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Autism and Protein Deficiency

Many recent studies have confirmed that all types of autism involve a malfunction in the part of the body's system that deals with metal regulation (1).

It has also been observed that the digestive system of these children does not work well (2).

How are these two problems related? How can we solve this problem?

Certain metals such as iron, zinc and copper, are essential to the body, others such as cadmium, mercury, aluminum and lead are toxic. Too much or too little of any metal in the body will have a disrupting effect on the system. Not everything is understood about metal metabolism, but more studies are being done all the time that show the body's use of certain metals to have significant effects on the health of the entire system. Recent autism studies have focused on a certain metal binding protein, metallothionein (MT). MT is a biologically essential protein that has been shown to be heavily involved in the metal regulation of zinc, and copper as well as the chelation of toxic metals such as cadmuim, mercury and lead. MT proteins also assist in immune function, neuronal development, are heart protective, brain cell protective, involved in liver cell proliferation, the absorption and of nutrients in the small intestine, the breakdown of certain dietary proteins, cellular respiration, neuronal development, energy metabolism and have antioxidant properties(3).

Studies show that MT does not function properly in autistic children, although it is still unclear whether this is due to genetic factors or simply low levels of MT in the system (4).

Metalloththionein (MT) is a single chain protein. There are four kinds of MT. MT I and II are found all over the body, MTIII is found in the brain (mostly in the neurons of the hippocampus) and MT IV is manufactured in the GI tract. MT contains 61 amino acids, total, 20 of which are the sulfur containing essential amino acid, cysteine. MT has seven binding sites for metal in two core clusters. The principle metal binding ligands for these sites also contain cysteinal residues showing that a huge component of the MT metal regulating system is the essential amino acid, cysteine. The entire MT is composed of sulfur and protein (5).

Remember also that essential amino acids cannot be made by the body, but must be obtained in the diet. One of the problems identified with autism is a digestive system that cannot fully break down all protein into its basic components, the amino acids, and the system will only use amino acids to make systemic protein. This means that many necessary amino acids are unavailable to make systemic proteins such as MT (6).

Studies have proven MT to have an affinity for zinc and an even stronger affinity for cadmium, which will bind very much more strongly to the metal binding sites on MT (cadmium has a half-life of ten years in the body)(7).

Zinc is an essential metal. Adequate amounts of zinc are necessary for proper immune function. 90% of the body's zinc stays in the muscle and has a very slow rate of turnover, the remaining 10% is extremely metabolically active and very sensitive to changes in the levels of dietary zinc. Diabetes studies showed hypoglycemia and insulinemia to improve when cellular levels of zinc in mice were raised, whereas removing zinc from the diet worsened these conditions. It takes only 48 hours for all the zinc in the liver, a key area of zinc metabolism, to exchange with the zinc in the blood plasma. Zinc is also part of the make-up of over 300 enzymes and hundreds of zinc binding proteins. It is used in many of the body's systemic protein interactions as well as in the synthesis of the hormone melatonin and its precursor, seratonin, and it facilitates the proliferation of liver cells and has antioxidant properties when it is bound to the MT protein. Studies have shown that patients with depression, bipolar disorder, Parkinson's disease, Alzheimer's, and autism are have severe zinc imbalances (8).

Studies also show that children with autism are often overloaded with toxic metals, as well as zinc deficient and with MT proteins that don't function properly.

The presence of glutathione is critical for the healthy regulation of zinc in the body. In order for the MT system to work optimally, glutathione (a sulfur rich tripeptide) must be present in both a reduced (GSH) and oxidized (GSSG) state. GSH binds the metal to the MT while GSSG releases it. The ratio of both (GSH:GSSG) within the cell is called the redox ratio of the cell, a healthy redox ratio is between 30:1 and 100:1. (The redox potential of a substance is the likelihood of it undergoing this reduction-oxidation transformation, for instance, zinc has no redox potential at all) However, glutathione disulfide (GSSG) is also very necessary, while GSH enhances both the rate of zinc transfer and the number of zinc atoms released for cellular use, in the absence of GSSG, zinc release becomes much more inhibited (9).

A well-balanced redox ratio is important. For instance, in the case of the body being under high levels of oxidative stress, as is suspected in many autism cases, the GSSG levels rise causing, a condition where too much zinc is released from the MT this leads to the over inhibition of certain processes such as, cellular respiration and the inhibition of certain enzymes in energy metabolism. (10).

Studies also show that when the metal levels are high glutathione levels are reduced.(11)

In order for GSSG to be recycled into GSH there must be adequate amounts of the proper redox enzymes available and as you know, enzymes are made of systemic protein Could it be that not enough systemic protein is available for autistics to make the proper redox enzymes?

glutathione and autism

The structure of glutathione (GSH) is composed of the amino acids (AA) glutamic acid, glycine and once again, that sulfur containing essential amino acid, cysteine. Studies show autistic children to be deficient in glutathione.(12)

When toxic metals such as mercury and cadmium enter the system, MT will attempt to sequester the toxic material, this process requires zinc and GSH. If there is not enough MT, the body will make more if it can. (13)

MT manufacture requires sufficient amounts of: cysteine, serine, lysine, argenine, alanine, lysine, valine, aspartic acid, asparagine, glutamic acid, glutamine, proline, threonine, and methionine (also a sulfur containing amino acid). Exactly half of these are essential amino acids, and one-third of the total number of AAs is made up of the sulfur-rich cysteine. In order for the MT system to works properly the body must have available adequate cysteine (14)

Are autistic children deficient in amino acids?

Both glutathione and MT contain large amounts of sulfur. Sulfur is an essential mineral that is necessary for many systemic functions. Because of the condition of our soil today our main source of organic sulfur, plant food, is compromised. Besides the metal regulation functions that it performs, sulfur is needed for pancreatic release of digestive enzymes and if it is not present in the ileum of the intestine, then leaky gut will ensue. (15).

Sulfur is necessary for many enzyme reactions as well as modulation of the nervous system, maintenance and protection of the connective tissues, insulin production and support of the liver detoxification Phase II pathway . Sulfur, along with molybdenum, fuels the process that detoxifies certain food additives that may otherwise cause allergic reaction. Sulfur containing amino acids (SAA) are cysteine and methionine. (Studies also show that morbidity in HIV patients is decreased with increased SAA consumption. Methionine in particular has been shown to decrease symptoms in Parkinson's Disease and pancreatitis ) Methylsulfonylmethane (MSM) is a safe and effective form of organic sulfur(16).

Autistic children have been identified with high toxic metal levels, low levels of MT, MT systems that don't work, low levels of glutathione and zinc, low levels of sulfur and malfunctioning digestive systems (including leaky gut and food allergies). Various different theories for the cause of these malfunctions are proposed: genetic predisposition, pre- and postnatal nutritional deficiencies, possible toxic effects of infant immunizations, heavy metals exposure, and other environmental factors. However this condition came about, the challenge remains to somehow enable these impaired systems to function normally (17).

The functioning of any person's system will improve when it has adequate systemic protein.

Current therapies for autistic children involve zinc, amino acid and glutathione supplementation. The amino acid supplementation is usually protein specific. For instance, MT is one of the proteins in which autistic children are deficient, leaving them open to metal toxicity. Therefore, one therapy administers the 14 different amino acids in MT along with GSH are given orally to the patients in an effort to raise levels of body's metal regulation system(18).

The problem with oral GSH supplementation is it is just not very effective (19).

Glutathione and MT are systemic proteins and the best way to get the body to manufacture these is to enable it to fully digest its food, then it will create the proteins it needs, where it needs them, when it needs them.

Recent studies indicate that the digestive systems of autistic children do not fully break down food. Autistic people also show low levels of secretin and one of the current popular theories is that orally administering this hormone could clear up the poor digestion issues that are characteristic of autism. The digestive system is supposed to secrete this hormone when the stomach empties. It helps the stomach to produce digestive enzyme (pepsin), the pancreas to produce alkaline digestive fluids, and the liver to produce bile. However, there has only been one very small study (three children) demonstrating the successful use of this hormone with autism and it is unknown whether supplementation of this hormone over long periods of time would be harmful to the body(20).

The action of secretin is to flush digestive enzymes from the pancreas (21).

If there are inadequate amounts of digestive enzymes available to flush, how is secretin helping?

Could it not be possible that the main problem in autism is a critical deficiency of systemic protein and sulfur in general? Secretin is a systemic protein. It is a polypeptide consisting of 27 amino acids. MT is a low molecular weight protein consisting of 61 amino acids, glutathione is a tripeptide, and sulfur is an essential mineral. In order for the proper components to be available for systemic proteins such as MT, glutathione and secretin, dietary protein must be completely broken down into amino acids. If this does not happen, the partially broken down proteins will simply irritate the system resulting in conditions such as diarrhea and allergic responses such as rashes, inflammation, and mood disorders. (Partially broken down peptides putrefy in the system producing indican which is easily identifiable using the Urinary Indican Test) Partially broken down protein is not the same as amino acids and the body will not use it to make systemic protein. A body that cannot properly break down food will become protein deficient. If this protein deficiency continues then systemic malfunction will eventually occur. If food can be fully broken down then the systemic proteins will be available to create and support systemic proteins of all sorts.

Another piece of the autism puzzle that seems to be missing from the research is the concept of the limiting amino acid. This is a concept that has been applied years in agriculture successfully but we do not use it often in human nutrition. According to Donald Snyder, Ph.D, "In every native protein there is a particular essential amino acid that limits that protein's value to the overall diet. Once that limitation (minimum requirement) is met or exceeded, another amino acid becomes limiting and so on until there is derived a theoretically perfect balance of amino acids for optimal growth and performance. Further supplementation will not improve the diet." (22).

In other words essential amino acids must be given in a properly balanced ratio in order for them to be safe and effective. This means the excess of one essential amino acid can hamper the absorption of other AAs. Therefore it would be necessary for any AA therapy to be sure that their amino acid supplement was balanced so that the body could effectively use it. If the body is not digesting its dietary protein it is because the pancreas is not producing the necessary digestive enzymes Dr. Brice Vickery addressed this problem in the early 1980's when he found that all his patients with degenerative disk disease were also deficient in systemic protein and organic sulfur. After years of testing, Dr. Vickery solved the problem of the limiting amino acid that renders so many other amino acid blends ineffective or, especially in the case of cysteine, dangerous. He produced a perfectly balanced blend of essential amino acids (Platinum Plus Essential Amino Acids, US Patent 6,203,820) that actually enable the digestive system to produce the required enzymes to break dietary protein into amino acids. Vickery recorded that in ten to twelve hours of taking Platinum Plus his patient's spinal disks began to heal. This was proven through countless MRI's and CAT Scans. Further testing showed that combined with a certain program of use (The Vickery Protocol) Platinum Plus enabled the body to manufacture systemic proteins, which actually boosted the immune system to the point that it could heal other imbalance and disease conditions as well(23).

Heavy Metal Poisoning

Vickery added extra organic sulfur and molybdenum to his blend to support phase II liver detox pathways, helping the body to flush toxins such as heavy metals out of the system. Attached charts show how quickly Platinum Plus Essential Amino Acids enable the system to completely flush mercury, lead, and aluminum from the body.

Fibromyalgia

Vickery's testing showed all Fibromyalgia patients to have five common conditions, regardless of their symptoms:

  1. protein deficiency
  2. degenerating spinal disks
  3. sulfur deficiency
  4. heavy metal toxicity
  5. viral infection

When they follow the Protocol their bodies are able to heal.

Liver Disease

If the liver does not have adequate amounts of systemic protein it cannot make body fluid regulators like albumin, it cannot make repair proteins used by the blood, and it cannot keep up its two-phase detoxification system that the body uses to filter and clean the blood. These two pathways also require glutathione and molybdenum, respectively to work properly. If the body cannot supply these things, the liver becomes susceptible to disease. Vickery's research has shown Platinum Plus to allow the liver to heal itself of diseases such as hepatitis and start functioning normally again.

Hypoglycemia

Protein deficiency can also lead to hypoglycemia (as well as vice versa.) If amino acids are not available in sufficient quantities to manufacture the enzymes needed for gluconeogenesis and glycolysis, then blood sugars will remain low after pancreatic release of insulin. Proteins also transport the vitamins needed both of these processes. Platinum Plus blend allows the body to produce the systemic protein it needs to help maintain blood sugars at an optimal level.

Various viruses and bacteria

The body's immune system is also made up of various important systemic proteins. A lack of these proteins will lead to a weakened immune system that is less able to protect the body from viruses and bacteria such as staph, strep and hepatitis. Vickery's research shows that when the body has adequate protein it can fight off these invaders and keep them away.

Glutathione, MT and secretin are all systemic proteins, which the body will make itself if given adequate amounts of amino acids and co-nutrients. The Vickery Protocol provides a balanced blend of amino acids, sulfur and molybdenum, along with the necessary CO-nutrients to allow the body to heal its digestion, rebuild its immunity and balance its systems. Autism shows a remarkable resemblance to the protein deficiency cases that The Vickery Protocol has successfully helped. Dr. Vickery is currently following several autistic patients who appear to be using his Program with considerable success.


References:

  1. Walsh, W. Ph.D."The Doctor's Corner: Unlocking the Mysteries of Autism." 2002
  2. Walsh, W. Ph.D., "Mettalothionein Deficiency in Autism Spectrum Disorders" 2002
  3. Converse, Judy, "Diet, Supplements and Autism Spectrum Diagnosis:Is There Theraputic Value?," April 1, 2002
  4. McGuinnis, Woody, "Treatments, Bradstreet, Jeff, "Extra", Summary Of Defeat Autism Now, October 2001 Conference
  5. Andrews G.K., "Regulation of Metallothionein Gene Expression by Oxidative Stress and Metal Ions," Biochem Pharmacol 2000 Jan.1;59(1): 95-104
  6. Zijan Guo, Weiqing Zhong and Peter J. Sadler, "Metals in the Brain," RSC Education and Professional Development
  7. Ye, Bin, Maret, Wolfgang, and Vallee, Bert, L., "Zinc Metallothionein imported into liver mitochondria modulates respiration," Proclamation of the National Academy of Sciences of the USA, 2001 Feb. 27; 98(5): 2317-2322
  8. Chung, RS, Vickers, JC, Chuah, MI and West, AK, "Metallotionein-IIa promotes initial nuerite elongation and post injury neurite growth and facilitates healing after focal cortical brain injury," J. Neuroscience. 2003 April15; 23(8) 3336-3342. Appendix A: Background information for lead
  9. Gunes C, Huechel R, Georgiev O, Heinz-Mueller K, Lichtlen P, Bluthmann H, Aguzz A, and Shaffner W, "Embryonic lethality and liver degeneration in mice lacking the metal transcriptional activator MTF-1," The EMBO Journal, Vol. 17, No.10, pp.2846-2854,1998.
  10. Zhou, ZB et al, "Effect of Zn metallothionein on oxidative stress in liver of rats with severe thermal injury," Acta Pharmacol Sin, 2003 August; 24(8) 764-770.
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  12. Converse, Judy, "Diet, Supplements and Autism Spectrum Diagnosis: Is There Theraputic Value?," April 1, 2002
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  15. "Doctor Issued Patent on Biomarker Linking Autism, Add, and ADHD." PR Web March 20, 2003.
  16. Braithwaite, Stephen, "Investigation into Possible Exogenous Peptides", POSTER PRESENTED AT Durham Conference by University of Sunderland Autism Research Unit, 1995
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  18. Reichelt, Karl, Ph.D., "Opiod Peptides," Summary of Defeat Autism Now, Oct. 2001 Conference
  19. Tabrizian, Igor, MD, "Everything you wanted to know about molecular medicine but were afraid to ask," Nutrition Review Service, 2001.
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  23. Walsch, William et al, "Disordered Metal Metabolism in a Large Autism Population," Presented at the APA Annual Meeting, New Orleans, May 2001.
  24. Jiang LJ et al, "The glutathione redox couple modulates zinc transfer from metallothionein to zinc depleted sorbitol dehydrogenase." Proc Natl Acad Sci USA. 1998 Mar.31 ; 95(7):3483-8
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