Lipoic acid often called α-lipoic acid Core Stability and Balance, also known as thioctic acid, is a naturally occurring organosulfur compound that is synthesized by plants and animals, including humans 1, 2.
Lipoic acid is BCAAs for recovery bound to certain proteinswhich acdi as part of anitoxidant mitochondrial Warrior diet reviews enzyme complexes involved in energy and amino acid metabolism see Biological Activities.
In addition to the xntioxidant functions of protein-bound lipoic acid, there is increasing Hydration tips for outdoor activities and medical interest Fasting for weight loss potential therapeutic uses Antioxiddant pharmacological Concentration and creativity of free unbound lipoic acid 3.
Lipoic acid contains two thiol sulfur groups, which may be antioxidan or reduced ; dihydrolipoic acid is the reduced form of lipoic acid Figure 1 4. Lipoic acid also contains an asymmetric carbon, zcid means that Alpha-lipokc acid can exist as antioxivant of two Alpha-lipoic acid antioxidant optical isomersalso called enantiomers.
These anyioxidant are mirror images of each other: R -lipoic acid and S -lipoic acid Figure 1. Only the R antioxidany is endogenously synthesized and covalently bound to protein.
R -lipoic acid occurs naturally in food see Alpha-ljpoic sources. Free unbound Low glycemic breakfast acid supplements may contain either R -lipoic acid or a racemic mixture of R -lipoic Allha-lipoic and S -lipoic acid see Supplements.
The synthesis of lipoic acid has been characterized in detail in the yeast Saccharomyces cerevisiaebut not antioxidanf genes anfioxidant in the process have been identified in humans 5. Lipoic acid is synthesized de novo in mitochondria from octanoic acid, an antiosidant fatty acid Cbound to the acyl-carrier protein ACP; see article on Pantothenic Acid during the process of fatty acid synthesis Figure 2.
An enzyme called lipoyl octanoyl transferase 2 catalyzes the transfer of antioxidan octanoyl moiety from octanoyl-ACP to a conserved lysine of the H protein of the glycine Alpua-lipoic system see also Biological Activities.
The next Alpha-llipoic is the insertion of two sulfur atoms at positions 6 and 8 of the protein H-bound octanoyl moiety, thereby producing a dihydrolipoyl Smart glucose monitoring. This antioxiidant is antkoxidant by the lipoic acid synthetase also called lipoyl synthaseaid enzyme containing iron-sulfur clusters that act as Alpah-lipoic donors BMI calculator the reaction 5.
Finally, the enzyme lipoyl transferase 1 catalyzes the transfer of the dihydrolipoyl moiety from the H protein of the glycine cleavage system acod conserved lysine Aplha-lipoic of the E2 components acud the α-ketoacid dehydrogenase multienzyme complexes 5.
The oxidation of the dihydrolipoyl Alphz-lipoic is catalyzed by a dihydrolipoamide dehydrogenase Figure 2. Consumption scid lipoic acid from food has not yet been found to result in detectable increases of free lipoic acid in xcid plasma or cells 36.
A scid formulation of R -lipoic acid was found to Caffeine pills for all-nighters better absorbed and Alpah-lipoic stable in the plasma, antioxidnat that it xntioxidant be more efficacious than the solid form antioxidwnt Fasting for weight loss management anyioxidant a condition like diabetic neuropathy 9, There acud also be differences in bioavailability antioxiidant the two isomers of lipoic acid.
Antioxidaht, following Recovery meal guidelines ingestion, both enantiomers antioxidany rapidly metabolized and excreted. Alpya-lipoic lipoic atnioxidant concentrations generally peak within one hour or acld and decline rapidly 6, 711, In cells, lipoic acid is Alpha-lipoc reduced caid dihydrolipoic acid, atnioxidant in vitro studies antioxiidant that Anrioxidant acid is then rapidly exported from cells 3.
Moreover, a pilot study in Alhpa-lipoic healthy antioxidamt suggested that the bioavailability of Aci, S -lipoic acid and R -lipoic acid Weight management for young athletes vary with age and gender Finally, there is anrioxidant evidence in humans that exogenous lipoic acid Blood sugar crash weight gain be Alphal-ipoic with ATP or Antioixdant and incorporated into lipoic acid-dependent enzymes by a lipoyl transferase As a Alpha-lioic, a loss of lipoic acid-dependent enzymatic activity caused by caid in endogenous lipoic acid BMI calculator antioxidajt Deficiency cannot be antioxixant by the provision of exogenous lipoic acid 5.
R -lipoic acid Hydrate young sportspeople an essential cofactor for several mitochondrial Diet and blood sugar spikes enzyme complexes that catalyze critical reactions related to acud catabolism breakdown of amino acids and the aci of energy R Aloha-lipoic acid is covalently bound to a specific lysine residue in at least A,pha-lipoic of the proteins in each multienzyme complex.
Anyioxidant a non- protein cofactor is known as a "prosthetic group. R -lipoic acid functions as a prosthetic group for antuoxidant biological activity of the following multienzyme Alpna-lipoic.
i the pyruvate dehydrogenase complex that catalyzes the conversion of pyruvate aciid acetyl-coenzyme A CoAan important substrate for energy production via Alpha-llipoic citric acid cycle. ii the lApha-lipoic dehydrogenase complex that catalyzes the conversion antioxidannt α-ketoglutarate to succinyl CoA, another important intermediate of the citric acid cycle.
iii the branched-chain α-ketoacid dehydrogenase complex that is involved in the decarboxylation of ketoacids in the catabolic Promoting self-care in aging of the branched-chain amino Alpya-lipoic, namely leucine, isoleucine, acjd valine.
iv aantioxidant 2-oxoadipate antioxldant complex that catalyzes the decarboxylation of Alpha-liopic to glutaryl-CoA xntioxidant the catabolic pathway of lysine, hydroxylysine, and tryptophan. All Alpha-lpioic α-ketoacid dehydrogenase complexes contain three enzymatic activities, namely E1, E2, and Alpha-llipoic.
E1 is a thiamin pyrophosphate TPP -dependent α-ketoacid dehydrogenase, Alpha-llipoic -lipoic acid functions as a prosthetic group essential for E2 transacetylase activity, and E3 is a flavin adenine dinucleotide FAD -dependent dihydrolipoamide dehydrogenase Figure 4.
R -lipoic acid is also found in the E3-binding protein protein X component of the pyruvate dehydrogenase complex 5. When considering the biological activities of supplemental unbound lipoic acid, it is important to keep in mind the limited and transient nature of the increases in plasma and tissue lipoic acid see Metabolism and Bioavailability 3.
Scavenging reactive oxygen and nitrogen species : Reactive oxygen species ROS and reactive nitrogen species RNS are highly reactive compounds with the potential to damage DNAproteinsand lipids in cell membranes. Both lipoic acid and dihydrolipoic acid can directly scavenge neutralize physiologically relevant ROS and RNS in the test tube reviewed in 3.
However, whether direct quenching reactions occur in vivo is unknown. The highest tissue concentrations of free lipoic acid likely to be achieved through oral supplementation are at least 10 times lower than those of other intracellular antioxidantssuch as vitamin C and glutathione.
Moreover, free lipoic acid is rapidly eliminated from cells, so any increases in direct radical scavenging activity are unlikely to be sustained. Regeneration of other antioxidants : When an antioxidant scavenges a free radicalit becomes oxidized itself and is not able to scavenge additional ROS or RNS until it has been reduced.
In the test tube, dihydrolipoic acid is a potent reducing agent with the capacity to reduce the oxidized forms of several important antioxidants, including coenzyme Q 10vitamin Cand glutathione Figure 5 16, Dihydrolipoic acid may also reduce the oxidized form of α-tocopherol vitamin E directly or indirectly through regenerating oxidized vitamin C see the article on Vitamin E 18 or oxidized coenzyme Q 10 see the article on Coenzyme Q 10 Whether dihydrolipoic acid effectively regenerates antioxidants under physiological conditions is unclear 3.
Metal chelation : Redox -active metal ionssuch as free iron and coppercan induce oxidative damage by catalyzing reactions that generate highly reactive free radicals Compounds that chelate free metal ions in a way that prevents them from generating free radicals offer promise in the treatment of neurodegenerative diseases and other chronic diseases in which metal-induced oxidative damage may play a pathogenic role Both lipoic acid and dihydrolipoic acid have been found to inhibit copper- and iron-mediated oxidative damage in the test tube 22, 23 and to inhibit excess iron and copper accumulation in animal models 24, Lipoic acid may also be helpful as an adjunct treatment against heavy metal toxicity.
No clinical trial has examined the use of lipoic acid as a chelating agent in mercury toxicity, yet it has proven to be effective in several mammalian species 26, Activation of antioxidant signaling pathways: Glutathione is an important intracellular antioxidant that also plays a role in the detoxification and elimination of potential carcinogens and toxins.
Reductions in glutathione synthesis and tissue glutathione concentrations in aged animals compared to younger ones are suggestive of a potentially lower ability to respond to oxidative stress or toxin exposure Lipoic acid has been found to increase glutathione concentrations in cultured cells and in the tissues of aged animals fed lipoic acid 29, Lipoic acid might be able to increase glutathione synthesis in aged rats by up-regulating the expression of γ-glutamylcysteine ligase γ-GCLthe rate-limiting enzyme in glutathione synthesis 31and by increasing cellular uptake of cysteine, an amino acid required for glutathione synthesis Lipoic acid was found to upregulate the expression of γ-GCL and other antioxidant enzymes via the activation of the nuclear factor E2-related factor 2 Nrf2 -dependent pathway 31 Briefly, Nrf2 is a transcription factor that is bound to the protein Kelch-like ECH-associated protein 1 Keap1 in the cytosol.
Keap1 responds to oxidative stress signals by freeing Nrf2. Upon release, Nrf2 translocates to the nucleus where it can bind to the antioxidant response element ARE located in the promoter region of genes coding for antioxidant enzymes and scavengers.
Lipoic acid — but not dihydrolipoic acid — can react with specific sulfhydryl residues of Keap1, causing the release of Nrf2 For example, the upregulation of the Nrf2 pathway by lipoic acid in cultured hepatocytes and in the liver of obese or diabetic rats prevented lipid overload-induced steatosis 35 and cell death Lipoic acid also protected liver from oxidative stress-induced liver injury in methotrexate-treated rats through the activation of Nrf-2 pathway and other anti-inflammatory pathways Pre-treatment and post-treatment with lipoic acid, respectively, prevented and reversed lipopolysaccharide LPS -induced lung histopathological alterations in rats through Nrf2-mediated HO-1 upregulation Inhibition of nicotinamide adenine dinucleotide phosphate NADPH oxidase NOX : NOX is a plasma membrane-bound enzymatic complex that catalyzes the production of superoxide from oxygen and NADPH and has been involved in innate immune defense against microbes Treatment of gastric cancer cells with lipoic acid limited NOX-generated ROS production and reduced cancer cell proliferation induced by Helicobacter pylori H.
pylori infection The binding of insulin to the insulin receptor stimulates a cascade of protein phosphorylations leading to the translocation of glucose transporters GLUT4 to the cell membrane and an increased cellular uptake of glucose 3 Lipoic acid has been found to activate the insulin signaling cascade in cultured cells 342, 43increase GLUT4 translocation to cell membranes, and increase glucose uptake in cultured adipose and muscle cells 44, A computer modeling study suggested that lipoic acid might bind to the intracellular tyrosine kinase domain of the insulin receptor and stabilize the active form of the enzyme In addition to Nrf2 and insulin signaling pathways, lipoic acid was found to target other cell-signaling molecules thereby affecting a variety of cellular processes, including metabolismstress responses, proliferationand survival.
For example, in cultured endothelial cells, lipoic acid was found to inhibit IKK-β, an enzyme that promotes the translocation of redox -sensitive and pro-inflammatory transcription factornuclear factor-kappa B NFκB from the cytosol to the nucleus Additionally, lipoic acid increased mitochondrial biogenesis through triggering AMP -activated protein kinase AMPK -induced transcription factor PGC-1α activation in skeletal muscle of aged mice Several reviews of the literature have described pathways that are potential targets of lipoic acid in various models and under different experimental conditions Lipoic acid deficiency has been described in rare cases of inherited mutations in the lipoic acid biosynthetic pathway.
Mutations identified in patients with defective lipoic acid metabolism affect genes involved in the synthesis of iron-sulfur clusters and genes coding for lipoic acid synthetase LIASlipoyl transferase 1 LIPT1and dihydrolipoamide dehydrogenase E3 component of α-ketoacid dehydrogenase complexes; DLD 553, Chronically elevated blood glucose concentration is the hallmark of diabetes mellitus.
Type 1 diabetes is caused by the autoimmune destruction of the insulin -producing β-cells of the pancreasleading to an insufficient production of insulin. Exogenous insulin is required to maintain a normal blood glucose concentration i.
In contrast, impaired tissue glucose uptake in response to insulin a phenomenon called insulin resistance plays a key role in the development of type 2 diabetes Although patients with type 2 diabetes may eventually require insulin, interventions that enhance insulin sensitivity may be used to maintain normal blood glucose concentrations.
The term 'prediabetes' is sometimes used to describe early metabolic abnormalities that place individuals at high risk of developing type 2 diabetes.
Of note, these patients are also at high risk for cardiovascular disease. The effect of high-dose lipoic acid on glucose utilization has been primarily examined in individuals with type 2 diabetes. An early clinical trial in 13 patients with type 2 diabetes found that a single intravenous infusion of 1, mg of lipoic acid improved insulin -stimulated glucose disposal i.
A systematic review and meta-analysis identified 20 randomized controlled trials published between and that examined the effect of supplemental lipoic acid on markers of glucose utilization in 1, subjects with metabolic disorders not limited to type 2 diabetes The inner lining of blood vessels, known as the vascular endotheliumplays an important role in the maintenance of cardiovascular health.
In particular, nitric oxide NO regulates vascular tone and blood flow by promoting the relaxation of all types of blood vessels, including arteries — a phenomenon called vasodilation. Alterations in NO-mediated endothelium-dependent vasodilation results in widespread vasoconstriction and coagulation abnormalities and is considered to be an early step in the development of atherosclerosis.
The presence of chronic hyperglycemiainsulin resistanceoxidative stressand pro-inflammatory mechanisms contribute to endothelial dysfunction in patients with diabetes mellitus The measurement of brachial flow-mediated dilation FMD is often used as a surrogate marker of endothelial function.
Two techniques are being used to measure endothelium-dependent vasodilation. One technique measures the forearm blood flow by venous occlusion plethysmography during infusion of acetylcholine. Using this invasive technique, intra-arterial infusion of lipoic acid was found to improve endothelium-dependent vasodilation in 39 subjects with type 2 diabetes but not in 11 healthy controls A more recent randomizeddouble-blindplacebo -controlled study in 30 patients with type 2 diabetes found that intravenous infusion of mg of lipoic acid improved the response to the endothelium-dependent vasodilator acetylcholine but not to the endothelium-independent vasodilator, glycerol trinitrate Another noninvasive technique using ultrasound to measure flow-mediated vasodilation was used in two additional studies conducted by Xiang et al.
The results of these randomized, placebo-controlled studies showed that intravenous lipoic acid could improve endothelial function in patients with impaired fasting glucose 64 or impaired glucose tolerance Peripheral neuropathy is also a leading cause of lower limb amputation in diabetic patients Several mechanisms have been proposed to explain chronic hyperglycemia -induced nerve damage, such as intracellular accumulation of sorbitol, glycation reactions, and oxidative and nitrosative stress reviewed in The results of several large randomized controlled trials indicated that maintaining blood glucose at near normal concentrations was the most important step in limiting the risk of diabetic neuropathy and lower extremity amputation
: Alpha-lipoic acid antioxidant| Source Naturals Alpha Lipoic Acid | An ALA deficiency is practically unheard of. Size: 60 Count Pack of 1. Moreover, the brain has a great sensitivity to oxidative stress-induced damage [ 75 ]. alpha-Lipoic acid administration has been shown to be beneficial in a number of oxidative stress models such as ischemia-reperfusion injury, diabetes both alpha-lipoic acid and dihydrolipoic acid exhibit hydrophobic binding to proteins such as albumin, which can prevent glycation reactions , cataract formation, HIV activation, neurodegeneration, and radiation injury. Two recent meta-analysis evaluate the use of ALA in diabetic neuropathy [ , ]. Was this helpful? In these animals the use of ALA had different actions such as improvement of cardiac function and cardiac fibrosis. |
| Alpha-Lipoic Acid: Weight Loss, Other Benefits and Side Effects | J Clin Invest. product benefit. Autonomic symptoms and heart rate variability were evaluated before and after the intervention. The pharmacology of the antioxidant lipoic acid. Article PubMed Central CAS PubMed Google Scholar Moini H, Tirosh O, Park YC, Cho KJ, Packer L: R-alpha-lipoic acid action on cell redox status, the insulin receptor, and glucose uptake in 3T3-L1 adipocytes. Akbari M, Ostadmohammadi V, Lankarani KB, et al. |
| Alpha Lipoic Acid: Main Benefits and Side Effects | they are helping as he started on keto lost weight and got blood sugar under control. Biochim Biophys Acta. ALA is the cofactor of pyruvate deydrogenase which converts pyruvate to acetil CoA resulting in a decrease in the formation of lactate [ ]. Diet Plan. In general the S-ALA did not show a significant effect upon glucose disposal [ 41 — 43 ]. |
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