RE: malic AND acid AND aluminum - Limits: Humans

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Can you please explain your interpretation of these articles? L

From: csb-autism-rx [mailto:csb-autism-rx ]

On Behalf Of binstock

Sent: Monday, September 22, 2008 7:21 PM

To: csb-autism-rx

Subject: malic AND acid AND aluminum - Limits: Humans

malic AND acid AND aluminum

Limits: Humans

1: Vaccine. 2002 May 31;20 Suppl 3:S40-3.

Elimination of aluminum adjuvants.

Hem SL.

Department of Industrial and Physical Pharmacy, Purdue University,

West Lafayette, IN 47907, USA. hem@...

<mailto:hem%40pharmacy.purdue.edu>

In vitro dissolution experiments although perhaps not at typical

body concentrations and temperatures demonstrated that the

alpha-hydroxycarboxylic acids present in interstitial fluid (citric

acid, lactic acid, and malic acid) are capable of dissolving

aluminum-containing adjuvants. Amorphous aluminum phosphate adjuvant

dissolved more rapidly than crystalline aluminum hydroxide adjuvant.

Intramuscular administration in New Zealand White rabbits of aluminum

phosphate and aluminum hydroxide adjuvants, which were labelled with

26Al, revealed that 26Al was present in the first blood sample (1 h) for

both adjuvants. The area under the blood level curve for 28 days

indicated that three times more aluminum was absorbed from aluminum

phosphate adjuvant than aluminum hydroxide adjuvant. In vivo studies

using 26Al-labelled adjuvants are relatively safe because accelerator

mass spectrometry (AMS) can quantify quantities of 26Al as small as

10(-17) g. A similar study in humans would require a whole-body exposure

of 0.7 microSv per year compared to the natural background exposure of

3000 microSv per year. The in vitro dissolution and in vivo absorption

studies indicate that aluminum-containing adjuvants which are

administered intramuscularly are dissolved by alpha-hydroxycarboxylic

acids in interstitial fluid, absorbed into the blood, distributed to

tissues, and eliminated in the urine.

PMID: 12184363

2: J Inorg Biochem. 2001 Jun;85(2-3):143-54.

Aluminum speciation studies in biological fluids. Part 7. A quantitative

investigation of aluminum(III)-malate complex equilibria and their

potential implications for aluminum metabolism and toxicity.

Venturini-Soriano M, Berthon G.

Equipe de Chimie Bioinorganique Médicale, ICMPS-CNRS FR1744,

Université Sabatier, 118 route de Narbonne (Bât. 3SC), 31062

Toulouse, France.

As a nonessential element, aluminum may be toxic at both

environmental and therapeutic levels, depending on ligand interactions.

Dietary acids that normally occur in fruits and vegetables and commonly

serve as taste enhancers are good ligands of the Al(3+) ion. Malic acid

is one of these and also one of the most predominant in food and

beverages. The present paper reports an examination of its potential

influence on aluminum bioavailability through speciation calculations

based on Al(III)-malate complex formation constants especially

determined for physiological conditions. According to the results

obtained, malate appears to be extremely effective in maintaining

Al(OH)(3) soluble over the whole pH range of the small intestine under

normal dietary conditions. In addition, two neutral Al(III)--malate

complexes are formed whose percentages are maximum from very low malate

levels. When aluminum is administered therapeutically as its

trihydroxide, the amount of metal neutralized by malate peaks as its

solubility pH range regresses to its original limits in the absence of

malate. The enhancing effect of malate towards aluminum absorption is

therefore virtually independent of the aluminum level in the

gastrointestinal tract. The presence of phosphate in the

gastrointestinal juice is expected to limit the potential influence of

malate on aluminum absorption. Under normal dietary conditions,

phosphate effectively reduces the fraction of aluminum neutralized by

malate but without nullifying it. Aluminum phosphate is predicted to

precipitate when aluminum levels are raised as with the administration

of aluminum hydroxide, but a significant amount of neutral aluminum

malate still remains in solution. Even therapeutic aluminum phosphate is

not totally safe in the presence of malate, even at low malate

concentrations. As plasma simulations predict that no compensatory

effect in favor of aluminum excretion may be expected from malate,

simultaneous ingestion of malic acid with any therapeutic aluminum salt

should preferably be avoided.

PMID: 11410234

3: J Am Coll Nutr. 1992 Jun;11(3):340-8.

Why aluminum phosphate is less toxic than aluminum hydroxide.

Berthon G, Daydé S.

Inserm U305, Equipe Bioréactifs: Spéciation et Biodisponibilité,

Université Sabatier, Toulouse, France.

Initially characterized in uremic patients undergoing hemodialysis,

toxic effects due to high aluminum (Al) body loads were subsequently

observed in a number of conditions, in particular following ingestion of

Al-containing antacids. Among compounds of this class, aluminum

phosphate (AlPO4) was recognized as safer than aluminum hydroxide

(Al(OH)3), which was thought to result from its lower solubility and

thus absorption in the gastrointestinal (gi) tract. However, while

virtually insoluble at acid pH, AlPO4 is more soluble than Al(OH)3 under

alkaline conditions, leading to the hypothesis that Al is predominantly

absorbed in the acidic region of the gi tract. Our present results

suggest otherwise. Al bioavailability depends on the solubility of the

salt ingested as well as on the physicochemical properties of the Al

soluble complexes formed in the gi fluid. Anions of dietary acids may

indeed dissolve significant fractions of Al salts and form absorbable Al

complexes. It is in these terms that the well documented increase of Al

gi absorption by citrate has been interpreted from computer-based

speciation studies. Using similar calculations, we now demonstrate that

a series of dietary acids (namely malic, oxalic, tartaric, succinic,

aspartic and glutamic acids) can also dissolve significant amounts of

Al(OH)3 and form Al neutral complexes available to the gi membrane. In

contrast, both effects are far less apparent when Al is administered as

AlPO4. We conclude from this observation that the lower toxicity of

AlPO4 vs Al(OH)3 stems from its better capacity to resist dissolution

and neutral complex formation in the presence of acids commonly present

in food.

Publication Types:

* Comparative Study

* Research Support, Non-U.S. Gov't

* Review

PMID: 1619187

4: Food Addit Contam. 1990;7 Suppl 1:S155-7.

Potential toxicity of presumably insoluble aluminum salts in presence of

common dietary acids.

Dayde S, Berthon G.

INSERM U305, Université Sabatier, Toulouse, France.

It has recently been shown that aluminum absorption may occur

following the administration of oral aluminium-containing

phosphate-binders and antacids. Computer simulations based on relevant

aluminium complex equilibria have been used in the present work to

investigate the potential influence of the simultaneous ingestion of

common dietary acids on this phenomenon. It results from these studies

that aluminium absorption may be favoured to various extents in the

presence of citric, malic, oxalic, succinic and tartric acids.

PMID: 2262026

5: J Toxicol Clin Toxicol. 1989;27(6):355-67.

The use of chelating agents in the treatment of aluminum overload.

Domingo JL.

Laboratory of Toxicology and Biochemistry, School of Medicine,

University of Barcelona, Reus, Spain.

Desferrioxamine (DFO), traditionally used as an iron chelator has

been shown to increase urinary aluminum output in humans and

aluminum-loaded mice, rats and rabbits. However, major side-effects of

DFO treatment have been observed and the drug may accumulate in dialysis

patients receiving repeated doses. In recent years, it has been reported

that some dicarboxylic or tricarboxylic acids such as succinic, malic or

citric may be considered as possible alternatives to DFO in the

management of aluminum accumulation. Ethylene-di-(o-hydroxyphenylacetic

acid)-like compounds may also have potential as alternatives to DFO in

the treatment of aluminum accumulation and aluminum-induced toxicity.

Investigation of new therapeutic agents with lower toxicity than DFO and

clinical advantages in administration and cost is clearly encouraged.

Publication Types:

* Review

PMID: 2697761

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[Guest guest]

,

If I had the whole-text of each article, I'd attempt an interpretation.

Given only abstracts, I'm standing amid a great cloud of unknowing. The

malic acid issue you identfied remains important. I posed the question

to a list of clinicians and researchers. Thus far, no one has responded.

Re: malic AND acid AND aluminum - Limits: Humans

Posted by: " john leon " jjleon1@...

Date: Mon Sep 22, 2008 9:17 pm ((PDT))

,

Can you please explain your interpretation of these articles? L

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