Dose-proportionality of oral thioctic acid — coincidence of assessments via pooled plasma and individual data

Breithaupt-Grögler, Kerstin; Niebch, G.; Schneider, Edith; Erb, Katharina; Hermann, Róbert; Blume, Henning; Schug, Barbara; Belz, G. G.

doi:10.1016/s0928-0987(98)00061-x

Cited by 91 publications

(76 citation statements)

References 13 publications

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“…This result corresponds to previous studies that revealed that ϳ80% of LA was renally excreted (14,54). Although the amount of R-LA absorption in plasma and tissues was higher than that of S-LA, both enantiomers were found in plasma at a similar time after oral administration of the racemic mixture to healthy volunteers (52,53). Thus, the question remains of whether there are other/additional mechanisms involved in the absorption and secretion of LA at such high concentrations found in food supplements.…”

Section: Discussionsupporting

confidence: 90%

“…hSMVT may thus play an important role in the absorption of R-LA in the intestine and other tissues in the body (16). Studies in healthy volunteers showed R-LA in plasma and that its bioavailability was higher than S-LA after administration of racemic LA (52,53), suggesting that hSMVT transports exclusively R-LA across epithelial cells. However, the detailed pharmacokinetics of LA in humans is not fully characterized.…”

Section: Discussionmentioning

confidence: 99%

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Interaction of α-Lipoic Acid with the Human Na+/Multivitamin Transporter (hSMVT)

Zehnpfennig

Wiriyasermkul

Carlson

et al. 2015

Journal of Biological Chemistry

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Background: Transport of ␣-lipoate by hSMVT and its stereospecificity have been elusive. Results: Using hSMVT expressed in oocytes and in Pichia pastoris yielded detailed information about the stereospecificity of hSMVT-mediated lipoate transport and binding. Conclusion: hSMVT can bind two molecules of R-(ϩ)-␣-lipoate, its physiological substrate.Significance: In addition to biotin, pantothenate, and iodide, hSMVT mediates the transport of lipoate.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Interaction of α-Lipoic Acid with the Human Na+/Multivitamin Transporter (hSMVT)

Zehnpfennig

Wiriyasermkul

Carlson

et al. 2015

Journal of Biological Chemistry

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“…In 3T3-L1 adipocytes, similar results were reported with respect to the ability of LA to protect against the H 2 O 2 -induced loss of insulin-stimulated glucose uptake (21). Because therapeutic concentrations of LA fall within this micromolar range (17,18,22), it is possible that the protective effect of LA on insulin action in vitro is linked to its therapeutic effect in vivo.…”

Section: Discussionsupporting

confidence: 68%

“…Pretreatment with LA, at micromolar concentrations, protected the effects of insulin (21). Because the therapeutic effects of LA occur at plasma concentrations in the micromolar range (17,22), it is possible that protection against oxidative stress is one mechanism by which LA improves insulin action. However, the potential effect of LA on oxidative stress in muscle cells has not been evaluated.…”

mentioning

confidence: 99%

Protection Against Oxidative Stress—Induced Insulin Resistance in Rat L6 Muscle Cells by Micromolar Concentrations of α-Lipoic Acid

et al. 2001

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In diabetic patients, ␣-lipoic acid (LA) improves skeletal muscle glucose transport, resulting in increased glucose disposal; however, the molecular mechanism of action of LA is presently unknown. We studied the effects of LA on basal and insulin-stimulated glucose transport in cultured rat L6 muscle cells that overexpress GLUT4. When 2-deoxy-D-glucose uptake was measured in these cells, they were more sensitive and responsive to insulin than wild-type L6 cells. LA, at concentrations ≤1 mmol/l, had only small effects on glucose transport in cells not exposed to oxidative stress. When cells were exposed to glucose oxidase and glucose to generate H 2 O 2 and cause oxidative stress, there was a marked decrease in insulinstimulated glucose transport. Pretreatment with LA over the concentration range of 10-1,000 µmol/l protected the insulin effect from inhibition by H 2 O 2 . Both the R and S isomers of LA were equally effective. In addition, oxidative stress caused a significant decrease (~50%) in reduced glutathione concentration, along with the rapid activation of the stress-sensitive p38 mitogen-activated protein kinase. Pretreatment with LA prevented both of these events, coincident with protecting insulin action. These studies indicate that in muscle, the major site of insulin-stimulated glucose disposal, one important effect of LA on the insulin-signaling cascade is to protect cells from oxidative stress-induced insulin resistance. Diabetes 50: [404][405][406][407][408][409][410] 2001

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“…Even though little information currently exists as to the general intake of LA from dietary sources, controlled studies in rodents suggest that 20-40% of LA given orally is absorbed into the plasma (9,10). Plasma LA levels typically reach a maximum between 0.5 and 2 h after intake in a variety of animal species studied (1), and a single 600 mg dose given to rats was shown to produce a peak plasma concentration of 13.8 lM.…”

Section: Bioavailability and Metabolic Fate Of Lamentioning

confidence: 99%

Is α‐lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity

et al. 2008

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SummaryThe chemical reduction and oxidation (redox) properties of a-lipoic acid (LA) suggest that it may have potent antioxidant potential. A significant number of studies now show that LA and its reduced form, dihydrolipoic acid (DHLA), directly scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) species and protect cells against a host of insults where oxidative stress is part of the underlying etiology. However, owing to its limited and transient accumulation in tissues following oral intake, the efficacy of nonprotein-bound LA to function as a physiological antioxidant has been questioned. Herein, we review the evidence that the micronutrient functions of LA may be more as an effector of important cellular stress response pathways that ultimately influence endogenous cellular antioxidant levels and reduce proinflammatory mechanisms. This would promote a sustained improvement in cellular resistance to pathologies where oxidative stress is involved, which would not be forthcoming if LA solely acted as a transient ROS scavenger.

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Dose-proportionality of oral thioctic acid — coincidence of assessments via pooled plasma and individual data

Cited by 91 publications

References 13 publications

Interaction of α-Lipoic Acid with the Human Na+/Multivitamin Transporter (hSMVT)

Interaction of α-Lipoic Acid with the Human Na+/Multivitamin Transporter (hSMVT)

Protection Against Oxidative Stress—Induced Insulin Resistance in Rat L6 Muscle Cells by Micromolar Concentrations of α-Lipoic Acid

Is α‐lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity

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