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Olfactory and gustatory symptoms of psychiatric patients were ameliorated completely or partially by zinc supplementation, that is, their sense of smell and taste are improved so they tend to eat better. In a small study (Am J Clin Nutr 53:16, 1991), 30 mg zinc per day intake increased the short-term recall of visual images. Since it is known that essential-fatty-acid metabolites stimulate intestinal zinc, taking fatty acids with zinc supplements is clearly warranted. Zinc deficiency impairs vitamin A metabolism, and inhibits prostaglandin synthesis from essential-fatty acids, either by blocking linoleic acid (LA) desaturation to gamma linolenic acid (GLA), or by inhibiting the mobilization of dihomo-gamma-linolenic acid (DGLA) from the tissue membrane stores. Zinc and vitamins B3, B6, and C are necessary for the conversion of essential-fatty acids to PgE1 (prostaglandin E1), an anti-inflammatory that is protective from the excessive gastric secretion. Zinc is known to help in the healing of gastric and peptic ulcers. This is probably because zinc is required for the synthesis of gastric mucosa. Zinc controls over 200 enzymes, one of which is necessary for the stomach to produce hydrochloric acid. Note this quotation: “We took hair samples from 31 boys and 15 girls, and had them analyzed by Dr. P. J. Barrow of the Dept of Environmental Health, University of Aston, Birmingham. Twenty-four of the boys and seven of the girls had zinc values below the normal range” —from 1979 survey of hyperactive children belonging to the H.A.C.S.G. “Our May 1981 research paper: ‘A Lack of Essential Fatty Acids as a Possible Cause of Hyperactivity in Children’ was based on these findings.”

 

>>>Dietary fat influences the effect of zinc deficiency on liver lipids and fatty acids in rats force-fed equal quantities of diet; Eder K, Kirchgessner M J Nutr 1994 Oct, 124:101917-26.

Abstract:

Previous studies showed that zinc deficiency influences the fatty acid composition of rat tissues, but the influence of dietary fat on the effects of zinc deficiency was not considered at that time. The present study was conducted to investigate the effect of zinc deficiency on lipid concentrations in the liver and on fatty acid composition of liver phospholipids in rats fed diets containing coconut oil or fish oil, using a bifactorial experimental design. To ensure an adequate food intake, all rats were force-fed. The zinc-deficient rats fed the coconut oil diet developed fatty livers, whereas zinc-deficient animals fed the fish oil diet did not. The zinc-deficient rats in both dietary-fat groups had lower levels of linoleic acid, arachidonic acid, and total n-6 (that is, Omega-6) fatty acids in the liver phospholipids, especially in the phosphatidylcholine, but greater concentrations of n-3 (that is, Omega-3) fatty acids compared with zinc-adequate controls. We conjecture that zinc deficiency influences incorporation of polyunsaturated fatty acids into phosphatidylcholine. The lower levels of arachidonic acid are replaced in the zinc-deficient animals fed a coconut oil diet by docosapentaenoic (DPA) and docosahexaenoic (DHA) acids (VLCFAs), and in the zinc-deficient animals fed a fish oil diet by eicosapentaenoic acid (EPA). The replacement of arachidonic acid by other fatty acids in the phospholipids is likely to have implications for prostaglandin synthesis. The study shows that the type of dietary fat influences the effects of zinc deficiency on fatty acid composition and especially on lipid concentrations in the liver. >>>

 

In zinc deficiency, one is more susceptible to toxin-producing bacteria or enteroviral pathogens that activate guanylate and adenylate cyclases, stimulating chloride secretion, producing diarrhea and diminishing absorption of nutrients, thus exacerbating an already compromised mineral status, lowering zinc levels still further. In addition, zinc deficiency may impair the absorption of water and electrolytes, delaying the termination of normally self-limiting gastrointestinal disease episodes. Diarrhea always brings the specter of dehydration that may be recognized by sunken eyes, decreased skin turgor (dried out), or strong, body odor. One study showed zinc supplementation could reduce the duration of diarrhea by 20 to 30%, reduce incidence of diarrhea by 38%, and reduce acute, respiratory infections such as pneumonia up to 48%—American Journal of Clinical Nutrition, August 1998.  Interestingly, sugar-free, shredded coconut will stop diarrhea, even coconut macaroons will!

 

Parasites are better able to survive in the zinc-deficient hosts than in well-nourished hosts. The production of interleukin-4 in the spleen of zinc-deficient mice is depressed, leading to depressed levels of IgE, IgG(1) and eosinophils; and the function of T-cells and antigen-presenting cells is impaired by zinc deficiency as well as by energy restriction. Thirty days of suboptimal intake of zinc can lead to 30-80% losses in defense capacity! Supplementation with zinc or iron, or both, improved indicators of vitamin A status. The results of this study agree with previous observations of a metabolic interaction between zinc and vitamin A, and suggest an interaction between iron and vitamin A metabolism. A big aid to controlling diarrhea, while working to alleviate the cause, is to feed one teaspoon of raw, carob powder two or three times a day. Bananas are helpful too, replacing lost potassium.

 

Children that are unsettled, frequently demanding attention, upset much of the time, and those whose sleep is regularly broken during the night can be very wearying on parents to say the least. Additionally, recent studies show that in sleep-deprived people the part of the brain responsible for language slowed down tremendously. Furthermore, after a sleepless night, a person will do only half as well on memory tests as when well rested (Students take note!). Sleep deprivation produces more insulin and cortisol, both damaging to health and well-being. Dr. Joseph T. Hart, a pediatrician of Portland, Oregon, has found that by supplementing zinc you may be able to eliminate the problem of sleeplessness. He has supplied zinc drops to hundreds of children, and in the majority of the cases, the chronic sleeplessness has disappeared! Additionally, copper, iron, and magnesium, as well as vitamin A deficiencies will adversely affect sleep. Dr. K. M. Hambridge of Denver, Colorado, observed that zinc-fed babies were much less irritable. Hart reports that zinc supplementation also produces improvement in appetite, and reduces daytime irritability, diarrhea, skin rashes, and pallor. In older children, whose wakefulness was followed by climbing out of bed and getting in with their parents, the habit was lost. This is understood when we realize the synthesis of serotonin involves vitamin B6 and zinc enzymes, and since serotonin is necessary for melatonin synthesis, a zinc deficiency may result in low levels of both hormones. Unfortunately, zinc levels tend to be low when there is excess copper and cadmium. Moreover, high estrogen levels from soy and flax tend to cause increased absorption of copper and cadmium. Cadmium affects verbal ability more and lead affects performance measures more. The high estrogen can create anxiety in the child.

 

Many consider soy to be good food. Aside from considerations of genetic altering taking place, one study states that genetic activation of an enzyme (aromatase) involved in the conversion of testosterone into estrogens was increased by genistein and, to a lesser extent, diadzein. The soy extract stimulated one of the estrogen receptors (b receptor) greater than genistein and diadzen, although the latter two were stimulatory themselves. Genistein decreased receptors for testosterone-like molecules (androgens) significantly, while diadzein affected them only half as much. This, in effect, produces more estrogen from available testosterone making the woman more susceptible to breast cancer and less sexual, and it makes the man more feminine with less sexual drive! Prevention Magazine™ (September 2003) reported on a study that found that feeding genistein to pregnant and breastfeeding animals produced male offspring with lower testosterone levels and smaller sexual organs! Soy milk is not a suitable food for children or adults!

 

Zinc also helps get rid of the terrible two’s. Within a week you can often see a definite settling down, and reduction of tantrums and of the terrorizing of the poor mother! Zinc is being successfully used for learning disabled children, for children with seizures, skin lesions, and histories of infections. Zinc is essential for new tissue formation. It is essential for white blood cell and antibody formation. It helps neutralize toxic minerals in the body, such as lead, mercury, cadmium, and copper. It also seems to make other nutrients work better. High lead, copper, manganese, or mercury levels have been found to be associated with ADHD, impulsivity, and inability to inhibit inappropriate responding. New research from Israel and the UK indicates the hyperactivity of ADHD is linked to zinc deficiencies. Studies have also found evidence of a connection between low levels of zinc and three other common childhood diseases: treatment resistant depression, childhood-onset diabetes, and epilepsy. Zinc is an antagonist to toxic metals like cadmium, mercury, and arsenic, and adequate levels are required to balance the adverse effects of these toxic substances on cellular calcium and other enzymatic processes. Additionally, in one study, “…damage of liver cell, such as lobular necrosis and portal inflammation, were relieved. From these results, organic germanium is considered to have beneficial effect on the protection of liver from cadmium intoxication”. No such protection against mercury was observed—Hyo Min Lee and Yong Chung, The Institute for Environmental Research, Yonsei University, Korea.

 

Nevertheless, it is interesting to note this: “With ADHD, once you make the necessary craniosacral correction, it’s over—you don’t have to worry about it anymore. The correction, when appropriate, usually involves resolving compression in the neck area (atlas occipital region) that occurs during the birth process. I estimate about 50% of individuals with ADHD fall into this category.”—Dr. John Upledger. Many find craniosacral correction helpful to autism.

 

Violent behavior in young men appears to be linked to an imbalance in the relationship of copper and zinc, according to a study published in the Journal Physiology & Behavior. “Our preliminary findings show that young men who have varying levels of angry, violent behavior also have elevated copper and depressed zinc levels; the non-assaultive controls in our study did not”, said William Walsh, Ph.D. Any white spots on finger or toe nails, face noticeably pale? Definitely supplement zinc. Don’t let the doctor ignore a low Alkaline Phosphatase (alk phos) reading for a lack of this zinc dependent enzyme means you need zinc. The commercial zinc tablets (primarily sulfates) are particularly painful for many because free zinc binds to already damaged mucosal cells directly. The zinc drops are preferable. Consult with your medical professional about this possibility. In the case of pallor, check for anemia and low thyroid activity also. Anemia is often the first sign of hypothyroidism. When body temperatures are low, the marrow makes less red cells! Very important is the observation that anemia in hypothyroidism is often not diagnosed because hypothyroids have a lower volume of plasma which causes a false high estimation of the amount of hemoglobin in the blood. A strong desire to chew ice is a sure sign of iron deficiency anemia. Zinc and selenium along with vitamin A, glutathione, and vitamin B6 are essential to formation of T3 thyroid hormone. Vitamin B6 and magnesium deficiency predominates in hyperactive kids also.

 

Zinc is vital in another pervasive problem affecting autistic. Subnormal values for the essential amino acids Valine and Leucine are common. Leucine and isoleucine are commonly found to be deficient in the mentally and physically ill. RDA for Leucine is 16 mg per kg of body weight per day. Animal protein provides 70 mg per gram. RDA for isoleucine is 12 mg per kg of body weight. Animal protein supplies 42 mg per gram. MTBE, a gasoline additive that is contaminating drinking water, inhibits the amino acid cascade of valine; causing itching, skin difficulties, and occasionally hair loss. MTBE also blocks the synthesis of glycine. Glycine is required as a neuroinhibitor in the spinal cord, to regulate acetylcholine, the transmitter that powers muscle movement. Without enough glycine to modulate the acetylcholine, muscles can become chronically tense, and tend to cramp spontaneously. Valine and leucine are “branched-chain”, essential, amino acids, and their digestion and uptake from food require proper peptidase function in the small intestine. This is why one should supplement a digestive enzyme containing peptidase (GI–Zyme™ - Mannatech™, SpectraZyme™, Peptizyde™, EnZym-Complete™). Leucine aminopeptidase is one such enzyme. To be active, it requires zinc and a gut pH between 6.5 and 8.5. Peptidase dysfunction and resulting, excess-peptide uptake is what much of autism is about. Zinc deficiency can cause both peptidase dysfunction and growth failure. As indicated, mercury also inhibits both zinc and the peptidase enzymes.

 

The latest Government survey shows 81% of the kids are not getting the RDI of zinc! A high percentage of females with Anorexia Nervosa have low serum zinc. Incidentally, it has now been established that both plasma and serum zinc concentrations are subject to acute variations, being highest in the morning and falling after a meal. Stress alone can cause a rapid fall in plasma zinc values, as can certain steroid drugs such as oral contraceptives. Furthermore, all manner of infections tend to reduce both plasma and serum zinc levels in a way that is not necessarily related to primary nutritional zinc status. Only repeated low plasma zinc tests can provide grounds for suspecting zinc deficiency. The only true indicator is a Red Blood Cell Tissue test. How much is in the cell is all that counts. Zinc is not stored in the fashion of some other minerals and must be supplied each day in adequate amounts. It is also a water-soluble nutrient and easily lost from cooked foods. On the other hand, supplementing zinc in very high amounts over long term is dangerous. Excessive zinc intake will eventually affect the balance and proper ratios to numerous other important nutrients that may include iron, copper, manganese, calcium, selenium, nickel, phosphorus, as well as Vitamins A, B1, C, and others. It may cause, or contribute to gastrointestinal problems, hair loss, anemia, loss of libido, impotence, prostatitis, ovarian cysts, menstrual problems, depressed immune functions, muscle spasms, sciatica, renal tubular necrosis/interstitial nephritis, dizziness, and vomiting, among others. Unless already in excess, a supplement of copper and manganese must be taken when supplementing zinc.

 

While the branched-chain aminos are usually deficient, Maple Sugar Urine Disease (MSUD) derives its name from the sweet, burnt sugar smell caused by an excess of these amino acids. The disorder affects the way the body metabolizes the three branch-chain amino-acids Leucine, Isoleucine, and Valine. These amino acids accumulate in the blood causing a toxic effect that interferes with brain function.

 

One type of phagocyte cell is the macrophage. In the brain, this is called myelinophage, in the liver, kupffer cells. The primary function of these cells is to break down and remove substances the immune system marks as ‘non-self’. These pivotal cells in many immunologic functions are adversely affected by zinc deficiency, which can dysregulate intracellular killing, cytokine production, and phagocytosis. Dr. Woody McGinnis says zinc deficiency is involved in warts, acne, stretch marks, asthma, and frequent infections. One study of hyperactive kids showed almost 50% were deficient in stomach acid, most likely because of a zinc deficiency common to ADHD. Zinc citrate, the form in mothers’ milk, is quite bioavailable in restoring zinc levels, but zinc picolinate, OptiZinc®, or liquid, ionic forms seem more certain of assimilation.

 

Several studies have found that most children with ADHD have deficiencies of certain minerals, such as magnesium and zinc that are commonly depleted by exposure to toxic metals, and most show significant improvement after supplementation with these minerals. Magnesium is the most common, significant, mineral deficiency among ADHD children, but zinc is commonly deficient among children with ADHD and disruptive behavior disorders.

 

Studies have found the level of free, fatty acids significantly lower in children with ADHD and autism. In 1981, Colquhoun and Bunday proposed that hypothesis based on a survey of hyperactive children. These children showed clinical signs consistent with a deficiency of essential, fatty acids: excessive thirst, frequent urination, dry skin and hair, brittle nails, and skin problems. Blood biochemical studies subsequently provided supporting evidence for the hypothesis. Peet and colleagues reported that a dietary analysis of 20 patients with schizophrenia yielded significant relationships between the status of dietary, Omega-3, fatty acids and the severity of both schizophrenia symptoms and tardive dyskinesia. A higher consumption of Omega-3, fatty acids correlated with less severe symptomatology. There is also a case report in the literature of a 77-year old patient with Alzheimer’s dementia who improved clinically over several months when placed on a regimen of increased fish consumption. Symptom improvements included regaining the ability to dress himself, decreased restless and destructive behavior, improved fine motor skills, and enhanced insight into his condition. An imbalance of fatty acids control the amino acid balance.

 

Clinical expression of fatty-acid deficiency is often seen in patients with candidiasis. Galland (1985) reported nearly 66% of candidiasis patients that he studied had two or more clinical signs of fatty-acid deficiency. Non-specific signs such as dry, stiff hair; dry, scaly skin; brittle nails, and follicular dermatitis where noted in many of these patients.

 

So, ensuring the presence of all the essential amino acids is another problem area. In order for the body to properly synthesize protein, all the essential amino acids must be present simultaneously, and in proper proportions. If one or more essential amino acids are missing or in poor supply, utilization of all amino acids is reduced in the same proportion as the one that is lowest or missing! Protein, in proper proportion for one’s metabolic type, must be eaten with every meal. Amino acid assimilation and utilization are controlled by fatty acids (GLA/EPA) that must be in balance. High, dietary sugar and high-glycemic food intake causes release of high levels of insulin that disrupts fatty-acid balance. Additionally, the essential branch-chain-amino acid (BCAA) levels are significantly decreased by insulin.

 

Valine, one of the three essential BCAA, competes with tyrosine and tryptophan in crossing the blood-brain barrier. The higher the Valine level, the lower the brain levels of tyrosine and tryptophan, and there is a decreased production of serotonin and of the thyroid and catecholamine hormones. An excess of Valine may cause hallucinations and “crawling skin”. Biotin is essential for metabolism of branched chain amino acids, and may be involved in copper metabolism. Walsh finds Biotin very useful in the “slender malabsorber group”. Adults require 14 mg Valine per Kg of body weight per day. First-class protein provides 48 mg per gram. One of the implications of this competition is that tyrosine and tryptophan nutritional supplements need to be taken at least an hour before or after meals or supplements that are high in branched chain amino acids. Any acute, physical stress (including surgery, sepsis, fever, trauma, starvation) requires higher amounts of Valine, Leucine, and Isoleucine (the 3 essential BCAA) than any of the other amino acids. During periods of Valine deficiency, all of the other amino acids are less well absorbed by the GI tract. Valine is “useful in muscle, mental, and emotional upsets, and in insomnia and nervousness”—Borrman.

 

The well-documented phytates of cereal grains sequester many divalent ions including calcium, zinc, iron, and magnesium so as to impair bone growth and metabolism. Though magnesium is found in nuts, whole grains, legumes, and leafy green vegetables, these also contain phytates and fibers that bind magnesium and allow little absorption. When eating legumes and green veggies, you may want to supplement with a product containing the plant enzyme, Cellulase, that breaks the bonds and releases vitamin B12, magnesium, and other minerals for your body to use. Cellulase will also pull mercury out of the body and reduce the burden greatly, but without kidney function, only redistribution takes place. Further, there are antinutrients in cereal grains that directly impair vitamin D metabolism [Batchelor 1983; Clement 1987]; and rickets is routinely induced in animal models via consumption of high levels of cereal grains [Sly 1984].

 

Less well appreciated is the ability of whole grains to impair biotin metabolism. High doses of Alpha Lipoic Acid can compete with biotin (a B-vitamin) and interfere with its activity in the body also. A supplement of biotin would be indicated. Watkins 1990, Blair 1989; Kopinksi 1989 have shown that biotin deficiencies can be induced in animal models by feeding them high levels of wheat, sorghum, and other cereal grains. Biotin-dependent carboxylases are important metabolic pathways of fatty-acid synthesis, and deficiencies severely inhibit the chain-elongation and desaturation of 18:2 n6 (linoleate) to 20:4 n6 (arachidonic acid). Human dietary supplementation trials with biotin have shown this vitamin to reduce fingernail brittleness and ridging that are associated with deficiencies of this vitamin [Hochman 1993].

 

Biotin, also known as vitamin H or Coenzyme R, is one of the twelve B vitamins. It is one of the best supplements to improve the appearance of hair, nails, and skin. It also increases metabolism of carbohydrates, fats, and proteins, and it is essential for the creation and utilization of fats and amino acids. Large quantities of biotin, far above dietary reference amounts, have been shown to be highly valuable for reducing blood glucose, increasing insulin sensitivity and general anti-glycation effects.

 

When yeast levels are high, there are high levels of arabinose. According to Dr. Shaw, this can cause a functional deficiency of B6, lipoic acid, and biotin. A lack of biotin will cause hypoglycemia and excess ammonia. A biotin deficit can also lead to depression, muscle pain, fungal infections of the skin, rashes, nausea, sleepiness, acidosis, fine and brittle hair, dry skin, hair loss, seborrheic dermatitis, and a poor fatty acid profile due to interference with the Desaturase enzymes. It serves as a carrier of carbon dioxide. A deficit of biotin can be caused by prolonged antibiotic treatment, the frequent ingestion of raw egg whites sans the yellow, the regular use of more than a hundred milligrams of Alpha Lipoic Acid, or the use of certain anticonvulsant drugs, primarily Dilantin, primidone, and Tegretol™. (See this article by Dr. Sloan, http://author.emedicine.com/PED/topic238.htm.)

 

Those with multiple sclerosis or those who have antibodies to myelin protein (as found in many of the autistic) might also want to note that biotin is involved in the synthesis of fats in the nervous system, and so should probably be given special attention in the MS diet.

 

The amounts people are using to overcome this problem are rather high. A product called Biotin 5000 Yeast Free by Nutricology/Allergy Research Group has 5 mg of Biotin per capsule. Most Biotin supplements are measured in mcg, which is a much smaller measurement. Phone (800) 782-4274 or (510) 639-4572 or website www.nutricology.com. However, some caution must be exercised. Biotin must be balanced with inositol, another B-vitamin, to avoid fatty-liver damage.

 

A British allergist has found that adults taking 500 mg of the amino acid L-histidine, twice daily, improved gastric acid production in allergic patients. (Children should use one-half that amount.) If the allergies are severe, start with 2 to 3 grams per day and taper down to 1 gram as allergies improve. Improvements are because of increased histamine production. Actually, this can be a dangerous thing as histidine is a powerful chelator, and it can quickly drain the child of minerals already in short supply. Worse, histidine is a powerful carrier of copper. It transports copper from the intestinal milieu into the portal blood and from there to organs and tissues in the body. And don't think you can displace copper with zinc once the copper is on histidine - you cannot. Only glutathione, cysteine, and thionein can intercept this copper transport, but that's one of the big problems in autism, isn't it? These sulfur players have gone AWOL, and copper is excessive at the expense of zinc ; so, use this only under direction of a knowledgeable doctor. Having first been intrigued, Dr. Woody McGinnis declined to use it!

 

The amino acid L-glycine also increases gastric acid output. It may be used at 500 to 2000 mg daily in divided doses. This is often seen in its metabolite form Dimethyl (DMG) or Trimethyl (TMG) glycine. TMG (betaine) has been used for many years in the treatment of hyperactivity even though the mode of action has remained unclear. In giving up one methyl molecule, it becomes DMG, long used in autism (according to Mr. Dave Humphrey of Kirkman Labs, 1-500 mg tablet of Kirkman’s N,N,N, Trimethylglycine supplies approximately 250 mg DMG). Betaine hydrochloride (600 mg supplying 485 mg Betaine and 115 mg hydrochloride) is Betaine stabilized with hydrochloride. It has the advantage of providing hydrochloric acid to aid digestion and activate Secretin, and at that time, it becomes the methyl donor, trimethylglycine (TMG). Incidentally, Glycine, in any form, aids in production of HCl. The overmethylated should likely not use TMG/DMG. While I believe the above is accurately presented. Some affirm that betaine HCl and TMG, though very similar, have very different actions.

 

SAM (SAMe) is the most important methyl-group donor in cellular metabolism. It is utilized in synthesis of carnitine, CoQ10, creatine, methycobalamin (B12), L-methylnicotinamide, N-methyltryptamine, phosphatidylcholine, and polyamines, and a number of other methyl reactions including Phase II liver detoxification. SAMe is an active, lipotrope form of Methionine, and it is a cofactor in a number of critical biochemical reactions, being found in almost every tissue of the body. SAMe has been used in clinical studies to treat depression, schizophrenia, demyelination diseases, liver disease, dementia, arthritis, peripheral neuropathy, and other conditions. Several studies have confirmed that SAMe is up to 15% more effective in the treatment of depression than traditional pharmaceutical antidepressants. SAMe improves and normalizes the liver function. SAMe is essential for the production of glutathione, a powerful antioxidant that protects the body from the damaging effects of free radicals. SAMe reduces the number of trigger points, reduces fatigue, reduces morning stiffness, and improves mood in fibromyalgia patients. SAMe improves the binding of neurotransmitters to their receptor sites in the brain. SAMe is essential for the regeneration of neuron axons following injury. SAMe is also essential for the formation of myelin sheaths that surround axons. In tests, SAMe has shown great promise in the treatment of Peripheral Neuropathy, and HIV related peripheral neuropathy. Alzheimer’s and Parkinson’s patients have very low levels of SAMe.

 

The synthesized SAM is expensive, but your body produces SAMe naturally by utilizing six specific nutritional supplements. The combining of ATP (the energy molecule) and magnesium with methionine produces SAMe. In this chain reaction, called the SAMe Cycle, the ATP/magnesium/methionine reaction produces SAMe, and when TMG donates a methyl group to the resulting homocysteine, dimethylglycine (DMG) remains, while the B6, folic acid, and B12 convert the homocysteine into methionine and SAMe. These nutrients produce SAMe and DMG naturally at a fraction of the cost of the commercial pharmaceutical substitutes. Assuming normal methylation (there are over- and under-methylated states totaling about 70% of autistic children), the homocysteine is recycled to methionine and to SAM in this SAMe Cycle. This resulting SAMe is vital to countless metabolic reactions throughout the body, including the production of serotonin. A portion of homocysteine is metabolized to cysteine in what is called the Sulfation Pathway. When the pathways from cysteine to glutathione and taurine are blocked because of heavy metals toxicity or a lack of vitamins B6 and C, zinc, selenium, and molybdenum, one will lack the glutathione and sulfates needed to detoxify the body, a condition called PST. It would appear that a supplement of vitamins B2, B6 (P5P), B12, folic acid, magnesium, and niacin (NADH) would be very desirable to produce SAMe naturally rather than buying this very expensive supplement. Supplementation of methyl donors TMG or DMG, as indicated by ones methylation status, would also be valuable in speeding the SAMe Cycle. Ensuring adequate protein, and even supplementing a small amount of D-L-methionine and serine, would be logical. These added nutrients would tend to restore normalcy to the production and recycling of homocysteine, and to the production of SAMe, taurine, glutathione, and sulfates reducing the threat of cysteine toxicity. Those who have done this report cognitive and behavioral improvements.

 

Dr. Bill Walsh critiqued the above: “Your dialogue seems to focus on the toxic possibilities of the cystathionine pathway and cysteine itself. Actually, this is a vitally important pathway and cysteine is absolutely necessary for proper functioning. Most autism-spectrum patients are very depressed in cysteine, but may experience dramatic and disturbing symptoms after oral cysteine. Many have suggested that oral cysteine interacts with yeast overgrowth to provoke the symptoms. A more likely possibility is that oral cysteine promotes the PREMATURE synthesis of metallothionein that, in cases of zinc deficiency, can produce extraordinary (albeit temporary) zinc deficiency symptoms. We have learned that the best way to provide cysteine is using oral GSH that breaks down into cysteine and two other amino acids.” This is true, but for the few, there is still a threat of excess cysteine that is exceedingly toxic.

 

“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. Disruption of the SAM cycle by excess cystathionine beta synthetase and methyl-tetra-hydrofolate (a metabolite of folic acid) results in an increased cysteine pool (possibly to toxic levels), and decreased methyl groups available for DNA methylation and for the normal formation of NADH.

 

It is of interest to note that Dr. Walsh of The Pfeiffer Treatment Center recently determined that more than 50% of children with autism were undermethylated with high histamine and need TMG,; whereas 15% were overmethylated with low histamine, and do not do well on TMG. If TMG/DMG makes the child hyperactive, he needs folic acid to make up for the folate being excreted, or he needs to reduce or discontinue the TMG/DMG because it is overmethylating. Supplement glycine, vitamins B6 and B12 instead. Calcium stimulates the mast cells to release histamine unless it is properly balanced with vitamin D3 and magnesium, a natural, “Calcium Channel Blocker”. Expressed differently, undermethylated autistics thrive on magnesium, methionine, Vitamins C and D, DMG or TMG, tyrosine, tryptophan, phenylalanine, pantothenic acid, and inositol, but tend to get worse on calcium (unless adequate magnesium and vitamin D3 is supplied), DMAE, and choline.

 

When histamine is released from the mast cells excessively, it chelates trace minerals, particularly zinc and copper, and it will cause one or more of the following symptoms depending upon the degree of excess histamine: Eyes itch, burn, or become watery; nose itches, sneezes, and produces more mucus; skin itches and develop rashes or hives; sinuses become congested and cause headaches; lungs wheeze or have spasms; there are stomach cramps; and diarrhea.

 

The DMG, by a secondary pathway, with the help of vitamin B2, produces serine, and if necessary enzymes and nutrients are available, cystathionine, cysteine, taurine, and the vital sulfates. The importance of the above process is seen by the fact that a build up of homocysteine not only tends to heart problems, but it negatively impacts the formation of vital sulfated sugars (GAGs) interfering, as it does, with the normal pathway to cysteine and the final sulfates needed for Phase II detoxification and GAG sulfation. Benefits of DMG are improved speech, better eye contact, reduced frustration, better sleep, better bile flow, increased levels of glutathione, and a significant boost to immune function. Use vitamins B2 and B6, magnesium, and DMG and its co-nutrient, vitamin B12, before buying SAMe. To provide the necessary methionine, get some protein into the kid!

 

Use of betaine hydrochloride, as recommended herein, produces HCl to aid digestion, and the betaine released is TMG. Additional folic acid supplementation may be necessary because TMG, in reducing to DMG, causes an excretion of folate, and its deficiency causes hyperactivity. The piddling amounts of folic acid in some TMG formulations may not be adequate to avoid depletion of folate resulting in hyperactivity in the Subset that needs folate. Dr. Bernard Rimland’s experience indicates a need of two, 800 mcg folic acid tablets with each 125 mg tablet of DMG to overcome this hyperactivity. For the overmethylated subset, TMG/DMG is contraindicated. Use of TMG by the undermethylated subset does significantly reduce homocysteine by methyl donation in becoming DMG, but additional vitamins B6 (200 to 500 mg) and B12 (500 to 1000 mcg, preferably as sublingual tablets) are probably needed to metabolize homocysteine.

 

“Some people take large doses of vitamin B12 in an effort to relieve stress, increase their energy level or cure pernicious anemia. But this practice may also deplete their melatonin supply. In a 1992 Japanese study, nine healthy men were given three daily doses of vitamin B12 for a total of 3 milligrams a day. Vitamin B12 caused a significant decrease in their average twenty-four-hour melatonin levels.”— “Your Body’s Natural Wonder Drug: Melatonin”, by Russel J. Reiter, Ph.D., and Jo Robinson.

 

Folic acid deficiency can be caused by use of Depakote™, Tegretol™, aspirin, Pepcid®, methotrexate, Dilantin™, Zantac®, oral contraceptives, and 21 other commonly used drugs. Genetically, some simply need more folate than others. Just as DMG/TMG consumes folic acid, and that causes hyperactivity, these drugs can do so also. Folic acid deficiency symptoms include: harm to DNA that causes abnormal cellular development, especially in those with the most rapid rates of turnover (red cells, leukocytes, and epithelial cells of the stomach and gut, vagina, and uterine cervix). There will be birth defects (Spina bifida, cleft lip and palate, small head, and possibly Down’s), cervical dysplasia, elevated homocysteine leading to heart problems (and that affect the fetus and its future development), increased osteoporosis, headache, fatigue, hair loss, anorexia, insomnia, diarrhea, nausea, and increased infections. Studies have shown that taking a larger dose of folic acid (up to 4,000 micrograms) at least one month before and during the first trimester may be beneficial. Folic acid is necessary for the production of red blood cells, thus a deficiency can result in anemia leading to tiredness, weakness, diarrhea, and weight loss. In today’s world, adults should consider supplementing 800 mcg of folic acid, but “supplementation of 800 mcg of folic acid will harm 15% of the population, and probably will result in increased incidence of anxiety disorders, OCD, eating disorders, and suicide”—Dr. Wm.Walsh. These are natural sources of folic acid: green leafy vegetables, nuts, beans and citrus fruits. It’s also found in many fortified breakfast cereals (watch serving sizes) and some vitamin supplements. These will not yield their treasures unless cooked with butter or served with olive oil!

 

Pfeiffer Treatment Center found that more than 45% of children with autism are undermethylated with high histamine. An indeterminate percentage, with poor protein intake or malabsorption will have low levels of L-histidine and low histamine, yet are undermethylated, bringing that to well over 50% that are undermethylated. This is related to DPP-IV impairment and to disturbed sulfur metabolism. Increases in certain inflammatory markers, such as IL-6 and TNF(a), lead to decreases in methylation. Low levels of serotonin, dopamine, and norepinephrine, high, whole-blood histamine, and elevated, absolute basophils characterize this condition. This population has a high incidence of seasonal allergies, OCD tendencies, oppositional-defiant disorder, competitiveness, perfectionism, high libido, sparse body hair, seasonal depression, and several other characteristics. They have a genetic tendency to be very depressed in calcium, magnesium, methionine, and vitamin B6 with excessive levels of folic acid. “Folate trapping” occurs when hydroxycobalamin (B12) is deficient in the presence of adequate methyl-tetrahydrofolate. When this situation occurs, the methyl group on methyl-tetrahydrofolate is trapped because “it wants to leave (to become tetrahydrofolate) but can’t get away”. From then on, folate no longer is able to participate in its metabolic pathways, and megaloblastic anemia results. Large doses of supplemental folate can bypass the folate trap, and megaloblastic anemia will not occur. However, the neurologic/psychiatric abnormalities associated with B12 deficiency ensue progressively. In fact, folic acid administration may cause neuropathy in patients with latent or overt pernicious anemia if these patients are not receiving vitamin B12. So, it would seem that the undermethylated would definitely need vitamin B12 to alleviate this condition.  Of interest is that only 400 mcg to 800 mcg folic acid is necessary for adults to reduce homocysteine.

 

Additionally, a subacute degeneration of the brain and spinal cord can occur by the demyelination of nerve sheaths caused by a folic acid or vitamin B12 deficiency. In a study published in the Journal of Inherited Metabolic Diseases (1993;16(4):762-770), it was shown that some people have genetic defects that preclude them from naturally producing methylcobalamin (B12). The scientists stated that a deficiency of methylcobalamin directly caused demyelination disease in people with this inborn defect. Since demyelination is one concern for a large segment of autism, it is probably wise to supplement vitamin B12 in the form methylcobalamin. Regular vitamin B12 will convert to Methycobalamin in presence of adequate SAMe. It should be noted that vitamin B12 is essential in synthesizing essential fatty acids needed in myelin. “Vitamin B12 deficiency is widespread—nearly 40% of the US population may be lacking. A vast majority of these people are completely unaware of their deficiency. Although age can have an effect, lifestyle choices are by far the biggest factor in this condition”—Dr. Joseph Mercola.

 

A correction: “My previous message was written hurriedly & contained TWO errors. The message should have stated: ‘Our assessment of a patient’s methylation status includes (1) analysis for whole blood histamine, (2) a special absolute basophil test, (3) review of symptoms and medical history, and (4) a physical exam. Overmethylated children react very badly to methylating agents. They generally exhibit LOW blood histamine and LOW basophils. Also, most exhibit distinctive symptoms associated with methylation disorders, and this greatly aids the diagnosis process. Classic symptoms of overmethylation include severe food/chemical sensitivities, anxiety, emotionalism, depression, hyperactivity, absence of seasonal allergies, etc.’”—Email 12/20/02 from Dr. Wm. Walsh. Many overmethylated patients have too much dopamine and serotonin activity. An overload of Fe+++ (iron) would be expected to aggravate this condition. Such patients thrive on folate/B12 therapy. Zinc deficiency results in impaired absorption of folic acid, so they will likely need a zinc supplement. Elevated copper/zinc ratios can be especially serious for persons with low blood histamine. This combination of imbalances has been associated with anxiety, panic disorders, paranoia, and (in severe cases) hallucinations.

 

Speaking of genetics, most think anything genetic is set in stone and bound to happen. The truth is, it is a tendency at best, and usually takes a trigger to cause it to manifest. Hudson Freeze, a professor of glycobiology (the study of glyconutrients) at the Burnham Institute in La Jolla, California is grappling with a different kind of childhood disease, even more rare than neuroblastoma but just as deadly. It takes at least 50 genes to make and tailor a typical sugar-protein chain (glycoprotein), Freeze notes. The failure of even a single gene to function properly can be problematic, even catastrophic. Resulting ailments include low blood sugar, blood-clotting problems, seizures, failure to thrive, gastrointestinal (vomiting, diarrhea), delayed psychomotor development, neurological dysfunction, and mental retardation. Additionally, it takes many different enzymes and ATP energy molecules to make those many steps successfully. Many things can intervene along the way. Marked changes in glycoprotein synthesis have been observed in vitamin-A deficiency.

 

Freeze keeps photos of his patients pinned to his computer and laboratory shelves. One shows a smiling, young-German boy suffering from a form of Carbohydrate-deficient Glycoprotein Syndrome (CDGS) that does not cause mental retardation. Doctors were flummoxed by the boy’s symptoms: low blood sugar, protein loss through the intestines, and a general “failure to thrive”. They stumbled upon a treatment when they prescribed adding a sugar called mannose to his diet. The boy’s symptoms disappeared over the next few months. Addition of mannose to culture media containing fibroblasts from CDGS patients with mannose-deficient oligosaccharides resulted in correction of the deficiency in vitro, consistent with the direct utilization of mannose by fibroblasts for the synthesis of mannose-containing glycoproteins. Studies in humans have shown dietary mannose is preferentially utilized to synthesize glycoproteins. Radio labeled mannose is directly incorporated in serum glycoproteins in healthy, human subjects ingesting different dietary amounts of the sugars. Between 1 and 8 hours after ingestion, radiolabel mannose in glycoproteins increased 2- to 6-fold in liver, lungs, skeletal muscle, and heart—Berger V, Perier S, Pachiaudi C, et al.; Dietary specific sugars for serum protein enzymatic glycosylation in man. Metabolism 1998; 47(12):1499-1503.

 

A healthy body can break down plant carbohydrates, restructure them into small sugars, and then use those sugars to build the glycoforms required for accurate cellular communication and resultant good health. Enzymes are the tools the body uses to build the “glyco” portion of glycoforms. These enzymatic conversions are complicated and require not only the presence of the needed enzymes, but specific vitamins and minerals as well. For example, fifteen enzymatic conversions are required to change galactose to fucose. Each enzymatic reaction requires ATP energy molecules that are often lacking in many chronic conditions, thus the conversion is not made. Additionally, these five amino acids, threonine, asparagine, serine, glycine, and hydroxyproline, are needed to link with these carbohydrates to form glycoproteins that are necessary for immune function and blood globulin formation. (These amino acids are often deficient. Yet, as indicated, when dietary mannose was supplied, there was a 2-to-six fold increase in glycoproteins! WSL.)

 

Changes in carbohydrate structures on cell surfaces have been shown to be characteristic of many disease conditions. A 1998 review addressed the association of many cancers with changes in glycoconjugates. Cancers in which such changes have been noted include leukemia and intestinal, pancreatic, liver, ovarian, endometrial, prostate, urinary tract, lung, and breast cancers. Diseases that have been clearly related to deficiencies in the ability of cells to synthesize glycoproteins include leukocyte adhesion deficiency, hereditary erythroblastic multinuclearity with positive acidified serum lysis test, and carbohydrate-deficient glycoprotein syndrome. Cystic fibrosis and inflammatory diseases, such as rheumatoid arthritis, osteoarthritis, ulcerative colitis, and Crohn’s disease all are associated with alterations in glycoforms. Some blood-related and vascular disorders, including many diseases of the cardiovascular system, exhibit abnormal glycoproteins.

 

Another 1998 paper looked at studies that attempted to correct faulty glycoconjugate metabolism by directly administering the necessary sugar through diet. This paper cites a case in which a patient was successfully treated with dietary supplement therapy of the sugar, mannose. The authors stated, “. . . the finding that mannose, but not glucose, corrected glycosylation. . . was surprising. . . Mannose offers an attractive therapy because it should be easy to administer and is nontoxic. . .There is scant information on the availability of mannose in food, but dietary mannose is probably insufficient to supply all glycosylation.” The authors continued, “Human and animal ingestion studies show that mannose is readily absorbed, elevates blood mannose levels by 3- to-10-fold, and is cleared over several hours. Some of the mannose in the studies was incorporated into glycoproteins, especially those made by the liver and intestine, and mannose was also found on glycoproteins in the brain and in the fetus”. The authors concluded: “It is likely that mannose is actively transported in the intestine and kidney”.

 

We now know that carbohydrates are fundamental to health in far more important ways than simple energy production. Carbohydrates act as recognition determinants in cell-cell communication and, as such, they are vital to every aspect of human health. “Almost without exception, whenever two or more living cells interact in a specific way, cell-surface carbohydrates will be involved.”

 

Glyconutritional supplements are designed to make the necessary sugars available to the cells more quickly and in greater quantity. The more substrate provided, the fewer steps the enzymatic conversion system has to take and the more the system functions at optimal capacity—Excerpts from Dr. Reg McDaniel’s paper presented to an invitation only group at the U.S. Patent Agency. Complete paper available on request.

 

It is interesting to note that the essential sugar, galactose, removed from the diet when casein free, is recognized to increase the expression of the DPP-IV gene, and thus to increase the amount of DPP-IV in the mucosal membrane of the intestinal tract according to Dr. Mark Brudnak, Ph.D., N.D. This is the enzyme needed to break down casein and gluten, yet we reduce it when we remove milk! Galactose can be found in figs, grapes, peas, tomatoes, hazelnuts, beans, and pectin supplements. It is further interesting to note that there are receptor sites for mannose throughout the body and brain, particularly lining the entire gastrointestinal tract. Among other things, mannose activates macrophages enabling them to more efficiently break down cell walls of invaders to better identify them and thus alert the immune system. These 10 vital sugars must be supplemented. The body cannot make enough for optimal health from glucose and galactose.   

 

Mannatech™ has documented records of 45 genetic conditions whose symptoms of physical and mental malfunction have disappeared using the only patented combination of a stabilized, standardized form of mannose and other glyconutrients, including galactose. Genetics are not set in stone. Information is available on request to WillissL@aol.com.

 

The compounds benzoate and hippurate, as measured in urine, have been markers of intestinal bacterial overgrowth, but they can convey additional information. Using a major hepatic detoxification pathway, benzoate is conjugated with glycine to form hippurate. This detoxifies benzoic acid, but glycine also detoxifies phenols, and individuals with up-regulated hepatic detoxification pathways are frequently depleted in glycine. This situation will be reflected as an elevation of benzoate without concurrent elevation of hippurate. Intestinal dysbiosis with weakened mucosal epithelium is a common reason for toxemia and the resulting up-regulation of the hepatic pathways (primarily Phase I). This loss of glycine would interfere with glutathione production (opioids have been shown to decrease hepatic glutathione also), down-regulating Phase II, and lead to an excess of cysteine probably. This lack of glutathione would tend to hypothyroidism among many other things. The upregulation of the detoxification pathways (especially Phase I) will deplete the body of many needed substances, and render many drugs ineffective. This is why one must be very careful about using such herbs as milk thistle, ginkgo biloba, angelica, coltsfoot, fo-ti, licorice, bistort, bupleurum capsicum, ginger, Pau D’Arco, royal jelly, and sheep sorrel, all of which up-regulate Phase I liver detoxification. Glycine supplementation, along with the B-complex vitamins, particularly vitamin B6, can relieve the hepatic pathway demand for glycine, and probably enhance glutathione production—reducing cysteine levels and contributing to proper thyroid function. Some individuals have an inborn error of glycine metabolism, which means increased glycine intake can result in elevated glycine levels in the blood that manifest themselves as severe mental retardation in infants susceptible to this condition. This is a very rare, metabolic problem, but it should be evaluated in any individual who is going to be supplemented with glycine (DMG/TMG).

 

 

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