| Description: |
Alpha-lipoic acid 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. Alpha-lipoic acid has therapeutic effects on joint inflammation and erosion in an animal model via NF-kappa B down regulation, it inhibits TNF-alpha induced NF-kappa B activation through blocking of MEKK1-MKK4-IKK signaling cascades. Lipoic acid is a novel treatment for Alzheimer's disease and related dementias. |
| Targets: |
MMP(e.g.TIMP) | NF-kB | Nrf2 | MAPK | TNF-α | IkB | ROS | IKK |
| In vitro: |
| Pharmacol Ther. 2007 Jan;113(1):154-64. | | Lipoic acid as a novel treatment for Alzheimer's disease and related dementias.[Pubmed: 16989905 ] | Alzheimer's disease (AD) is a progressive neurodegenerative disorder that destroys patient memory and cognition, communication ability with the social environment and the ability to carry out daily activities. Despite extensive research into the pathogenesis of AD, a neuroprotective treatment - particularly for the early stages of disease - remains unavailable for clinical use.
METHODS AND RESULTS:
In this review, we advance the suggestion that Lipoic acid (LA) may fulfil this therapeutic need. A naturally occurring precursor of an essential cofactor for mitochondrial enzymes, including pyruvate dehydrogenase (PDH) and alpha-ketoglutarate dehydrogenase (KGDH), LA has been shown to have a variety of properties which can interfere with pathogenic principles of AD. For example, LA increases acetylcholine (ACh) production by activation of choline acetyltransferase and increases glucose uptake, thus supplying more acetyl-CoA for the production of ACh. LA chelates redox-active transition metals, thus inhibiting the formation of hydroxyl radicals and also scavenges reactive oxygen species (ROS), thereby increasing the levels of reduced glutathione. Via the same mechanisms, downregulation redox-sensitive inflammatory processes is also achieved. |
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| In vivo: |
| Curr Top Med Chem. 2015;15(5):458-83. | | Lipoic Acid: its antioxidant and anti-inflammatory role and clinical applications.[Pubmed: 25620240] | Lipoic acid (LA) is an antioxidant able to produce its effects in aqueous or lipophilic environments.
METHODS AND RESULTS:
Lipoate is the conjugate base of lipoic acid, and the most prevalent form of LA under physiological conditions. It presents a highly negative reduction potential, increases the expression of antioxidant enzymes and participates in the recycling of vitamins C and E. Due to these properties, LA is called the "universal antioxidant". LA is also involved with anti-inflammatory action, independently of its antioxidant activity. This review was carried out, aiming to identify, analyze, and rationalize the various clinical, physiopathological and/or physiological situations in which LA, through oral supplementation, was tested on human and animal (rats and mice) models. LA was mainly tested in cardiovascular diseases (CVD), obesity, pain, inflammatory diseases and aging. LA uses in CVD and obesity, in humans, are controversial. On the other hand, beneficial effects on inflammation and pain were observed. LA supplementation in animal models may prolong life, has neuroprotective effects and presents positive effects against cancer. Differences observed in human and animal models can be due, in part, to different treatments (LA combined with other antioxidants, different doses) and to the variety of biomarkers investigated in animal experiments.
CONCLUSIONS:
These results suggest the need for further clinical trials to guide health professionals regarding the safety of prescription of this supplement. | | Free Radic Biol Med. 1999 Aug;27(3-4):309-14. | | Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial.[Pubmed: 10468203] | Alpha-Lipoic acid (ALA), a naturally occuring compound and a radical scavenger was shown to enhance glucose transport and utilization in different experimental and animal models.
METHODS AND RESULTS:
Clinical studies described an increase of insulin sensitivity after acute and short-term (10 d) parenteral administration of ALA. This revealed significantly different changes in MCR after treatment (+27% vs. placebo; p < .01). This placebo-controlled explorative study confirms previous observations of an increase of insulin sensitivity in type-2 diabetes after acute and chronic intravenous administration of ALA.
CONCLUSIONS:
The results suggest that oral administration of alpha-Lipoic acid can improve insulin sensitivity in patients with type-2 diabetes. The encouraging findings of this pilot trial need to be substantiated by further investigations. |
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