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What is MHPG? Why 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 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 systemic 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-glucurate. The calcium-d-glucurate prevents an enzyme produced by the bacteria in the intestine (beta-glucuronidase) 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-glucurate.

 

An exciting new bit of information indicates that resveratrol, when taken orally, has virtually no unmetabolized resveratrol entering the bloodstream. Why is this exciting? To be useful, a nutrient must be bioavailable; that is, it must be readily absorbed into the bloodstream, and it must survive long enough to reach the cells that need it. For all resveratrol’s benefits, getting it to where it is needed poses an extraordinary problem, because even though resveratrol taken orally is well absorbed by the gut (at least 70%), its bioavailability turns out to almost zero. This apparent “paradox” can be traced to its rapid and extensive metabolism into two types of chemical derivatives: sulfates and glucuronides (both desperately needed to enhance Phase II liver detox). Most resveratrol is converted into these metabolites in the gut and they are readily absorbed. The liver completes the process within about half an hour. This makes resveratrol an unsurpassed supplement to enhance both legs of Phase II detoxification! Additionally, resveratrol turns off the cancer promoting genes such as bcl-2 and mcl-1, while turning on cancer-suppression genes like P53 and Bax! Do not buy the versions with Quercetin, and do not give it at the same time you supplement quercetin for that defeats our purposes. A lot of vitamin C increases glutathione and (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 7,500 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. Adequate vitamin C (preferably sodium ascorbate) at these times 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 and glutathione (a 30% increase). 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,

 

There are four thing’s one should look for when supplementing vitamin C: 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) Vitamin C in amounts 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, 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. This is, apparently, what happened to me. Many fear to use sodium ascorbate for fear of excessive amounts of sodium depleting potassiou. Dr. Bernard Rimland and others using Sodium Ascorbate in high amounts say this has not been a problem. I would urge no more than 2000 mg day (adult) unless fighting inflammation. 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 symptoms of detoxification. 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. This is likely because the source is corn.

 

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