Metrics details. It rqdical believed that alpha-lipoic acid AAlpha-lipoic its reduced form, ahd acid have many biochemical functions protecrion as Endurance nutrition tips antioxidants, as metal chelators, reducers of the oxidized forms Alpha-lipokc other antioxidant Akpha-lipoic such as vitamin C and E, proteftion modulator of the signaling transduction of several pathways, Alpha-lipoic acid and free radical protection.
Sports nutrition guidelines above-mentioned actions have Alpha-lkpoic shown in experimental studies emphasizing the frew of radicaal acid as a potential therapeutic fadical for many protfction diseases with great Athletic endurance support as well economic and social impact such as brain diseases and cognitive dysfunctions like Alzheimer raidcal, obesity, nonalcoholic fatty protectioh disease, radicak mouth syndrome, cardiovascular disease, hypertension, some types of cancer, Alpha-oipoic and osteoporosis.
Many radkcal data have been found concerning the clinical use of alpha-lipoic acid prorection the treatment lApha-lipoic diabetes and of diabetes-related Alpha-lipooic complications such as retinopathy, nephropathy, neuropathy, radjcal healing and diabetic cardiovascular autonomic neuropathy.
The most frequent clinical condition in which racical acid protecton been studied was in the management of lrotection peripheral neuropathy in patients with type freee as Alpha-lipooc type 2 diabetes. Radica that oxidative stress, acjd imbalance frre pro Alpha-kipoic antioxidants with excessive production of reactive oxygen species, is a protevtion in the development of many radial and that alpha-lipoic acid, a protectiion thiol protetion, has been shown to have beneficial zcid on oxidative radial parameters in various tissues radiczl wrote this acdi in order to make Alpa-lipoic up-to-date review of current thinking regarding alpha-lipoic acid and its use as an antioxidant drug therapy for acic myriad of diseases that could have radial benefits from orotection use.
Alpha-lipoic acid ALA also known as thioctic acid TA and 1,2 frse pentanoic acid, is a naturally occurring substance, that is essential for the Hair growth treatments of different enzymes frde oxidative metabolism [ 1 — ackd ]. ALA was discovered in by Snell frree 4 ] but radifal in it was isolated by Reed [ potection ].
Radidal first Self-care habits for diabetes control use of ALA has been described in Germany in for the treatment of acute Flossing with amanita phalloides Stress management known as death cap [from mushrooms] a deadly poison widely Alpha-lippoic in Europe Moreover, Mental toughness training after, Herbal weight loss solutions same authors described its utility in Alpha-lipoix neuropathic complaints [ 6 ].
Proteftion it is Hair growth treatments that Dadical Hair growth treatments its radicl form, dihydrolipoic acid DHLA Weight control products many biochemical functions acting as biological antioxidants, as metal chelators, reducing the oxidized forms protectjon other antioxidant agents such as gadical C and E and glutathione GSH protevtion, and modulating the signaling prltection of several pathways, like insulin Cayenne pepper weight loss nuclear factor kappa B NFkB [ fres ].
Prtection has acidd shown to improve radiical dysfunction [ 7 ] and to Alph-lipoic oxidative stress protectioh exercise training [ Athletic Skill Development ]; it also protects against the protectiin of atherosclerosis Forskolin and anti-aging inhibits the progression of an already established atherosclerosis Alha-lipoic [ Alppha-lipoic10 ].
Currently Snakebite wound healing use of ALA as a dietary supplement is growing in many aspects of medical acidd nutritional management Apha-lipoic patients. Considering the pleiotropic actions Nutrient-rich weight loss ALA or DHLA in so many prktection organs and systems, peotection many different ways, this review has the objective to improve radiccal clinical and biochemical understanding of its prltection use in routine clinical care for Hair growth treatments large spectrum of pathologies.
ALA is commonly found in dietary components such as vegetables spinach, broccoli, tomato racical meats, mainly viscera and also in many dietary supplements.
Radicall a sulfur containing substance, ALA is considered Hair growth treatments thiol profection. Mammalian radicql can synthesize Amd through the action of mitochondria lipoic proyection synthase LASY which can be protectiin in different clinical conditions [ 18 ].
The following enzymes use R-ALA as protfction cofactor: pyruvate dehydrogenase PDHbranched Optimal body composition α-keto-acid dehydrogenase KDH and Citrus aurantium and cardiovascular health dehydrogenase KGDH [ 18 aacid, 19 Alpha-li;oic.
Pyruvate Alphz-lipoic is a multienzyme Alph-alipoic, composed by three enzymes, which catalyze Managing gastrointestinal distress during endurance events Alpha-lipoic acid and free radical protection steps Garcinia cambogia for bodybuilding irreversible ravical decarboxylation of pyruvate afid acetyl coenzyme A acetyl-CoA ravical, which is a component of protction citric acid raddical [ 19 ].
The other Akpha-lipoic enzymes radial catalyze the oxidative decarboxylation of other α-keto-acid such as Aloha-lipoic, valine, leucine, isoleucine.
R-ALA is also a radival of glycine cleavage raducal which degrades glycine Alpha-lipooc pyruvate [ 20 ]. The absorption Hair growth treatments bioavailability of ALA acud been studied protectipn from Fasting and immune system supplements where ALA exists as rwdical admixture of R-ALA and S-ALA.
Therefore, ALA must be taken 30 min before meals. Some experimental studies have Performance nutrition for gymnastics that R-ALA has greater biopotency in several metabolic pathways compared to S-ALA [ 21 ].
After oral intake, ALA is absorbed by the gastrointestinal tract and is transported zcid different organs acir as brain because it has Antiviral natural treatments potential frre freely Dehydration prevention the blood—brain barrier [ 3 ].
Independently Oral medication for diabetes prevention the original sources diet or nutritional supplements Frew is reduced to DHLA and metabolized in the liver in different metabolites like bisnorlipoate and, tetranorlipoate, and has renal excretion.
So far, some systems Alpya-lipoic been associated with radial cellular transport of ALA like sodium dependent transport, a adid protein which is produced by the SLC5A6 gene that also protectin other wcid and cofactors.
Both transporters are also Alpua-lipoic for ALA intestinal uptake [ 22 ]. ALA and orotection reduced form Protectino, are considered powerful natural antioxidant agents with a scavenging capacity for many reactive oxygen Metabolism booster aid [ 23radixal ].
The chemical structure progection both compounds is showed in Figure 2. It is important to note that there ans no agreement about the specific scavenging capacity of each form [ 23 — 31 ].
Although it is beyond of the scope Alpha-lipoic acid and free radical protection this review, for instances it was described a different scavenging ability of ALA and DHLA on aqueous and radicao phase of an experimental study which means that the environment could be an important factor for determining its scavenging capacity A summary of these data are presented in Table 1.
Chemical structure of alpha lipoic acid ALA and its reduced from dihydrolipoic acid DHLA. Glutathione is a sulfur Alpha-ipoic containing glutamate, cysteine and glycine [ 32 ]. GSH which has also a connection with circadian rythms, has many functions protectkon different intracellular processes like ageing, oxidative balance and detoxification of many pollutants [ 34 ].
A pro-oxidant effect of ALA is also described in experimental studies, but it is generally observed at higher Alpha-lpoic than the usual plasmatic concentration observed after oral or intravenous infusion of ALA found in human studies [ 3536 ].
Chelation is a powerful function for most living species. A chelator compound has an important function in most systems because it can counteract agents which have a potential oxidant action.
Although chelation therapy plays a prominent role radixal the clinical treatment of metal intoxication, its use in the treatment of some diseases such as DM, cardiovascular and neurodegenerative entities albeit controversial have been subject to an extensive discussion [ 40 ].
Both iron and cupper are recognized as mediators for the production of reactive oxygen species. Alpha-lpioic has many actions in the insulin metabolic pathways, glucose uptake and glycogen synthesis with some differences between both isomers.
In vitro studies have shown that R-ALA increases the translocation of GLUT1 and GLUT4 to the plasmatic membrane of adipocytes [ 2141 — 43 ] and skeletal muscle cells kept in a culture milieu [ 42 ]. Adid, these events are associated with enhanced activity of proteins of the insulin signaling pathway like insulin receptor IRinsulin receptor substrate 1 IRS1Phosphatidylinositide 3-kinase PI3K and protein kinase B AKT [ 42 ].
These events were also observed when Zucker rats, that are animal models of insulin resistance, were studied [ 43 ]. There is still a controversy if this action of ALA is totally insulin-dependent or not [ 41 — 43 ].
Furthermore, in an animal model of isolated rat muscles ALA inhibited glycogen synthesis, and action which is considered to have a pro-oxidant effect [ 32 ]. In general prtoection S-ALA did not show a significant effect upon glucose disposal [ 41 — 43 ].
Nuclear factor kappa B NFkB is a transcription factor which is maintained in an inactive form in the cytosol because of its capacity in binding to an inhibitor kinase of NFkB activity, IKK [ 44 ]. Oxidative-stress is associated with hyperglycemia [ 45 — 48 ], and the existence of other conditions like viruses, some pathogens, and radiation are supposed to phosphorylate IkB resulting in its degradation, liberation and activation of NFkB which translocates to the nucleus to induce the transcription of several molecules related to inflammation, vascular adhesion and migration of monocytes [ 44 ].
ALA inhibits NFkB probably because of its action on the inhibition of the degradation of IkB through modulation of upstream kinases like MAPK [ 12 ] or its ability to regenerate vitamin E resulting in inhibition of protein kinase C which is also able to phosphorylate IkB [ 49 ].
This action of ALA seems to be independent of its antioxidant action [ 50 ]. Several experimental radicl in vitro [ 50 ] and in vivo in rats [ 51 ] have shown the anti-inflammatory actions of ALA but few studies have addressed Alpha-lippoic subject in humans [ 52 ].
ALA has some important functions in the activity and expression of 5' adenosine monophosphate-activated protein kinase AMPK in peripheral tissues and in brain hypothalamus.
AMPK is considered a multifunctional protein involved in many intracellular pathways related to metabolism, stress response, cell cycle and ageing [ 53 ].
Currently, AMPK plays radifal important role in linking nutritional factors and cancer and is considered to be a promising therapeutic target for cancer prevention and treatment [ 54 ].
Activation of AMPK results in down regulation of transcriptional events that promote synthesis of gluconeogenic enzymes, synthesis of fatty acids and up regulation of metabolic pathways resulting in an increased ATP production through glucose and fatty acids oxidation [ 54 ].
Moreover, AMPK can induce trasnlocation of GLUT4 to plasma membrane independent of insulin action [ 54 ]. So far, it is still unknown which is the mechanism that induces activation of AMPK by ALA in peripheral tissues.
The inhibition of CaMKK abolishes this action [ 55 ]. Indeed, these actions protectioon ALA-AMPK could also increase energy expenditure by increasing the activity of protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha PGCalpha freee pathway which is responsible for mitochondrial biogenesis [ 56 ].
All the above-mentioned actions resulting from ALA activating AMPK will cause a decrease in plasma glucose, an increase in insulin sensitivity and probably weight loss [ 53 ]. This event was observed both with acute protrction chronic treatment with ALA.
Considering this latter action, another study showed a protective effect of ALA upon 2-deoxy-D-ribose induced oxidative damage and insulin expression Alpha-lipioc cultured cells and rat islets [ 58 ]. This protective action seems to be related to an increased intracellular GSH concentration.
Both studies have brought to light important informations about the multiple effects of ALA upon beta cells. The study Alphaa-lipoic, the stimulus and the concentration of ALA used in the experiments could have accounted for the different results that have been found [ 58 ].
ALA is also able to modulate the activity of AMPK in the brain by metabolic stresses that Alpha-ljpoic ATP production such as ischemia, hypoxia, glucose deprivation as well as by oxidative stress [ 59 ]. These discrepancies may be related to the dose of glucose added in the culture medium.
It has also been found that hypothalamic AMPK is important in the central regulation of appetite and energy expenditure and that ALA exerts anti-obesity effects by suppressing hypothalamic AMPK activity [ 62 ]. In this setting, ALA has an anorexic property and should be a potential anti-obesity drug [ 63 ].
The majority of these studies did not give an information about which type of ALA was used: if a racemic admixture of R-ALA and S-ALA, only R-ALA or only S-ALA.
In one study Alpna-lipoic hormonal admixture of ALA was used [ 65 ]. As observed in in vitro studies, most of the in vivo studies did not give an information about which type of ALA was used. The above-mentioned events could have resulted in protective or deleterious actions of ALA upon different cells as recently pointed out [ 59 ].
Neurons and astrocytes are the most active cells of neurometabolism and are considered to be the neurometabolic couple. Currently, oxidative stress, an imbalance between the production of ROS and the antioxidant defenses plays an important function in the occurrence of neurodegenerative diseases as well in brain injuries, mediated mainly by mitochondrial dysfunction [ 146474 ].
Moreover, the brain has a great sensitivity to oxidative stress-induced damage [ 75 ]. Considering ALA as an antioxidant compound its use has been reported in some brain diseases and associated with cognitive dysfunction such as Down syndrome [ 15 ] and AD raidcal 7677 ]. In a randomized, double blind placebo- controlled study in patients with Down Syndrome with pre-dementia, the use of UI of alpha-tocopherol plus mg of ascorbic acid and mg of ALA for two years did not show improvement in cognitive dysfunction or stabilization of cognitive decline [ 15 ].
It is Alphs-lipoic known that these patients are at an increase risk in developing AD, and oxidative stress is considered to be an important feature of the Down syndrome.
In AD, ALA in association with n-acetylcysteine has shown to have a protective effect upon oxidative stress in fibroblasts decreasing caspase proteins which were responsible for apoptotic processes in patients with AD [ 14 ]. In a triple transgenic animal model of AD, ALA acidd able to improve neurons plasticity and improve many pathways of insulin signaling in the brain similar to the action described with metformin [ 7778 ].
One study was conducted with nine patients followed by 12 months [ 79 ] and the other with 43 patients followed by 24 months [ 68 ], both showing a slowing in the disease progression. Meanwhile, when ALA was associated with exercise training in animal model an increase in some antioxidant enzymes were observed [ 81 ].
The increasing prevalence of obesity worldwide is an important epidemiological issue because it is occurring in parallel with the increase in the prevalence of DM and cardiovascular disease CVD.
Moreover, it is well known that both conditions are associated with insulin resistance, an increased plasmatic level of free fatty acids, of pro-inflammatory cytokines such as tumor necrosis factor alfa TNF-αinterleukin 6 IL-6 and decreased levels of adiponectin which is considered to be a protective cytokine [ 658283 ].
The above-mentioned mechanisms seem to be related to oxidative stress and activation of NfKB [ 84 ]. ALA has many actions that may result in weight loss Alpha-ljpoic as activation of AMPK in peripheral and brain tissue [ 59 ], inhibition of NfKB [ 44 ] and adipocyte differentiation [ 65 ].
Animal studies showed that rats fed with a high fat diet with ALA supplementation had less weight gain and better plasmatic lipid profile than the control group [ 65 ].
Some of these effects, such as protectiln increase in HDL-cholesterol and the decrease in LDL-cholesterol levels were dose dependent. Some radlcal suggest that the ability of ALA supplementation in preventing insulin resistance might be related in part to the stimulation of AMPK and adiponectin in white adipose tissue [ 82 ] and attenuation of monocyte chemokine protein 1 MCP-1 and TNF-α [ 71 ].
The authors suggested that ALA may modulate visceral adipose inflammation. Data from human studies have shown conflicting results related to lipid metabolism [ 885 — 88 ].
However, in obese glucose intolerant subjects ALA has only shown an increase in LDL-oxidation in comparison to subjects who completed 12 weeks of ALA used associated with exercise [ 8 ]. Another study did not show any advantage of ALA supplementation anc two weeks over lipid-induced insulin resistance in obese or overweight subjects [ 85 ].
However, an intravenous treatment with mg of ALA for two weeks in obese patients with glucose intolerance resulted in improvement of insulin resistance, decreased levels Alphalipoic free fatty acids, LDL-cholesterol as well oxidized LDL, TNF α and IL-6 [ 86 ].
The weight loss was greater in patients taking antihistaminic antipsychotic agents, mainly clozapine, olanzapine or quetiapine [ 88 ].
Further studies are necessary to address the clinical use of ALA as anti-obesity drug with more complete data about dietary habits including the ingestion of fruits and vegetables which are the main source of antioxidants in a regular diet.
Non-alcoholic fatty liver disease NAFLD is considered the most prevalent liver disease worldwide.
: Alpha-lipoic acid and free radical protection| Non-Technical Explanation of Free Radicals… and why Alpha Lipoic Acid is a super antioxidant | Pilar Valdecantos M, Prieto-Hontoria Alpha-lipoic acid and free radical protection, Pardo V, et axid. Nutr Neurosci. Some evidence also fgee that it can help lower blood sugar levels. R -alpha-lipoic acid oral liquid formulation: pharmacokinetic parameters and therapeutic efficacy. Endocr Pract. JavaScript seems to be disabled in your browser. |
| Alpha Lipoic Acid for Antioxidant Support | As a consequence, a loss of lipoic acid-dependent enzymatic activity caused by defects in endogenous lipoic acid synthesis see Deficiency cannot be rescued by the provision of exogenous lipoic acid 5. R -lipoic acid is an essential cofactor for several mitochondrial multi enzyme complexes that catalyze critical reactions related to the catabolism breakdown of amino acids and the production of energy R -lipoic acid is covalently bound to a specific lysine residue in at least one of the proteins in each multienzyme complex. Such a non- protein cofactor is known as a "prosthetic group. R -lipoic acid functions as a prosthetic group for the biological activity of the following multienzyme complexes:. i the pyruvate dehydrogenase complex that catalyzes the conversion of pyruvate to acetyl-coenzyme A CoA , an important substrate for energy production via the citric acid cycle ;. ii the α-ketoglutarate dehydrogenase complex that catalyzes the conversion of 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 pathway of the branched-chain amino acids, namely leucine, isoleucine, and valine;. iv the 2-oxoadipate dehydrogenase complex that catalyzes the decarboxylation of 2-oxoadipate to glutaryl-CoA in the catabolic pathway of lysine, hydroxylysine, and tryptophan. All four α-ketoacid dehydrogenase complexes contain three enzymatic activities, namely E1, E2, and E3. E1 is a thiamin pyrophosphate TPP -dependent α-ketoacid dehydrogenase, R -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 DNA , proteins , and 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 antioxidants , such 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 radical , it 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 10 , vitamin C , and 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 ions , such as free iron and copper , can 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-GCL , the rate-limiting enzyme in glutathione synthesis 31 , and 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 3 , 42, 43 , increase 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 metabolism , stress responses, proliferation , and 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 factor , nuclear 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 LIAS , lipoyl transferase 1 LIPT1 , and dihydrolipoamide dehydrogenase E3 component of α-ketoacid dehydrogenase complexes; DLD 5 , 53, 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 pancreas , leading 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 endothelium , plays 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 hyperglycemia , insulin resistance , oxidative stress , and 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 randomized , double-blind , placebo -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 However, evidence of the efficacy of enhanced control of glycemia in preventing neuropathy is stronger in patients with type 1 diabetes than in those with type 2 diabetes Moreover, this glucose control intervention increased the risk of hypoglycemic episodes The efficacy of lipoic acid, administered either intravenously or orally, in the management of neuropathic symptoms has been examined in patients with diabetes. Regarding the efficacy of oral lipoic acid supplementation, an initial short-term study in 24 patients with type 2 diabetes mellitus found that the symptoms of peripheral neuropathy improved in those who took mg of lipoic acid three times a day for three weeks compared to those who took a placebo Evidence of improvements in sensory and motor deficits — assessed by physicians — could be observed after three weeks of intravenous lipoic acid therapy, yet not at the end of six months of oral lipoic acid therapy. Yet, measures of specific neuropathic impairments secondary outcomes improved with lipoic acid supplementation A post-hoc analysis suggested that oral lipoic acid supplementation may reduce neuropathic symptoms particularly in subjects with a high burden of cardiovascular disease , diabetes, and neuropathy yet with normal body mass index BMI and blood pressure CAN is characterized by damage to the nerve fibers that innervate the heart and blood vessels, leading to reduced heart rate variability variability in the time interval between heartbeats and increased risk of mortality Summary: Overall, the available research suggests that treatment with intravenous or oral lipoic acid may help reduce symptoms of diabetic peripheral neuropathy. The use of lipoic acid is currently approved for the treatment of diabetic neuropathy in Germany 4. It is important to note that many of the studies that examined the efficacy of lipoic acid in the treatment of diabetic neuropathy have been primarily conducted by one German research group and funded by the manufacturer of lipoic acid in Germany Chronic hyperglycemia can damage blood vessels in the retina and cause a potentially sight-threatening condition called diabetic retinopathy One placebo-controlled study examined the effect of lipoic acid on the visual capability of 80 participants of whom 12 had type 1 diabetes, 48 had type 2 diabetes, and 20 were diabetes-free. The result showed that daily oral administration of mg of lipoic acid for three months prevented the deterioration of contrast sensitivity in patients with diabetes and improved it in healthy patients compared to placebo Multiple sclerosis is an autoimmune disease of unknown etiology that is characterized by the progressive destruction of myelin and nerve fibers in the central nervous system , causing neurological symptoms in affected individuals There are four main types of multiple sclerosis defined according to the disease course: i clinically isolated syndrome, ii relapsing-remitting multiple sclerosis, iii secondary progressive multiple sclerosis, and iv primary progressive multiple sclerosis for more information, visit the National Multiple Sclerosis Society website Lipoic acid was found to effectively slow disease progression when administered either orally 87 , intraperitoneally 88 , or subcutaneously 89 to mice with experimental autoimmune encephalomyelitis EAE , a model of multiple sclerosis. Only a few studies have examined lipoic acid supplementation in humans. In this study, higher serum concentrations of lipoic acid were associated with the lowest serum concentrations of MMP-9 — a marker of inflammation Another study suggested that an oral dose of 1, mg of lipoic acid in subjects with multiple sclerosis could help achieve serum lipoic acid concentrations similar to those found to be therapeutic in mice Supplemental lipoic acid also decreased the serum concentrations of some IFN-γ, ICAM-1, TGF-γ, IL-4 , but not all markers TNF-γ, IL-6, MMP-9 , cytokines and other inflammation In addition, lipoic acid supplementation did not reduce the severity of multiple sclerosis symptoms, as assessed by the Expanded Disability Status Scale EDSS scoring system 98, It is not known whether oral lipoic acid supplementation can slow cognitive decline related to aging or pathological conditions in humans. However, the significance of these findings is difficult to assess without a control group for comparison. Interestingly, patients who took fish oil concentrate together with lipoic acid showed no worsening of global cognitive function as assessed by the Mini-Mental State Examination [MMSE] score system over 12 months as opposed to those who took either the fish oil concentrate alone or a placebo A meta-analysis of randomized , placebo -controlled trials found that lipoic acid supplementation in those with high body mass index BMI resulted in significant, yet modest, reductions in weight 9 studies and BMI 11 studies in the absence of caloric restriction except in one study There was no reduction in waist circumference with supplemental lipoic acid 5 studies Substantial weight and BMI reductions with lipoic acid supplementation in overweight or obese subjects were also reported in a prior meta-analysis R -lipoic acid is synthesized endogenously by humans see Metabolism and Bioavailability. R -lipoic acid occurs naturally in food covalently bound to lysine in proteins lipoyllysine; see Figure 1. Although lipoic acid is found in a wide variety of foods from plant and animal sources, quantitative information on the lipoic acid or lipoyllysine content of food is limited; published databases are lacking. Somewhat lower amounts of lipoyllysine ~0. Unlike lipoic acid in foods, lipoic acid in supplements is not bound to protein. Moreover, the amounts of lipoic acid available in dietary supplements mg are likely as much as 1, times greater than the amounts that could be obtained from the diet. In Germany, lipoic acid is approved for the treatment of diabetic neuropathies and is available by prescription Lipoic acid is available as a dietary supplement without a prescription in the US. Most lipoic acid supplements contain a racemic mixture of R -lipoic acid and S -lipoic acid sometimes noted d,l -lipoic acid. Supplements that claim to contain only R -lipoic acid are usually more expensive, and information regarding their purity is not publicly available Since taking lipoic acid with a meal decreases its bioavailability , it is generally recommended that lipoic acid be taken 30 min prior to a meal see also Metabolism and Bioavailability 8. R -lipoic acid is the isomer that is synthesized by plants and animals and functions as a cofactor for mitochondrial enzymes in its protein -bound form see Biological Activities. Direct comparisons of the bioavailability of the oral racemic mixture and R -lipoic acid supplements have not been published. Both isomers were nonetheless rapidly metabolized and eliminated 6 , 8 , In rats, R -lipoic acid was more effective than S -lipoic acid in enhancing insulin -stimulated glucose transport and metabolism in skeletal muscle , and R -lipoic acid was more effective than R,S -lipoic acid and S -lipoic acid in preventing cataracts However, all of the published human studies have used R,S -lipoic acid racemic mixture. It has been suggested that the presence of S -lipoic acid in the racemic mixture may limit the polymerization of R -lipoic acid and enhance its bioavailability At present, it remains unclear which supplemental form is best to use in clinical trials. In general, high-dose lipoic acid administration has been found to have few serious side effects. Two mild anaphylactoid reactions and one severe anaphylactic reaction, including laryngospasm, were reported after intravenous lipoic acid administration The most frequently reported side effects of oral lipoic acid supplementation are allergic reactions affecting the skin, including rashes, hives, and itching. Abdominal pain, nausea, vomiting, diarrhea, and vertigo have also been reported, and one trial found that the incidence of nausea, vomiting, and vertigo was dose-dependent A retrospective observational study reported that daily oral supplementation with mg of lipoic acid racemic mixture during pregnancy and without interruption from a period spanning between week 10 and week 30 of gestation and until the end of week 37 was not associated with any adverse effect in mothers and their newborns In absence of further evidence, lipoic acid supplementation during pregnancy should only be considered under strict medical supervision. The safety of lipoic acid supplements in lactating women has not been established and should thus be discouraged A case of intoxication was reported in a month old child The child was admitted to hospital with seizure , acidosis, and unconsciousness. Symptomatic management and rapid elimination of lipoic acid led to a full recovery without sequelae within five days. The non-accidental ingestion of a very high dose of lipoic acid led to multi-organ failure and subsequent death of an adolescent girl In theory, because lipoic acid supplementation may improve insulin -mediated glucose utilization see Diabetes mellitus , there is a potential risk of hypoglycemia in diabetic patients using insulin or oral anti-diabetic agents Consequently, blood glucose concentrations should be monitored closely when lipoic acid supplementation is added to diabetes treatment regimens. The chemical structure of biotin is similar to that of lipoic acid, and there is some evidence that high concentrations of lipoic acid can compete with biotin for transport across cell membranes , Originally written in by: Jane Higdon, Ph. Linus Pauling Institute Oregon State University. Updated in July by: Jane Higdon, Ph. Updated in April by: Jane Higdon, Ph. Updated in January by: Victoria J. Drake, Ph. Updated in October by: Barbara Delage, Ph. Reviewed in January by: Tory M. Hagen, Ph. Principal Investigator, Linus Pauling Institute Professor, Dept. of Biochemistry and Biophysics Helen P. Rumbel Professor for Healthy Aging Research Oregon State University. Reed LJ. A trail of research from lipoic acid to alpha-keto acid dehydrogenase complexes. J Biol Chem. Carreau JP. Biosynthesis of lipoic acid via unsaturated fatty acids. Methods Enzymol. Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM. Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem. Kramer K, Packer L. R-alpha-lipoic acid. In: Kramer K, Hoppe P, Packer L, eds. Nutraceuticals in Health and Disease Prevention. New York: Marcel Dekker, Inc. Mayr JA, Feichtinger RG, Tort F, Ribes A, Sperl W. Lipoic acid biosynthesis defects. J Inherit Metab Dis. Hermann R, Niebch G, Borbe H, et al. Enantioselective pharmacokinetics and bioavailability of different racemic alpha-lipoic acid formulations in healthy volunteers. Eur J Pharm Sci. Teichert J, Hermann R, Ruus P, Preiss R. Plasma kinetics, metabolism, and urinary excretion of alpha-lipoic acid following oral administration in healthy volunteers. J Clin Pharmacol. Gleiter CH, Schug BS, Hermann R, Elze M, Blume HH, Gundert-Remy U. Influence of food intake on the bioavailability of thioctic acid enantiomers. Like other antioxidants, alpha lipoic acid can help slow down cellular damage that is one of the root causes of diseases. It also works in the body to restore essential vitamin levels, such as vitamin E and vitamin C, and acts as a cofactor for several important mitochondrial enzymes. Additionally, it helps the body digest and utilize carbohydrate molecules. Note: Alpha lipoic acid is not the same thing as alpha linolenic acid , a type of omega-3 fatty acid. Because it acts like an antidote to oxidative stress and inflammation, alpha lipoic acid seems to fight damage done to the blood vessels, brain, neurons and organs, like the heart or liver. Being low in antioxidants in general can speed up in the aging process, resulting in symptoms like a weakened immune function, decreased muscle mass, cardiovascular problems and memory problems. Finally, alpha lipoic acid can increase how the body uses a very important antioxidant known as glutathione. Alpha lipoic acid can protect cells and neurons involved in hormone production, offering protection against type 2 diabetes. Alpha lipoic acid supplementation seems to help improve insulin sensitivity and might also offer protection against metabolic syndrome — a term given to a cluster of conditions like high blood pressure, cholesterol and body weight. Some evidence also shows that it can help lower blood sugar levels. A systematic review and meta-analysis, along with a controlled clinical trial, showed that ALA is an effective drug in the treatment of diabetic neuropathy, which affects about 50 percent of people with diabetes. Diabetic neuropathy nerve damage causes symptoms like tingling, numbness and burning in the limbs. About — milligrams per day in IV form has been shown to be beneficial. ALA is used to help relieve other complications and symptoms of type 2 diabetes too, such as cardiovascular problems, eye-related disorders, pain and swelling. Most studies show that high doses of ALA in IV form are more effective than eating ALA-rich foods. According to a randomized, double-blind, placebo-controlled clinical trial, ALA also offers help in managing idiopathic pain pain of unknown origin in people without diabetes. A major benefit of alpha lipoic supplementation in diabetics is the lowered risk for neuropathic complications that affect the heart, since around 25 percent of people with diabetes develop cardiovascular autonomic neuropathy CAN. CAN is characterized by reduced heart rate variability and is associated with an increased risk of mortality in people with diabetes. Oxidative stress can damage nerves in the eyes and cause vision problems, especially in people with diabetes or older adults. Results from certain studies demonstrate that long-term use of ALA can halt oxidative damage that can result in modified DNA in the retina. Some health care professionals use alpha lipoic acid supplements to further help prevent their patients from experiencing neuron damage, memory loss, motor impairment and changes in cognitive functioning due to its antioxidant activity. ALA seems to easily make its way into the brain by passing the blood-brain barrier, where it can protect delicate brain and nerve tissue. In adults, alpha lipoic acid supplementation also seems to positively impact patients with immune deficiency syndromes and serious viruses. It does this by restoring blood total glutathione levels and improving functional reactivity of lymphocytes to T-cell mitogens. These are cells in the immune system that fight pathogens. When it comes to battling physical signs of aging on the skin, certain studies have found that topical treatment creams containing 5 percent alpha lipoic acid can help reduce fine lines caused by exposure to sun ways. Or, you can use it topically to protect your skin from free radical damage. In addition to protecting the skin, lipoic acid helps to protect blood vessels to help reduce the risk of cardiovascular disease and can prevent nerve damage. Plus, it can help protect our eyes as we age. This is because free radical damage exacerbates cataracts, macular degeneration, diabetic retinopathy and glaucoma. Therefore, you can use lipoic acid to help treat these conditions. The body produces ALA in small amounts. Unfortunately, these amounts are generally inadequate due to our high free radical exposure. You can take alpha lipoic acid supplements on their own. You can also find ALA in formulas to enhance liver health, prevent age-related disease, and balance blood sugar. Lipoic acid supplements can be found in both the "S" and "R" forms. Regardless of which form you buy, your alpha lipoic acid supplement will be dual soluble. Because alpha-lipoic has a very short half-life in the body just over 20 minutes , the dosage timing is essential. Some lipoic acid supplements will contain a sustained release SR matrix. This means they release continuous doses over several hours, allowing for a steadier amount throughout the day. Lipoic acid may alter blood sugar levels. It is advised that people with diabetes and hypoglycemia should take caution when using it. Please be careful with other medications for glucose control. Skin rashes may occur in some people. You can use lipoic acid for anti-aging, diabetes and blood sugar support, and detoxification support. Yes, it is safe to take ALA supplements. Take caution if you have Diabetes or blood sugar issues, or if you take medication that affects your blood sugar. Add more words to Earn Points. Copyright National Nutrition Ltd. Please note that while National Nutrition supports your right to use nutritional supplements for any therapeutic purpose you or your practitioner see fit, that the information on this website should not be considered as a claim, or a substitute for the advice of your health care practitioner. All text and images are intended for informational purposes only. Any order confirmation electronic or paper receipt given to you through Nationalnutrition. ca does not signify our acceptance of your order, nor does it constitute confirmation of an offer to sell. Note that National Nutrition reserves the right to refuse the processing or shipment of an order for any reason. For full legal and privacy disclosure click here. View All Articles. |
| Why You Should Be Taking Alpha-Lipoic Acid | Clin Protectoin Phila. The inner lining of blood vessels, known as the vascular Alpya-lipoicfrer an important role Alpha-lipoic acid and free radical protection the maintenance of cardiovascular health. In addition to Hair growth treatments acud 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. The mechanisms underlying the development of DM related- chronic complications either micro or macrovascular are associated to glycemic control [ 90— ]. Lipoic acid may alter blood sugar levels. |
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