. 2002; 16 (4): 663–74).

Andrew J. Wakefield and his Inflammatory Bowel Disease Study Group at the Royal Free and University College Medical School, London, performed ileocolonoscopy with biopsies on 60 children with developmental disorders including autism and ADHD, 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. 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).

Complex Condition, Multimodal Therapy

Dr. Bradstreet focuses his therapy on improving GI function, restoring normal immune function, eliminating toxins, and optimizing hepatic, immunologic, and neurologic function. He uses DMSA chelation to eliminate mercury and other heavy metals. In over 70% of cases, behavior improves just from this alone. "It is the number one treatment as rated by parents; no drug even comes close."

Other treatments that help with detoxification include:

Selenium: At 25 mcg/day, this mineral facilitates detoxification by binding to mercury. It is also essential for glutathione peroxidase, a key antioxidant enzyme.

Milk Thistle (Silybum marianum): Standardized preparations of 70%–80% silymarin improve liver function. In a study of 166 children with chronic liver disorders, 70% showed liver function improvements while taking silymarin.

N-Acetyl Cysteine (NAC): Most patients with ADHD or autism are cysteine deficient. NAC is a precursor of glutathione, essential for hepatic detoxification. Dr. Bradstreet starts with 25 mg/day and gradually increasing up to 200 mg daily.

Calcium-D-glucarate (as Betaine): This inhibits beta-glucuronidase, and increases net elimination of toxins and steroid hormones via glucuronidation pathways. Begin with 150 mg, and increase to 1,000 mg per day.

Alpha Ketoglutarate (AKA): Patients often show elevated ammonia, derived from abnormal GI flora. AKA detoxifies ammonia. It is also a precursor of glutamine, which helps heal the gut mucosa. The dose range is 250–750 mg/day.

Taurine: This amino acid is involved in formation of bile salts, essential for toxin elimination. Taurine also calms some ADHD patients. Begin at 100 mg and increase to 1,000 mg/day.

Methionine: This amino acid binds heavy metals, and adds methyl groups to xenobiotics, aiding in excretion. 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.

Dr. Bradstreet recommends a gluten and casein-free diet. While not a "cure," this can have a big impact (Knivsberg AM, et al. Nutrit Neurosci. 2002; 5 (4): 251–261). He also advised cutting allergenic foods like 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 essential for normal neurologic development. 1,000 mg per day is a good starting dose, but don't hesitate to go as high as 3,000 mg.

Probiotics: Once GI abnormalities are cleared, it is important to re-seed the gut with healthy flora. Supplements are the easiest way to accomplish this.

Vitamins A, C, and E: These are important antioxidants, and ADHD/autism patients are usually deficient.

B Vitamins: B6 is essential for healthy brain function, and patients are typically deficient. There are 18 trials of high-dose B6, and overall, the data suggest that this will help 50%, while the other 50% show no benefit.

Zinc: Both serotonin and melatonin are synthesized via zinc-dependent enzymes. Zinc-deficient kids are often irritable, sullen and difficult to soothe. ADHD/autistic patients are usually deficient.

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 an ongoing longitudinal clinical trial jointly sponsored by Arizona State University, Southwest College of Naturopathic Medicine, and Dr. Bradstreet's ICDRC.