metallothionein: forgotten antioxidant: missing puzzle ... · metallothionein: forgotten...

Metallothionein: Forgotten Antioxidant: Missing Puzzle Piece For Alzheimer’s& Leaky Gut?By Michael McEvoy, FDN, CNC, CMTA - February 18, 2014 With 1 comment

Metallothionein is one of the most powerful antioxidants that the human body

produces. But it is one that doesn't get a lot of mainstream press, and its

somewhat complex in its functions. Within the antioxidant and anti-aging world,

there has been more emphasis on glutathione and other antioxidants such as

lipoic acid, CoQ10 and SOD. However, much recent experimental research has

found that metallothionein might play a vital role in preventing and halting the

neuronal degeneration of Alzheimer's disease, as well as protecting the

intestinal barrier from heavy metal toxicity.

Like its cysteine-rich counterpart glutathione, metallothionein has a powerful

capacity to inhibit free radicals, binding to toxic metals such as mercury, copper,

cadmium and arsenic, thereby increasing cellular detoxification.

Metallothionein: Potent Antioxidant Protector OfThe Brain & GutThere are 4 different types of metallothionein: MT-1, MT-2, MT-3 and MT-4. Although each similar in their molecular

compositions, the MT's have affinities for different organ systems.

MT-1 & MT-2 - Found ubiquitously throughout the body

MT-3 - Heavily expressed in the brain

MT-4 - Concentrated in epithelial tissues, esophagus, GI tract, upper stomach, skin

Metallothionein works synergistically with glutathione. They are both key, cysteine-rich antioxidants that have the ability to

bind to a wide variety of free radicals and toxins. When glutathione is oxidized, the toxic metals are transferred over to

metallothionein for removal and excretion.

There are overall, 22 known nutrients that work to promote metallothionein (MT's) expression. The most common nutrient in

these regards is the trace element zinc. Other important nutrient components of MT activity include: selenium (enhances

glutathione/MT relationship), and the amino acids: histidine, serine, arginine, threonine and lysine. (7)

Its well established that zinc is an extremely powerful promoter of metallothionein synthesis. Research has shown that both

metallothionein and zinc play powerful roles in preventing and restoring the damage in the gut barrier. Damage to the

intestinal barrier can lead to serious conditions, such as leaky gut, colitis and Crohn's Disease.

One of the primary reasons that taking high doses of zinc stops severe diarrhea is due to the immediate increase in

metallothionein from increased zinc status.

When inflammation ensues in the gut lining, MT production increases. When damage is induced to the liver, MT production

increases. When cortisol is increased under stress, metallothionein production increases. MT's protective effects are

ubiquitous and quite diverse.

In the brain, metallothionein is expressed as MT-3, and is a key antioxidant in the blood/brain barrier, capable of binding to

and preventing brain exposure to cadmium, mercury, arsenic, copper and other toxic metals. But what if metallothionein is

decreased in the brain?

Metallothionein Deficiency: The Alzheimer's ConnectionAlzheimer's disease features a tremendous increase in oxidative stress to the brain. Research has found strong associations

between mercury poisoning and Alzheimer's. Rats exposed to mercury develop the identical biochemical brain imbalances as

Alzheimer's in humans (4).

A 2013 study from the Proceedings of the National Academy of Sciences has found that copper toxicity plays an important role in

Alzheimer's disease development. According to the head of the study, Rashid Dean, PhD: “It is clear that, over time, copper’s

cumulative effect is to impair the systems by which amyloid beta is removed from the brain."

While copper is an essential nutrient, it becomes a powerfully reactive toxin when free and unbound. Now get this: A very

important feature of metallothionein is to bind to copper. MT rapidly binds to copper and also enhances its utilization.

However, if the copper is free and unbound, you have a situation of powerful free radical toxicity that ensues.

In Alzheimer's disease, studies have shown that metallothionein-3 (the form of MT expressed in the brain) is significantly

decreased. The expression of MT proteins in Alzheimer's is 1/3rd that of normal brains.

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Do we have a working theory here? Metallothionein, a powerful cysteine-rich, zinc-powered antioxidant, is protective of brain

cells, binds to a variety of toxic metals, including mercury and copper (zinc and copper are also antagonistic), the toxicity of

which are strongly implicated in Alzheimer's disease. A deficiency of metallothionein leads to an inability to scavenge toxic

mercury, cadmium, copper and other metals. Metals accumulate in tissues. End of story? Nope.

APOE4 Gene Mutations & MetallothioneinAPOE4 gene mutations are considered a major risk factor for the development of Alzheimer's disease. APOE (apoloprotein E)

are mediators of cholesterol metabolism. According to research, carriers of APOE4 double mutations have 10-30X higher risk

of developing Alzheimer's. However, these projections don't always play out in reality. At current estimates, 1/3rd of

Alzheimer's patients don't have APOE4 mutations.

Most of the recent research on APOE4 has centered around the accumulation of oxidized cholesterol in the brain,

contributing to the build-up of beta amyloid plaque. However, there is dissenting opinions as to whether the cholesterol

theory of Alzheimer's has merit. Stephanie, Seneff, PhD, an MIT scientist has reason to believe based upon literature that

statins, (cholesterol-lowering drugs) actually cause Alzheimer's.

University of Kentucky retired chemist Boyd Hayley, PhD has been very vocal on APOE4 mutations and Alzheimer's. He

believes that carriers of APOE4 mutations are susceptible to Alzheimer's because of APOE4's "lack of a cysteine" amino acid,

and consequently, the inability for APOE4 (a "housekeeping, protective protein") to scavenge mercury from the brain.

Whereas APOE2 bears cysteine, and is considered protective of mercury.

Remember that cysteine is a critically important sulfur-bearing amino acid in glutathione synthesis, as well as in

metallothionein synthesis.

Amazingly, recent research directly links APOE-3 and APOE-4 gene mutations with a decreased expression of metallothionein!

Pay close attention to future research that explores the relationship between APOE and metallothionein, as well as therapies

that may help to promote the synthesis and expression of important antioxidants like MT.

Metallothionein Promotion TherapyPreliminary trials are underway. The man leading the charge in the realm of metallothionein promotion therapy is William J.

Walsh, Phd. A longtime research scientist of brain biochemistry and advanced nutrient therapies, Dr. Walsh has reported very

positive initial success with metallothionein nutrient therapy among an Alzheimer's group.

There is no doubt that future research in this field is needed critically. Bringing attention and recognition to metallothionein

as an important, functional antioxidant is highly warranted.

Michael and Julie offer a variety of Health and Nutrition consulting services. Click Here to find out how you can benefit from a private

consultation.

If you would like to speak with Michael and Julie regarding your health & nutrition needs, or to

schedule a private consultation, please contact us here.

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SourcesSources:

http://www.ncbi.nlm.nih.gov/pubmed/12022471



(4) Boyd Hayley, Phd

Hijova, E: Institute of Experimental Medicine, Faculty of Medicine, Slovakia: ‘Metallothioneins and zinc: their functions and

interactions’, 2004

http://onlinelibrary.wiley.com/doi/10.1111/j.1432-1033.2004.04160.x/pdf

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(7) William J. Walsh, PhD: ‘Metallothionein’, Walsh Research Institute

Seneff, Stephanie, PhD: ‘APOE-4: The Clue As To Why Low Fat Diets & Statins May Cause Alzheimer’s’, 2009

http://www.ncbi.nlm.nih.gov/pubmed/8003488?dopt=Abstract&holding=f1000,f1000m,isrctn

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615750/

http://www.sciencedirect.com/science/article/pii/S0022214302044177

http://www.hindawi.com/journals/mi/2009/729172/



http://www.sciencedirect.com/science/article/pii/0896627391902722


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metallothionein: forgotten antioxidant: missing puzzle ... · metallothionein: forgotten...

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