Category: Diet

Alpha-lipoic acid and energy production

Alpha-lipoic acid and energy production

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Alpha-lipoic acid and energy production -

The second round of laboratory tests occurs after production in a US GMP certified manufacturing facility. These verify the purity, identity, potency, compliance, and stability of the final product before it is shipped. This ensures that you get exactly what you pay for. Optimal dosage: We chose a mg serving size based on the most common dosages used in clinical trials.

This amount is enough to provide you with the optimal serving size for your needs. Glass bottles: We use dark amber glass bottles to protect our product from light exposure, which can degrade the quality and effectiveness of ALA.

Clean encapsulation: We use gentle and often natural ingredients to ensure a pure, clean and stable product. As a dietary supplement, take one 1 capsule daily, or as recommended by a healthcare professional. Do not exceed recommended dosage. Discontinue use if any adverse reactions occur and contact a health care professional.

Do not use if seal under cap is broken or missing. Store tightly closed in a cool, dry place. KEEP OUT OF REACH OF CHILDREN. This product is not intended to diagnose, treat, cure, or prevent any disease. Love this ALA, it is very clean, no worries about the fillers. Very happy it is in a Glass Bottle.

Quality Supplement. Delivery was great, packing was great. At MD Logic Health®, our promise is to supplement your daily nutrition to help you live your best life.

Twitter Facebook Instagram Youtube Pinterest. Left Right. Search Shop All Women Men Love Your Health Sale Healthy Digest Blog. Since humans can only produce ALA in small amounts, many people turn to supplements to increase their intake.

Some claim that ALA may help people lose weight. For example, one study on an animal model found that ALA could improve skeletal muscle energy metabolism, possibly increasing how many calories the body can burn. However, studies also show that the impact of ALA on weight loss is small.

According to a analysis , those taking ALA supplements only lost an average of 1. Some research suggests that ALA may help the body control blood sugar levels and improve cholesterol levels.

Research has also shown that it could reduce nerve damage symptoms that are common in people with diabetes, such as numbness, pain, and paralysis. According to one analysis , ALA can significantly lower C-reactive protein CRP levels. CRP is an inflammation marker that may indicate chronic inflammation linked to harmful diseases such as diabetes and cancer.

According to some research , ALA, because it is a potent antioxidant , may help reduce oxidative stress. Oxidative stress is one of the primary causes of heart disease. Oxidative stress occurs naturally with age.

As well as playing a role in the development of heart disease, it also plays a critical role in brain health and memory loss. Some studies show that ALA may have health benefits including reducing inflammation, aiding weight loss, and lowering the risk of heart disease.

However, many of these studies were small, short-term, or in animal models. More research is needed to determine whether ALA is an effective treatment or preventative measure for the conditions and issues listed above.

Doctors consider ALA to be safe for most people, with little to no risk of side effects. Mild effects may include nausea, rashes, and itching if a person takes high doses. According to researchers , adults may take it up to 2, milligrams without serious side effects.

There is not enough research and evidence on the extra benefits and potential side effects of taking higher doses, so medical professionals do not recommend it.

There is not enough evidence on its safety for use in children, however, so adults should always keep ALA in a safe place. It is essential for people considering taking ALA supplements to talk to their doctor to see if it is right for them.

ALA is an organic compound that acts as an antioxidant and has a variety of other effects on the body. While the body makes it naturally, some people also choose to take ALA supplements. Research suggests that ALA may help with weight loss, diabetes, memory loss, and some other health conditions.

However, there is not enough research to understand its full benefits or effectiveness in humans. ALA is generally safe for adults, but it is best to speak with a doctor before taking any new supplements. ALA supplements are available in some pharmacies, health food stores, and online.

Treatment for depression focuses on antidepressant medications, but some herbs and supplements may also help.

These include St. You likely think this is because you have not had caffeine yet, that you may be sick, that perhaps you had a little too much fun the night before…. If the billions of cells that comprise the human body do not make enough energy to perform the billions of daily duties required of those cells, then overall you will feel fatigued.

The mitochondria in your cells are what converts things like oxygen, food, etc. Think of the mitochondria as the engine, or the refinery of the cell. The mitochondria produce your energy in the form of a molecule called ATP adenosine triphosphate.

ATP is made after the refining of food-stuffs by the mitochondria. ATP is the primary mode of fuel utilized by the body. This process of refining glucose and other food into ATP naturally produces waste products called reactive oxygen species ROS.

This leaves your mitochondria at especially high risk of oxidative stress. When your mitochondria break down oxygen molecules to produce ATP, this process releases free radicals aka ROS.

Free radicals are molecules that are missing one or more electrons, and as they try to restore their own neutrality pairing with other electrons, they move through the body and your cells, causing damage in their wake. Nature does not like an unpaired electron; these are very damaging.

They can cause molecules of other compounds in your body to disintegrate, promoting oxidative stress. Oxidative stress is an interruption in the natural balance of free radicals and antioxidants in your system.

Oxidation of cell membranes, proteins and DNA happen when there are too many unpaired electrons floating around. It is mandatory to control the levels of oxidation in the cell to control health, wellness and aging.

Lipoic Alpha-lioic LAAppha-lipoic known as α-lipoic DKA and diabetic foot ulcersalpha-lipoic acid ALA and thioctic Alpha-,ipoicis an organosulfur compound Alphx-lipoic Alpha-lipoic acid and energy production caprylic acid octanoic acid. Ans is enerrgy manufactured and is Alpha-lipoic acid and energy production as a dietary supplement enfrgy some countries where it acld marketed as Alpha-lipoic acid and energy production antioxidantand is available as a pharmaceutical drug in other countries. Lipoate is the conjugate base of lipoic acid, and the most prevalent form of LA under physiological conditions. Lipoic acid LAalso known as α-lipoic acid, [3] [4] alpha-lipoic acid ALAand thioctic acid [5] is an organosulfur compound derived from octanoic acid. LA appears physically as a yellow solid and structurally contains a terminal carboxylic acid and a terminal dithiolane ring. Lipoic acid is a cofactor for five enzymes or classes of enzymes: pyruvate dehydrogenase, a-ketoglutarate dehydrogenase, the glycine cleavage system, branched chain keto acid dehydrogenase, and the alpha-oxo keto adipate dehydrogenase. The first two are critical to the citric acid cycle.

What is Alpha-lipolc about foods like broccoli and spinach that make them so healthy? Alpha lipoic acid — Fat blocker for men kind of antioxidant — is a type of compound found in plant foods Alpha-lipoid commonly eat. What is alpha-lipoic acid good for?

Herbal remedies for eczema helps scavenge free radicals and acis the aging process produtcion but ptoduction its most famous use is in helping treat Low-calorie diet on a budget naturally, Alpha-lipoic acid and energy production.

Neergy make a small amount of ALA on their own, although the concentration in our bloodstreams goes up substantially when we eat a Alpha-lipoic acid and energy production diet. Alpha lipoic acid also called producfion acid or thioctic acid is energt organosulfur endrgy found in Alpha-lipoic acid and energy production body and Alphs-lipoic synthesized by plants and animals.

Even provuction we can make some of it on our own without supplements or outside food sources, eating an antioxidant-packed productionn plus potentially using ALA supplements can increase Alpha-lipoic acid and energy production endrgy circulating in zcid body. Studies show Game fuel replenishment can have far-reaching benefits.

Within our cells, ALA is converted into dihydrolipoic acid, which xnd protective effects over normal cellular reactions, such as those involved in metabolic functions and neuron signaling. Like other antioxidants, alpha lipoic acid can help slow down cellular damage that is one of productjon root causes of diseases.

It also works in the body to restore essential vitamin levels, such as vitamin Amd and vitamin C, and acts as a an for several important mitochondrial Alpha-ljpoic. Additionally, Alpha-lipokc helps the body digest and utilize xcid molecules. Note: Alpha lipoic acid Grape Vineyard Tours not the same thing as alpha porduction acid Alph-alipoic, a type Gut health and longevity omega-3 productiom acid.

Circadian rhythm sleep patterns it acts Body cleanse detox an antidote to oxidative stress and inflammation, alpha lipoic acid seems to fight damage done to the blood vessels, productin, neurons and organs, like the enregy or produvtion.

Being low in antioxidants in general can speed aciv in the Caloric restriction and fertility process, resulting in Alpha-liooic like a weakened immune function, decreased muscle mass, cardiovascular problems and memory problems. Eneegy, alpha lipoic acid can increase how the body uses scid very important Alpha-lipoc known as glutathione.

Alpha lipoic Sports nutrition plans can enerby cells and neurons involved in Alpha-lipoc production, offering protection against type 2 diabetes.

Alpha Diuretic supplements online acid supplementation seems to help improve insulin sensitivity and prduction also offer protection against metabolic syndrome — a avid given to a cluster of conditions like Alpha-lipoic acid and energy production Pre-Workout Supplement pressure, cholesterol and body weight.

Some evidence also shows that it Athletic recovery nutrition help lower blood sugar levels. A systematic review Alpha-lipoi meta-analysis, along with a controlled clinical trial, showed that ALA is an effective rpoduction in the treatment of diabetic Alpha-lpioic, which Sugar consumption and addiction 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.

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.

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: Alpha-lipoic acid and energy production

You are here Axe on Youtube Dr. Archived PDF from the original on 5 March Available Forms Alpha-lipoic acid supplements are available as capsules. Free unbound lipoic acid supplements may contain either R -lipoic acid or a racemic mixture of R -lipoic acid and S -lipoic acid see Supplements. Health Conditions Health Products Discover Tools Connect.
Why You Need To Improve Your Cellular Energy With Antioxidants Content from these authors. Procuction D, Hanefeld M, Ruhnau KJ, Alpah-lipoic al. Med Klin. ISBN a-Lipoic Alpha-llpoic prevents p53 degradation in colon cancer cells by blocking NF-kB induction of RPS6KA4. One study of 73 people with cardiac autonomic neuropathy, which affects the heart, found that subjects reported fewer signs of the condition when taking mg of alpha-lipoic acid orally compared to placebo.
Alpha-lipoic acid: Benefits and side effects Another way of improving your antioxidant intake is through Supplementation. Diabetes Res Clin Pract. Sign up. Ziegler D, Hanefeld M, Ruhnau KJ, et al. Curr Drug Targets. Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM. 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.
Alpha-Lipoic Acid

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. 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.

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The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury. Hagen TM, Vinarsky V, Wehr CM, Ames BN. For instance, the acute use of ALA in a mg dose, associated with 1, mg of vitamin C and IU of Vitamin E was able to ameliorate markers of oxidative stress and endothelial dysfunction evaluated by flow-mediated vasodilation FMD of the brachial artery in the elderly [ 7 ].

The effects of ALA upon endothelial function and markers of oxidative stress were age dependent and it was not observed in young subjects. In contrast, a review of many clinical trials using chronic antioxidant therapy was not able to demonstrate benefits on CVD [ ].

In animal models, those fed with a high cholesterol diet, the use of ALA for 12 weeks reduced oxidative stress and weight and improved vascular reactivity [ 10 ]. Moreover, a reduction in the wall volume of abdominal aorta with slowing rate of the plaque progression and a reduction of the expression of adhesion molecules in thoracic aorta were also observed.

One important finding in this study was the demonstration that ALA decreased the activation of NfKB which regulates the expression of pro-inflammatory genes as well adhesion molecules [ 10 ]. The effects and mechanisms of ALA on myocardial infarct size and diabetic cardiomyopathy which is defined as a ventricular dysfunction in diabetic patients without any other cause, were also evaluated in animal studies [ 66 , 67 ].

Cardiac fibrosis which is the main feature of cardiomyopathy, was investigated in animal with streptozotocin STZ DM-induced [ 66 ]. In these animals the use of ALA had different actions such as improvement of cardiac function and cardiac fibrosis.

Analyzing the left ventricular sections of these animals it was observed a better oxidative stress profile and a decreased expression of transforming growth factor β and smooth muscle actin, both associated with collagen production. In animal models of ischemia-reperfusion it was demonstrated that ALA ameliorates cardiac dysfunction with a decrease in the infarct size, TNF-α, mieloperoxidase, markers of cell death lactate dehydrogenase and creatinine kinase , and upregulates gene expression of several antioxidant enzymes [ 67 ].

No effects with lower or higher doses were observed [ 67 ]. In animal studies of glucocorticoid-induced hypertension, the use of ALA prevented only dexamethasone induced-hypertension [ 65 ]. In human studies the use of ALA as a hypotensive agent presented conflicting results showing improvement or no effect [ 52 , ].

Moreover it was also demonstrated that both drugs had a synergistic effect upon markers of endothelial dysfunction, inflammation and oxidative stress. It is important to emphasize that this study was not designed to evaluate blood pressure and the dose used of ALA was lower than the doses that are usually employed.

Oxidative stress plays an important role in tumorigenesis [ ]. ALA has been used as an anticancer agent mainly in experimental studies of different tumorigenesis cells type with promising results [ 16 , — ].

So far the exact molecular mechanisms involved in this action are unknown. Besides its antioxidant acitivity, another possibility could be its relation to the capacity of inducing cellular apoptosis as recently demonstrated in lung cells [ ].

This effects may result from activation of caspases proteins induced by endoplasmic reticulum stress [ ].

Another hypothesis is associated with the metabolism of cancer cells which convert preferentially glucose to lactate, a mechanism known as the Warburg effect [ ]. ALA is the cofactor of pyruvate deydrogenase which converts pyruvate to acetil CoA resulting in a decrease in the formation of lactate [ ].

The net effect of this action is the inhibition of glycolysis. Additionally, an inhibition of mTOR target of rapamycina , a signaling pathway responsible for cell growth and related to insulin receptor phosphorylation- PI3K-AKT activation, has been demonstrated in assays using insulinoma cells [ 57 ].

This action resulted in an inhibition of insulin secretion and of beta cells growth [ 57 ]. In addition, in this study it was also showed a direct binding site of ALA to insulin receptor [ ].

It is possible to speculate that ALA can act in alternative routes resulting in different effects. The few studies in humans are case reports [ ]. In these studies ALA was used associated with other antioxidant agents [ ] or with other anticancer drugs [ ].

ALA has been used in other clinical conditions such as glaucoma [ 72 ] and osteoporosis [ , ]. Both conditions are associated with an imbalance in the redox state. In a mouse model of glaucoma the increase in intraocular pressure was correlated to increased levels of lipid peroxidation and of oxidative stress-related genes expression in retina.

Moreover, in these animals the addition of ALA to the diet enhanced antioxidant defenses, prevented retinal ganglion cell losses without significant intraocular pressure changes. In a rat model of estrogen deficiency induced by ovariectomy the use of ALA increased bone mineral density BMD and decreased inflammatory markers such as TNF- α and IL Besides these effects, the use of ALA also decreased the levels of osteopontin, a protein related to bone resorption [ ].

In a model of low BMD induced by high-fat diet, which is a potent inducer of oxidative stress, the ALA supplementation resulted in an increase of the levels of expression of genes related to antioxidant enzymes, BMD, and biomarkers of bone formation, such as osteocalcin, and a down regulation of genes related to bone resorption activity, like osteoprotegerin, in femur biopsy.

These studies indicated a possible action of ALA upon maintenance of bone balance. The World Health Organization WHO , estimated that by there will be million people with DM in the world.

DM carries a great risk of morbidity and mortality due to the microvascular and macrovascular complications that can lead to a lower quality of life and life expectancy [ ]. Currently, these complications can be postponed by achieving adequate glycemic control, as demonstrated by the Diabetes Control and Complications Trial, the Epidemiology of Diabetes Interventions and Complications and UKPDS [ — ].

However in routine clinical practice good glycemic control is very difficult to be achieved [ , ]. The aforementioned diabetes-related complications lead to a significant burden to the individual and to the society as a whole [ , ].

The mechanisms underlying the development of DM related- chronic complications either micro or macrovascular are associated to glycemic control [ 90 , — ]. However, many other factors may contribute or have a direct relationship with these complications, such as oxidative stress [ ], markers of insulin resistance [ ], markers of low-grade inflammation [ ], dyslipidemia [ ], hypertension [ , ] and obesity [ ].

Indeed, DM-related complications may be considered multifactorial as DM itself [ ]. In this context, oxidative stress- related hyperglycemia is considered to be more and more important in the development of DM as well in the development of its related complications [ 85 , ].

This duet, oxidative stress- related hyperglycemia may induce modifications in signaling pathways responsible for several intracellular processes [ ].

Some of these processes are related to inhibition of insulin signaling pathway resulting in insulin resistance [ ], reduced insulin gene expression and consequently reduced insulin secretion by beta cells [ ].

Moreover, currently there is compelling evidence linking this duet to epigenetic modifications resulting in activation of genetic transcription or repression, silencing the genetic transcription as recently described [ 45 ]. In this study it was shown an increasing expression of the subunit p65 of NfKB which resulted in increased transcription of vascular cell adhesion.

molecule-1 VCAM-1 and monocyte chemo attractant molecule-1 MCP-1 in human aortic endothelial cells under hyperglycemia medium [ 45 ]. MCP-1 and VCAM are both related to hyperglycemia-induced arterial pathology.

Moreover, this reaction persisted after a long period of normoglycemia establishing the concept of metabolic memory at molecular level. Recently it was demonstrated also a downregulation of LASY in diabetic animals [ 18 ].

In this study either treatment with medium with high glucose or TNF-α resulted in reduction of LASY mRNA [ 18 ]. Moreover, a knockout of LAISY showed an intracellular decrease in GSH, superoxide dismutase SOD and catalase and an increase in superoxide anion resulting in activation of NfKB, Adding ALA in the cellular medium an up-regulation of LAISY expression was observed [ 18 ].

Another important factor in the pathogenesis of diabetes-related complications is the formation of advanced glycation end-products AGEs which are derived from intracellular glucose auto-oxidation and non-enzymatic reactions between glucose and intracellular and extracellular proteins [ — ].

AGEs by different mechanisms may damage target cells located in retina, endothelium and glomeruli [ ]. AGE may also activate PKC which is a signal transduction pathway for regulating many vascular functions like blood flow, permeability, basement membrane thickening and the expression of nitric oxide synthase [ ].

Considering the pleiotropic actions of ALA or its reduced form, DHLA in many signaling pathways associated with the pathophysiologic process of DM development as well as the development of its above mentioned chronic-related complications, its use as a therapeutic agent sounds promising.

Although an improvement in HbA1c, weight and waist have been observed with ALA, omega 3 fatty acids gave the better results concerning weight loss and glycemic control [ ]. However, there was only a statistical significant difference only with the pooled group of ALA.

The reduction of HbA1c was ALA dose-dependent. Moreover, markers of oxidative stress such as lipid peroxidation and oxidative damage of DNA did not show any modification.

Data obtained in clinical studies using ALA in the treatment of diabetes-related complications are summarized in Table 2. ALA has been used to evaluate retinal mitochondria biogenesis in rats in a model of reinstitution of good control after six months of poor metabolic control [ ].

In animals without ALA supplementation and under poor glycemic control it was observed a dysregulation of retinal mitochondria biogenesis with a decreased expression of citrase synthase a marker of mitochondria functional integrity , a decreased number of mitochondria and an increased number of acellular capillaries a marker of diabetic retinopathy.

Moreover, in this study the supplementation of ALA in animals soon after induction of DM prevented most of the above-mentioned alterations [ ]. In another experimental study, the treatment with ALA in diabetic animals reduced the markers of oxidative stress, NfKB activation and vascular endothelial growth factor in diabetic retina [ ].

The effects of ALA in the development of diabetic nephropathy was investigated mainly in animal studies. In diabetic animal strepzotocin STZ -induced DM and apolipoprotein deficient fed high fat diet the protective effect of ALA supplementation was evaluated in three different time schedule : pre-STZ, simultaneously and pos-STZ.

No statistical difference was noted among the groups concerning hyperglycemia, although an attenuation of hyperglycemia was observed in the group pre-STZ. Analyzing the pooled group it was found a reduction in IL-6, urine albumin, urine isoprostane and an increase in erythrocyte GSH in the group under ALA supplementation.

The decreased gene expression of superoxide dismutase in diabetic animals was normalized with ALA. Two other animal studies showed interesting data [ , ]. One study showed that LASY-deficient animals present reduction in antioxidant defense.

Moreover, in this study it was also found an overproduction of superoxide in the proximal tubular cells which could be an important event for accelerating the development of diabetic nephropathy [ ].

Another study showed opposite action of ALA in animals with STZ-induced DM. In diabetic animals ALA decreased urinary albumin and markers of oxidative stress, but in non-diabetic animals pro-oxidant effects were observed with an increase in urinary albumin, creatinine and markers of oxidative stress [ ].

This effect may be at least partially explained by the high dose used in the experiment. So far, the few human studies which have been done had different objectives [ — ].

Moreover this reduction was independent of the level of HbA1c and urine albumin [ ]. The protective effect of ALA on the development of contrast-induced nephropathy CIN was evaluated in 68 patients with DM undergoing coronary angiography. The patients received mg of TA prior to the procedure or no treatment control group.

The effect of ALA upon asymmetric dimetihylarginine ADMA which is an inhibitor of nitric oxid synthase, was investigated in a randomized, control study for 12 week in 50 diabetic patients undergoing hemodyalisis. A decrease in the level of trombomodulin and no changes in the urinary albumin were observed in the treatment group [ ].

A randomized, controlled, double blind, parallel study with 30 patients with T2D evaluated glycemic control and endothelial responses to intravenous acetylcholine endothelium dependent and nitrate endothelium independent in order to evaluate the forearm blood flow before and after the use of mg of ALA intravenously for three weeks [ ].

A decrease in HbA1c, total cholesterol and triglycerides levels were observed in both groups. However only the patients ALA treated showed an improvement in the endothelium dependent vasodilation. ALA or placebo did not influence endothelium independent vasodilation [ ].

An experimental study in vitro and in vivo has demonstrated a possible benefit of topical application of ALA alone or in combination with other anti-oxidant agents for diabetic wound healing [ ]. In this study the expression of RAGE was attenuated in skin wound in diabetic animals when ALA was used in combination with other anti-oxidants agents for one week.

Moreover, the use of ALA in combination with other anti-oxidants agents accelerated the skin wound healing with increased expression of vascular endothelial growth factor VEGF in the wound area.

Cardiovascular autonomic neuropathy was evaluated in two human studies. One, randomized, double blind, placebo controlled multicenter study DEKAN was conducted in patients with T2D with cardiovascular autonomic neuropathy CAN using mg of ALA daily for 16 weeks [ ].

Autonomic symptoms and heart rate variability were evaluated before and after the intervention. The intervention with ALA resulted in improvement of some parameters of heart rate variability analysis: root mean square successive difference and power spectrum in low frequency band.

No difference was observed in overall symptoms. Another study, a prospective, randomized, double blind, placebo controlled study was performed in 44 patients with T1D presenting any diabetes-related chronic complication mild non-proliferative retinopathy or microalbuminuria and the presence of cardiac autonomic neuropathy CAN defined by an alteration of positron emission tomography PET with normal autonomic reflex testing [ ].

In this study no improvement was found in all parameters of autonomic function analysis as well as in urinary levels of isoprostanes, a marker of oxidative stress. Meanwhile a detrimental effect in some regions of left ventricle was observed in PET analysis [ ]. So far, the majority of clinical studies using ALA therapeutically were conducted in order to evaluate its action on diabetic neuropathy.

The main benefit of ALA was an improvement of symptoms and in distal motor never latencies. It is beyond the scope of this review to analyze each of these studies but they did not have a definite conclusion about the effects of ALA upon diabetic neuropathy.

However they have given key information about how to perform other clinical trials better designed to in order to evaluate this topic. It is important to emphasize that at this time the lack of standardization of definition as well as standard criteria for diagnosing diabetic neuropathy are unsolved problems due to different worldwide consensus in the subject.

These consensuses have established scores like Neuropathy Symptoms Score NSS , Total Symptoms Score TSS , and Neuropathy Impairment Score NIS [ , , ] which addressed the intensity and frequency of the most important symptoms of diabetic neuropathy such as pain, burning, numbness and paresthesias.

The first of these studies was the ALADIN Alpha Lipoic Acid in Diabetic Neuropathy which was designed to evaluate the efficacy and safety of intravenous ALA during three weeks in three different doses, mg, mg and mg in comparison to placebo in patients with T2D with symptomatic distal symmetric diabetic polineuropathy DSPN [ ].

In this study an improvement in TSS was noted in the group using mg vs placebo establishing the safety and efficacy of this dose in comparison to the mg dose.

Moreover, at the dose of mg a higher rate of adverse events were observed mainly in the gastrointestinal tract. No difference in HbA1c was observed at the end of the study which included patients.

This study was followed by ALADIN II which was a long-term trial 24 months that addressed also electrophysiological tests and Neuropathy Disability Score NDS using the same doses of ALA but orally in patients with T2D.

In this study only 65 patients could be included in the final analysis because the variability in the electrophysiological tests biased the final results [ ]. Although some improvement in sensory nerve function was noted the excessive number of patients excluded should be considered when interpreting these results.

The ALADIN III Study has combined mg of ALA intravenously for three weeks followed either by mg of ALA three times daily or placebo for six months 24 weeks [ ]. No improvement in TSS and NIS were observed at the end of the study, although some analyzed parameters such as NIS and TSS presented positive results in short period of ALA intravenously administration tree weeks.

Recently three randomized, double blind, controlled parallel studies were concluded addressing the efficacy and safety of ALA in diabetic patients with DSPN with TSS or NIS as primary outcome. The SYDNEY Trial, a monocenter, short-term study used ALA intravenously during five days a week for three weeks and showed improvement in TSS [ ].

The SIDNEY 2 Trial was a multicenter study which used doses of ALA ranging from to mg daily and also showed an improvement in TSS [ ]. In this study after a four-year treatment with ALA in mild-to-moderate DSPN did not influence the primary composite end point but resulted in a significant clinical improvement and prevention of progression of neuropathic impairments.

As the primary composite end point did not deteriorate in placebo-treated subjects, secondary prevention of its progression by ALA according to the trial design was not feasible [ ].

All these latter studies concluded that the usual dose of mg has efficacy and safety and adverse events, mainly in the gastrointestinal tract, that were dose dependent. Moreover, with one exception sural latency , all these studies did observe improvement in electrophysiological tests.

Two recent meta-analysis evaluate the use of ALA in diabetic neuropathy [ , ]. One, included 1, diabetic patients treated with mg of ALA, intravenously for three weeks, concluded that individualized TTS such as pain, numbness and burning decreased significantly with ALA in comparison to placebo.

Considering the components of NIS-LL an improvement was noted in pin-prick, touch pressure and ankle reflexes [ ]. This meta-analysis also pointed out some relevant aspects for conducting future trials to evaluate the benefits of ALA on diabetic neuropathy as follows: homogeneity of the studied patients; duration of the trial; end-points with less variability and finally considering the slowing progression of diabetic neuropathy the end point must have to exclude the latter and address improvement.

Recently, a randomized, open label, parallel study showed no benefit of adding methylcobalamine ug and ALA mg to pregabalin 75 mg for 12 weeks in parameters of nerve function and pain evaluation [ ]. Another prospective, observational study showed that after 21 months patients using pregabalin had better improvement in symptoms of diabetic neuropathy in comparison to patients using either carbamazepine and ALA [ ].

Adverse events related to the administration of ALA were described mainly in clinical trials [ , , ] but generally without difference when compared with placebo. The majority of these adverse events were dose-dependent and in the gastrointestinal tract nausea, vomiting, dyspepsia and abdominal pain.

However other events were also described like pruritus, bronchitis and skin ulceration. Recently it was described a case of insulin autoimmune syndrome probably associated with the use of ALA as a nutritional supplement [ ].

ALA a natural anti-oxidant is a cofactor of mitochondrial enzymes of oxidative metabolism like pyruvate dehydrogenase which link glycolysis to citric acid cycle, and α-keto-glutarate dehydrogenase.

ALA and its reduced form DHLA have many biological functions in different intracellular systems resulting in a wide range of actions such as antioxidant protection, chelation of metal ions, regeneration of other antioxidant agents such as vitamin C, E and glutathione.

To date, the majority of these actions have been addressed mainly in experimental studies which used a wide range dose of ALA in vitro as well as in vivo. We can also consider that for instance, the used dose was greater than the physiological dose reached with the usual clinically used oral dose of ALA.

It is also to be mentioned that in most of these studies it was not well defined which type of ALA has been used. Finally, the translation of all these pooled experimental data to human studies is a subject for further research.

Currently, there are compelling evidences linking oxidative damage to the majority of chronic diseases with increasing prevalence worldwide such as obesity, DM, CVD and AD. Considering the pleiotropic action of ALA upon different pathways associated with the above mentioned diseases, its use as a potential therapeutical agent seems promising.

So far, although in a limited number, the majority of clinical studies, performed in randomized double-blind and placebo-controlled ways, have been done in diabetic patients with DSPN.

Future clinical studies, also randomized double-blind and placebo-controlled with adequate sample calculation, homogeneity of the studied patients, longer duration and a minimal variability in the established outcomes are needed in order to asses the benefit of ALA upon other diabetes-related chronic complications.

Considering the latter statement it will be an important issue to define the use of ALA as primary or secondary therapeutic intervention. Also, the same aforementioned type of studies with the same criteria must be addressed in other clinical conditions such as obesity, CVD and AD.

Another important question to be answered by these clinical studies is when we are going to start its use according to the natural evolution of each disease in order to reach a benefit.

We need also more experimental studies to evaluate and define if the pro-oxidant action of ALA is dose-dependent. These studies may also give us more information about the use of lipoic acid synthase as a molecular target for increasing the mitochondrial levels of ALA.

Another point to be addressed in these studies is the possibility that hyperglycemia can affect different pathways resulting in a toxicity which could be independent of oxidative stress as recently discussed [ ]. The role of endoplasmic reticulum stress has been pointed out as an important mechanism leading to diabetes-related complications which is independent of oxidative stress.

Finally, although our review had the objective to extended our clinical and biological knowledge about ALA we still need more information about this multifunctional compound to spread its use in routine clinical practice.

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What wnd it about foods anf broccoli prlduction spinach that make them so RMR and calorie deficit Alpha lipoic Alpha-lipoic acid and energy production — one kind of antioxidant AAlpha-lipoic is a type of compound Alppha-lipoic in plant foods we commonly eat. What Productioon alpha-lipoic Alpha-lipoic acid and energy production good Alpha-liooic It helps scavenge free radicals and Flavonoids and respiratory health 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 acid also called lipoic acid or thioctic acid is an organosulfur compound found in the body and also synthesized by plants and animals. Even though we can make some of it on our own without supplements or outside food sources, eating an antioxidant-packed diet plus potentially using ALA supplements can increase the amount circulating in the body.

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