Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential

Kate Petersen Shay, Régis F. Moreau, Eric J. Smith, Anthony R. Smith, Tory M. Hagen

Research output: Contribution to journalReview article

497 Citations (Scopus)

Abstract

Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well-defined as a therapy for preventing diabetic polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age. How do the biochemical properties of LA relate to its biological effects? Herein, we review the molecular mechanisms of LA discovered using cell and animal models, and the effects of LA on human subjects. Though LA has long been touted as an antioxidant, it has also been shown to improve glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa B. LA and its reduced form, dihydrolipoic acid, may use their chemical properties as a redox couple to alter protein conformations by forming mixed disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting that some of its therapeutic potential extends beyond the strict definition of an antioxidant. Current trials are investigating whether these beneficial properties of LA make it an appropriate treatment not just for diabetes, but also for the prevention of vascular disease, hypertension, and inflammation.

Original languageEnglish (US)
Pages (from-to)1149-1160
Number of pages12
JournalBiochimica et Biophysica Acta - General Subjects
Volume1790
Issue number10
DOIs
StatePublished - Oct 1 2009

Fingerprint

Dietary supplements
Thioctic Acid
Dietary Supplements
Therapeutics
Phase II Metabolic Detoxication
Antioxidants
Detoxification
Protein Conformation
Vascular Cell Adhesion Molecule-1
Diabetic Neuropathies
NF-kappa B
Pets
Medical problems
Matrix Metalloproteinases
Vascular Diseases
Disulfides
Chemical properties
Oxidation-Reduction
Free Radicals
Glutathione

Keywords

  • Aging
  • Alpha-lipoic acid
  • Antioxidant
  • Diabetes
  • Dietary supplement
  • Glutathione

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Alpha-lipoic acid as a dietary supplement : Molecular mechanisms and therapeutic potential. / Shay, Kate Petersen; Moreau, Régis F.; Smith, Eric J.; Smith, Anthony R.; Hagen, Tory M.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1790, No. 10, 01.10.2009, p. 1149-1160.

Research output: Contribution to journalReview article

Shay, Kate Petersen ; Moreau, Régis F. ; Smith, Eric J. ; Smith, Anthony R. ; Hagen, Tory M. / Alpha-lipoic acid as a dietary supplement : Molecular mechanisms and therapeutic potential. In: Biochimica et Biophysica Acta - General Subjects. 2009 ; Vol. 1790, No. 10. pp. 1149-1160.
@article{9dbe3851e1bd4eb99bbf1c933a66c55d,
title = "Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential",
abstract = "Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well-defined as a therapy for preventing diabetic polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age. How do the biochemical properties of LA relate to its biological effects? Herein, we review the molecular mechanisms of LA discovered using cell and animal models, and the effects of LA on human subjects. Though LA has long been touted as an antioxidant, it has also been shown to improve glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa B. LA and its reduced form, dihydrolipoic acid, may use their chemical properties as a redox couple to alter protein conformations by forming mixed disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting that some of its therapeutic potential extends beyond the strict definition of an antioxidant. Current trials are investigating whether these beneficial properties of LA make it an appropriate treatment not just for diabetes, but also for the prevention of vascular disease, hypertension, and inflammation.",
keywords = "Aging, Alpha-lipoic acid, Antioxidant, Diabetes, Dietary supplement, Glutathione",
author = "Shay, {Kate Petersen} and Moreau, {R{\'e}gis F.} and Smith, {Eric J.} and Smith, {Anthony R.} and Hagen, {Tory M.}",
year = "2009",
month = "10",
day = "1",
doi = "10.1016/j.bbagen.2009.07.026",
language = "English (US)",
volume = "1790",
pages = "1149--1160",
journal = "Biochimica et Biophysica Acta - General Subjects",
issn = "0006-3002",
publisher = "Elsevier",
number = "10",

}

TY - JOUR

T1 - Alpha-lipoic acid as a dietary supplement

T2 - Molecular mechanisms and therapeutic potential

AU - Shay, Kate Petersen

AU - Moreau, Régis F.

AU - Smith, Eric J.

AU - Smith, Anthony R.

AU - Hagen, Tory M.

PY - 2009/10/1

Y1 - 2009/10/1

N2 - Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well-defined as a therapy for preventing diabetic polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age. How do the biochemical properties of LA relate to its biological effects? Herein, we review the molecular mechanisms of LA discovered using cell and animal models, and the effects of LA on human subjects. Though LA has long been touted as an antioxidant, it has also been shown to improve glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa B. LA and its reduced form, dihydrolipoic acid, may use their chemical properties as a redox couple to alter protein conformations by forming mixed disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting that some of its therapeutic potential extends beyond the strict definition of an antioxidant. Current trials are investigating whether these beneficial properties of LA make it an appropriate treatment not just for diabetes, but also for the prevention of vascular disease, hypertension, and inflammation.

AB - Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well-defined as a therapy for preventing diabetic polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age. How do the biochemical properties of LA relate to its biological effects? Herein, we review the molecular mechanisms of LA discovered using cell and animal models, and the effects of LA on human subjects. Though LA has long been touted as an antioxidant, it has also been shown to improve glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa B. LA and its reduced form, dihydrolipoic acid, may use their chemical properties as a redox couple to alter protein conformations by forming mixed disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting that some of its therapeutic potential extends beyond the strict definition of an antioxidant. Current trials are investigating whether these beneficial properties of LA make it an appropriate treatment not just for diabetes, but also for the prevention of vascular disease, hypertension, and inflammation.

KW - Aging

KW - Alpha-lipoic acid

KW - Antioxidant

KW - Diabetes

KW - Dietary supplement

KW - Glutathione

UR - http://www.scopus.com/inward/record.url?scp=69949104384&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69949104384&partnerID=8YFLogxK

U2 - 10.1016/j.bbagen.2009.07.026

DO - 10.1016/j.bbagen.2009.07.026

M3 - Review article

C2 - 19664690

AN - SCOPUS:69949104384

VL - 1790

SP - 1149

EP - 1160

JO - Biochimica et Biophysica Acta - General Subjects

JF - Biochimica et Biophysica Acta - General Subjects

SN - 0006-3002

IS - 10

ER -