Comprehensive Guide to Managing Autism - 14

Solutions to the Problems

Olfactory and gustatory symptoms of psychiatric patients 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 leads to an impairment of vitamin A metabolism, as well as to an inhibition of prostaglandin synthesis from essential fatty acids, either by blocking linoleic acid desaturation to gamma linolenic acid, or by inhibiting the mobilization of dihomo-gamma-linolenic acid from the tissue membrane stores. Zinc and vitamins B₃, B₆, biotin, and C are necessary for the conversion of essential fatty acids to PgE1 (prostaglandin E1) 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 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. 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. 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, 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. 

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. 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.  

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, 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 and mercury, and adequate levels are required to balance the adverse effects of these toxic metals 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. 

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 Alpha Phosphatase (alk phos) reading for a lack of this zinc dependent enzyme means you need zinc. The commercial zinc tablets are particularly painful for many because free zinc binds to already damaged mucosal cells directly. The zinc drops then are preferable. Consult with your medical professional about this possibility. In the case of pallor, check for anemia and low thyroid activity also. Iron deficiency anemia is often the first sign of hypothyroidism. 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 anemia. Zinc and selenium 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. These 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 (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 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.  

While the branched-chain aminos are usually deficient, Maple Sugar Urine Disease (MSUD), that derives its name from the sweet, burnt sugar, or maple syrup smell of the urine, is caused by an excess of these aminos. 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 probably the most bioavailable way to restore zinc levels. 

Several studies have found that most children with ADHD have deficiencies of certain minerals that are commonly depleted by exposure to toxic metals, such as magnesium and zinc, 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 disorder.  

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.    

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 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 period 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. 

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. 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.  

SAM is the most important methyl-group donor in cellular metabolism. It is known to be utilized in synthesis of carnitine, CoQ10, creatine, methycobalamin, 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 is a cofactor in a number of critical biochemical reactions and is 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 five specific nutritional supplements. The combining of ATP (the energy molecule) and magnesium with methionine produces SAMe, and the combination of vitamin B₆, folic acid, vitamin B₁₂, and Trimethylglycine (TMG) that actively combats high homocysteine levels also produces SAM. In this chain reaction, 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 beneficial amino acid products. Not only does this combination of TMG, B₆, folic acid, and B₁₂ greatly improve your health and well being, it also saves you money. These nutrients produce SAMe and DMG naturally at a fraction of the cost of the commercial pharmaceutical substitutes. It is of interest to note that The Pfeiffer Treatment Center found that 45% of children with autism were undermethylated with high histamine, and need TMG, but not folic acid; whereas 15% were overmethylated with low histamine, and do not do well on TMG. These need folate. Expressed differently, if TMG/DMG makes the child hyperactive, he needs folate to balance the TMG/DMG, or perhaps, he needs to reduce or discontinue the TMG/DMG because it is overmethylating, and supplement glycine instead.   

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 formation. Benefits of DMG/TMG 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 TMG and its co-nutrients, folic acid and vitamin B₁₂, before buying SAMe. Magnesium and TMG both produce SAMe when adequate methionine is present. Get some protein into the kid!  

Dr. Shattock of England (a pharmacist) and others suggest that TMG is a higher priced Betaine hydrochloride long used to improve digestion and utilization of foods. The manufacturer denies this, but in any case, use of betaine hydrochloride, as recommended herein, produces HCl to aid digestion, and the betaine released is TMG. Additional folic acid, vitamin B₆ and B₁₂ supplementation may be necessary because TMG reduces to DMG that causes an excretion of folate, and its deficiency causes hyperactivity. The piddling amounts of folic acid, Pyridoxine HCl (B₆), and cyanocobalamin (B₁₂) in some TMG formulations is probably not adequate to avoid depletion of folate resulting in a homocysteine buildup and hyperactivity. Dr. Bernard Rimland’s experience indicates a need of two, 800 mcg folic acid tablets with each 125 mg tablet of DMG. TMG does significantly reduce homocysteine by methyl donation in becoming DMG, but additional vitamin B₆ (200 to 500 mg) and B₁₂ (500 to 1000 mcg, preferably as sublingual tablets), and folic acid (1600 mcg per each DMG) is probably needed. TMG/DMG, which is supposed to reduce hyperactivity, produces hyperactivity without the folate, vitamin B_6, and B₁₂. Got that? :-). 

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 than others. Use of DMG/TMG requires a greater intake of 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, cervical dysplasia, elevated homocysteine leading to heart problems, increased osteoporosis, headache, fatigue, hair loss, anorexia, insomnia, diarrhea, nausea, and increased infections. 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 supplement 800 mcg of folic acid.  

“A small percentage of autistic spectrum patients have methylation defects due to deficient methyl groups. The Autism Research Institute, San Diego, has in the past advocated DMG for all autistic spectrum patients. The methylation defect, when present, can cause a defect in sulfation. However, this is measurable, and if present, trimethylglycine (TMG—betaine) will provide more methyl groups (than DMG—WSL), and in addition, decrease the abdominal complaints present in patients with such deficiency.”—Dr. Hugh Fudenberg. Note that sulfation is a problem with the PST group of children. 

Pfeiffer Treatment Center found 15% were overmethylated which results in excessive levels of dopamine, norepinephrine, and serotonin. Typical symptoms include chemical and food sensitivities, under achievement, upper body pain, and an adverse reaction to serotonin-enhancing substances such as Prozac, Paxil, Zoloft, St. John's Wort, and SAMe. They have a genetic tendency to be very depressed in folates, niacin, and vitamin B₁₂, and biochemical treatment focuses on supplementation of these nutrients. These persons are also overloaded in copper and methionine, and supplements of these nutrients must be strictly avoided. If the child is hyper, it is likely because he is not getting enough folic acid to balance the DMG. Or, looking at it another way, he is being overmethylated by the DMG. In that case, reduce or discontinue the DMG, and add glycine. If you continue with the DMG, you must add folic acid and vitamin B₁₂.  

Pfeiffer Treatment Center found that 45% of children with autism were undermethylated with high histamine. Too much calcium entering the mast cells because of a lack of magnesium and manganese (calcium channel blockers) triggers release of histamine. An increased intake of methionine methylates, and thus detoxifies, histamine. These patients tend to obsessive-compulsive tendencies, oppositional-defiant disorder, or seasonal depression that are associated with low serotonin levels. Seventy-five percent of the undermethylated have seasonal allergies. They generally exhibit perfectionism, competitiveness, and other distinctive symptoms and traits, and often are suicidally depressed. They have a genetic tendency to be very depressed in calcium, magnesium, methionine, and vitamin B₆, with excessive levels of folic acid. These undermethylated persons may benefit nicely from Paxil, Zoloft, and other serotonin-enhancing medications, although nasty side effects are common. A more natural approach is to directly correct the underlying problem using methionine, calcium, magnesium, and vitamin B₆. SAMe, and inositol (this from Dr. Wm. Walsh). These would benefit from TMG/DMG.  

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 SAM. 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 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. 

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. He 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—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. 

“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 that ‘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 and 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! It is further interesting to note that there are receptor sites for mannose throughout the body, particularly lining the entire gastrointestinal tract. These essential sugars must be supplemented.    

Mannatech™ has documented records of 30 genetic conditions, symptoms of which have similarly disappeared using the only patented combination of a stabilized, standardized form of mannose and other glyconutrients. 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 detoxes phenols. 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. This loss of glycine would interfere with glutathione production, and lead to an excess of cysteine probably. The upregulation of the detoxification pathways will deplete the body of many needed substances, and render many drugs ineffective. This lack of glutathione would tend to hypothyroidism among many other things. Opioids have been shown to decrease hepatic glutathione. 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).