Autism and Protein Deficiency
by Dr. Brice Vickery
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?
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.
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
, and 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:
- Walsh, W. Ph.D."The Doctor's Corner: Unlocking the Mysteries
of Autism." 2002
- Walsh, W. Ph.D., "Mettalothionein Deficiency in Autism Spectrum
Disorders" 2002
- Converse, Judy, "Diet, Supplements and Autism Spectrum Diagnosis:Is
There Theraputic Value?," April 1, 2002
- McGuinnis, Woody, "Treatments, Bradstreet, Jeff, "Extra",
Summary Of Defeat Autism Now, October 2001 Conference
- Andrews G.K., "Regulation of Metallothionein Gene Expression
by Oxidative Stress and Metal Ions," Biochem Pharmacol 2000 Jan.1;59(1):
95-104
- Zijan Guo, Weiqing Zhong and Peter J. Sadler, "Metals in the
Brain," RSC Education and Professional Development
- 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
- 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
- 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.
- 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.
- Fischer, E. and Davie E., "Recent excitement regarding metallothionein,"
Proceedings of the National Academy of Sciences of the USA, 1998 March31;
95(7): 3333-3334.
- Converse, Judy, "Diet, Supplements and Autism Spectrum Diagnosis:
Is There Theraputic Value?," April 1, 2002
- Walsh, William J,Ph.D. "Metallothioneun Deficiency in Autism
Spectrum Disorders" Pfeiffer Treatment Center, Illinois, 2002.
- "Human Protein Po4733-Metallothionein-IF (MT-IF) (HQPO376) Bioinformatic
Harvester
- "Doctor Issued Patent on Biomarker Linking Autism, Add, and ADHD."
PR Web March 20, 2003.
- Braithwaite, Stephen, "Investigation into Possible Exogenous
Peptides", POSTER PRESENTED AT Durham Conference by University
of Sunderland Autism Research Unit, 1995
- Journal articles regarding autism, food allergy, gastrointestinal
abnormalities, gluten, dairy, and the effects of the opiate properties
of milk and wheat. Live journal.com 2003-10-26
- Reichelt, Karl, Ph.D., "Opiod Peptides," Summary of Defeat
Autism Now, Oct. 2001 Conference
- Tabrizian, Igor, MD, "Everything you wanted to know about molecular
medicine but were afraid to ask," Nutrition Review Service, 2001.
- Beisel, William R, "Zinc and the Immune system," Department
of Molecular Biology and Immunology, Johns Hopkins School of Hygiene
and Public health, DOI:10.1006/rwei 1999.0636
- "Zinc and health: Session V, Zinc and the Central Nervous System"
Office of Dietary Supplements, national Institute of Health, 2004
- Mendez-AlvarezE et al, "Effects of aluminum and zinc on the oxidative
stress caused by 6-hydroxydopamineauto-oxidation: relevance for the
pathogenesis of Parkinson's disease," Biochem Biophys Acta
2002 march 16; 1586(2): 155-68 (antioxidant effects of zinc due to MT)
- Walsch, William et al, "Disordered Metal Metabolism in a Large
Autism Population," Presented at the APA Annual Meeting, New Orleans,
May 2001.
- 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
- Hwang C., et al, "Oxidized redox state of glutathione in the
endoplasmic reticulum" Science. 1992 Sep.11; 257(5076):1496-502.
- Maret,W,. "metallothionein/disulfide interactions, oxidative
stress, and the mobilization of cellular zinc." Neurochem Int.1995
Jul;27(1):111-7.
- Maret, W., Assistant Professor of Biochemistry, "Research activities:
Molecular Mechanisms of Zinc Metallothionein and Cellular Zinc Distribution."
Harvard Medical School Center for Biochemical and biophysical Sciences
and Medicine
- "Glutathione: GSH" Woodlands Healing Research Center, September,
2002
- Baral, Mattew, ND, "Autism, A Holistic Approach" Southwest
College of Naturopathic Medecine and Health Sciences, Bulletin, 2003.
- Metals: Toxicology II, Chemistry 412
- Lichtlen P. and Shaffner W., "Putting its fingers on stressful
situations: the heavy metal transcription factor MTF-1" Bioessay
2001;23(11) 1010-1017
- Quig D. "Cysteine metabolism and metal toxicity" Alternative
Medicine Review, 1998 Aug;3(4) 262-70
- Owens, Susan "Sulfation" Summary of Defeat Autism Now, Oct.
2001 Conference
- Komarnisky, LA et al, "Sulfur: its clinical and toxicologic aspects,"
Nutrition, 2003 jan;19(1): 54-61.
- Parcell, Steven, ND Cand. "Sulfur in Human Nutritiiion and Applications
in Medicine" Alternative Medicine Review, 2002;7(1) 22-44.
- Haas, Elson, MD, "Sulfur" Staying Healthy with Nutrition"
Celestial Arts, March 1992. Excerpt, Healthworld Online, 2004.
- Liska, Deanne, Ph.D. "The Detoxification Enzyme Systems"
Alternative medicine Reviews 1998; 3(3) 187-198.
- Walsh, William Ph.D. "Disordered Metal Metabolism" Summary
of Defeat Autism Now! Conference Oct. 2001
- Bradstreet, Jeff, "Vaccines" Summary of Defeat Autism Now!
Conference, Oct. 2001
- El Dahr, Jane, "Mercury" Summary of Defeat Autism Now! Conference,
Oct 2001
- "Autism and Genes," Autism Research at NIDH, National Institute
of Child Health and Human Development, NIH Pub. No. 01-4961 June 2001
- Schettler, Ted, MD, "Windows of Vulnerability: An Overview of
Brain Development and Susceptibility to Environmental Contaminants"
Pollution, Toxic Chemicals and Mental Retardation: A National Summit
- Walsh, William Ph.D., "Unlocking the Mysteries of Autism"
NOHA News, Vol XXVII, No. 4 Fall 2003 pp. 3-5
- Holmes, Amy MD, "Heavy metal Detoxification and metallothionein
promotion" healing Center Online, March 2002.
- Kidd, Parris Ph.D. "Strategies for repleting cellular glutathione"
Hepatitis Discussion and Support, Sept. 2000
- Lloyd, John Wills, "Autism and Secretin" University of Virginia
Curry School of Education, June 13, 2001.
- "Study Shows Seceretin Fails to Benefit Children with Autism"
National Institute of Child Health and Human Development, Dec. 1999:
(last modified 2004)
- "Control of Pancreatic Exocrine Secretion" The Pancreas.
(last updated 1995)
- Snyder Donald, Ph.D. "Protein Fundamentals: Essential and Limiting
Amino Acids" Proper Nutrition Inc. 2004
|