taking lipoic acid as a dietary supplement is bad for you



J

John 'The Man

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Autoreactivity to lipoate and a conjugated form of lipoate in primary biliary cirrhosis.

Bruggraber SF, Leung PS, Amano K, Quan C, Kurth MJ, Nantz MH, Benson GD, Van de Water J, Luketic V,
Roche TE, Ansari AA, Coppel RL, Gershwin ME.

Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis Medical
School, 95616, USA.

BACKGROUND & AIMS: Although considerable effort has been directed toward the mapping of peptide
epitopes by autoantibodies, the role of nonprotein molecules has been less well studied. The
immunodominant autoantigen in primary biliary cirrhosis (PBC), E2 components of pyruvate
dehydrogenase complexes (PDC-E2), has a lipoate molecule bonded to the domain to which
autoantibodies are directed. METHODS: We examined sera from patients with PBC (n = 105), primary
sclerosing cholangitis (n = 70), and rheumatoid arthritis (n = 28) as well as healthy volunteers (n
= 43) for reactivity against lipoic acid. The lipoic acid hapten specificity of the reactive
antibodies in PBC sera was determined following incubation of aliquots of the sera with human serum
albumin (HSA), lipoylated HSA (HSA-LA), PDC-E2, lipoylated PDC-E2, polyethylene glycol (PEG),
lipoylated PEG, free lipoic acid, and synthetic molecular mimics of lipoic acid. RESULTS: Anti-
lipoic acid specific antibodies were detected in 81% (79 of 97) of antimitochondrial antibody (AMA)-
positive patients with PBC but not in controls. Two previously unreported specificities in AMA-
positive sera that recognize free lipoic acid and a carrier-conjugated form of lipoic acid were also
identified. CONCLUSIONS: We hypothesize that conjugated form(s) of native or xenobiotic lipoic acid
mimics contribute to the initiation and perpetuation of autoimmunity by at first breaking self-
tolerance and participating in subsequent determinant spreading. The variability in the
immunoreactive carrier/lipoate conjugates provides an experimental framework on which potential
mechanisms for the breakdown of self-tolerance following exposure to xenobiotics can be
investigated. The data have implications for patients taking lipoic acid as a dietary supplement.

PMID: 14724823 [PubMed - indexed for MEDLINE] Gastroenterol Hepatol. 2004 Feb;27(2):47-50.
 
If I read this correctly, it merely indicates that extracellular ALA may provoke a certain form of
autoimmunity in individuals (mostly women) already at risk for it. While this would certainly seem
to contraindicate it for this subset of the population, they're a long way from proving that ALA can
provoke the condition in a general, healthy population. This risk may not be fully genetically
determined either but rather may have to do with prior exposure to infectious organisms and their
foreign chemistry.

Does anyone know if propylene glycol falls into the list of suspect chemicals? It mentions
polyethylene glycol (PEG). Are the two similar enough?

People have been taking large doses of ALA for a while now. I'd expect a simple statistical survey
to reveal an increase in risk for antimitochondrial antibody diseases. To my knowledge ALA isn't
implicated in any type of liver failure. If I'm not mistaken, haven't the biggest problems been with
hypoglycemia and biotin?

Of course, I'm not a youngster into all sorts of freaky things like 6-bromohexanoate bovine serum
albumin conjugate mainlining, so the risk may be greater than I think.

FYI, this doesn't seem to be the first paper these individuals have published on the topic.

J Immunol. 2003 May 15;170(10):5326-32. Related Articles, Links Click here to read Immunization
with a xenobiotic 6-bromohexanoate bovine serum albumin conjugate induces antimitochondrial
antibodies.

Leung PS, Quan C, Park O, Van de Water J, Kurth MJ, Nantz MH, Ansari AA, Coppel RL, Lam KS,
Gershwin ME.

Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of
California, Davis, CA 95616, USA.

The E2 subunit of pyruvate dehydrogenase complex (PDC-E2) is the major autoantigen recognized by
antimitochondrial Abs (AMA) in primary biliary cirrhosis (PBC). Recently, we replaced the lipoic
acid moiety of PDC-E2 with a battery of synthetic structures designed to mimic a xenobiotically
modified lipoyl hapten on a 12-aa peptide that was found within the immunodominant autoepitope
of PDC-E2 and demonstrated that AMA in PBC reacted against several organic modified mimotopes as
well as, or sometimes significantly better than, the native lipoyl domain. Based on this data,
we immunized rabbits with one such xenobiotic organic compound, 6-bromohexanoate, coupled to
BSA. One hundred percent of immunized rabbits developed AMA that have each and every
characteristic of human AMAs with reactivity against PDC-E2, E2 subunit of branched chain 2-oxo-
acid dehydrogenase, and E2 subunit of 2-oxoglutarate dehydrogenase complex. The rabbit AMA also
inhibited enzymatic function of PDC-E2 and, importantly, binds to peptide sequences not present
in the xenobiotic carrier immunogen. In contrast, BSA-immunized controls did not produce such
activity. Our observation that animals immunized with a xenobiotic BSA complex produce
autoantibodies that react not only with the xenobiotic, but also with mitochondrial autoantigens
recognized by autoimmune PBC sera, suggests that environmental xenobiotic agents can be a risk
factor for the induction of PBC.

PMID: 12734383 [PubMed - indexed for MEDLINE

Autoimmun Rev. 2002 Feb;1(1-2):37-42. Related Articles, Links Click here to read Antimitochondrial
antibodies in primary biliary cirrhosis: the role of xenobiotics.

Long SA, Van de Water J, Gershwin ME.

Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis
School of Medicine, TB 192, One Shields Avenue, Davis, CA 95616, USA.

Primary biliary cirrhosis is an enigmatic autoimmune disease of women characterized by
antimitochondrial antibodies and destruction of intrahepatic bile ducts. The etiology of PBC is
unknown, but we present data herein that the disease may be induced by xenobiotic (i.e.
chemicals) exposure. In particular, we postulate that halogenated compounds will bind to the
autoantigen, break tolerance, and lead to an intense mucosal response.

Publication Types:

* Review
* Review, Tutorial

PMID: 12849056 [PubMed - indexed for MEDLINE]

> Autoreactivity to lipoate and a conjugated form of lipoate in primary biliary cirrhosis.
>
> Bruggraber SF, Leung PS, Amano K, Quan C, Kurth MJ, Nantz MH, Benson GD, Van de Water J, Luketic
> V, Roche TE, Ansari AA, Coppel RL, Gershwin ME.
>
> Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis
> Medical School, 95616, USA.
>
> BACKGROUND & AIMS: Although considerable effort has been directed toward the mapping of peptide
> epitopes by autoantibodies, the role of nonprotein molecules has been less well studied. The
> immunodominant autoantigen in primary biliary cirrhosis (PBC), E2 components of pyruvate
> dehydrogenase complexes (PDC-E2), has a lipoate molecule bonded to the domain to which
> autoantibodies are directed. METHODS: We examined sera from patients with PBC (n = 105), primary
> sclerosing cholangitis (n = 70), and rheumatoid arthritis (n = 28) as well as healthy volunteers
> (n = 43) for reactivity against lipoic acid. The lipoic acid hapten specificity of the reactive
> antibodies in PBC sera was determined following incubation of aliquots of the sera with human
> serum albumin (HSA), lipoylated HSA (HSA-LA), PDC-E2, lipoylated PDC-E2, polyethylene glycol
> (PEG), lipoylated PEG, free lipoic acid, and synthetic molecular mimics of lipoic acid. RESULTS:
> Anti-lipoic acid specific antibodies were detected in 81% (79 of 97) of antimitochondrial antibody
> (AMA)-positive patients with PBC but not in controls. Two previously unreported specificities in
> AMA-positive sera that recognize free lipoic acid and a carrier-conjugated form of lipoic acid
> were also identified. CONCLUSIONS: We hypothesize that conjugated form(s) of native or xenobiotic
> lipoic acid mimics contribute to the initiation and perpetuation of autoimmunity by at first
> breaking self-tolerance and participating in subsequent determinant spreading. The variability in
> the immunoreactive carrier/lipoate conjugates provides an experimental framework on which
> potential mechanisms for the breakdown of self-tolerance following exposure to xenobiotics can be
> investigated. The data have implications for patients taking lipoic acid as a dietary supplement.
>
> PMID: 14724823 [PubMed - indexed for MEDLINE] Gastroenterol Hepatol. 2004 Feb;27(2):47-50.
 
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