Autism

Protein Deficiency and Autism

Dr. Brice E. Vickery
©2007 SuperNutrient Corporation

Autistic children have been identified with high toxic metal levels, low levels of metallothionein (MT), metallothionein (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, nutritional deficiencies in pregnancy or the toxic effects of infant immunizations. However this condition came about, the challenge remains to somehow enable these impaired systems to function normally.

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. 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) which occurs in critically low levels in autistic children. MT 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, heart protective functions, brain cell protective functions, liver cell proliferation and the breakdown of casein and gluten in the small intestine.

A huge component of the MT metal regulating system is the essential amino acid, cysteine. The entire MT is composed of sulfur and protein. 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; in turn, many necessary amino acids are unavailable to make systemic proteins such as MT. Remember also that essential amino acids cannot be made by the body, but must be obtained in the diet. 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 amino acids is made up of the sulfur–rich cysteine. Both glutathione and MT contain large amounts of sulfur. Sulfur is an essential mineral (meaning that it must be acquired through diet) that is necessary for many systemic functions. Sulfur is necessary for many enzyme reactions as well as modulation of the nervous system, maintenance and protection of the connective tissues, and support of liver detoxification.

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. 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. The effect is the over inhibition of certain processes such as cellular respiration and the inhibition of certain enzymes in energy metabolism. Studies have shown that patients with depression, bipolar disorder, Parkinson’s disease, Alzheimers, and autism are severely deficient in zinc. In a healthy system, zinc is the primary metal that is bound and released by MT. In a system challenged by too much copper, cadmium, mercury or lead, these metals will compete for the MT binding sites.

Many of the current therapies for autistic children involve amino acid and glutathione supplementation. The amino acid supplementation is usually protein specific; the 14 different amino acids in MT along with GSH are given orally to the children. The problem with oral GSH supplementation is that reduced glutathione (GSH) has a very high redox potential; somewhere between the mouth and the specific site in the body where GSH is needed, it will oxidize leaving GSSG which is not helpful unless it is in proper ratio to GSH. Alpha–lipoic acid is a more effective way to get the body to produce glutathione but it tends to cause an overgrowth of unfriendly bacteria in the gut. 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.

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.

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 of three amino acids, 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 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.

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 sulfur. Years of testing produced a blend of essential amino acids that actually enable the pancreas to produce the enzymes to break dietary protein into amino acids. These amino acids then recombine into systemic proteins that not only rebuild damaged spinal disks, but when used along with the Vickery Protocol have proven to allow the body to fix many other problems as well, such as metal toxicity. 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.

At http://www.supernutrient.com , posted charts show how quickly Platinum Plus Essential Amino Acids enable the system to completely flush mercury, lead, and aluminum from the body. Use of the Vickery Protocol along with Platinum Plus will cause GSH levels to rise dramatically and all sorts of systemic proteins will become available to the system, including immune system proteins like MT and hormones like secretin.

Research: 

Fatty Acid Metabolism and Alpha XP Factor as Expressed in Autism

Fatty Acid Metabolism and Alpha XP Factor as Expressed in Autism

Dr. Brice E. Vickery
©2007 SuperNutrient Corporation

Fatty acid metabolism (FAM) is a complex process, which begins with digestion and ends with physiological regulation and energy production processes in the body. Autism has been reported as being associated with FAM:

  1. Studies have located FAM disorders ranging from maldigestion and taurine deficiency within the digestive system to beta oxidation malfunction within the cell
  2. This article will go through FAM starting in the stomach and ending in the cell, linking issues currently being investigated in autism with Alpha XP factor, critical deficiency of systemic protein in the body.

Dietary protein must be fully digested down to amino acids in order for the system to make systemic proteins such as enzymes, transporter proteins, repair proteins and binding proteins. When this digestive process stops happening, it becomes the limiting factor in a person’s ability to maintain their health. A continuing state of poor protein degradation will eventually cause systemic failure of various kinds. This limiting factor is the Alpha XP factor.

The Alpha XP Factor© was discovered in the early 1980’s by Dr. Brice E. Vickery. Clinical studies show it as the probable cause or major contributing factor to many unsolved conditions such as hypoglycemia, degenerative disk disease, chronic fatigue, fibromyalgia, arthritis, and even osteoporosis. The factor was named alpha; first, x; unknown, and P for protein, (which also means first nutrient.) Before Vickery’s discovery, doctors assumed that normal serum protein levels meant that the cells were receiving adequate amounts of amino acids for systemic protein production. Dr. Vickery found that in nine out of ten persons, this is not the case. Alpha XP is the rule rather than the exception.

Digestive system:

Major digestion of dietary fat occurs in the small intestine where it must mix with the protein lipase if it is to break down into fatty acids, which can then be used for the production of systemic fats such as phospholipids, which form the cell membrane and chylomicrons, which comprise lipoproteins such as HDL and LDL. Lipase is a protein which will quickly denature in the aqueous environment of the intestine and is protected from unfolding by other substances such as the protein colipase. Without this cysteine rich polypeptide, lipase would become destabilized by the action of bile salts and denature, becoming useless. However fat digestion also needs bile salts, which emulsify fats in preparation for their total degradation by lipase. When fats are completely broken down into free fatty acids and a mixture of mono- and diacylglycerols monoglycerolsl, they must be prepared for transport through the aqueous environment of the blood to the cells. They are absorbed into the intestinal wall where they are resynthesised back into triacylglycerols. Fats cannot tolerate aqueous environments such as blood or plasma unless the body first coats them with protein. Various types of apoproteins are manufactured in the liver and intestine that bind with these fats. The apoprotein B–100 is manufactured in the gut and binds with triacylglycerols, cholesteryl esters, phospholipids and free cholesterol to form chylomicrons (These lipoproteins reach the bloodstream via the lymphatic vessels. They pass fatty acids to adipose tissues until there are only chylomicron remnants left. These remnants are absorbed by the liver, repackaged as VLDL, and sent out to the tissues again. The VLDL loses fatty acids to tissue along the way and gradually becomes less dense becoming LDL and then HDL.) Free fatty acids are transported through the blood by the serum protein, albumin.

  1. Surveys of autistic children have found them deficient in the following amino acids: taurine, lysine, phenalalanine, methionine, cysteine tyrosine leucine, glutamine,isoleucine, and valine.
  2. Autisic children in general are found to have more essential amino acid deficiencies than control group children.
  3. The amino acid taurine, (a derivative of cysteine) is necessary for the synthesis of bile salts.
  4. The enzyme lipase contains the amino acids glutamine, leucine and lysine. If autistics don’t have enough amino acids to make lipase, how will they digest their fats?
  5. Seven of the eleven essential amino acids are necessary for the protein albumin: methionine, lysine, tryptophane, valine, phenalalanine, leucine.and arginine.(although some doctors only consider arginine to be semi-essential because it is synthesized by humans, most of it is hydrolyzed to urea and orthinine) If autistic patients are low in five of the seven essential amino acids required to make albumin, how can they make adequate amounts for fatty acid transport?
  6. Colipase is an enzyme rich in leucine and cysteine, in a segment of pancreatic colipase 112 amino acids long, all eleven amino acids were expressed with leucine expressed 11 times and cysteine 10 times. The next most frequently expressed were lysine and isoleucine. (7). If autistic patients are low in the amino acids needed to make colipse, how will their pancreatic lipase be able to function properly?
  7. Out of an Apo B100 fragment of 347 amino acids, 197 were essential amino acids, the most frequently expressed being leucine (40), isoleucine (38) and lysine(32), three of the amino acids deficient in autistic children. If autistic children have inadequate amino acids for Apo B–100, how will they make chylomicrons?

Cell:

For the most part, the body’s energy reserves are stored as triacylglycerides, which are broken down to free fatty acids and glycerol by lipases. Glycerol is metabolized by glycolosis, which occurs in the cell cytoplasm and is made up of nine reactions each catalyzed by a specific enzyme, ultimately resulting in ATP, or energy. Free fatty acids (FFAs) must get into the mitochondria in order to produce energy in the krebs cycle. First the FFAs are “activated” in the cytoplasm, which means they are converted into fatty acyl–CoAs of varying lengths. The short and medium chain fatty acids can pass directly through the mitochondrial membrane but the long chain acyl–CoAs must engage in a series of three reactions with carnitine, a special amino acid that is transported into the mitochondrial membrane by a specific membrane bound transport complex (afterwards free carnitine returns to the cytoplasm. Once fatty acly–CoA is inside the mitochondria it is ready to enter the beta-oxidation process, which produces the necessary acetyl–CoA for the krebs cycle. Beta-oxidation also requires a CoA dehydrogenase enzyme specific to the chain length of the fatty acyl–CoA (short, medium, long, or very long). Each round of B–oxidation produces 1 mole each of acetyl–CoA, NADH, and FADH2. The Acetyl–Coa then heads to the krebs cycle where it helps produce ATP.

  1. Autistic children are reported to have abnormally high levels of dietary peptides such as casein, gluten, lactalbumin ,and lactoglobulin in their systems showing that they are not breaking down their dietary protein. How will they be able to produce all the amino acids that they need to synthesize systemic proteins such as glycolytic enzymes or acyl-CoA.
  2. The acyl–CoA protein segment of the fatty acyl–Coa in the cell cytoplasm is also made up of amino acids, the sequences peppered through with essential amino acids. Studies also show that this protein is formed from lipids by enzyme activity Amino acids are needed to form these two proteins.
  3. Autistic children are frequently found to be deficient in carnitine, while new studies show that increases in carnitine levels improve FAM. If carnitine is low, how can the body produce three carnitine transport enzymes?
  4. Autistic children are frequently found to be deficient in carnitine, while new studies show that increases in carnitine levels improve FAM. If carnitine is low, how can the body produce three carnitine transport enzymes?

Fatty acids are also the building blocks of phospholipids. These are lipoproteins, which along with various membrane proteins, make up the cell membrane. Phospholipids are shown to be low in many autistic patients. The fatty acid component of these phospholipids is subject to wear and tear and so must be removed by a phospholipase enzyme. A fatty acid transferase/ligase enzyme then repairs the damaged membrane. These two enzymes have shown highly unstable activity in autism, resulting in leaky cell membranes, affecting the function of membrane proteins, causing inflammatory conditions and cell damage. Could it be that these proteins cannot work properly because the general balance of essential amino acids in the autistic body is so far off that all the other amino acids are drastically limited in their ability to perform and so proteins such as phospholipases and fatty acid transferases begin to malfunction?

Summary list of autistic symptoms suggesting Alpha XP factor:
Substance: Needed for:
Low taurine bile salts
Low glutamine, leucine lysine lipase
Low cysteine, leucine colipase
Low leucine, isoleucine, lysine apo B–100
Low methionine, lysine, tryptophane, valine, phenalalanine, leucine.and argenine albumin
Low carnetine membrane fatty acid transfer
Low LCAD cellular beta oxidation
Low leucine, lycine, LCAD
Low phospholipids cell membrane integrity
Unstable cell repair enzymes cell membrane integrity and function

The story of FAM is directly tied in with the story of protein metabolism. If dietary proteins cannot be broken down into amino acids then there cannot be adequate amounts of systemic protein to support FAM through the actions of digestive enzymes, protective protein coating, transport proteins, energy cycle proteins, and repair proteins. There are clinical studies that show if the correct balance of essential amino acids is administered, one that stays within the bounds of the essential limiting amino acid factor, then the basic protein deficiency now known as the primary unknown protein factor or the “Alpha XP Factor” can be overcome. The body’s supply of digestive enzymes picks up, and vitamin, mineral and fatty acid metabolism is supported more completely. Once Alpha XP is taken care of then the body can digest proteins down to amino acids thereby fulfilling the body’s primary need for systemic protein. The first guard against Alpha XP is adequate amounts of digestive enzyme production to fully digest dietary proteins into amino acids. When this is achieved, co–enzymes, such as vitamins, co–factors, such as minerals, and hydrophobic systemic fats, such as fatty acids have a much higher chance of working properly. Stress, illness, and aging are all precursors of Alpha XP and lead to lower and lower levels of systemic protein. Looking at the protein deficiencies and instabilities that research has uncovered in the disease, autism, it is quite plausible that Alpha XP factor may be a large part of the problem.

Research: