Dr. Chris Shade about Mercury detox

In an effort to have a more intelligent discussion on the benefits of AC chelation, I am making the following post. Please refrain from name calling, hurling insults or engaging in other childish behavior.

Contrary to popular belief, the half life of ALA is not 3 hours (http://www.mskcc.org/mskcc/html/69117.cfm); it is only around 30 minutes (20 minutes in some people). ALA itself is actually not a potent chelator of mercury.

A simplified representation of what happens is that ALA enters a cell where it can be reduced to dihydrolipoic acid (DHLA). Now DHLA is a chelator of mercury (it contains two thiols). However, DHLA is quickly expelled from the cell. DHLA is a powerful reactive anti-oxidant and is quickly oxidized back to ALA by recycling other molecules such as converting Cystine to Cysteine. The Cysteine is then available to enter the cell where it can be used to make glutathione (GSH). See: http://bit.ly/bzTQ6t for a diagram.

This process quickly breaks down when the ALA undergoes Beta-oxidation and is broken down into several metabolites. These metabolites include tetranorlipoic acid, bisnorlipoic acid, and 3-kto-lipioc acid. These metabolites maintain their peak levels in the plasma for 3 hours and are still detectable after 10 hours. From Cutler’s book:

For lipoic acid, the literature indicates that it and its metabolite bisnorlipoic acid should be present in reasonable concentrations for 3-4 hours.

In a yahoo group posting, Cutler comments further:

I can't really tell you exactly why ALA is best every 3 hours.

Bisnorlipoic acid has a similar structure to ALA (except that it is missing two carbon atoms). It is more stable and can bind various metals, but not mercury. Its reduced form though most likely is a chelator of mercury. There is not much written about these metabolites and thus it is unclear what the exact effects are. The validity of this 3 hour ALA dosing theory lies on ability of some of these metabolites (which are only a small fraction of the original ALA dose) to be readily transformed into their reduced forms to mop up any loose mercury. It remains a theory. I am skeptical that a small ALA dose (12.5mg of which only 6.25 mg is biological available) can yield enough metabolites (in reduced form) to flood the entire bloodstream to mop up rogue mercury for 3 entire hours.

Furthermore, it requires that a significant portion of the ALA be metabolized through a pathway that yields a significant amount of DHLA. From the book (Lipoic Acid: Energy Production, Antioxidant Activity and Health Effect), there are three metabolic pathways from lipoic acid. The most favored pathway is via a twofold B-oxidation which yields the metabolite R-tetranorlipoic acid, but also severely limits the mean residence time of DHLA in the plasma.

However, it has been established that ALA increases the excretion of mercury. It has also been established that ALA increases glutathione production which does transport mercury out of the body.

Glutathione though only has one thiol and so some do not believe that it is not a chelator of mercury. From Molecular Biology and Toxicology of Metals by Rudolfs Zalups:

In a situation where there are twice as many molecules of glutathione to inorganic mercuric ions, there will be a tendency for each inorganic mercuric ion to be bonded to the sulfur atoms of two molecules of glutathione in a linear II coordinate covalent complex

Thus, two molecules of glutathione will bind with one mercury to form a conjugate. Note that normally glutathione concentrations in the cell are quite plentiful unless the glutathione is severely depleted by mercury or other toxins. Also remember, ALA increases glutathione production in the cell.

A glutathione mercury conjugate will only move mercury out of a cell and not into a cell.

However, cysteine can also form conjugate bonds with mercury (i.e. two molecules of cysteine with one mercury). These bonds are more dangerous since a cysteine mercury conjugated molecule can move mercury into cells or just as easily be excreted. But that is why using the NAC supplement might not be advisable for those with mercury issues (since NAC rapidly hydrolyzes to free cysteine).

Tory Hagen (Professor & Jamieson Chair in Healthspan Research, Linus Pauling Institute, Oregon State University) who has published numerous peer reviewed papers on lipoic acid says:

Lipoic acid is known to chelate mercury in vitro as well as it hastens Hg’s removal from the body. But the mercury removal in vivo is actually a glutathione-dependent process and not directly from LA.

David Carlson (Director R&D GeroNova Research Inc) says:

The literature is mixed in terms of whether or not LA or DHLA are effective chelators in vivo. While the usual dogma concerning the mechanism of action & the benefits of LA involve its tissue uptake and reduction to DHLA, our studies do not support this as a primary mechanism. Most LA is B-oxidized, and mono or bis-methylated almost instantly before any significant amounts of DHLA form or accumulate.

So if Hagen is correct, then the AC protocol using ALA may be an effective protocol for mercury excretion provided that there is enough biologically available cystine for ALA to cause an increase in glutathione production. However, ALA doesn’t supply the cystine or cysteine (which is most often the rate limiting precursor for glutathione). Thus, the AC ALA protocol is far from optimal. It also explains why (if there is not enough cysteine available) some children show no mercury excretion (in urine tests) at the end of an ALA only chelation round.

DMSA combines with cysteine upon ingestion and the mercury that gets excreted is a cysteine mercury complex. In other words, DMSA wastes cysteine. It is not a big issue if enough cystine is available in sufficient quantities and the DMSA dosage is small (a bigger issue with the large DMSA dosages with the Dan protocol). If you are deficient in cystine/cysteine, then you making the resulting glutathione deficiency worse

In conclusion, I am skeptical about the AC ALA protocol theory. It works for some, but not others. Thus, if it is working for you, then keep doing it. If a urine heavy metal test does not show any mercury being excreted after ALA only rounds, then AC ALA is not performing the intended task and you should be looking at plan B.