Comprehensive Guide to Managing Autism - 23

What Is MHPG? Why Should We Measure It?

MHPG (3 methoxy-4-hydroxyphenylglycol) is a natural breakdown product of a class of neurotransmitters (chemical messengers that pass across the narrow space, or synapse, between neurons) called catecholamines. One of the catecholamine neurotransmitters that is broken down to MHPG is norepinephrine (NE). Since the 1970s, the urine of autistic children has been known to contain abnormally low amounts of MHPG (Young, J.G. et al., Decreased 24-Hour Urinary MHPG in Childhood Autism. Am J.Psychiatry 136, August 1979, pp. 1055-7).  

In order for the body to get rid of MHPG, it has to convert it, in a process called “conjugation”, either to MHPG sulfate or MHPG glucuronide—the two pathways referenced above.  

By measuring the amount of MHPG sulfate, MHPG glucuronide, and total MHPG (the sum of the sulfate and the glucuronide) excreted in the urine in 24 hours, we can find out two things:  

      1. The turnover rate of the catecholamine neurotransmitters, especially NE, in the body. It is the use (i.e., the release) of NE that leads to the breakdown of NE to MHPG. Low total urinary excretion of MHPG suggests that smaller than normal amounts of NE are being released into the synapses of the brain. (Young, J.G., et al. Cerebrospinal Fluid, Plasma, and Urinary MHPG in Children, Life Sciences, Vol. 28, 1981, pp. 2837-45) and Peyrin, L, Urinary MHPG Sulfate as a Marker of Central Norepinephrine Metabolism: A Commentary, J. Neural Trans [Gen.Sect], Vol. 80, 2990, pp.51-65) C. Barthelemy and Associates found this was accompanied with higher than normal levels of NE in the urine—J Autism Dev Disord, 1988 Dec, 18:4, 583-91. These findings suggest that autistic behaviors might be related to an abnormal functional imbalance among monoamines either at a molecular level or at a system level.

      2. The relative efficiency of the two main conjugation pathways for MHPG (and by extension, for other phenolic compounds, such as salicylates and artificial food colors):  sulfoconjugation and glucuronidation. 

If needed, you can strengthen the effect of the glucuronidation by supplying calcium-d-glucarate. The calcium-d-glucarate prevents the bacteria in the intestine from removing the glucuronides that were conjugated with (attached to) the toxins. When the bacteria remove the glucuronides, the now unconjugated toxins can be reabsorbed from the gut back into the body. Wilner’s Chemists carries calcium-d-glucarate. A lot of vitamin C (according to one doctor) will increase the glucuronidation pathway activity. 

Let’s digress a moment to understand vitamin C. This is a two edged sword, and has hurt as many as it has helped. When we find a truth for ourselves, we think it applies to everyone in the world, and so the great Linus Pauling did as much harm as he did good. His recommendations nearly killed me :-(. For maybe two years, I was taking increasingly larger doses of Vitamin C in an amino acid formulation, and observed a soft, frequent stool with undigested food, and increasing deficiency symptoms of the very nutrients I was ingesting in large amounts! After I finally realized it was the vitamin C that was doing me in, and ceased taking so much (only 7500 mg) my problems turned around, and eventually I recovered most of the ground lost. Thirty years later, I still have minor problems that are probably traceable to that episode.  

There are many who have gotten great results, Pauling of course, and Dr. Rimland and his son and daughter have taken many grams of Sodium Ascorbate, and swear by it. The disease fighting T-cells depend upon adequate vitamin C, and levels of vitamin C do drop during infection, sickness, especially collagen diseases, surgery, pregnancy, and high stress, including the stress of radiation, drugs, alcohol, fever, burns, exposure to cold, and cigarette smoking. It increases the immune function, especially enhancing the activity of neutrophils, lymphocytes, and natural killer cells. It also increases the levels of the antibodies IgA, IgG, and IgM, which are needed to fight infection. In large amounts, vitamin C is strongly antiviral, especially against herpes, shingles, hepatitis, and polio, because it stimulates production of interferon. It has strong antihistamine properties, inhibiting release and enhancing degradation of histamine. Large amounts, coupled with vitamin B₆, are strongly diuretic, relieving edema. At these times of need, increasing vitamin C intake is most helpful and well tolerated. Normally, however, an adult should take no more than 1,000 to 2000 mg, preferably Ester C™ or buffered C (calcium, not sodium).  

There are four thing's one should look for: 1) A loose stool, that will indicate the system is not digesting foods because of a too-fast, passage time. The tolerance amount for this effect on the bowel is highly variable with each individual. 2) Amounts of vitamin C larger than 1000 mg (adult) chelates many toxic things, including mercury, lead, cadmium, and nickel, and is one reason it is beneficial, but it also chelates copper, and zinc, and probably other things I know not. I became copper anemic. It took me a couple of years or longer to overcome that. 3) If taking ascorbic acid, as many do, it will make the system horrendously acid and disrupt all enzyme functions, and stop stomach acid production causing all digestion of protein, and assimilation of vitamins A, C, B-complex, and most minerals to largely cease being digested and assimilated. This is apparently what happened to me. 4) If taking sodium ascorbate, which many do to minimize the acidity problem, one may become overloaded with sodium and deplete potassium. This can lead to many health problems, including palpitations, which I have suffered ever since that incident, controlling them only with high doses of potassium. So, if you continue to use vitamin C in high amount, use only Ester C™. There are several reasons: it is neutral in pH, it has a three-times-longer half-life, so you get better results with less frequent dosing, and it is four times as effective, so you don’t need the extreme doses. I would urge no more than 2000 mg day. If taking larger amounts, one must test saliva and urine to determine that the system is not acidic, and must not allow soft, loose stools to continue, but must cut back until all stools are formed and normal, showing no undigested food.  

Never discontinue these high doses abruptly. The enzymes necessary to handling those large amounts of vitamin C don’t disappear when the vitamin level is reduced. They keep merrily clearing the vitamin C until it is possible to develop subclinical scurvy before the body realizes it no longer needs all those enzymes. That’s just another thing we are not normally told when we are urged to use those huge amounts of vitamin C. This principle probably applies to other things as well. Additionally, most natural antioxidants, such as Coenzyme Q10 and Vitamins C & E are phenolic in nature, and so large amounts of vitamin C would be an unacceptable burden on the PST child.  

There is no doubt that when vitamin C is used medically in huge amounts it can be life saving. Dr. Rimland saved his daughter’s life. A famous publisher saved his life. Vitamin C intravenously, when chelating mercury, has protected many from the terrible detox symptoms. Unfortunately, it’s dangerous in the hands of the uninformed. Now, you know. Additionally, ascorbic acid is used as a preservative and antioxidant in foods. The use of this phenolic can make barbiturates more toxic, and is pharmaceutically incompatible with sodium salicylate, sodium nitrate, theobromine, and methenamine. As many as twenty percent of the people tested are reactive to ascorbic acid.

Sulfation Ratio as a Measure of PST Activity

Conjugation means the joining of two dissimilar molecules. In the body, MHPG and phenolic compounds can be conjugated (joined) to sulfate (sulfoconjugation) or to glucuronide (glucuronidation). In either case, the conjugation of MHPG and phenols facilitates their removal from the brain, and its excretion by the kidneys. The ratio of the amount of MHPG conjugated to sulfate to the amount conjugated to glucuronide is the “sulfation ratio” of MHPG. The sulfation ratio of MHPG is a measure of the efficiency with which the enzyme PST is functioning in the body. Certain areas of the brain appear to lack the glucuronidation pathway, and in those areas deficient PST activity might allow the accumulation of toxic phenolic compounds.  

We know that when the body is faced only with a small load of phenolic compounds (such as those allowed on the Feingold diet), even a rather PST-deficient individual will sulfoconjugate a normal proportion of these phenolic substances. In this case, the term used for the behavior of PST is “first order kinetics.” With first order kinetics, the greater the need for an enzyme, the faster it works. Enzymes also work faster in an acidic environment.  

As we increase the phenolic load through this “first order segment” of the sulfoconjugation curve, sulfoconjugation keeps pace with the increasing need. As larger amounts of phenolic compounds are introduced into the body (such as may be done in candida overgrowth, or the use of food colorings and such things), the enzyme PST can become saturated so that a higher proportion of the phenolic load is conjugated to glucuronide instead of sulfate. By this process, the sulfoconjugation curve transitions from its first order segment into its saturation segment where the sulfoconjugation rate can no longer increase as a function of need. With additional phenolic loading, the glucuronidation pathway is utilized relatively more heavily, and the sulfation ratio falls. This allows a buildup of the harmful toxins being discussed. 

PST is like a donkey, when loaded too heavily, he lies down. Remove a few pounds and he will trot all day. Unload the PST system with the Feingold diet and by removal of toxins from the home. Studies show indoor air often contains 2 to 5 times more hazardous chemicals than outdoor air, even in highly industrialized areas! In rural areas, this can be 5 to 10 times more indoors! Benzene and formaldehyde are the two major toxic substances in the home, but carbon monoxide is likely to be high in winter. All load the P'ST donkey. This chronic exposure to indoor toxins has been linked to a vast spectrum of illness ranging from asthma, chronic sinus infections, headaches, insomnia, anxiety, fatigue, skin rashes, watery eyes, burning sensations in eyes, throat, and nasal passages, breathing difficulties, and joint pain, to full-blown, multiple chemical sensitivities. Carbon monoxide robs the system of oxygen and causes malaise and lethargy. Always leave a window open a bit to provide ventilation even in winter! Remember: “A small percent of autistic spectrum patients have methylation defects due to deficient methyl groups;...The methylation defect, when present, can cause a defect in sulfation. However, this is measurable, and if present, trimethylglycine (TMG) will provide more methyl groups, and in addition, decrease the abdominal complaints present in patients with such deficiency”—Dr. Hugh Fudenberg. TMG may need to be accompanied by significant amounts of vitamins B₁₂ and folic acid. 

Yeast and other fungi, as well as the exposure or intake mentioned above, all produce phenyls, and as phenyls build up they reduce norepinephrine, and interfere with NE’s function in the synapse. Pronounced increases in catecholamine excretion also occur when exposed to noise, although it appears that preexisting magnesium deficiency is necessary for this effect to occur. The effect of magnesium status on the behavioral and biochemical response to noise completes the cycle. Urinary catecholamine excretion increases progressively with increasing dietary magnesium deprivation even without noise stress. The addition of noise further increases excretion of NE, but not of epinephrine. The more pronounced the noise, and the greater the magnesium deficit, the higher the catecholamine excretion, with epinephrine and NE excretion reaching 5 and 10 times control levels under extreme, but nonlethal, conditions. Many Autistics are so hyper to noise they are living with this stress constantly. This produces very adverse effects in the brain, and affects many functions throughout the body as airways and cerebral blood vessels constrict. This loss of blood flow to the brain in the autistic is judged to be a major cause of autistic symptoms.  

NE is the neurotransmitter whose effect in the brain is augmented by stimulant drugs such as amphetamine and methylphenidate (Ritalin). Children whose learning was affected by the challenge dose of artificial color mixture proved to be those who had an earlier “positive” effect with this type of stimulant medication. In other words, children who respond to the Feingold Diet, that eliminates all artificial colors and certain other compounds, are the same children who lack sufficient NE effect in their brains, and who respond to Ritalin™. (Swanson, J.M. and Kinsbourne, M., Food Dyes Impair Performance of Hyperactive Children on a Laboratory Learning Test. Science 207, March 1980, pp. 1485-7). Mary Coleman investigated the effectiveness of Ritalin and vitamin B₆ on hyperactive children. One group was given Ritalin; a second group was given vitamin B₆, and a third group was given a placebo. Both the vitamin B₆ and Ritalin™ groups improved significantly as compared to the placebo group, and there was no difference between the Vitamin B₆ and Ritalin™ groups. The study was published in Biological Psychiatry, 1979. Dr. Robert Sinaiko, MD, says, “The children upon whom I have obtained the 24-hour, urine MHPG test have thus far sorted themselves into four groups”—three of which respond to the Feingold Diet.  

In addition to the behavioral aspects, normally, NE’s role in the regulation of immunity is one of “fine tuning” and adjusting the timing of the various phases in the immune response. In addition to being reduced by a build up of phenols, some evidence suggests that the brain’s supply of NE may become depleted if the immune system is constantly stimulated by allergy or infection as it is in most autistic. We have seen above that the amino acid L-histidine is reduced by allergies, by the drugs used to treat them, and by metal toxicities leading to reduced histamine, HCl, and NE. This interferes with cysteine metabolism by reducing the available sulfite oxidase and cysteine dioxygenase that require histidine and molybdenum. The lack of histidine and molybdenum, and the presence of heavy metals, mercury, cadmium, lead, and arsenic, that bind the sulfhydryl molecules, can well be the reason for low available sulfate creating the PST phenomenon.  

A reduction of norepinephrine (NE) and/or dopamine, or too much acetylcholine activity causes diarrhea, irritable bowel syndrome, cramps, nervous stomach, increased saliva, and raised insulin levels, and, as stated, airways and cerebral blood vessels constrict. A lack of dopamine is a problem in some patients with chronic anxiety, Parkinsonism, one case of drug induced dyskinesia, schizophrenia, dyslexia, ADHD, and autism. This phenolic (dopamine) is strongly vasodilative, and lowers pressure at which peristalsis begins. Other findings on phenolic exposure have been depressed serotonin, elevated histamine and prostaglandins, abnormal complement (an immune component that accounts for inflammatory attack on antigens), and immune-complex formation (a clumping of antigens and antibodies that when undestroyed can trigger a complement attack that damages self). It would seem most helpful, then, to enhance the production of NE, dopamine, and nitric oxide (NO) except in those with low muscle tone where acetylcholine seems reduced.   

So, if you want to protect against the harmful effect of the PST/sulfoxidation problem, and perhaps get your kid off Ritalin™, what can you do? In addition to shielding the body from sources of the toxins as outlined above, eliminating candida and allergens, ingesting sulfate, and taking Epsom salts baths, how can we ensure adequate NE is available? Be sure that you eat an adequate intake of protein. Levels of dopamine and norepinephrine, that counter acetylcholine, can be raised by eating a high protein meal (avoid fatty meats and cheese that rob the brain of oxygen and reduce alertness), and by using a supplement of the amino acids histidine, tyrosine, tyramine, and phenylalanine, and the mineral molybdenum. You can also eat of the high tyramine content foods listed below. Tyramine is an intermediate step between tyrosine and epinephrine. The manufacturer says it is the same thing as norepinephrine, and that it helps some kids who have ADD/ADHD. The supplement NADH also raises noradrenaline. Additionally, supplement Ambrotose® and Phyt•Aloe® from Mannatech™, and TMG. Clinical studies on Autism and ADHD are available on request.  

Tyrosine prevents reduction of norepinephrine levels that are associated with stress. Many clinical studies, along with a large body of anecdotal evidence, indicate that tyrosine may prove to be a vital substance in alleviating depression, as well as the irritating symptoms of premenstrual syndrome. By increasing dopamine, it controls familial tremors. The importance of Tyrosine is based on the fact that it is a direct precursor to Thyroxin (Triiodo tyrosine) as well as being a precursor to Adrenaline and Noradrenaline. Thyroxine is, of course, a primary Thyroid hormone. Thyroxine deficiency results in a series of conditions including excess weight gain, cold hands and feet, and decreased basal metabolism. The catecholamines Adrenaline and Noradrenaline are critical in the following conditions: In Science magazine, it was reported that Tyrosine lowers blood pressure by increasing Norepinephrine metabolites which through feedback shut down sympathetic output. In this same issue it was stated that Tyrosine increased blood pressure 38% to 49% in hypotensive rats through accelerated peripheral synthesis of catecholamine. A study by Dr. I. Goldberg in Lancet revealed that catecholamine also controls immune system output. Allergy sufferers have responded well to Tyrosine. In the American Journal of Psychiatry, Dr. Alan J. Gelenberg postulated that a lack of available tyrosine results in a deficiency of noradrenaline at a specific brain location, which in turn relates to mood problems such as depression.  

Do not take phenylalanine, tyramine, or tyrosine with the antidepressants that contain Monoamine Oxidase Inhibitors (MAOI), and never take MAOI (including St. John's Wort) with the following high tyramine (amino acid) content foods for (rarely) the combination can cause severe high blood pressure, stroke, or even death: aged cheese, aged meats, pods of broad beans, beer, wines, pickled herring, yogurt, liver, yeast extract, ripe bananas, soy sauce, anchovies, avocado, or sour cream (ask your doctor for a complete list and discuss this with him); and avoid cold, flu, and weight loss medications. Avoid these for two weeks after you quit the MAO inhibitor. Do not take a MAO inhibitor if you have congestive heart failure or abnormal liver function. 

Tyramine can be purchased from DEWS. It is reasonably priced. DEWS is probably the only place you will find this, because DEWS invented a method of making it relatively inexpensively. (800) 360-5298 or (817) 282-7326.  

The following nutrients have been found to inhibit MAO reducing losses of neurotransmitters: dimethylaminoethanol (DMAE), Vitamins B₁, B₂, B₆, B₁₂, C (ascorbyl palmitate), and E, para–aminobenzoic acid (PABA), folic acid, beta–carotene, calcium, magnesium, zinc, chromium picolinate, selenium, reduced glutathione (an antioxidant), and St. John’s Wort (hypericum). A coenzyme, vitamin B-complex supplement of moderate potency should be supplemented.  

As previously stated, until you have unloaded the donkey, it may be desirable to limit the colored foods that are high in phenols and malonic acid.  

One mother writes (edited): “On 1/6/99 all hell broke loose—Kyle woke up in excruciating pain, so much so that he had to hold his hands in the air most of the time. He behaved as though his hands were being sawed off with a dull blade, minute-by-minute, hour-by-hour, day-by-day, with no relief for 7 days. Two days later it was gone and he was back to normal. But the pain slowly reemerged in the next weeks and months, and his ability to use his hands never reverted to where it was just prior to ‘The Event’. His handwriting went from slightly larger than normal to HUGE, uneven, and mostly illegible. He suddenly couldn’t type or play the cello or piano without difficulty. There is no other explanation for what happened other than a yeast die-off reaction. When I finally found Great Plains Lab and Dr. William Shaw, they said they had seen it happen with other autistic children. Kyle always has had red ears, therefore, probably has had this PST problem for years. Could this happen with metals toxicity? (I wrote: Yes, mercury can adversely affect sulfoxidation.) 

“The Yeast die off plus other possible offending toxins and phenol-containing foods, including occasional use of Tylenol™, led to a series of other symptoms in the ensuing weeks and months, including tingling and pain in the extremities (including tongue), fatigue, muscle weakness, reduced mobility of hands/feet/tongue, headaches, blotchy skin and ‘hot spots’, hypoglycemic-like reactions, increased brain fog and spaciness, sinus allergies, visual regression, ringing in the ears, sore throats, fevers, dry and irritated eyes, increased auditory sensitivity, and significant regression in writing, keyboarding, and in playing his cello. On July 12, 1999, Kyle began having spasms on the right side of his face, head, shoulder, and arm. The spasms quickly got much worse until he was having them about 3-times a minute all day long this lasted for three weeks. More tests and another EEG were done, all negative. During June, Kyle suffered an attack of hay fever type allergies, and I gave him a generic version of Benadryl Ultratabs™ anti-histamines according to label: 2 tablets every 4-6 hours, but discontinued them just a week before the onset of the spasms. Now I realize this may not have been desirable usage for him, what with the red dye and other possible toxic content.  

“Some time in the fall I began putting an orange in Kyle’s lunch every day since he could no longer have apples. During the fall, I gave him Tylenol™ a few times for severe pain. In December 1999 and January 2000, I began diligently making salads every night for dinner, including tomatoes and red and orange peppers, because of course, they are such healthy foods. Every week he seemed worse, and in more pain. SAMe no longer seemed to work at all, and I had to give Tylenol™ more often. After his muscle biopsy in February 2000, he was given a prescription of Tylenol with Codeine, then his headaches became excruciating. Until you told me, I did not know how toxic Tylenol™ was to Kyle, and that it was actually contributing to his chronic pain and headaches. We were in a vicious cycle. 

“It finally makes sense why the pain would not go away: between the yeast die off (Nystatin and probiotics), the allergy medicine, the Tylenol™, the oranges, and the salads, he was being bombarded with things that were toxic to him! All of this on top of the trauma his body went through with the initial die-off must have put his system over the edge. I’m still confused over that initial onset, but maybe the combination of PST deficiency, extremely high titers to measles and herpes virus 6, a very sick gut, plus a sudden flood of yeast toxins from the die-off created a very dangerous health situation, and resulted in the many bizarre symptoms that we have seen since that time. 

“At the ‘Biological Treatments for Autism Conference’ in Orlando last May, I posed Kyle’s case to the entire panel of doctors who specialize in autism at that conference. Interestingly, no one made a connection between Kyle’s symptoms and PST Deficiency, nor had any of them heard of symptoms similar to Kyle’s. It seems incredible to me that in one, phone conversation you knew what Kyle’s problem was, and none of those doctors did! In addition to numerous deficiencies, he was suffering from an overload of a variety of toxins (both natural and synthetic), each contributing their own ‘poisoning’ characteristics, to create a confusing hodgepodge of symptoms that could change as the level of each toxin would fluctuate. 

“So many thanks to you, for helping me to understand WHY this has been happening so that I can do things differently. Without your help and advice, this horror could have gone on forever!  

“I am now ‘holding the course’ as you advised (as recommended herein—WSL), and the improvement is awesome. Not just the pain, but also the hyperactivity (pacing, jumping, hand and body shaking) has reduced tremendously in just one week!  

“My family is deeply indebted to you for your kindness, and the sharing of this unique knowledge that you have. I will do my best to pass this knowledge on to others that need it. Thank you so very, very much for everything!”  

In August of 2000, Kyle and family spent two weeks camping, and then he and his father spent a week of canoeing in Alaska. This outing has proved Kyle is once again a strong, active, young man, with little or no pain attending him. In lieu of Epsom salts baths, Kyle used a magnesium-sulfate cream during these outings. Kyle and family enjoyed the outing tremendously, all the more for they had thought it was never again to be. 

Pacing and stomping is likely a sign of restless legs. This is described as ants crawling under the skin until one cannot hold the legs still. They must be moved. This will often manifest at bedtime. It can be caused by too great an intake of calcium, or a lack of magnesium and vitamin B₆. One report told that a balancing of calcium/magnesium benefited, but the addition of adequate zinc stopped the restless legs syndrome. There are many possible causes of restless leg syndrome. Stronger associations include kidney failure, some nerve disorders, vitamin deficiencies, pregnancy, iron deficiency, and some medications (such as antidepressants). About 50% of those who have restless leg syndrome have relatives with the same condition.