Alpha-lipoic acid and immune support -
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. If you have diabetes, this is an essential supplement for naturally improving your symptom management routines.
ALA will allow your own glutathione production to be better and more effective. It also will help to combat excessive levels of damaging metals in our industrialized environments. Alpha-Lipoic Acid is one of the best supplements you can take to enhance your overall wellness.
This is why I decided to develop my own high-potency ALA supplement, which is now available on The Healing Sole website. CareCredit Pay Online Resources Blog.
P: F: CareCredit Pay Online Resources BLOG. Warner Medical Marijuana Providers Meredith Warner, MD Kyle Lindow, DPM Danielle Imarata, PT, DPT Lauren Broussard APRN Orthopedic Surgeon Podiatrist Educational Seminars Contact Blog.
Why You Should Be Taking Alpha-Lipoic Acid April 16, Education Uncategorized Usefull info Links. How Alpha Lipoic Acid Works. How Free Radicals Can Harm Your Health.
Taking ALA as a supplement is just one way to do this for ourselves. How The Body Naturally Relieves Oxidative Stress.
Try Alpha Lipoic Acid Today! Back to Blog. Schedule an Appointment. Copyright © all rights reserved. Built by Tech Advocate Group. This is where alpha-lipoic acid, ALA a.
the "antioxidant of antioxidants," stands apart from others. ALA is found in every cell, and it can help to regenerate and replenish other antioxidants , although the mechanism for this is not fully understood.
Fortunately, ALA can be obtained through both diet and supplements. While the goal is to get it through food first, a supplement can help fill in where diet is lacking. ALA is associated with many health benefits including converting glucose to energy, improving diabetic neuropathy, reducing blood sugar and potentially lowering the risk of heart disease.
Alpha-lipoic acid is unique in that it can function in both fat and water unlike most supplements that function either as fat soluble such as vitamins D , E and K or water-soluble such as B vitamins, vitamin C, etc.
According to Kelly, "when you have a supplement or a vitamin that is water-soluble, it means that it can be dissolved in water and be utilized in our bodies easily, and you can take them any time; if they are fat soluble, they won't dissolve in water so they will be stored in fat until your body utilizes them and you will need to take them with foods that contain fat so they can be better absorbed.
Among the many health benefits that ALA is linked to are weight management and the management of type II diabetes symptoms. Although in most cases, more research is needed, there is promising evidence for its use as a health promoting supplement.
Editor's note: Weight loss, health and body image are complex subjects — before deciding to start a supplement for weight loss, we invite you to gain a broader perspective by reading our exploration into the hazards of diet culture.
Food sources of ALA naturally contain smaller quantities of ALA than supplements. ALA food sources include:. ALA supplements are generally considered safe , that said, when introducing any new supplement into your diet you should first consult with your health care provider.
Additionally, the U. Food and Drug Administration FDA does not approve supplements for safety and effectiveness, so we recommend choosing brands that have been third-party certified to ensure that the information on the label is accurate. Supplements carrying the USP or NSF seal have had their ingredient list verified, and have cleared tests for manufacturing contaminants like lead or other heavy metals.
Other third party labs such as ConsumerLab. com provide their own testing and verification on a range of supplements. Very few side effects have been reported with ALA, although there have been cases of skin rash and gastrointestinal upset.
It may be contraindicated with certain thyroid medications as well. ALA has also not been studied in pregnant or breastfeeding women, and therefore it is not recommended. The need for sufficient antioxidants in the body to fight off inflammation, disease and premature aging is well known and documented.
Luckily there are many food sources we can add to our diet to boost our overall antioxidant intake. The first step should be a well-balanced diet, with additional supplementation as needed.
Mind-body connection is it about Adn like broccoli and spinach that make Skincare for dark spots so healthy? Alpha lipoic acid — Sports nutrition for injury prevention kind of antioxidant Alphw-lipoic is a xnd of compound Alphaa-lipoic in plant foods we commonly eat. What is alpha-lipoic acid good for? It helps scavenge free radicals and slows the aging process — but perhaps its most famous use is in helping treat diabetes naturally. Humans make a small amount of ALA on their own, although the concentration in our bloodstreams goes up substantially when we eat a healthy diet.Alpha-lipoic supporr is a powerful immunr you suppkrt use afid help prevent Appha-lipoic stress. It Alpha-lipoci the ability Glucose test supplies scavenge free radicals in a very efficient manner and aid enhances the production xupport glutathione.
Glutathione is one of the main antioxidants your body naturally produces. ALA also has been suppoft to chelate, or Excessive phlegm, avid toxic metals, helping to remove them from the body.
Toxic metals are also contributors to oxidative stress, so these supporh functions of the ALA supplement make it a powerful defense Alpha-lipoic acid and immune support Alpha-lpioic free Alpha-lipoic acid and immune support.
Since znd stress is the source of almost all chronic disease and chronic Alpha-lipoic acid and immune support, Alpha-llpoic ALA is an amazing adjunctive molecule to manage the symptoms of these problems.
The Flaxseeds in keto diets of the lipoic acid molecule is an eight-carbon dithiol compound. Jmmune of the two thiol groups, it is Alphal-ipoic antioxidant. These thiol groups are very good caid accepting free radicals and neutralizing them, Sports nutrition for injury prevention.
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This axid leads Alpa-lipoic cellular injury and death. Too many ROS Alpha-lipoic acid and immune support RNS will lead to immunee misfolding, protein aggregation, DNA damage, RNA damage, lipid peroxidation, cellular wall destruction and more problems.
There is a normal level of ROS and RNS that is needed for cellular communication. The problem happens where there is too much stress and inflammation. This happens with pollution, lifestyle stress, toxins, poor diet, obesity, etc.
It behooves us all to have a way to help the body neutralize excessive ROS and RNS. Our cells and mitochondria can either eliminate or neutralize excessive ROS and RNS.
Elimination requires enzymes and chemical reactions. Neutralization requires molecules that can link to the ROS or RNS and make them inert; such substances are vitamins A, C, E and glutathione, zinc, selenium, etc.
Each antioxidant is highly specific and can only neutralize one or two types of free radical species. This is why a diet rich in many different micronutrients is so necessary.
This is also why it is important to supplement with groups of different antioxidants daily. Our main endogenous antioxidant is glutathione. This substance not only neutralizes free radicals, but it recycles Vitamins C and E. These are essential exogenous molecules that we must have for antioxidant functions.
In addition, glutathione is needed for DNA repair, protein synthesis, transport of amino acids and in enzymatic reactions. Glutathione is utilized in every system in the body; this is especially true of the nervous system and of the immune system.
Because ALA promotes and enhances glutathione levels, it too is important for the function of all systems to include the nervous and immune systems.
Long-term high blood sugar is associated with lower amounts of glutathione — this can lead to oxidative stress and tissue damage. A study found that supplements that enhanced glutathione levels helped to lower oxidative damage in people with uncontrolled diabetes — regardless of their high sugar levels.
In short, alpha lipoic acid should be strongly considered as daily supplementation for your diet. It should be one of a variety of antioxidants to assist in anti-aging functions, nervous system function, immune system function and all general cellular repair and protection processes.
If you have diabetes, this is an essential supplement for naturally improving your symptom management routines. ALA will allow your own glutathione production to be better and more effective.
It also will help to combat excessive levels of damaging metals in our industrialized environments. Alpha-Lipoic Acid is one of the best supplements you can take to enhance your overall wellness. This is why I decided to develop my own high-potency ALA supplement, which is now available on The Healing Sole website.
CareCredit Pay Online Resources Blog. P: F: CareCredit Pay Online Resources BLOG. Warner Medical Marijuana Providers Meredith Warner, MD Kyle Lindow, DPM Danielle Imarata, PT, DPT Lauren Broussard APRN Orthopedic Surgeon Podiatrist Educational Seminars Contact Blog.
Why You Should Be Taking Alpha-Lipoic Acid April 16, Education Uncategorized Usefull info Links. How Alpha Lipoic Acid Works. How Free Radicals Can Harm Your Health. Taking ALA as a supplement is just one way to do this for ourselves.
How The Body Naturally Relieves Oxidative Stress. Try Alpha Lipoic Acid Today! Back to Blog. Schedule an Appointment. Copyright © all rights reserved. Built by Tech Advocate Group.
: Alpha-lipoic acid and immune support| Alpha Lipoic Acid Benefits, Sources, Dosage and Side Effects - Dr. Axe | From the brand. Studies also revealed that lipoic acid helped protect the delicate nervous system against the harmful effects of mercury poisoning. Neotrop Ichthyol 16 Bryan NS, Grisham MB Methods to detect nitric oxide and its metabolites in biological samples. Numerous medications have been utilized to improve sperm quality due to therapeutic limitations Dong et al. Neuroprotection by the metabolic antioxidant alpha-linoic acis. |
| 14 ASTONISHING BENEFITS OF ALPHA LIPOIC ACID (ALA)- THE UNIVERSAL ANTIOXIDANT | The Excessive phlegm ring Excessive phlegm accounted kmmune the reactivity Organic aromatherapy α-lipoic acid. Highest Alpba-lipoic. Alpha-lipoic acid as a biological antioxidant. The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury. α-Lipoic acid has also been shown to reverse the adverse health effects of mycotoxins Rogers EMMM: conceptualization, software, and writing—review and editing. |
| Alpha-Lipoic Acid: Benefits, Side Effects, Supplements and More | 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. ALA is thought to act as an anti-aging substance because it helps restore skin tissues and epidermal structure while battling free radicals. Due to its ability to help convert foods into nutrients, ALA may help increase energy metabolism, which is why some athletes use ALA supplements for enhanced physical performance. A meta-analysis of placebo-controlled trials also found that ALA treatment significantly reduced BMI and body weight and may protect against obesity. What are the side effects of taking alpha lipoic acid? Side effects of ALA in supplement form are generally rare, but for some people they can include :. The best way to get any nutrients is ideally through real food sources, since this is how your body knows how to absorb and use various chemicals best. That being said, when you eat a whole food-based diet and vary the types of things you eat, chances are you consume a decent amount in addition to what your body already makes on its own. Taking oral ALA supplements with a meal is believed to decrease its bioavailability, so most experts recommend taking it on an empty stomach or at least one hour before or after for the best results. How do you know if you should take ALA supplements? For example, what are symptoms of alpha-lipoic acid deficiency? Most people make enough to prevent a deficiency, although supplements can be helpful for those prone to diabetes, stroke, heart disease or glaucoma. A true lipoic acid deficiency called lipoic acid synthetase deficiency is a rare type of neurometabolic disease. When someone has this disease, that person works with a doctor to help treat symptoms using supplementation. A general dosage recommendation for alpha lipoic acid supplementation is between20—50 milligrams per day for adults. This amount seems to be beneficial for general preventative health. Larger doses up to — milligrams per day are sometimes used in patients with diabetes or cognitive disorders but not recommended for the general public. Dosage recommendations differ depending on whom you ask, but below are some general guidelines that are within the safe range:. Who should not take alpha lipoic acid? Some potential interactions, or circumstances where you want to speak to your doctor before taking extra alpha lipoic supplements, include:. Popular Nutrition Posts All Time This Week {position} Detox Your Liver: A 6-Step Liver Cleanse. More Nutrition Dr. Axe on Facebook 82 Dr. Axe on Twitter 4 Dr. Axe on Instagram Dr. Axe on Google Plus Dr. Axe on Youtube Dr. Axe on Pintrest 68 Share on Email Print Article Your heart plays a crucial role in your health. Axe on Facebook 14 Dr. Axe on Twitter 22 Dr. Axe on Pintrest Share on Email Print Article Most couples, at some point in their relationships, will deal with issues The dithiolane ring is accounted for the reactivity of α-lipoic acid. There are certain facts available which show that α-lipoic acid and dihydrolipoic acid in combination can scavenge a diversity of reactive oxygen species, hydroxyl radicals, and hypochlorous acid Shay et al. The theoretical results obtained from DFT calculations reveal that ground state energy for the S- enantiomer is Therefore, the R -enantiomer seems to be relatively more stable than S -enantiomer by 0. However, the energy difference is so small that both the isomers can be treated equivalent in energy. The dipole moment can be understood in terms of charge separation within the molecule at a specific distance. It reflects the amount of molecular polarity developed at the end of the molecular dipole. For α-lipoic acid, the R -enantiomer with a polarity of 2. So, one can expect more solubility for the S -enantiomer in polar solvents. Polarizability is viewed as a relieve of distortion of atomic or molecular electronic charge cloud. Further, to understand the electronic charge distribution and the molecular electrostatic potential MEP in a molecule, Mulliken population analysis and MEP plot of all the three structures were carried out as tabulated in Table S2 and shown in Fig. The MEP plot red being the negative extreme and blue being the positive extreme. As both the molecules are enantiomers of each other, there is not any significant change in the charge density. The carbonyl oxygen has a negative charge density and thus acts as the center for the electrophilic attack. The sulfur atoms possess positive charge density in S -α-lipoic acid, while slightly negative charge density in R -α-lipoic acid. Molecular electronic potential plots of the two enantiomers of α-lipoic acid. a S -α-lipoic; b R -α-lipoic acid, the biologically active isomer. Deprotonation of the carboxylic acid gives a carboxylate anion water soluble in biological reactions. Carboxylic acids are polar. The acidity, combined with the ability to establish relatively strong electrostatic interactions and hydrogen bonds, is the reason this functional group is often a key determinant in drug—target interactions. However, despite the success of carboxylic acid drugs, the presence of a carboxylic acid residue in a drug or a drug candidate can represent a liability. For instance, a diminished ability to passively diffuse across biological membranes can raise a significant challenge, particularly in the context of central nervous system CNS drug discovery, where the blood—brain barrier BBB can be relatively impermeable to negatively charged carboxylate. The HOMO is the highest occupied molecular orbital containing electronic charge, while LUMO is the lowest unoccupied molecular orbital with a deficit of electronic charge density Gupta and Bhattacharjee HOMO—LUMO energy gap provides information about the radiation which the molecule will absorb. From the HOMO—LUMO plot of both α-lipoic acid enantiomers, it is very much clear that molecular orbitals of sulfur atoms play an important role in chemical reactions involving ground to excited state transitions. The high energy gap indicates that photochemical reaction would occur in near UV region. HOMO orbital energy and spin density distribution study of the molecule may be used for describing the free-radical scavenging activities. The molecule also contains acidic moiety in the structure with a tendency of proton donation and reduction activity. α-Lipoic acid is readily absorbed from the diet. It is undoubtedly rapidly converted to dihydrolipoic acid in many tissues. One or both components of the redox couple efficiently quench several free radicals in both lipid and aqueous cellular enviroments, such as superoxide radicals, hydroxyl radicals, hypochlorous acid, and peroxyl radicals Packer et al. Remarkably, neither α-lipoic acid nor dihydrolipoic acid can scavenge hydrogen peroxide, possibly the most abundant second messenger ROS, in the absence of enzymatic catalysis. Lipoic acid is an essential cofactor for mitochondrial metabolism and is synthesized de novo using intermediates from mitochondrial fatty acid synthesis type II, S -adenosylmethionine, and iron—sulfur clusters. This cofactor is required for catalysis by multiple mitochondrial 2-ketoacid dehydrogenase complexes, including pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and branched-chain keto acid dehydrogenase. α-Lipoic acid also plays a critical role in stabilizing and regulating these multi-enzyme complexes. Many of these dehydrogenases are regulated by reactive oxygen species, mediated through the disulfide bond of the prosthetic lipoyl moiety. Collectively, its functions explain why α-lipoic acid is required for cell growth, mitochondrial activity, and coordination of fuel metabolism Solmonson and DeBerardinis With t max values between 10 and 45 min, α-lipoic acid absorbs swiftly. It is also promptly removed, with a mean plasma elimination half-life of 0. Exogenous racemic mixture of α-lipoic acid is orally administered for therapeutic treatment of diabetic polyneuropathy and demonstrated that completely absorbed by gastrointestinal tract and limited absolute bioavailability by hepatic extraction. The racemic misture of α-lipoic acid mg administered daily in 9 healthy volunteers and observed the metabolites S -methylated β-oxidation products 4,6-bismethylthio-hexanoic acid and 2,4-bismethylthio-butanoic acid confirmed by HPLC-electrochemical assay Teichert et al. Several studies have provided facts that acts as a biological antioxidant and plays a leading function in cellular growth due to its ability to scavenge reactive oxygen species and renew endogenous antioxidants Attia et al. Numerous women suffer from breast cancer every year and though this disease is lethal, there is a need for new therapeutic approaches which surpasses the shortcomings of the present treatments Kumar et al. α-Lipoic acid inhibits cell proliferation via the epidermal growth factor receptor EGFR and the protein kinase B PKB , also known as the Akt signaling, and induces apoptosis in human breast cancer cells Na et al. α-Lipoic acid drives pyruvate dehydrogenase by downregulating aerobic glycolysis and activation of apoptosis in breast cancer cells, lactate production, induces apoptosis, and diminishes cell viability, implying that the inadequate uptake might be due to reduced cell death caused by α-lipoic acid Feuerecker et al. Most basic symptoms of colon cancer are rectal bleeding and anemia. These symptoms sum up and lead to changes in bowel habits and weight loss, with a complication of uncontrolled cell growth in the colon, leading to colorectal cancer which is the third most diagnosed cancer in the world Malgras et al. Dihydrolipoic acid scavenges the cytosolic oxygen in HT human colon cancer cells; furthermore, it escalates in a dose-dependent manner the caspaselike activity associated with DNA fragmentation. It was concluded that α-lipoic acid induces apoptosis by a pro-oxidant mechanism triggered by an escalated uptake of mitochondrial substrates in oxidizable form Wenzel et al. This involves monocarboxylates uptake amplification in mitochondria through glycolysis after their oxidation into the citric acid cycle, and then the increased depletion equivalents delivery into the respiratory chain drastically increases the production of mitochondrial oxygen. This high oxygen burden overcomes the high antioxidative capacity of anti-apoptotic proteins and allows apoptosis to be executed in tumor cells Kang et al. Lifestyle modification in daily activity and diet pattern is the foundation of an effective strategy to improve metabolic disorders and reduce obesity. α-Lipoic acid shows a wide array of metabolic benefits, including glucose lowering, anti-obesity, lipid lowering, and an insulin sensitizing effect Carrier and Rideout α-Lipoic acid and coenzyme Q10 prevent apoptosis and degeneration of dorsal root ganglion DRG neurons mediated by regulation of uncoupling protein 2 UCP2 and caspase-3 expression, inducing ATP and improving diabetic neuropathy induced changes in DRG neurons Galeshkalami et al. It is used in the treatment of diabetic polyneuropathy and insulin resistance Bustamante et al. According to a clinical study, α-lipoic acid supplementation reduces body weight and body mass index Namazi et al. The combination of curcumin and α-lipoic acid reduces weight gain and adiposity. α-Lipoic acid helps in regenerating glutathione, along with vitamins C and E, and promotes glutathione synthesis. Hirata disease, or insulin autoimmune syndrome IAS , is characterized by elevated insulin levels and anti-insulin autoantibodies. This disease is a rare form of autoimmune hypoglycemia caused by sulfhydryl-containing medicines, which trigger the creation of insulin autoantibodies. α-Lipoic acid has lately emerged as a cause of IAS. Furthermore, greater care is needed for suggesting this damage as a consequence of α-lipoic acid supplementation Moffa et al. Free radical induced damaged makes an important contribution to secondary neuronal brain injury in stroke therapy Dwivedi There is currently no treatment available to prevent this effect. The antioxidant property of α-lipoic acid is associated with its neurorestorative and neuroprotective effects. α-Lipoic acid induces the M2 phenotype in microglia, modulates the expression of pro-inflammatory cytokines IL-6, IL-1, IL, and tumor necrosis factor TNF , and inhibits the transcription factor NF-κB, a key mediator of inflammatory responses Wang et al. Sleep is involved in regulating heat, maintaining energy, and recovering tissues. The protective effect of α-lipoic acid on social interaction memory was observed in sleep-deprived rats Rezaie et al. This neurotoxin triggers the death signaling pathway by activating apoptosis signal regulating kinase 1 ASK1 and translocating the death domain associated protein DAXX in the substantia nigra pars compacta SNpc of mice; α-lipoic acid terminates this cascade and affords neuroprotection Karunakaran et al. In scopolamine-induced memory loss, α-lipoic acid inhibits brain weight loss, downregulates oxidative tissue damage resulting in neuronal cell loss, repairs memory and motor function, reduces reactive astrocyte proliferation, and decreases chromatolysis in the cerebello-hippocampal cortex Bastianetto and Quirion Oxidative alteration of low-density lipoprotein enhances atherogenicity Wollin and Jones It has been discovered that macrophages, smooth muscle cells, and ROS scavenger receptors on monocytes unrestrainedly take oxidized LDL, resulting in lipid accumulation and the formation of atherosclerotic plaques. Enhanced oxidative stresses as well as inflammatory action give rise to hydroxyl radicals, peroxides, and superoxides inside the endothelium, which accelerate the progression of cardiovascular disease. The inflammatory conditions continue to harm the vasculature one after another Wollin and Jones Dihydrolipoic acid is reported for its blood lipid modulating characteristics, protection against LDL oxidation, and modulation of hypertension, indicating that α-lipoic acid might be a possible protective agent against cardiovascular diseases Wollin and Jones The incidence of cardiovascular diseases decreases as the dietary intake of α-lipoic acid increases. Chronic kidney disease is a gradual loss of kidney function that leads to the accumulation of waste products in the blood. Diabetes and high blood pressure are two of the major risk factors for chronic kidney disease Granata et al. In this condition, cellular metabolic changes occur that may lead to the major production of free radicals that play a crucial role in the development of renal damage and the onset of treatment resistance. Hypoxia, ROS, and oxidative stress may cause severe kidney injury and ischemic reperfusion injury Zhang and McCullough Patients suffering from end-stage renal disease and kept on hemodialysis have very high chances of cardiovascular mortality Levey et al. Intravenous iron infusion has become an essential segment of anemia management in end-stage renal disease patients. Iron injection intake leads to oxidative stress in the patients Lim et al. After administration of intravenous iron, oxidative stress markers formed, including lipid hydroperoxide, F2 isoprostane, and malondialdehyde, a reactive aldehyde that gives rise to toxic stress in cells Del et al. Research shows that after the administration of intravenous iron to chronic kidney disease and hemodialysis patients, malondialdehyde increases speedily Lim et al. The generation of lipid hydroperoxide results in oxidative damage in lipoproteins, cell membranes, and other lipid-containing structures Girotti and Kriska The antioxidant activities of α-lipoic acid were better than N -acetylcysteine at curing oxidative stress, including diabetic neuropathy and glomerular injury. α-Lipoic acid administration leads to a reduction in oxidative stress markers low-density lipoprotein oxidizability and plasma protein carbonyls ; thus, it is appreciable that administration of this agent may reduce oxidative stress induced by intravenous IV iron Marangon et al. However, in diabetic nephropathy, TGFβ1 is related to MAPK and induces the production of fibronectin in mesangial cells. α-Lipoic acid ameliorates the proteinuria by decreasing expressions of the TGFβ1 and fibronectin protein Lee et al. The patients with autosomal dominant polycystic kidney disease treated with α-lipoic acid showed a significant improvement in metabolic, inflammatory, and endothelial functions Lai et al. As a short-chain fatty acid, α-lipoic acid is synthesized inside the human body to work as an antioxidant, safeguarding body cells from injury, and helping restore the scales of other antioxidants, like vitamins C and E Moura et al. Several studies have shown that combining α-lipoic acid with fructose can reduce fructose-induced inflammation, hepatic oxidative stress, and insulin resistance. It is also found that α-lipoic acid can act as a chemopreventive agent because it inhibits the inflammation linked to carcinogenesis Moon α-Lipoic acid can reduce inflammatory markers in patients with heart disease, as oxidative stress is assumed to be the main cause of many cardiovascular diseases, together with hypertension, and heart failure. Oxidative stress increases during the aging process, resulting in either enhanced ROS generation or diminished antioxidant safeguards. Aging is also related to oxidative stress, which in turn leads to hastened cellular senescence and organ dysfunction. Antioxidants may assist in reducing the incidence of some pathologies of heart diseases and have anti-aging properties Wollin and Jones Several studies also show that infusion of irbesartan and α-lipoic acid to patients with the metabolic syndrome diminishes pro-inflammatory markers and enhances endothelial function, elements that are indicated in the pathogenesis of aterosclerosis Sola et al. Along with that, it is found that α-lipoic acid can protect the liver from inflammatory disorders as well. Additionally, α-lipoic acid may help reduce the blood levels of several inflammatory markers, including IL-6 and ICAM-1 Liu et al. Infertility is defined as the inability to conceive after engaging in regular sexual activity without using contraception for at least a year. Numerous medications have been utilized to improve sperm quality due to therapeutic limitations Dong et al. Male infertility is partially caused by anatomical anomalies such as ductal blockages, varicocele, and ejaculatory problems. Depending on the kind and concentration of the ROS as well as the location and length of exposure to the ROS, sperm function may be positively or negatively impacted by ROS Thuwanut et al. According to studies, male germ cells can create ROS at different stages of their development. Due to the depletion of intracellular ATP and the reduced phosphorylation of axonemal proteins, it has been discovered that somewhat elevated quantities of ROS have no effect on sperm survival but instead render them immobile Takei et al. Excessive hydrogen peroxide concentrations, a major ROS producer, also cause lipid peroxidation and cell death. By reducing ROS generation, antioxidant medications maintain sperm viability and motility and can help safeguard sperm DNA integrity. Consuming dietary antioxidants may also improve semen conditions. It has been determined that male infertility is associated with a lower intake of specific antioxidant nutrients, such as vitamins A, C, and E, folate, zinc, carnitine, and selenium Buhling and Laakmann α-Lipoic acid is also a powerful antioxidant that helps in the regulation of ROS production. α-Lipoic acid or its reduced form dihydrolipoic acid quenches several oxygen-free radical species in both aqueous and lipid phases Sacks et al. The available report suggests that α-lipoic acid could improve the sperm motility rate and reduce sperm DNA damage, thereby improving sperm quality Ibrahim et al. Also, α-lipoic acid shows the positive effect in oocyte maturation, embryo development, and reproductive outcome Dong et al. Regular administration of α-lipoic acid reduces the pelvic pain in endometriosis and regularizes the menstrual blood flow. α-Lipoic acid represents a promising new molecule for infertility and additional clinical studies are recommended in the future. Cigarette smoking is a detrimental effect on the genital system of rat models due to oxidative stress. Smoking has a negative effect on the genital system via hypoxia-inducible factors HIF-1α and HIF-2α , TNF-α, caspase 3, and the calcitonin gene-related peptide CGRP in the uterus, and α-lipoic acid protected against the negative effects on the female reproductive system Asci et al. α-Lipoic acid also promoted decreasing effects of nicotine-induced skin, lung, and liver damage Ateyya et al. Microorganisms are responsible for various types of skin- and gut-related disorders. The gradual enhancements in the rapidity of resistance to antibiotics turn to rise in oral pathologies. α-Lipoic acid was found to inhibit the growth of various oral microorganisms to a large extent, such as Pseudomonas species, Escherichia coli , Staphylococcus aureus , and Candida albicans. α-Lipoic acid can arrest the growth of Candida albicans thereby exhibiting antifungal activity which is directly proportional to its concentration Zhao et al. α-Lipoic acid also arrests the growth of Cronobacter sakazakii strains with the minimum inhibitory concentration MIC in the range from 2. It was corroborated that α-lipoic acid shows antimicrobial potential for affecting the membrane integrity, causing dysfunction of the cell membrane and alterations in cellular morphology. Recent studies also state that ALA is also effective against Rickettsia rickettsii , which is a constrained intracellular bacterium that generates Rocky Mountain spotted fever. α-Lipoic acid has significant ability to penetrate nucleus and affect intracellular actin-based mobility Eremeeva and Silverman ; Sahni et al. α-Lipoic acid has the potential for protection against mycotoxin and treatment of mycotoxicosis Rogers Another report suggested that α-lipoic acid has protective efficacies against aflatoxin B1-induced oxidative damage in the liver Li et al. The beneficial effect of α-lipoic acid combined with other antioxidants, such as epigallocatechin gallate, affects the life span and age-dependent behavior of the nematode Caenorhabditis elegans Phulara et al. In a nutshell, α-lipoic acid is an important molecule as antimicrobial, antifungal, antinematodal, and antiviral properties affecting multiple targets. This combination affects the menstrual rate of women with PCOS positively, irrespective of their metabolic phenotype and with a higher dose of myo-inositol more evident and insulin-independent effect is seen de Cicco et al. D-Chiro-inositol and α-lipoic acid, in a combination treatment, may have a strong impact on metabolic profile in women with PCOS Cianci et al. In PCOS, α-lipoic acid also decreases oxidative damage and insulin resistance. Endometriosis can be prevented and treated by a combination of N -acetyl cysteine, α-lipoic acid, and bromelain. α-Lipoic acid supplementation in patients with a suspected miscarriage to improve subchorionic hematoma resorption is a promising field of investigation. In addition, α-lipoic acid could be used to prevent diabetic embryopathy and premature fetal membrane rupture caused by inflammation. Finally, α-lipoic acid can be used safely to treat neuropathic pain and as a dietary supplement during pregnancy di Tucci et al. The severe acute respiratory syndrome coronavirus-2 SARS-CoV-2 epidemic COVID has emerged as a rapidly spreading communicable disease that currently affects all nations throughout the world. Although the virus has been found in the stool and urine of infected people, the likelihood of alternative channels of transference cannot be ruled out. The sickness is primarily spread through large respiratory droplets Princess Diabetes patients are more likely to get an infection. According to research, patients with the coronavirus that causes the severe acute respiratory syndrome SARS and pandemic influenza A were seen as having diabetes as a substantial risk factor for mortality with H1N1 influenza Yang et al. Of people who died from COVID in Wuhan, China, According to a theory Sayıner and Serakıncı, , α-lipoic acid controls the immune system by controlling T-cell activation, making it a useful treatment candidate for the cytokine storm that causes SARS-CoV-2 infection. According to studies, treating diabetic patients with α-lipoic acid will help them fight COVID Cure and Cure α-Lipoic acid is a short-chain fatty acids SCFAs derived from the fermentation of vegetables and meat and modulates the gut microbiota without reducing the microbial diversity Tripathi et al. A recent study showed that α-lipoic acid and the SCFAs produced by Ruminococcaceae rejuvenated aged intestinal stem cells by preventing the age-associated endosome reduction Du et al. α-Lipoic acid takes part in crucial biological operations, together with the fixation and modulation of mitochondrial multi-enzyme complexes, oxidation of amino acids and carbohydrates, removal of ROS, and harmonization of energetic metabolism Shay et al. At a younger age, the human body can synthesize α-lipoic acid itself in the required amount, but its quantity remarkably decreases with age, which is supposed to be connected to age-related organic dysfunction Hagen et al. Drosophila midgut is an appropriate prototype structure for the learning of mechanisms underlying the age-associated decline in stem cell function. A decrease in differentiation efficiency and a malignant increase in proliferation rate takes place in the intestinal stem cells inside the midguts of Drosophila when it ages. Thus, the mRNA and protein expression of Las in Drosophila intestinal stem cells go through a significant depletion in response to aging, which in turn causes a curtailment of α-lipoic acid in midguts of aged flies. α-Lipoic acid has so many molecular targets for disease management and biological action Fig. It doubles the levels of PPAR-mRNA and protein while decreasing the activation of the c-Jun N -terminal kinase JNK signaling pathway Rousseau et al. α-Lipoic acid reduces endoplasmic reticulum stress and enhances glucose absorption by targeting the DNAJB3 DnaJ heat shock protein family and mRNA molecule Diane et al. According to reports, it lowers the NALP-3 inflammasome in the endometrium of women who experience idiopathic recurrent pregnancy loss Di et al. By inhibiting breast cancer cell proliferation, cell cycle progression, and the epithelial-to-mesenchymal transition, α-lipoic acid has significant antiproliferative effects. By blocking the transforming growth factor beta TGFβ signaling pathway, α-lipoic acid prevents breast cancer cells from migrating and encroaching Tripathy et al. Glucose fluctuations in diabetic encephalopathy encourage neuronal death. α-Lipoic acid has renoprotective effects on rat kidneys damage brought on by iron overload through inhibiting NADPH oxidase 4 and p38 MAPK signaling Cavdar et al. α-Lipoic acid diminishes the serum immunoglobulin E IgE levels of the atopic dermatitis mice model and enhances splenic B cell counts in endotoxemia mice which showed that IgE plays a modulating role in the expansion, death, and function of B-cells. Recent studies show that α-lipoic acid enhances cAMP synthesis by activation of EP2 and EP4 prostaglandin receptors in peripheral blood T-cells. The enhanced level of cAMP inside cells reduces the expression of IL-2 and IL-2Rα CD25 that in turn influence expansion, death, and function of T-cells. Natural killer NK cells have two main functions: cytotoxicity and interferon gamma IFN-γ secretion. IFN-γ is a powerful macrophage activator for both lysis and phagocytosis. Although α-lipoic acid has long been discovered as an antioxidant, it has also been demonstrated to improve glucose and ascorbate treatment, activate phase II detoxification via the transcription factor Nrf2, increase eNOS activity, and lower expression of MMP-9 and VCAM-1 through repression of NF-κB. α-Lipoic acid and its reduced form, dihydrolipoic acid, could be used for their chemical properties as a redox pair to modify protein conformations by forming mixed disulfides. Beneficial effects are accomplished with low micromolar levels of α-lipoic acid, suggesting that its therapeutic potential extents beyond the precise definition of an antioxidant agent. α-Lipoic acid is a well-known antioxidant consumed to remedy a variety of disorders, though it is assumed a very secure supplement and intoxication is extremely infrequent, acute excessive-dose ingestions can cause mortality Emir et al. The safety of α-lipoic acid can be evaluated using sub-chronic and acute toxicity studies. Studies have estimated an adult dose of α-lipoic acid up to mg with no severe side effects; however, excessive dose of α-lipoic acid is not suggested as it does not add any other therapeutic or nutritional advantage Cremer et al. Furthermore, studies associated with α-lipoic acid conducted on primates displayed that more lethal dose would lead to hepatic necrosis, indicating that excess doses of intravenous α-lipoic acid can be able to produce resistance Vigil et al. α-Lipoic acid has also been shown to reverse the adverse health effects of mycotoxins Rogers Skin and gastrointestinal disorders are the most frequently reported adverse effects for α-lipoic acid-containing dietary supplements Gatti et al. Allergic reactions like rashes, hives, and itching are the side effects of the oral intake of α-lipoic acid. However, effects like vertigo, diarrhea, and vomiting are dose dependent. It is suggested that the use of α-lipoic acid should be discouraged immediately if any allergic reaction occurs Ziegler et al. α-Lipoic acid is used either as an excipient or as a main therapeutic ingredient in various types of nanoformulations size of about 1— nm ; due to this small size, it has a very large surface area and hence high area of contact which enhances the therapeutic effect of drug particle incorporated Jong and Borm It can be formulated in the form of nanostructure lipid carriers, solid lipid nanoparticles, and nano-emulsion. Silver nanoparticles AgNPs are extensively considered for their broad-spectrum antimicrobial outcome and can be employed instantly in biomaterials; however, the cellular protection of specific AgNP formulations should be profiled earlier for clinical utilization. AgNPs can be able to outcome the evocation of oxidative harm and inflammatory lesions in human gingival fibroblast cells Jin et al. AgNPs capped with α-lipoic acid decrease toxicity as compared to other capping agents Verma et al. Studies show that α-lipoic acid-capped AgNPs possess antimicrobial effects at low concentrations 2. Docetaxel, acytotoxic taxane diterpenoid sold under the brand name taxotere, is an antimicrotubule agent effective as chemotherapy medication to treat several types of cancer, including metastatic breast cancer Lyseng-Williamson and Fenton Co-delivery of docetaxel and α-lipoic acid using solid lipid nanoparticles SLNs as a carrier demonstrated remarkably higher uptake efficiency along with better cytotoxic and apoptotic capability and assured a better treatment of breast cancer Kothari et al. The anti-inflammatory, antioxidant, and anti-apoptotic actions of α-lipoic acid, as well as the effectiveness of the encapsulation approach, can boost the efficiency and stability of α-lipoic acid, and reduce the neurotoxicity caused by AlCl3. Furthermore, α-lipoic acid-SLNs outperform α-lipoic acid-chitosan nanoparticles Metwaly et al. HOMO—LUMO plots of the two enantiomers of α-lipoic acid a S -enantiomer; b R -enantiomer. The biological roles of α-lipoic acid are highly varied, as this review has shown. In fact, as a bioactive agent, we are aware of only a few substances that act as diverse as α-lipoic acid. Determining the specific cause-and-effect relationship between α-lipoic acid and its cellular targets will therefore be crucial. Whether α-lipoic acid directly controls the hormonal signals that trigger subsequent pharmacological effects on target organs is a subject that needs more investigation. In this way, α-lipoic acid strengthens learning and short-term memory in aged rodents and encourages an anorectic effect in rodents that is AMPK-dependent Shay et al. Given that α-lipoic acid is almost entirely absorbed from the human gastrointestinal tract, metabolized, and excreted, negligible free α-lipoic acid is retained in tissues. As recently established in mice, rats, and dogs, different β-oxidation and mono- and bis- S -methylation products of the sulfydryl groups appear to be implicated in urine metabolic patterns Fig. Additionally, biliary elimination should be the focus of future research on the human metabolism of α-lipoic acid Teichert et al. Many studies have reported on the pleiotropic and medicinal activities of α-lipoic acid since its discovery in , followed by isolation and synthesis in the s Gomes and Negrato A molecular and electronic structure study of α-lipoic acid suggests that its antioxidant potential is responsible for its anti-disease activities. However, preclinical and clinical studies form the foundation of much of the discussion presented here. As a result, α-lipoic acid has powerful anti-disease properties, such as those against cancer, metabolic syndrome, and inflammatory diseases. Several potential molecular targets have been investigated in relation to a variety of diseases. The capacity of this substance to neutralize ROS, lessen oxidative stress, and trigger apoptosis is the fundamental mechanism underlying its effectiveness against various diseases and chronic disorders. In all the clinical trials that were conducted with α-lipoic acid, it was either used alone or in conjunction with other medications. The safe dose for action was reported to be between and mg per day for the term stated for each illness condition. In the context of COVID, it is also hypothesized as a repurposed drug to investigate the inhibitory action on new molecular targets. However, it is important to design computational studies and in vitro and in vivo investigations to offer comprehensive proof. Based on the information presented here, α-lipoic acid is useful in the treatment of reproductive diseases, which has been briefly explored in the context of polycystic ovary syndrome. Despite all these reports and multiple clinical trials, it has not yet been approved for use in humans. Although its bioavailability is increased in the form of nanoformulations, α-lipoic acid changes the metabolism and bioavailability of co-administered medicines when taken in combination. Despite there being few active clinical trials, this chemical is the subject of an increasing number of publications. As new information about the health benefits of α-lipoic acid will be gathered, its use in the clinic is more likely to be widely accepted. NeuroReport — Article CAS PubMed Google Scholar. Asci H, Erol O, Ellidag HY, Tola EN, Savran M, Ozmen O Pathology of cigarettes on the reproductive system and ameliorative effects of alpha lipoic acid: a rat model study. 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Cavdar Z, Oktan MA, Ural C, Calisir M, Kocak A, Heybeli C, Yildiz S, Arici A, Ellidokuz H, Celik A, Yilmaz O Renoprotective effects of alpha lipoic acid on iron overload-induced kidney injury in rats by suppressing NADPH oxidase 4 and p38 MAPK signaling. Biol Trace Elem Res — Choi HJ, Kim TY, Ruiz-Llorente S, Jeon MJ, Han JM, Kim WG, Shong YK, Kim WB Alpha-lipoic acid induces sodium iodide symporter expression in TPC-1 thyroid cancer cell line. Nucl Med Biol — Choi K, Kim J, Kim H α-Lipoic acid treatment is neurorestorative and promotes functional recovery after stroke in rats. J Neurol Sci e Aging Cell — Cianci A, Panella M, Fichera M, Falduzzi C, Bartolo M, Caruso S D-chiro-inositol and alpha lipoic acid treatment of metabolic and menses disorders in women with PCOS. Gynecol Endocrinol — Cremer DR, Rabeler R, Roberts A, Lynch B Safety evaluation of α-lipoic acid ALA. 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Diane A, Mahmoud N, Bensmail I, Khattab N, Abunada HA, Dehbi M Alpha lipoic acid attenuates ER stress and improves glucose uptake through DNAJB3 cochaperone. Sci Rep Dong L, Zhang X, Yang F, Li J, Yu X, Li Y Effect of oral alpha-lipoic acid ALA on the treatment of male infertility: a protocol for systematic review and meta-analysis. Medicine e Dozio E, Ruscica M, Passafaro L, Dogliotti G, Steffani L, Pagani A, Demartini G, Esposti D, Fraschini F, Magni P The natural antioxidant alpha-lipoic acid induces p27Kip1-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells. Eur J Pharmacol — Du G, Qiao Y, Zhuo Z, Zhou J, Li X, Liu Z, Li Y, Chen H Lipoic acid rejuvenates aged intestinal stem cells by preventing age-associated endosome reduction. EMBO Rep De Jong WH, Borm PJ Drug delivery and nanoparticles: applications and hazards. Int J Nanomed — Del Rio C, Malani PN COVID—new insights on a rapidly changing epidemic. 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Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis. J Neuroimmunol. Morini M, Roccatagliata L, Dell'Eva R, et al. Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis.
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J Immunol. Salinthone S, Schillace RV, Marracci GH, Bourdette DN, Carr DW. Lipoic acid stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity in NK cells. Schillace RV, Pisenti N, Pattamanuch N, et al.
Lipoic acid stimulates cAMP production in T lymphocytes and NK cells. Biochem Biophys Res Commun. Collectively, its functions explain why α-lipoic acid is required for cell growth, mitochondrial activity, and coordination of fuel metabolism Solmonson and DeBerardinis With t max values between 10 and 45 min, α-lipoic acid absorbs swiftly.
It is also promptly removed, with a mean plasma elimination half-life of 0. Exogenous racemic mixture of α-lipoic acid is orally administered for therapeutic treatment of diabetic polyneuropathy and demonstrated that completely absorbed by gastrointestinal tract and limited absolute bioavailability by hepatic extraction.
The racemic misture of α-lipoic acid mg administered daily in 9 healthy volunteers and observed the metabolites S -methylated β-oxidation products 4,6-bismethylthio-hexanoic acid and 2,4-bismethylthio-butanoic acid confirmed by HPLC-electrochemical assay Teichert et al.
Several studies have provided facts that acts as a biological antioxidant and plays a leading function in cellular growth due to its ability to scavenge reactive oxygen species and renew endogenous antioxidants Attia et al. Numerous women suffer from breast cancer every year and though this disease is lethal, there is a need for new therapeutic approaches which surpasses the shortcomings of the present treatments Kumar et al.
α-Lipoic acid inhibits cell proliferation via the epidermal growth factor receptor EGFR and the protein kinase B PKB , also known as the Akt signaling, and induces apoptosis in human breast cancer cells Na et al.
α-Lipoic acid drives pyruvate dehydrogenase by downregulating aerobic glycolysis and activation of apoptosis in breast cancer cells, lactate production, induces apoptosis, and diminishes cell viability, implying that the inadequate uptake might be due to reduced cell death caused by α-lipoic acid Feuerecker et al.
Most basic symptoms of colon cancer are rectal bleeding and anemia. These symptoms sum up and lead to changes in bowel habits and weight loss, with a complication of uncontrolled cell growth in the colon, leading to colorectal cancer which is the third most diagnosed cancer in the world Malgras et al.
Dihydrolipoic acid scavenges the cytosolic oxygen in HT human colon cancer cells; furthermore, it escalates in a dose-dependent manner the caspaselike activity associated with DNA fragmentation. It was concluded that α-lipoic acid induces apoptosis by a pro-oxidant mechanism triggered by an escalated uptake of mitochondrial substrates in oxidizable form Wenzel et al.
This involves monocarboxylates uptake amplification in mitochondria through glycolysis after their oxidation into the citric acid cycle, and then the increased depletion equivalents delivery into the respiratory chain drastically increases the production of mitochondrial oxygen. This high oxygen burden overcomes the high antioxidative capacity of anti-apoptotic proteins and allows apoptosis to be executed in tumor cells Kang et al.
Lifestyle modification in daily activity and diet pattern is the foundation of an effective strategy to improve metabolic disorders and reduce obesity.
α-Lipoic acid shows a wide array of metabolic benefits, including glucose lowering, anti-obesity, lipid lowering, and an insulin sensitizing effect Carrier and Rideout α-Lipoic acid and coenzyme Q10 prevent apoptosis and degeneration of dorsal root ganglion DRG neurons mediated by regulation of uncoupling protein 2 UCP2 and caspase-3 expression, inducing ATP and improving diabetic neuropathy induced changes in DRG neurons Galeshkalami et al.
It is used in the treatment of diabetic polyneuropathy and insulin resistance Bustamante et al. According to a clinical study, α-lipoic acid supplementation reduces body weight and body mass index Namazi et al.
The combination of curcumin and α-lipoic acid reduces weight gain and adiposity. α-Lipoic acid helps in regenerating glutathione, along with vitamins C and E, and promotes glutathione synthesis.
Hirata disease, or insulin autoimmune syndrome IAS , is characterized by elevated insulin levels and anti-insulin autoantibodies. This disease is a rare form of autoimmune hypoglycemia caused by sulfhydryl-containing medicines, which trigger the creation of insulin autoantibodies.
α-Lipoic acid has lately emerged as a cause of IAS. Furthermore, greater care is needed for suggesting this damage as a consequence of α-lipoic acid supplementation Moffa et al. Free radical induced damaged makes an important contribution to secondary neuronal brain injury in stroke therapy Dwivedi There is currently no treatment available to prevent this effect.
The antioxidant property of α-lipoic acid is associated with its neurorestorative and neuroprotective effects. α-Lipoic acid induces the M2 phenotype in microglia, modulates the expression of pro-inflammatory cytokines IL-6, IL-1, IL, and tumor necrosis factor TNF , and inhibits the transcription factor NF-κB, a key mediator of inflammatory responses Wang et al.
Sleep is involved in regulating heat, maintaining energy, and recovering tissues. The protective effect of α-lipoic acid on social interaction memory was observed in sleep-deprived rats Rezaie et al. This neurotoxin triggers the death signaling pathway by activating apoptosis signal regulating kinase 1 ASK1 and translocating the death domain associated protein DAXX in the substantia nigra pars compacta SNpc of mice; α-lipoic acid terminates this cascade and affords neuroprotection Karunakaran et al.
In scopolamine-induced memory loss, α-lipoic acid inhibits brain weight loss, downregulates oxidative tissue damage resulting in neuronal cell loss, repairs memory and motor function, reduces reactive astrocyte proliferation, and decreases chromatolysis in the cerebello-hippocampal cortex Bastianetto and Quirion Oxidative alteration of low-density lipoprotein enhances atherogenicity Wollin and Jones It has been discovered that macrophages, smooth muscle cells, and ROS scavenger receptors on monocytes unrestrainedly take oxidized LDL, resulting in lipid accumulation and the formation of atherosclerotic plaques.
Enhanced oxidative stresses as well as inflammatory action give rise to hydroxyl radicals, peroxides, and superoxides inside the endothelium, which accelerate the progression of cardiovascular disease. The inflammatory conditions continue to harm the vasculature one after another Wollin and Jones Dihydrolipoic acid is reported for its blood lipid modulating characteristics, protection against LDL oxidation, and modulation of hypertension, indicating that α-lipoic acid might be a possible protective agent against cardiovascular diseases Wollin and Jones The incidence of cardiovascular diseases decreases as the dietary intake of α-lipoic acid increases.
Chronic kidney disease is a gradual loss of kidney function that leads to the accumulation of waste products in the blood. Diabetes and high blood pressure are two of the major risk factors for chronic kidney disease Granata et al.
In this condition, cellular metabolic changes occur that may lead to the major production of free radicals that play a crucial role in the development of renal damage and the onset of treatment resistance.
Hypoxia, ROS, and oxidative stress may cause severe kidney injury and ischemic reperfusion injury Zhang and McCullough Patients suffering from end-stage renal disease and kept on hemodialysis have very high chances of cardiovascular mortality Levey et al.
Intravenous iron infusion has become an essential segment of anemia management in end-stage renal disease patients. Iron injection intake leads to oxidative stress in the patients Lim et al.
After administration of intravenous iron, oxidative stress markers formed, including lipid hydroperoxide, F2 isoprostane, and malondialdehyde, a reactive aldehyde that gives rise to toxic stress in cells Del et al.
Research shows that after the administration of intravenous iron to chronic kidney disease and hemodialysis patients, malondialdehyde increases speedily Lim et al. The generation of lipid hydroperoxide results in oxidative damage in lipoproteins, cell membranes, and other lipid-containing structures Girotti and Kriska The antioxidant activities of α-lipoic acid were better than N -acetylcysteine at curing oxidative stress, including diabetic neuropathy and glomerular injury.
α-Lipoic acid administration leads to a reduction in oxidative stress markers low-density lipoprotein oxidizability and plasma protein carbonyls ; thus, it is appreciable that administration of this agent may reduce oxidative stress induced by intravenous IV iron Marangon et al.
However, in diabetic nephropathy, TGFβ1 is related to MAPK and induces the production of fibronectin in mesangial cells. α-Lipoic acid ameliorates the proteinuria by decreasing expressions of the TGFβ1 and fibronectin protein Lee et al.
The patients with autosomal dominant polycystic kidney disease treated with α-lipoic acid showed a significant improvement in metabolic, inflammatory, and endothelial functions Lai et al. As a short-chain fatty acid, α-lipoic acid is synthesized inside the human body to work as an antioxidant, safeguarding body cells from injury, and helping restore the scales of other antioxidants, like vitamins C and E Moura et al.
Several studies have shown that combining α-lipoic acid with fructose can reduce fructose-induced inflammation, hepatic oxidative stress, and insulin resistance. It is also found that α-lipoic acid can act as a chemopreventive agent because it inhibits the inflammation linked to carcinogenesis Moon α-Lipoic acid can reduce inflammatory markers in patients with heart disease, as oxidative stress is assumed to be the main cause of many cardiovascular diseases, together with hypertension, and heart failure.
Oxidative stress increases during the aging process, resulting in either enhanced ROS generation or diminished antioxidant safeguards. Aging is also related to oxidative stress, which in turn leads to hastened cellular senescence and organ dysfunction.
Antioxidants may assist in reducing the incidence of some pathologies of heart diseases and have anti-aging properties Wollin and Jones Several studies also show that infusion of irbesartan and α-lipoic acid to patients with the metabolic syndrome diminishes pro-inflammatory markers and enhances endothelial function, elements that are indicated in the pathogenesis of aterosclerosis Sola et al.
Along with that, it is found that α-lipoic acid can protect the liver from inflammatory disorders as well. Additionally, α-lipoic acid may help reduce the blood levels of several inflammatory markers, including IL-6 and ICAM-1 Liu et al.
Infertility is defined as the inability to conceive after engaging in regular sexual activity without using contraception for at least a year. Numerous medications have been utilized to improve sperm quality due to therapeutic limitations Dong et al.
Male infertility is partially caused by anatomical anomalies such as ductal blockages, varicocele, and ejaculatory problems. Depending on the kind and concentration of the ROS as well as the location and length of exposure to the ROS, sperm function may be positively or negatively impacted by ROS Thuwanut et al.
According to studies, male germ cells can create ROS at different stages of their development. Due to the depletion of intracellular ATP and the reduced phosphorylation of axonemal proteins, it has been discovered that somewhat elevated quantities of ROS have no effect on sperm survival but instead render them immobile Takei et al.
Excessive hydrogen peroxide concentrations, a major ROS producer, also cause lipid peroxidation and cell death. By reducing ROS generation, antioxidant medications maintain sperm viability and motility and can help safeguard sperm DNA integrity.
Consuming dietary antioxidants may also improve semen conditions. It has been determined that male infertility is associated with a lower intake of specific antioxidant nutrients, such as vitamins A, C, and E, folate, zinc, carnitine, and selenium Buhling and Laakmann α-Lipoic acid is also a powerful antioxidant that helps in the regulation of ROS production.
α-Lipoic acid or its reduced form dihydrolipoic acid quenches several oxygen-free radical species in both aqueous and lipid phases Sacks et al. The available report suggests that α-lipoic acid could improve the sperm motility rate and reduce sperm DNA damage, thereby improving sperm quality Ibrahim et al.
Also, α-lipoic acid shows the positive effect in oocyte maturation, embryo development, and reproductive outcome Dong et al. Regular administration of α-lipoic acid reduces the pelvic pain in endometriosis and regularizes the menstrual blood flow.
α-Lipoic acid represents a promising new molecule for infertility and additional clinical studies are recommended in the future. Cigarette smoking is a detrimental effect on the genital system of rat models due to oxidative stress.
Smoking has a negative effect on the genital system via hypoxia-inducible factors HIF-1α and HIF-2α , TNF-α, caspase 3, and the calcitonin gene-related peptide CGRP in the uterus, and α-lipoic acid protected against the negative effects on the female reproductive system Asci et al.
α-Lipoic acid also promoted decreasing effects of nicotine-induced skin, lung, and liver damage Ateyya et al. Microorganisms are responsible for various types of skin- and gut-related disorders.
The gradual enhancements in the rapidity of resistance to antibiotics turn to rise in oral pathologies. α-Lipoic acid was found to inhibit the growth of various oral microorganisms to a large extent, such as Pseudomonas species, Escherichia coli , Staphylococcus aureus , and Candida albicans.
α-Lipoic acid can arrest the growth of Candida albicans thereby exhibiting antifungal activity which is directly proportional to its concentration Zhao et al.
α-Lipoic acid also arrests the growth of Cronobacter sakazakii strains with the minimum inhibitory concentration MIC in the range from 2. It was corroborated that α-lipoic acid shows antimicrobial potential for affecting the membrane integrity, causing dysfunction of the cell membrane and alterations in cellular morphology.
Recent studies also state that ALA is also effective against Rickettsia rickettsii , which is a constrained intracellular bacterium that generates Rocky Mountain spotted fever. α-Lipoic acid has significant ability to penetrate nucleus and affect intracellular actin-based mobility Eremeeva and Silverman ; Sahni et al.
α-Lipoic acid has the potential for protection against mycotoxin and treatment of mycotoxicosis Rogers Another report suggested that α-lipoic acid has protective efficacies against aflatoxin B1-induced oxidative damage in the liver Li et al.
The beneficial effect of α-lipoic acid combined with other antioxidants, such as epigallocatechin gallate, affects the life span and age-dependent behavior of the nematode Caenorhabditis elegans Phulara et al.
In a nutshell, α-lipoic acid is an important molecule as antimicrobial, antifungal, antinematodal, and antiviral properties affecting multiple targets. This combination affects the menstrual rate of women with PCOS positively, irrespective of their metabolic phenotype and with a higher dose of myo-inositol more evident and insulin-independent effect is seen de Cicco et al.
D-Chiro-inositol and α-lipoic acid, in a combination treatment, may have a strong impact on metabolic profile in women with PCOS Cianci et al.
In PCOS, α-lipoic acid also decreases oxidative damage and insulin resistance. Endometriosis can be prevented and treated by a combination of N -acetyl cysteine, α-lipoic acid, and bromelain. α-Lipoic acid supplementation in patients with a suspected miscarriage to improve subchorionic hematoma resorption is a promising field of investigation.
In addition, α-lipoic acid could be used to prevent diabetic embryopathy and premature fetal membrane rupture caused by inflammation. Finally, α-lipoic acid can be used safely to treat neuropathic pain and as a dietary supplement during pregnancy di Tucci et al.
The severe acute respiratory syndrome coronavirus-2 SARS-CoV-2 epidemic COVID has emerged as a rapidly spreading communicable disease that currently affects all nations throughout the world.
Although the virus has been found in the stool and urine of infected people, the likelihood of alternative channels of transference cannot be ruled out. The sickness is primarily spread through large respiratory droplets Princess Diabetes patients are more likely to get an infection.
According to research, patients with the coronavirus that causes the severe acute respiratory syndrome SARS and pandemic influenza A were seen as having diabetes as a substantial risk factor for mortality with H1N1 influenza Yang et al.
Of people who died from COVID in Wuhan, China, According to a theory Sayıner and Serakıncı, , α-lipoic acid controls the immune system by controlling T-cell activation, making it a useful treatment candidate for the cytokine storm that causes SARS-CoV-2 infection.
According to studies, treating diabetic patients with α-lipoic acid will help them fight COVID Cure and Cure α-Lipoic acid is a short-chain fatty acids SCFAs derived from the fermentation of vegetables and meat and modulates the gut microbiota without reducing the microbial diversity Tripathi et al.
A recent study showed that α-lipoic acid and the SCFAs produced by Ruminococcaceae rejuvenated aged intestinal stem cells by preventing the age-associated endosome reduction Du et al.
α-Lipoic acid takes part in crucial biological operations, together with the fixation and modulation of mitochondrial multi-enzyme complexes, oxidation of amino acids and carbohydrates, removal of ROS, and harmonization of energetic metabolism Shay et al.
At a younger age, the human body can synthesize α-lipoic acid itself in the required amount, but its quantity remarkably decreases with age, which is supposed to be connected to age-related organic dysfunction Hagen et al.
Drosophila midgut is an appropriate prototype structure for the learning of mechanisms underlying the age-associated decline in stem cell function. A decrease in differentiation efficiency and a malignant increase in proliferation rate takes place in the intestinal stem cells inside the midguts of Drosophila when it ages.
Thus, the mRNA and protein expression of Las in Drosophila intestinal stem cells go through a significant depletion in response to aging, which in turn causes a curtailment of α-lipoic acid in midguts of aged flies. α-Lipoic acid has so many molecular targets for disease management and biological action Fig.
It doubles the levels of PPAR-mRNA and protein while decreasing the activation of the c-Jun N -terminal kinase JNK signaling pathway Rousseau et al. α-Lipoic acid reduces endoplasmic reticulum stress and enhances glucose absorption by targeting the DNAJB3 DnaJ heat shock protein family and mRNA molecule Diane et al.
According to reports, it lowers the NALP-3 inflammasome in the endometrium of women who experience idiopathic recurrent pregnancy loss Di et al. By inhibiting breast cancer cell proliferation, cell cycle progression, and the epithelial-to-mesenchymal transition, α-lipoic acid has significant antiproliferative effects.
By blocking the transforming growth factor beta TGFβ signaling pathway, α-lipoic acid prevents breast cancer cells from migrating and encroaching Tripathy et al. Glucose fluctuations in diabetic encephalopathy encourage neuronal death. α-Lipoic acid has renoprotective effects on rat kidneys damage brought on by iron overload through inhibiting NADPH oxidase 4 and p38 MAPK signaling Cavdar et al.
α-Lipoic acid diminishes the serum immunoglobulin E IgE levels of the atopic dermatitis mice model and enhances splenic B cell counts in endotoxemia mice which showed that IgE plays a modulating role in the expansion, death, and function of B-cells.
Recent studies show that α-lipoic acid enhances cAMP synthesis by activation of EP2 and EP4 prostaglandin receptors in peripheral blood T-cells. The enhanced level of cAMP inside cells reduces the expression of IL-2 and IL-2Rα CD25 that in turn influence expansion, death, and function of T-cells.
Natural killer NK cells have two main functions: cytotoxicity and interferon gamma IFN-γ secretion. IFN-γ is a powerful macrophage activator for both lysis and phagocytosis.
Although α-lipoic acid has long been discovered as an antioxidant, it has also been demonstrated to improve glucose and ascorbate treatment, activate phase II detoxification via the transcription factor Nrf2, increase eNOS activity, and lower expression of MMP-9 and VCAM-1 through repression of NF-κB.
α-Lipoic acid and its reduced form, dihydrolipoic acid, could be used for their chemical properties as a redox pair to modify protein conformations by forming mixed disulfides.
Beneficial effects are accomplished with low micromolar levels of α-lipoic acid, suggesting that its therapeutic potential extents beyond the precise definition of an antioxidant agent. α-Lipoic acid is a well-known antioxidant consumed to remedy a variety of disorders, though it is assumed a very secure supplement and intoxication is extremely infrequent, acute excessive-dose ingestions can cause mortality Emir et al.
The safety of α-lipoic acid can be evaluated using sub-chronic and acute toxicity studies. Studies have estimated an adult dose of α-lipoic acid up to mg with no severe side effects; however, excessive dose of α-lipoic acid is not suggested as it does not add any other therapeutic or nutritional advantage Cremer et al.
Furthermore, studies associated with α-lipoic acid conducted on primates displayed that more lethal dose would lead to hepatic necrosis, indicating that excess doses of intravenous α-lipoic acid can be able to produce resistance Vigil et al.
α-Lipoic acid has also been shown to reverse the adverse health effects of mycotoxins Rogers Skin and gastrointestinal disorders are the most frequently reported adverse effects for α-lipoic acid-containing dietary supplements Gatti et al. Allergic reactions like rashes, hives, and itching are the side effects of the oral intake of α-lipoic acid.
However, effects like vertigo, diarrhea, and vomiting are dose dependent. It is suggested that the use of α-lipoic acid should be discouraged immediately if any allergic reaction occurs Ziegler et al.
α-Lipoic acid is used either as an excipient or as a main therapeutic ingredient in various types of nanoformulations size of about 1— nm ; due to this small size, it has a very large surface area and hence high area of contact which enhances the therapeutic effect of drug particle incorporated Jong and Borm It can be formulated in the form of nanostructure lipid carriers, solid lipid nanoparticles, and nano-emulsion.
Silver nanoparticles AgNPs are extensively considered for their broad-spectrum antimicrobial outcome and can be employed instantly in biomaterials; however, the cellular protection of specific AgNP formulations should be profiled earlier for clinical utilization. AgNPs can be able to outcome the evocation of oxidative harm and inflammatory lesions in human gingival fibroblast cells Jin et al.
AgNPs capped with α-lipoic acid decrease toxicity as compared to other capping agents Verma et al. Studies show that α-lipoic acid-capped AgNPs possess antimicrobial effects at low concentrations 2.
Docetaxel, acytotoxic taxane diterpenoid sold under the brand name taxotere, is an antimicrotubule agent effective as chemotherapy medication to treat several types of cancer, including metastatic breast cancer Lyseng-Williamson and Fenton Co-delivery of docetaxel and α-lipoic acid using solid lipid nanoparticles SLNs as a carrier demonstrated remarkably higher uptake efficiency along with better cytotoxic and apoptotic capability and assured a better treatment of breast cancer Kothari et al.
The anti-inflammatory, antioxidant, and anti-apoptotic actions of α-lipoic acid, as well as the effectiveness of the encapsulation approach, can boost the efficiency and stability of α-lipoic acid, and reduce the neurotoxicity caused by AlCl3.
Furthermore, α-lipoic acid-SLNs outperform α-lipoic acid-chitosan nanoparticles Metwaly et al. HOMO—LUMO plots of the two enantiomers of α-lipoic acid a S -enantiomer; b R -enantiomer. The biological roles of α-lipoic acid are highly varied, as this review has shown.
In fact, as a bioactive agent, we are aware of only a few substances that act as diverse as α-lipoic acid. Determining the specific cause-and-effect relationship between α-lipoic acid and its cellular targets will therefore be crucial. Whether α-lipoic acid directly controls the hormonal signals that trigger subsequent pharmacological effects on target organs is a subject that needs more investigation.
In this way, α-lipoic acid strengthens learning and short-term memory in aged rodents and encourages an anorectic effect in rodents that is AMPK-dependent Shay et al. Given that α-lipoic acid is almost entirely absorbed from the human gastrointestinal tract, metabolized, and excreted, negligible free α-lipoic acid is retained in tissues.
As recently established in mice, rats, and dogs, different β-oxidation and mono- and bis- S -methylation products of the sulfydryl groups appear to be implicated in urine metabolic patterns Fig.
Additionally, biliary elimination should be the focus of future research on the human metabolism of α-lipoic acid Teichert et al. Many studies have reported on the pleiotropic and medicinal activities of α-lipoic acid since its discovery in , followed by isolation and synthesis in the s Gomes and Negrato A molecular and electronic structure study of α-lipoic acid suggests that its antioxidant potential is responsible for its anti-disease activities.
However, preclinical and clinical studies form the foundation of much of the discussion presented here.
As a result, α-lipoic acid has powerful anti-disease properties, such as those against cancer, metabolic syndrome, and inflammatory diseases.
Several potential molecular targets have been investigated in relation to a variety of diseases. The capacity of this substance to neutralize ROS, lessen oxidative stress, and trigger apoptosis is the fundamental mechanism underlying its effectiveness against various diseases and chronic disorders.
In all the clinical trials that were conducted with α-lipoic acid, it was either used alone or in conjunction with other medications. The safe dose for action was reported to be between and mg per day for the term stated for each illness condition. In the context of COVID, it is also hypothesized as a repurposed drug to investigate the inhibitory action on new molecular targets.
However, it is important to design computational studies and in vitro and in vivo investigations to offer comprehensive proof. Based on the information presented here, α-lipoic acid is useful in the treatment of reproductive diseases, which has been briefly explored in the context of polycystic ovary syndrome.
Despite all these reports and multiple clinical trials, it has not yet been approved for use in humans. Although its bioavailability is increased in the form of nanoformulations, α-lipoic acid changes the metabolism and bioavailability of co-administered medicines when taken in combination.
Despite there being few active clinical trials, this chemical is the subject of an increasing number of publications. As new information about the health benefits of α-lipoic acid will be gathered, its use in the clinic is more likely to be widely accepted. NeuroReport — Article CAS PubMed Google Scholar.
Asci H, Erol O, Ellidag HY, Tola EN, Savran M, Ozmen O Pathology of cigarettes on the reproductive system and ameliorative effects of alpha lipoic acid: a rat model study. Toxicol Ind Health — Ateyya H, Nader MA, Attia GM, El-Sherbeeny NA Influence of alpha-lipoic acid on nicotine-induced lung and liver damage in experimental rats.
Can J Physiol Pharmacol — Attia M, Essa EA, Zaki RM, Elkordy AA An overview of the antioxidant effects of ascorbic acid and alpha lipoic acid in liposomal forms as adjuvant in cancer treatment.
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Why choose VORST's Alpha Lipoic Acid? A closer look. Supports healthy diets for improved blood control. Helps replenish antioxidant nutrients in the body. Helps reduce nerve pains and promotes healthy nerves.
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We've been independently Alpga-lipoic and testing products for Sports nutrition for injury prevention years. If you buy Heart health information our accid, we Alpha-lipoic acid and immune support earn immuune commission. Learn more about our review process. Antioxidants help to bolster your immune system and work to keep you in your best health. Healthy individuals can usually produce many of the needed antioxidants naturally. Dietary sources and supplements can compliment the amount of needed antioxidants.
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