What is Lipoic Acid?
A List of Important Functions for Lipoic Acid:
- Lipoic acid acts as a powerful antioxidant both inside and outside of the cells [1, 2].
- Lipoic acid scavenges several reactive oxygen species (ROS) .
- Lipoic acid helps to regenerate both fat and water-soluble antioxidant vitamins (such as vitamins C and E) [2, 1].
- Lipoic acid improves sugar and fat metabolism .
- Lipoic acid is an essential cofactor for mitochondrial respiratory enzymes that improves mitochondrial function . Lipoic acid exerts a “rejuvenating” impact on mitochondria by protecting them against the higher levels of ROS they produce during the aging process .
- Lipoic acid also has anti-inflammatory action, independently of its antioxidant activity .
Production of Lipoic Acid in the Human Body
A healthy body makes enough lipoic acid to supply its energy requirements; therefore, there is no daily requirement for this supplement. However, several medical conditions appear to be accompanied by low levels of lipoic acid – specifically, diabetes, liver cirrhosis, and heart disease .
In Europe, lipoic acid is licensed for the treatment of diabetic neuropathy. It has been shown to enhance insulin sensitivity, improve microcirculation in the limbs, and reduce neuropathic symptoms [1, 6].
Also, lipoic acid produced in the body decreases with age, which could increase free radical-induced damage. Lipoic acid supplementation in animal models can prolong life, has neuroprotective effects, and has positive effects on cancer .
Health Benefits of Lipoic Acid
1) Acts as a Powerful Antioxidant
2) Can Help with Weight Loss
Even without dieting, lipoic acid can greatly improve glucose and fat metabolism. As a result, more of the sugars and fats in foods will be broken down and used for energy instead of being stored as fat. This will also cause the consumer to feel the need to eat less .
In obese patients with type 2 diabetes, people treated with lipoic acid lost significantly more weight and had lower triglyceride levels .
3) Promotes Muscle Regeneration After Exercise
By increasing blood total antioxidant capacity, lipoic acid protects DNA and fatty acids from oxidative stress due to exercise .
Lipoic acid helps shift chemicals inside the cells and cytokines towards favoring the regeneration of injured muscles . In physically active males, lipoic acid significantly elevates H2O2 but reduced NO generation before or after exercise. Lipoic acid increases IL-6 and IL-10 levels at 20 min after exercise and decreases IL-1β and TNF-α before and after exercise.
4) Decreases Inflammation
Abnormal inflammatory responses contribute to diseases such as diabetes, Alzheimer’s disease and multiple sclerosis . Lipoic acid was shown to have an anti-inflammatory effect in subjects with multiple sclerosis , metabolic syndrome , and diabetes .
Lipoic acid can reduce inflammatory markers in subjects with organ transplants .
5) Prevents and Improves Diabetes
Lipoic acid has beneficial effects both in the prevention and in the treatment of diabetes .
In type 2 diabetic patients, lipoic acid improved metabolic indices and erectile dysfunction. Lipoic acid supplementation reduced BMI, HbA1C, total cholesterol, HDL-cholesterol and triglycerides .
6) Helps with Diabetes-Associated Complications
People with diabetes are more prone to oxidative stress, which means there is an imbalance of free radicals to antioxidants. Oxidative damage plays a key role in the development of diabetes-associated disorders and diseases [7, 8].
Lipoic acid has drawn considerable attention as an antioxidant for use in managing diabetic complications such as retinopathy, neuropathy and other vascular diseases .
Lipoic acid Helps with Neuropathies
In Europe, alpha-lipoic acid is licensed for the treatment of diabetic neuropathy (nerve damages due to high blood sugar in diabetics). It has been shown to enhance insulin sensitivity, improve microcirculation and reduce neuropathic symptoms [1, 6].
Studies show that lipoic acid improves these nerve damage symptoms such as stabbing and burning pain, asleep numbness, and prickling sensations [35, 36, 37, 38]. Lipoic acid also improves the function of motor nerves and reduced blood glucose .
Lipoic acid is a well-tolerated and effective long-term treatment for diabetic neuropathy. In mild-to-moderate cases, lipoic acid treatment for four years improved symptoms and prevented progression of neuropathic impairments .
In type 1 diabetic patients with autonomic diabetic neuropathy (damages to the nerve that control vital functions of the autonomic nervous system, such as blood pressure and heart rate), lipoic acid improved systolic blood pressure, dizziness, instability upon standing, leg edema and erectile dysfunction .
In diabetics, lipoic acid improved cardiac autonomic neuropathy .
Lipoic Acid Prevents Cardiovascular Complications
People with impaired glucose metabolism have blood vessel damages and impaired blood vessel function. Lipoic acid can improve blood vessel function by decreasing oxygen-derived free radicals .
In adolescents with type 1 diabetes, lipoic acid improved blood vessel function .
In children and adolescents with asymptomatic type 1 diabetes, lipoic acid improved left ventricular (heart chamber that pumps the blood throughout the body) function, suggesting that it may help prevent cardiomyopathy (damage to the heart muscles) .
In aged type 2 diabetes complicated with acute brain infarction (tissue death from blood clots), lipoic acid significantly reduced the patient’s oxidative stress, blood glucose and cholesterol levels .
In patients with type 2 diabetes, lipoic acid increases vasodilatation (widening of blood vessels) in response to ACh .
7) Helps Combat Metabolic Syndrome
In patients with metabolic syndrome, lipoic acid improves blood vessel cell function and reduces proinflammatory markers .
In obese subjects with impaired glucose tolerance, lipoic acid improved insulin sensitivity and decreased free fatty acids, triglycerides, total cholesterol, and LDL cholesterol. Lipoic acid also decreased proinflammatory markers and increased adiponectin .
8) Helps Lower Blood Pressure
Lipoic acid may have a beneficial effect in preventing the development of hypertension (elevated blood pressure) by lowering the level of inflammatory cytokines in the blood, thus preventing pathological changes to blood vessel cells and normalizing changes in blood pressure .
Several clinical trials have shown that lipoic acid inhibits the overproduction of endothelin I, the main vasoconstrictor (narrower of blood vessels) . Furthermore, lipoic acid significantly increases the synthesis of NO, the main vasodilator (widener of blood vessels) .
Lipoic acid improves blood vessel cell function .
However, clinical studies show that lipoic acid is not very effective in lowering blood pressure on its own. However, it can more effectively reduce blood pressure when used in combination with other antioxidants such as L-carnitine .
9) Decreases Bad Cholesterol
10) Prevents Atherosclerosis
Many studies suggest the potential role of lipoic acid in the prevention and treatment of atherosclerosis (hardening of the arteries) and related cardiovascular disease .
Lipoic acid improves blood vessel structure and function [1, 5]. Lipoic promotes anti-inflammatory and antithrombotic (blood clot-reducing) pathways and increases nitric oxide-mediated vasodilatation (blood vessel widening) .
Lipoic acid can decrease atherosclerotic plaque burden .
One study indicates that lipoic acid may increase the atherogenicity of LDL, but when it’s combined with exercise, this atherogenic effect is abolished .
11) Protects the Brain
In rats, urgent lipoic acid treatment given after stroke has a significant neurorestorative effect and promotes long-term functional recovery through enhanced anti-inflammatory and antioxidant actions .
Another study in rats showed that lipoic acid reduces brain damage and increase survival rate after a stroke .
12) Improves Alzheimer’s
When lipoic acid was given daily to patients with AD (receiving a standard treatment with cholinesterase inhibitors) the treatment led to a stabilization of cognitive functions .
In another study, in AD patients with dementia, lipoic acid slowed down the progression of the disease .
Levels of acetylcholine (Ach) are significantly decreased in Alzheimer’s. Many of the drugs that are currently used to treat this disease work to increase Ach levels. In rats, it was shown that lipoic acid raises the level of acetylcholine (Ach) and choline acetyltransferase (ChAT, an enzyme that increases available acetylcholine levels) and decreased the activity of acetylcholinesterase (AchE) in the brain .
13) May Help with Parkinson’s Disease
Parkinson’s disease is described as a disease with reduced dopamine function and loss neurons in the brain due to misfolded proteins, poor autophagy, increased oxidative stress and inflammation, and mitochondria dysfunction .
In a mouse model of Parkinson’s disease, lipoic acid improves motor dysfunction, protects against dopaminergic neurons loss, and decreases α-synuclein accumulation in the substantia nigra area of the brain. Further, lipoic acid inhibits the activation of nuclear factor-κB (NF-κB) and decreases pro-inflammatory molecules .
Lipoic acid reduces neuronal death in laboratory models of Parkinson’s disease .
14) Can Help Reduce Side Effects of Antipsychotics
Weight gain and other metabolic disturbances are major side effects of atypical antipsychotic drugs (AAPDs). In schizophrenia patients using AAPDs, lipoic acid reduced BMI (weight to height ratio) and total cholesterol levels .
Lipoic acid also promoted weight loss and reduced abdominal fat in overweight and clinically stable schizophrenia patients. Moreover, lipoic acid was well tolerated throughout the 12-week study .
Lipoic acid also improved metabolic risk factors in Schizophrenia patients. A study showed that lipoic acid increased adiponectin and decreased fasting glucose and aspartate aminotransferase (AST, a liver enzyme) .
15) Is Beneficial in Multiple Sclerosis
In a Russian study, lipoic acid reduced relapse frequency in multiple sclerosis patients and decreased corticosteroid use . Effects were further magnified by adding other antioxidants to the treatment.
Lipoic acid is highly effective at suppressing and treating MS in a mouse model .
16) Can Protect Your Eyes and Vision
Oxidative stress increases with aging and conditions such as diabetes, and it can have detrimental effects on vision. Lipoic acid can help by counteracting oxidative stress in the eyes.
A study has shown that lipoic acid improves vision and other symptoms in patients with glaucoma .
Lipoic acid also improves the vision-related quality of life in patients with age-related macular degeneration (AMD) .
Lipoic acid reduces retinal cell death in mice with retinitis pigmentosa – an inherited, degenerative eye disease .
17) Can Prevent Migraines
In patients with migraines, lipoic acid has the ability to reduce the frequency, duration, and intensity of migraines .
Lipoic acid improved the effectiveness of the migraine drug topiramate. The combination of lipoic acid and topiramate was significantly more effective at decreasing the frequency and duration of migraines than the drug alone. In addition, lipoic acid helped reduced topiramate-related side effects .
18) Alleviates Pain
Lipoic acid improves the quality of life in patients with neuropathies. A significant reduction was observed in a number of pain parameters, such as intensity, burning, unpleasantness and superficial pain .
Lipoic acid reduced the postoperative incidence of pain in patients with carpal tunnel syndrome .
Lipoic acid decreased sciatic pain caused by a herniated disc. Patients on lipoic acid reported a decreased need for analgesia .
Lipoic acid administered together with gamma-linolenic acid (GLA) reduced symptoms and functional impairment in patients with carpal tunnel syndrome .
19) May Help with Ulcers and IBD
In rats, lipoic acid protects against alcohol-induced stomach ulcers .
Other studies also showed that lipoic acid effectively attenuates ulcerative colitis in mice [85, 86]. However, in one study in mice with mild ulcerative colitis, lipoic acid actually increased oxidative damage to the colon and liver .
20) Improves Sperm Quality
In infertile men, lipoic acid significantly increases total sperm count, sperm concentration, and motility levels .
21) May Help with High-Risk Pregnancies
In high-risk pregnancies, lipoic acid can speed up the return to normal pregnancy conditions and improve the conditions of both the mother and the fetus . Additionally, smaller numbers of miscarriages were recorded with lipoic acid supplementation .
Lipoic acid decreases inflammation in women with gestational diabetes .
Lipoic acid reduced cervical inflammation after a preterm labor episode .
22) Prevents Bone Loss
In female rats with osteopenia, lipoic acid not only stopped the bone resorption but stimulated its formation .
23) May Improve Osteoarthritis
Lipoic acid decreased inflammation and ameliorated cartilage degeneration in rats with osteoarthritis .
24) Removes Toxic Metals from the Body
Lipoic acid protects against Cd-induced oxidative stress and kidney cell death in rats .
Lipoic acid attenuates liver damage caused by copper nanoparticles in rats .
In rats, administration of lipoic acid together with zinc and calcium ameliorated lead (Pb) toxicity and decreased lead body burden to near-normal. Lipoic acid does this by preventing the accumulation of lead within the blood and tissues .
25) Counters Other Toxic Compounds
Dimethylnitrosamine (DMN) is a waste product of several industrial processes. Lipoic acid reduces kidney damage caused by this chemical in male mice .
Lipoic acid reduced methylmercury-induced brain injury in rats .
Lipoic acid attenuates antimycin A-induced cell toxicity .
26) Promotes Wound Healing
Hyperbaric oxygen therapy is used as a treatment for wounds that won’t heal as a result of diabetes or radiation injury. Lipoic acid accelerates wound repair in patients affected by chronic wounds undergoing hyperbaric oxygen (HBO) therapy [109, 110, 111].
27) Is Beneficial for the Skin
Lipoic acid reverses skin damage caused by cigarette smoke .
28) Fights Cancer
Cell-based and animal model studies have shown that lipoic acid inhibits the initiation and promotion stages of cancer .
Lipoic acid-treated lung cancer cells had a decreased ability to survive .
Lipoic acid also increased the susceptibility of lung cancer cells to cisplatin, etoposide and paclitaxel-induced cell death .
29) May Increase Lifespan
A study showed that while lower doses of lipoic acid increased the total lifespan in mice, high doses decreased it .
It is well known that dietary restriction extends lifespan. When mice were first exposed to dietary restrictions and then allowed to feed as desired, the beneficial effect of dietary restriction was abolished. However, when mice were supplemented with lipoic acid in the second phase, the beneficial effect of dietary restriction on longevity was maintained .
Lipoic acid may improve longevity by:
- Fighting free radicals. Aging and reduced longevity are due in part to the action of free radicals. Lipoic acid is effective in protecting against the damage caused by free radicals .
- Rejuvenating mitochondria. Feeding old rats with acetyl carnitine and lipoic acid for a few weeks restored mitochondrial function and lowered oxidants to the level of young rats .
- Increasing telomerase. Lipoic acid may increase telomerase , thereby increasing telomere length and reversing the aging process.
30) Other Conditions in Which Lipoic Acid is Beneficial:
Because of its antioxidant and anti-inflammatory effects, lipoic acid is beneficial in many diverse conditions, whether it improves the disease directly, or metabolic and oxidative stress indices. Some of the conditions are listed below.
- Hypothyroidism: In patients with subclinical hypothyroidism, lipoic acid improves endothelial function, by decreasing oxygen-derived free radicals .
- HIV infection: In human immunodeficiency virus (HIV)-infected subjects with a history of unresponsiveness to highly active antiretroviral treatment, lipoic acid increased glutathione levels and enhanced or stabilized lymphocyte proliferation .
- Cystinuria: Lipoic acid inhibits cystine stone formation in mice .
- Liver Surgery: Lipoic acid reduced ischemia/reperfusion injury of the liver in humans undergoing liver surgery .
- Heart Surgery: In patients with coronary heart disease and those planned for coronary artery bypass graft operation, lipoic acid significantly decreased inflammation when blood is removed from the body (extracorporeal circulation) .
- High-fructose corn syrup caused pancreatic damage: Lipoic acid ameliorated metabolic changes and pancreatic lesions .
- Peripheral Artery Disease: 3 months of lipoic acid supplementation improved walking tolerance and delayed pain onset in peripheral arterial disease .
- Acute Coronary Syndrome: Lipoic acid ameliorates oxidative stress in patients with confirmed acute coronary syndrome (ACS) .
- Takotsubo syndrome: Takotsubo syndrome is a form of stress-induced heart muscle damage. Lipoic acid treatment improves the innervation of adrenergic nerve cells in the hearts of patients with Takotsubo syndrome .
- Heart Failure: Lipoic acid effectively decreases heart cell death [5, 5], can prevent progressive heart remodeling and even improve heart function .
- Olfactory Loss: Infections of the upper respiratory tract sometimes result in the loss of the sense of smell. Lipoic acid improves olfactory function .
- Burning Mouth Syndrome: A single study indicates significant improvement upon treatment with lipoic acid , while other studies found no significant effect [137, 138, 139].
- Idiopathic dysgeusia: In patients with idiopathic dysgeusia, an altered perception of taste, lipoic acid caused significant symptomatic improvements .
- Sickle Cell Disease: In patients with sickle cell disease, lipoic acid treatment protected a subset of patients from oxidative damage to fat and proteins .
- Polycystic ovary syndrome: Lipoic acid together with d-chiro-inositol (DCI) improved clinical and metabolic health in women with polycystic ovary syndrome . Supplementation of myoinositol and lipoic acid improved reproductive outcome and metabolic profiles in PCOS women undergoing in vitro fertilization .
- Chronic Spinal Cord Injury: In men with chronic spinal cord injury, lipoic acid reduced fasting blood sugar, body weight, BMI, waist circumference and blood pressure. Lipoic acid also decreased food intake .
Lipoic Acid Mechanisms
Increases antioxidants and antioxidant enzymes:
- Increased glutathione (GSH) [33, 5, 58, 85].
- Increases superoxide dismutase (SOD) [25, 44, 5, 85].
- Increases catalase (CAT) .
- Increases Nrf-2 .
Decreases markers of oxidative stress:
- Decreases malondialdehyde (MDA) [33, 44, 58, 85].
- Decreases myeloperoxidase (MPO) .
- Decreases troponin-I levels .
- Decreases Nox4 and p22phox (CYBA) .
- Reduces both Th1 and Th2 cytokines .
- Decreases TNF-α [17, 33, 5, 20, 145, 97].
- Decreases IL-2 , IL-4 [20, 146], IL-1β  and IL-17 .
- Can increase , but mostly decreases IL-6 [20, 21, 145].
- Increases IL-10 .
- Decreases CRP .
- Decreases NO [17, 33, 85], but can also increase NO .
- Decreases iNOS .
- Suppresses NK cell activation .
- Decreases TGF-beta [33, 146].
- Decreases IFNγ [20, 146].
- Decreases NF-κB [5, 97].
- Decreases MMP-2 [33, 20] and MMP-9 [66, 20].
- Decreases ICAM-1 [66, 20, 146, 145] and VCAM-1 .
- Decreases MCP-1 (CCL2) [20, 145] and RANTES (CCL5) .
- Increases heme oxygenase (HO-1, HMOX1) .
Improves fat metabolism:
- Activates AMPK [147, 148].
- Modestly reduced nonesterified fatty acids (NEFA) .
- Increases LDL receptor (LDL-R) .
- Decreases PPARγ , C/EBPα, and C/EBPβ .
- Increases SIRT1 .
- Increases PDK4 .
- Increases PPARβ (PPARD) .
Beneficial for the cardiovascular system:
Improves brain function:
- Increases acetylcholine (ACh) and choline acetyltransferase (ChAT) and decreases acetylcholinesterase (AChE) in the hippocampus .
- Increases VGlut1 .
Protects cells and mitochondria:
- Increases Bcl-2 .
- Decreases Bax, caspase-3 and caspase-9 activity .
- Increases PGC-1α (PPARGC1A), TERT .
How to Supplement With Lipoic Acid
Recommended oral therapeutic dosages of lipoic acid range from 600 – 1,800 mg daily . Studies show that increased dosage is also followed by increased side effects.
Oral lipoic acid has a limited bioavailability of about 30% . Studies show that there is significant inter-subject variability in peak blood lipoic acid concentrations, due to individual differences in gut absorption .
Potential Risks and Side Effects
Urticaria and itching are the most common adverse events, but they are generally mild and transient .
Lipoic acid is also associated with a dose-dependent increase in nausea, vomiting, and vertigo . Higher doses of 1,200 mg and 1,800 mg have more frequent adverse effects . An oral dose of 600 mg once daily appears to provide the optimum risk-to-benefit ratio .
This is particularly the case in the elderly population, where 600 mg dose was well tolerated, but higher doses caused intolerable flushing and intolerable upper gastrointestinal side effects. However, subjects taking gastrointestinal prophylaxis medications had no upper gastrointestinal side effects .
Lipoic acid (possible overdose) can cause refractory convulsions in children .
One study in mice suggests that prophylactic and abundant intake of lipoic acid causes fatty liver and liver injury . There is one recorded case of lipoic acid causing acute cholestatic hepatitis in humans . It may be prudent to monitor cholesterol and liver enzymes with long-term lipoic acid supplementation.
Finally, in rats, it was shown that lipoic acid reduces the absorption of iron. Lipoic acid supplementation could potentially trigger iron deficiency anemia . No such events have been reported in humans though.
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