Comprehensive Guide to Managing Autism - 5

Serotonin Connection

Serotonin (5-HT) content of blood platelets is variously reported to be excessive in 30% to 50% of autistic due to an errant peptide or to a variant gene (note that those with more than one autistic offspring are apt to fall into this category). It may be that a serotonin transporter is trying to reduce an excess of serotonin from the blood (caused by a sluggish Phase II, liver enzyme system not clearing the spent hormone). This high platelet level of serotonin is surprising in view of the limited protein intake of most autistic. McBride and colleagues recently presented results of a study that confirmed the importance of controlling for race and ethnicity in studies of platelet 5-HT. African-American and Hispanic-American subjects had higher levels of platelet serotonin when compared to Caucasian-American subjects. Interestingly, subjects with autism, who had a sibling with autism, had higher platelet, 5-HT levels than subjects without a sibling with autism. Platelet 5-HT levels have been demonstrated to be stable after the age of 9 years, supporting the hypothesis that platelet 5-HT levels are under genetic regulation.  

In platelets, thimerosal (mercury) causes aggregation, increase of arachidonic acid metabolism, and exocytotic release of serotonin. The herb feverfew contains a chemical (parthenolide) that inhibits the release of serotonin from platelets facilitating a more regular blood flow, and is said to be a benefit in migraine. One study, however, shows it to be toxic to the liver and to peripheral mononuclear blood cells (immune cells) and to inhibit Phase I liver enzymes. The cytochrome p450 (Phase I) enzyme pathway is the only way a baby has to deal with endotoxin from the gut. The Phase I system is one of several shut down temporarily by DPT and other vaccines, and suppressed by mercury. With these toxins (and those of candida) being given off when the liver is impaired, they can have severe consequences, including SIDS. Pharmacological evidence suggests more than 50% of the patients with autism may have an abnormality in serotonergic neurotransmission; however, no consistent patterns of behavior or of symptoms have been identified that relate to this high platelet level of serotonin.  

Nevertheless, Dr. Robert Reisinger, DMV, describes the final mechanism of death in infants who have temporary liver dysfunction, and E. Coli in the gut: “One bottle of formula is enough to change a baby’s gut dramatically, and it takes two weeks of breast feeding to return the gut to normal. How can this happen? E. Coli is the main culprit. This bacterium is putrefactive and protein loving. The protein content of human breast milk is lower than in any other mammal, and the protein content of formula or any other milk supplement has a direct influence on the numbers of E. Coli in the gut often raising it to 1000 times higher levels. Not only does the acid gut and very low protein content of breast milk provide a more hostile environment for E. Coli, but breast milk also contains neutralizing factors against E. Coli. When E. Coli is elevated, absorption into the bloodstream over hours of time of small amounts of bacterial endotoxin not detoxified by a temporarily dysfunctional reticulo-endothelial system results in removal of blood platelets and fibrinogen from the circulating blood. The result is release of relatively large amounts of serotonin from platelets into the blood plasma (in some experiments the increase of plasma serotonin is almost 100-fold). This serotonin shock can cause such serious vasoconstriction as to cause sudden heart failure. Serotonin initiates, in some cases, the coronary chemoreflex (Becold-Jarisch reflex) in which there is inhibition of sympathetic outflow and increased activity of the cardiac (efferent) vagus, leading to profound bradycardia, hypotentions, and cardiovascular collapse. The complex pathogenesis of endotoxemia depending on time and dosages, also involves release of norepinephrine, epinephrine, corticosteroids, etc. However, if death occurs early in the course of this syndrome, it is due primarily to serotonin effect. Serotonin is associated with deep sleep and in certain circumstances strongly inhibits respiratory movements… Endotoxin also has a more direct effect on cellular respiration, since it interferes with oxidative metabolism of mitochondria in vitro as well as in vivo... Between three and six hours, vascular capillary permeability has become more substantial, and varying amounts of edema and hemorrhage by diapedesis are apparent. After six to eight hours or more, fibrin-platelet clots have formed, and disseminated intravascular coagulation (DIC) is present in lungs, kidneys, and other organs and tissues.”  

“For nonautistic children, serotonin synthesis capacity (of the brain) was more than 200% of adult values until the age of 5 years and then declined toward adult values. Serotonin synthesis capacity values declined at an earlier age in girls than in boys. In autistic children, serotonin synthesis capacity increased gradually between the ages of 2 years and 15 years to values 1.5 times adult normal values and showed no sex difference.”—Developmental Changes in Brain Serotonin Synthesis Capacity in Autistic and Nonautistic Children. Chugani DC, Muzik O, Behen M, Rothermel R, Janisse JJ, Lee J, Chugani HT, Department of Pediatrics, Children's Hospital of Michigan, Detroit 48201, USA.  

This imbalance in allocation of available serotonin, a tryptophan deficiency, a vitamin B₆ deficiency, a magnesium deficiency, or a deficiency of the enzyme tryptophan hydroxylase, or some combination, leaves a deficit for the brain. Evidence of serotonin deficiency in autism comes from a pharmacological study using tryptophan depletion. Tryptophan depletion leads to reduced serotonin synthesis, release, and neurotransmission. McDougle and colleagues found exacerbation of behaviors such as whirling, flapping, pacing, stomping, banging and hitting self, rocking, toe walking, and anxiety in more than 50% of the adults with autism after tryptophan depletion. Deficiencies in the brain chemical transmitter serotonin have been identified as a potential cause of suicide. There is evidence showing that aggressive dyscontrol—be it violence, rage, impulsivity, or disinhibition—is often linked to disturbances in serotonin metabolism. This study is consistent with the finding of decreased ratio of serum tryptophan to large neutral amino acids in idiopathic infantile autism relative to controls, which would lead to a lower basal level of serotonin synthesis, vulnerability to tryptophan depletion, and response to pharmacological manipulations that increase 5-HT neurotransmission.  

Drugs that inhibit transport of serotonin: the tricyclic antidepressants, and the Selective Serotonin Reuptake Inhibitors (SSRI), and Monoamine Oxidase Inhibitors (MAOI) that hold more serotonin in the synapse between brain cells longer greatly reduce the above symptoms. Normally, the enzyme MAO removes some serotonin from the synapse while a major part is sucked back into the neuron that created it (reuptake). In the autistic with the above behaviors, there needs to be more serotonin available in the synapse. That can best be ensured by increasing the supply in the neuron—naturally—by increasing the precursor it needs to make serotonin. This is accomplished by supplementing 5-HTP, and/or by conserving it from destruction in the synapse by supplementing magnesium and vitamin B₆. Folic acid is added to the regimen since requirements increase with pyridoxine-magnesium therapy and males with fragile X syndrome (a subgroup of autism) benefit specifically from folate supplementation. Vitamin B₆ may not be responsive if folic acid is depleted, so it should probably always be accompanied by folic acid, and vitamin B₁₂. 

Another nutrient, inositol, has been used in the treatment of obsessive-compulsive disorder as well as the compulsive behaviors demonstrated by some autistic children. Doses vary from 1-6 grams, three times daily. Tryptophan is prescribed in orthomolecular therapy in cases of insomnia, depression, and obsessive-compulsive disorders. Based on studies done in animals, some digestive enzymes may also have an effect on neurotransmitter levels, especially dopamine.  

Serotonin is found in many foods we eat such as grapes, avocado, tomato, orange, plums, pineapple, bananas, and spinach. Eating carbohydrates with tryptophan supplements or protein meals increases conversion of tryptophan to serotonin by stimulating the pancreas to secrete insulin. Insulin increases the relative concentration of tryptophan in the blood by causing the body tissues to soak up competing amino acids from the blood so the tryptophan has less competition in transferring from blood to brain.  

Tryptophan is the precursor to serotonin, tryptamine, melatonin, and indolamine, all neurotransmitters. Dehydration seems to cause a severe depletion of brain tryptophan. Tryptophan is the natural brain regulator for salt absorption in the body. This lack of tryptophan and its neurotransmitter products will establish lower than normal salt reserves. This will lead to a higher sugar content in the blood in an effort to balance osmotic forces. If blood sugar is to come down, a slight increase in salt intake will be necessary. In Type I  diabetes, there may be severe salt shortage, leaving the brain no alternative but to raise the level of sugar even more to compensate. One of the most effective ways to raise tryptophan, serotonin and endorphin levels in the brain is exercise. Another is the adequate intake of pure water. Tryptophan and water are essential to homeostasis, the balanced function of all body systems. A correction of tryptophan levels will bring many dividends in good health, feelings of well-being, and relief of depression. 

Foods that supply tryptophan: dairy products, turkey, bananas, complex carbohydrates, and nuts. Selling tryptophan for human consumption is illegal in the United States; however, it is available for use with animals. You can buy pure pharmaceutical grade tryptophan from BIOS  Biochemicals 8987-309 E. Tanque Verde, No 340, Tucson, AZ 85749-9399 (Phone 520–326–7610). Do not inquire about usage, or mention human use. Tryptophan can increase both the effectiveness and the toxicity of certain antidepressant drugs, including Prozac and monoamine oxidase inhibitors (MAO). Mix them only if so directed by your doctor. 

For those on anti-seizure medications, it should be noted that behavioral side effects of the barbiturate-related agents, Phenobarbital and phenytoin (Dilantin™), may include irritability and depression as well as aggressive behaviors such as biting, pinching, and kicking. 

The anxiety produced by a lack of serotonin creates another problem. When the environment is not perceived as “safe”, the nervous system will function adaptively to facilitate fight-flight behaviors. Fear and stress tend to produce illness, but fear, stress, and illness result in a retraction of the voluntary “social engagement system”, leading to compromised social abilities. Depressing this neural system has several behavioral consequences including flat effect, aprosody (can’t pay attention), difficulty in phoneme recognition, articulation problems, hypersensitivity to sounds, and behavioral state regulation issues. Stress also has observable effects on intestinal micro biota. Release of ACTH from fear and anger leads to increased jejunal E. Coli, loss of Bifidobacteria and Lactobacillus from fecal samples, and increased levels of the pathogenic Bacteroides fragilis. Although these symptoms are nonspecific regarding differential psychiatric or behavioral diagnosis, many children with developmental disorders share them. The high level stresses these children suffer must be countered by a variety of antioxidants (Vitamin C, E, selenium) to avoid systemic damage. The excess cortisol this produces should be countered by supplementing 100 to 200 mcg of chromium, 400 mg magnesium, 50 mg pantothenic acid, and 500 mg vitamin C, and by various relaxation techniques, including a good back rub. It is reported that high stress induced levels of cortisol were present in one-third, and that the hippocampus (involved in memory) was 14% smaller than normal! 

Marked disturbances of uptake of deuterated phenylalanine and tryptophan from intestine into blood were found in a portion of autistic patients (group A). In another group of the patients, a remarkable decrease in turnover of tyrosine in blood was found (group B)....These findings might suggest that the supply of tyrosine (from phenylalanine metabolism) and free tryptophan to the brain (in group A), or supply of tyrosine to the brain (group B) might be decreased. We postulated that in some of autistic patients there might exist decreases in synthesis of catecholamine or serotonin. Based on the hypothesis, we started a new treatment with L-DOPA and 5-HTP in small doses, and found significant effects in some patients. However, in some, the amino acids caused marked aggravation of the symptoms—Naruse H; Hayashi T; Takesada M; Nakane A; Yamazaki K; Source: No To Hattatsu, 1989 Mar, 21:2, 181-9. The amino acids Phenylalanine and Tyrosine are precursors to L-dopa, epinephrine, and norepinephrine. One Mom reported significant increase in cognitive awareness and speech after supplementing Phenylalanine. One hundred to 500 mg on an empty stomach before bedtime would be a good choice. Do not exceed 1000 mg. 

Yet, studies in Australia revealed that high levels of tyrosine were present in many hyperactive children (dietary tyrosine is found in a variety of food products, including yeast extracts, cheese, coffee, citrus fruits, chocolate, and cream). 

Dr. Felix Sulman began his research on those who suffer from high serotonin levels because of an inability to metabolize serotonin. He found that serotonin is a stress neuro-hormone leading even rabbits, the most docile of creatures, to be aggressive. He coined the term “Serotonin Irritation Syndrome.” He found that those who were unable to break down serotonin (PST kids) would have the levels increase. An increase in serotonin in turn increases noradrenaline. They “were in effect being poisoned by the serotonin produced by their own bodies. The irritation victims suffered from migraines, hot flashes, irritability, sleeplessness, pains around the heart, difficulty in breathing, a worsening of bronchial complaints, irrational tension and anxiety, with horrifying nightmares. It also caused his volunteers to sleep badly—that is, always on the edge of consciousness so that they were not properly rested—and to wake after only a few hours of sleep.” He also found it caused pregnant women to abort—October 1977: Slater, et al, Inhibition of REM Sleep by Fluoxetine, a Specific Inhibitor of Serotonin Uptake, October 1977, at p. 385. Children so often get coughs and colds, yet using a cough or cold medication with dextromethorphan could cause the serotonin syndrome, a very serious and potentially fatal adverse reaction and/or produce PCP reactions. This being the case, neither Prozac™ type SSRIs nor 5-HTP should be used by PST kids. Additionally, when animals were severely deprived of zinc, levels of brain catecholamines increased, that is, elevation of noradrenaline occurred consistently, dopamine increased irregularly and serotonin relatively, when compared to controls. Experimental zinc deficiency in humans leads reversibly to reduced sperm count combined with reduced serum testosterone 

More to the point, 95% of serotonin is found in the gut! It is here we are able to see exactly what happens when SSRIs are used. When Prozac™ is given, stimulation of nerve cells becomes larger in amplitude, and longer in duration, and 8 to 10 times as many cells are activated, thus SSRIs are very likely to cause nausea, vomiting, and diarrhea. Continued use of SSRIs cause some serotonin receptors to desensitize and fail to respond anymore, while others simply become less sensitive. As desensitization sets in, cells stop responding and constipation follows. These are not “side effects” as usually suggested, but the direct effects of holding serotonin on the nerve cell receptors too long (preventing reuptake). Similar effects occur in the brain. Glutathione increases sensitivity to dopamine and to serotonin. 

Inositol Therapy can help in two ways: it can sensitize the receptors, or it can replace the SSRIs! Rahman and Neuman reported that exogenous inositol reverses the desensitization of serotonin receptors (Rahman, 1993). Increased membrane phosphatidylinositol could enhance effects of synaptic serotonin as do SSRIs (Fux, 1996). Inositol has been proven as beneficial as SSRIs in the treatment of OCD, depression, and panic disorder in double blind placebo controlled studies (Benjamin, 1995; Fux, 1996). Doses vary from 1-6 grams, three times daily. 

Due to the possible negative effect of 5-HTP in PST kids, I suggest use of DMG or TMG, which have similar improvements reported, often within hours. Each child responds at a different level of intake, usually 1 to 4, 125 mg tablets of DMG, daily; so begin with one and slowly increase the amount. One to four DMG is the equivalent of one to two TMG 500 mg.  

“Using TMG is an attempt to force the methionine resynthesis pathway from homocysteine by an alternative pathway to the 5-methylfolate-B₁₂-methionine synthase before Cystathionine Beta Synthase (CBS) can convert homocysteine to cysteine. The byproduct is DMG. The purpose of this addition is to try to keep homocysteine in the form of methionine in order to rob CBS of substrate for overproduction of cysteine (which would be toxic—WSL). This is essentially a backup pathway, and is meant to complement the folate route for remethylation rather than supplant it. It does not interfere with the folate route”—David H. Swenson Ph.D. Nevertheless, to avoid hyperactivity, and to effect the conversion in those who are cystathionine Beta-synthase deficient, one must supplement vitamins B₆, B₁₂, and folic acid when supplementing TMG/DMG. Nevertheless, supplementing folic acid excessively may cause breakthrough seizures by altering drug serum concentrations; so check with your doctor on this. The effect of TMG, folic acid, and vitamin B₁₂ is to reduce homocysteine (which sometimes builds excessively due to a cystathionine beta-synthase, serine, magnesium, zinc, and/or vitamin B₆ deficiency that prevents transulfuration to cysteine and taurine), while controlling cysteine production, where overproduction can be toxic. Additionally, TMG works with folic acid, vitamins B₆ and B₁₂ and methionine to form S-adenosylmethionine (SAM) to donate methyl molecules that are vital to proper liver function and cellular replication. Supplements of SAMe are available, but it is relatively unstable, breaks down into cysteine, and is very expensive. For most, it is best to supplement TMG and the B-vitamins allowing the body to form SAMe. Methyl Caps™ by VRP supplies TMG and these vitamins in a tasteless form that can be taken with food or water: www.vrp.com or (800) 877-2447.    

What is methylation? Your body’s chief mechanism for cellular housekeeping is methylation, a crucial, chemical reaction that converts inorganic to organic forms. When methylation is inefficient and sluggish, toxic compounds build up. This detoxification is costly to the body’s resources, requiring large amounts of vitamins B₁₂, folic acid, methionine, betaine, taurine, glycine, cysteine, lecithin, and vitamin C. The most significant of these toxic compounds is homocysteine, a metabolite in the pathway from methionine to sulfate. Elevated homocysteine harms arteries, impairs circulation, damages cellular DNA, and contributes to atherosclerosis, heart disease, cancer, and many other conditions. In order for homocysteine to be recycled to SAMe and methionine for reuse, there must be adequate amounts of folic acid, and vitamins B₆ and B₁₂. TMG (betaine) and DMG are methyl donors aiding in methylation. Mercury decreases zinc and methionine availability, depresses rates of methylation, and increases free radicals. A potentially harm side effect of any detoxification is the production of massive amounts of free radicals. Normally, this is not a problem for the healthy body’s antioxidant defenses (especially glutathione, the principle antioxidant in the liver) are adequate to neutralize the free radicals, and protect not only your liver and kidneys, but all the cells threatened. When mercury and other poisons are being chelated, and the glutathione stores are depleted as in autism, then great damage can be done. 

DMG’s greatest benefit has received little publicity. Studies show it can have a dramatic effect on the immune system. A study at the University of South Carolina showed that when the immune system was challenged with a vaccine, those taking DMG had 400% more antibody production than controls. Before administering any vaccines, you may want to discuss the benefit this could be with your doctor. Additionally, the lymphocytes’ T-cell response was increased—J. Infect Dis 81:143(1):101-104. It has been shown to increase interferon levels indicating possible antiviral activity. Since many autistic kids have elevated T-cell activity indicative of autoimmunity, this may be contraindicated for them—another thing to discuss with your doctor, and to have him monitor. 

There is a newly available substance that works in this same circuit with DMG/TMG, S-adenosylmethionine (SAM), that, additionally, helps neurotransmitters bind to receptor sites. This makes the neurotransmitters more active. It is also said to increase serotonin levels. This would seem safer than trying to control usage of serotonin or other neurotransmitters by use of SSRIs. It has been proven more effective than the tricyclic antidepressants, helping the severely depressed who did not respond to other antidepressants, and it is without the significant side effects of those drugs, though therapeutic intake may include a dry mouth, agitation, and gastrointestinal problems. It is faster acting with no withdrawal period. I would urge its use, possibly along with small amounts of 5-HTP, to control the above listed “autistic” behaviors.  

It should be possible, then, to reduce these behaviors by increasing serotonin production naturally, rather than by use of transport inhibitors (SSRIs) (that typically deplete the already reduced supply still further, loads the system with fluoride, and inhibits Phase I liver enzyme function). If one determines that the child may respond to more serotonin in the synapse, the best way to meet the need is by supplementing magnesium and vitamin B₆, the natural conservers of serotonin, and TMG or SAMe, and if necessary, small amounts of 5-Hydroxy-Tryptophan (5-HTP), a metabolite of tryptophan that easily translates into increased serotonin and melatonin. It is of interest to note that Michael Murray, ND, says that only 3% of oral tryptophan is converted to serotonin, but 70% of 5-HTP is converted, so keep the servings small (30 to 50 or up to 100 mg on an empty stomach before bedtime). 5-HTP, TMG, and SAMe are available at any health food store.  

To ensure proper conversion to serotonin, supplement vitamin B₆. A good choice would be Super Nu Thera™, by Kirkman Laboratories. It is specifically formulated to help autistic children. They presently have one without vitamin A, so you can use cod-liver oil as your source of cis vitamin A. Some have had difficulty in getting their child to take Super Nu Thera because of a “not so great” taste. One “trick” that has worked for some is to place 1/8 - 1/4 of a teaspoon of plain ascorbic acid (vitamin C) into water with the Super Nu Thera. The taste and look are almost like orange juice. 

Some are fearful of the higher amounts of vitamin B₆ and magnesium in SNT. Dr. Bernard Rimland says that every child is different, but he has found the average amount of vitamin B₆ that is beneficial is around eight mg per pound of body weight per day. The French found virtually the same 17mg/kg/day. That is 500 mg per 60-pound child. Dr. Rimland’s adult child has taken 1000 mg for longer than twelve years. He suggests starting with 1/4 the target amount and increasing slowly over a 10-14 day period. The amount of magnesium necessary with the vitamin B₆ is 3-4 mg per pound of body weight. That would be up to 240 mg for that 60-pound child. He further states that in thirty years he has heard of only four cases of autistic children suffering neuropathy. He adds that if no benefit is seen in six weeks, stop giving the high amounts. It is imperative that these higher amounts of vitamin B₆ and magnesium be taken with the underpinning of a good multivitamin/mineral supplement to avoid induced deficiencies that probably account for every reported case of neuropathy. Vitamins B₆ and B₁ sit on opposite ends of a teeter-totter, with B₁ adding CO₂ to molecules, and B₆ removing CO₂. One of the switch points into the Krebs cycle is made up of two enzymes that run in opposite directions. One is dependent on B₁, the other on B₆. All B-vitamins are closely linked, and so must be supplemented together. In general, the B-vitamins move little bits of things around, with B₅ moving fatty acids, B₃ moving electrons and protons, B₁₂ moving methyl radicals. 

Some 42% don’t convert vitamin B₆ to its necessary metabolite pyridoxal 5`-phosphate (P5P), so taking that coenzyme form of the vitamin may be more effective. One Mom wrote, “Previously, I could not tolerate anything but a low dose of plain B₆. I think this was because I was very low on alpha-ketoglutaric acid needed to convert B₆ to P5P. (Alpha-ketoglutaric acid is destroyed by candida yeast.) When I first started on alpha-ketoglutaric acid combined with a very low dose B₆, I was told to take it in the morning because it may disturb sleep. Indeed, it sort-of made me jittery. I was told this would end in about two weeks. It did. It was just an adjustment period while my body’s enzymes were starting to work again. When I gave my daughter P5P, I gave it in the morning. After two weeks of 150 mg of P5P, my daughter could fall asleep at night (she weighed about 120 pounds at the time. She is not autistic, but her sleep problem was severe). Afterward, I just gave her 50 mg of P5P once or twice a week. This has been enough to keep the benefits.”  

Zinc is required for the conversion of pyridoxine to P5P as is vitamin B₂ and alpha-ketoglutarate. Too much B₆ without B₂ can deplete the body of B₂ possibly leading to Cheilosis—swollen, cracked, bright red lips, a common symptom of B₂ deficiency. Vitamin B₂ is necessary for cellular growth and acts with Vitamin A in helping maintain the health of mucous membranes and the integrity of epithelial tissue. Vitamin B₂ is needed in glutathione production, in mitochondrial function for energy, and in the pathway that converts homocysteine to SAMe and methionine. A shortage would hamper production of cysteine, glutathione, glutathione peroxidase, taurine, and the sulfate needed to detox Phase II toxins (PST). Vitamin B₂ is probably the most commonly deficient vitamin in America. Deficiency symptoms are: sensitive, easily-fatigued eyes; blurred vision; itching, bloodshot eyes; dizziness; inflammation of mouth; sore tongue; dermatitis; itching nose; and cracks in the corners of the mouth. Vitamin B₂ is an antioxidant that aids in utilizing oxygen. It lowers body pH. It aids in carbohydrate and fat metabolism. Radiation destroys 8% of B₂ in foods. Remember, these nutrients (Zinc, magnesium, a-ketoglutarate, and vitamins B₂ and B₆) are necessary to normalize the metabolism of, and to conserve the neurotransmitters serotonin, melatonin, and dopamine. Benefits reported are, variously, improved use of words, improved sleep, decrease in hyperactivity and irritability, better attention span, increased interest in learning, and reduced self-injurious or aggressive behavior.  

Studies show that when darkness is maintained, melatonin production is 3 times higher than daytime, but maintaining a bright, night lamp or TV in the bedroom prevents that increased melatonin production. For the pineal gland to function it must have distinct light/dark cycles. When you put the child to bed, make sure the room is dark, and do not turn on the light during the night for melatonin production stops immediately. Additionally, electromagnetic forces from a clock or other electrical machine in the bedroom will deplete this powerful antioxidant that protects the whole body. It is by this mechanism that a loss of melatonin to EMF is thought to increase the risk of breast cancer. 

Many studies have shown that attention deficit and/or hyperactivity disorders in children are linked to changes in the levels of thyroid hormone in the blood, and that irritability and aggressive behavior are linked to thyroid hormone levels and hypothyroidism. Make the iodine/morning temperature tests and support the thyroid if indicated. Hyperactivity is common symptom of magnesium deficiency. Magnesium supplements are recommended for treatment of hyperness in many conditions besides the treatment of ASD. Other supplements known to help with the hyperness are calcium, zinc, folic acid, and chromium. Additionally, in a placebo-controlled study on prisoners with a history of impulsive/aggressive behavior, the group taking lithium supplements had a significant reduction in aggressive behavior and infractions involving violence.  

Mercury causes decreased lithium levels, which is a factor in neurological diseases such as depression and Alzheimer’s. Chung and colleagues found that lithium protects brain cells against excess glutamate and calcium (that kill brain cells). Additionally, low levels of lithium cause abnormal brain cell balance and neurological disturbances related to lowered levels of neurotransmitters dopamine, serotonin, and norepinephrine. Lithium also is important in vitamin B₁₂ transport and distribution, and studies have found low lithium levels common in learning disabled children, incarcerated violent criminals, and people with heart disease. Lithium supplementation has been found to be an effective treatment adjunct in conditions such as bipolar depression, autism, and schizophrenia where mania or extreme hyperactivity is seen. A recent Harvard study showed EPA and DHA supplements to be more effective than psychiatric medications in combating bipolar depression.  

One group with high copper and low zinc, sodium, and potassium tended to have extreme tempers, while another group with low zinc and copper, but high sodium and potassium tended to be sociopathic (aggressive, antisocial). Some factors that have been documented in depression, impulsiveness, and violent behavior are low serotonin levels, abnormal glucose tolerance (hypoglycemia), and low chromium and folate levels, which mercury has also been found to be a cause of. One mechanism by which mercury has been found to be a factor in aggressiveness and violence is its documented inhibition of the brain neurotransmitter acetylcholinesterase. Low serotonin levels and/or hypoglycemia have also been found in the majority of those with impulsive and violent behavior. It was found that treatment (including nutritional therapy) of delinquent or violence prone individuals for metals related problems, usually produced significant improvements in mood, violent behavior, and functionality, with complete cure in the majority of cases. 

Aggressive and violent behavior was greatly reduced, and a fantastic increase in academic performance in math and English occurred in New York City Schools in a 1986 study (Schoenthaler 1986a, 1986b). The number of learning-disabled kids fell by an astonishing 74,000 in one year. They simply removed sugar from the school diet! They served nothing with more than 11% sugar (fruit). A vitamin A supplement (cod-liver oil), and balancing of zinc/copper ratios also affect the behaviors of these kids. Most are deficient in zinc. 

Since there is no indication that the ones with these problems of hyperactivity and aggressiveness are necessarily the ones with excess serotonin, platelet saturation, and no symptoms have been associated with that condition, I believe, where these behaviors are a problem, and the above nutrients have been first supplied and sugars greatly reduced, it warrants introducing SAMe and 5-HTP in small, increasing amounts while carefully observing behavior. If present symptoms worsen, reduce or discontinue the 5-HTP. As always, make such a potentially serious change only in consultation with your medical professional. First, make sure the child eats protein at every meal. Disguise it. Supplement amino acid powders, Seacure™ (a predigested concentrate of white fish), and Sunflower seeds (7.5% carbohydrate and 52 percent protein! Omega-6 content (Linoleic acid) of sunflower is 57%. Interestingly, no other oil comes close to Vitamin E—222 mg per 100 grams of oil. Whatever you do, get it down him. This is absolutely necessary for growth and development, and “normal” behavior. For sleep problems primarily, take 5-HTP (up to 100 mg) two to four hours before bedtime (each child may vary in how long it takes to work). This has solved the sleep problem for many. For the behavioral problems take 25 mg several times through the day. It could be a problem for school if the child is made to be drowsy, in that case reduce the amount or give it later in the day.  

Many find the solution to sleep problems with a supplement of melatonin (1/2 to 3 mg, 20 minutes before bedtime). Since 1/2 mg will restore normal nighttime levels, more does not necessarily work better. There are, potentially, several benefits to taking supplemental doses of melatonin other than improved sleep; for example, it promotes absorption of zinc, stimulates the thyroid, and as tests show, protects against brain damage from mercury poisoning reducing potential for Alzheimer’s (without it, glutathione was reduced 30%, and other damage occurred). It is a powerful antioxidant, able to enter every cell of the body. Dr. Reiter found melatonin to be 5.9 times more effective than glutathione and 11.3 times more effective than mannitol in fighting dangerous, hydroxyl radicals. It is reported that if you give the child a small dose of melatonin daily in the morning, and then the rest at night, it will ‘steady’ the melatonin levels so they don’t peak out at 2:00 a.m. causing him to awake. It seems to be successful with many of these kids. For a couple of days, the child may be pretty sleepy. To avoid problems at school, start this regime on a Saturday. Nevertheless, this could result in some degree of sleep disturbance, and may interfere with the circadian regulation of certain hormones.  

Glutathione has been mentioned several times. It is a small protein molecule composed of the amino acids cysteine, glutamine, and glycine. It is a powerful antioxidant found in fish and meats, and fruits and raw vegetables (asparagus, avocados, and walnuts). It is the body’s major detoxicant that binds to fat soluble toxicants, heavy metals, solvents, and pesticides, making them water soluble so they can be excreted through the kidneys (Phase II detoxification). It has been associated with prevention of cancer and cataract. It is greatly depleted in mercury poisoning, and children with autism are universally lacking in this vital nutrient, as are older people and diabetics. Increasing tissue levels is associated with improved good health in older folks. I believe it is the lack of glutathione that causes children to be heavily poisoned by heavy metals, pesticides, and arsenic. Never give your child Tylenol™ for it depletes the liver of all its glutathione in minutes! Haloperidol depletes glutathione, CoQ10, and NADH, all necessary to mitochondrial energy production. Candida’s main deleterious effect is avid binding of coenzyme Q10. When CoQ10 is depleted 25%, clinical symptoms occur, when levels drop 75%, death occurs. Additionally, Glutathione requires vitamins B₂, B₆, zinc, and selenium to be formed. Vitamin C (500 mg in two or more doses) increases its levels by 50%, Ambrotose® by 100%, Phyt•Aloe® by 200% (both by Mannatech™). When sulforaphane (from Phyt•Aloe’s cruciferous vegetables) reaches the cell, it also activates a group of proteins called Phase II enzymes. Supplementing milk thistle, whey protein, alpha lipoic acid, SAMe, and glutamine are known to increase glutathione. These latter ones have to be used with understanding as they are contraindicated in some children.  

These are the symptoms of glutathione deficiency: Coordination problems, generalized cell damage, mental disorders, various nervous system disorders, tremors and twitching; red cells tend to burst, white blood cells decline in function, and nerve tissue degenerates.  

Abstract: At a single evening dose of 5-10 mg of melatonin (MLT), the pineal gland hormone, can exert a positive effect on the frequency of epileptic attacks in children with sleep disturbances of various etiologies. We have shown that the sleep behavior can be normalized and existing epilepsy can be favorably influenced. Pretherapeutic MLT secretion profiles can provide new information concerning the origin and treatment of these disturbances. In vitro experiments suggest that this effect might be the result of the interaction between MLT and MLT-specific receptors in the neocortex. Due to its favorable safety profile, MLT can be liberally administered in the specified doses and be considered as a useful antiepileptic drug—Fauteck J Schmidt H Lerchl A Kurlemann G Wittkowski W Journal: Biol-Signals-Recept. 1999 Jan-Apr; 8(1-2): 105-10 1999 1422-4933. 

Hypoglycemia not only precipitates the release of glutamate in the brain, but that magnifies the toxic effect of all excitotoxins. Unfortunately, many foods have excitotoxins added to them as taste enhancers. 

Another abstract with no title credits says in part: Recent data indicate that melatonin inhibits brain glutamate receptors and nitric oxide production thus suggesting that it may exert a neuroprotective and antiexcitotoxic effect. Melatonin has been seen to prevent seizures in several animal models, and to decrease epileptic manifestations in humans....The results suggest that melatonin may have a useful role in mechanisms of neuroprotection, and they also indicate its use in other cases of untreatable epilepsy. Another study is of interest: Children’s Memorial Hospital, Chicago, in a report published by Lancet, found that, though their sleep problem was benefited, children with severe nervous–system damage, using a dosage of five mg melatonin, experienced an increased incidence of seizures that returned to previous levels on discontinuance. 

Additionally, Dr. Beth Malow, University of Michigan Health System, found that sleep apnea can be a contributing factor in seizures. Many that were unresponsive to medications were found to have a sleep apnea problem. Thirty-three percent of one study group had these sleep problems, and were prone to experience seizures at night. Medications often made the problem worse. 

Sleep can be poor because of sugar problems. When blood sugar drops in the middle of the night, the child will awake. If this be the case, 5-HTP or melatonin may not work until you remove the offending sugars and high glycemic foods from the diet, especially from the evening meals or snacks. Feed him at least 30% protein with each meal. Remember, sugar promotes candida, with its multiple problems (yeast grows 200 times faster), and sugar can actually make the child drunk and giggly!  

One of the keys to orderly brain function is glutamic acid. When sugar is consumed, the bacteria in the intestines, which manufacture vitamin B-complex, begin to die. The vitamin B-complex level declines, and the fatty acids they give off to nourish the cells of the gut lining is diminished. When the vitamin B-complex is lacking, the glutamic acid, a major brain fuel, is not properly processed and sleepiness occurs, with a decrease in short term memory function and a loss of numerical calculative ability. The removal of B-vitamins when foods are processed makes the situation even more tenuous. It is this loss of B-vitamins needed to process lipids (fats), coupled with a high glycemic, processed-food diet that creates the fatty acid deficiencies and imbalances. Vitamin B₁₂ therapy is based in part upon the role of vitamin B₁₂ in synthesizing essential fatty acids.