Lipoic acid is a natural antioxidant and anti-inflammatory compound with a suite of potential health benefits. Read on to learn more about how this essential nutrient may help improve your health.
What is Lipoic Acid?
Lipoic acid (LA), also known as alpha-lipoic acid (ALA), R-lipoic acid, or thioctic acid, is a disulfide-containing compound [1], found inside every cell of the body [2].
Some call it the “universal antioxidant” [3].
Alpha-lipoic acid is essential for certain enzymatic reactions, but there is no official recommended dietary intake of ALA [4].
Health Benefits of Lipoic Acid
While alpha-lipoic acid is generally accepted to be a healthy component of our diets, the FDA has not approved it as a supplement for any medical purpose or health claim. Talk to your doctor before supplementing with ALA.
Possibly Effective For
1) Skin Health
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 accelerated wound repair in patients affected by chronic wounds undergoing hyperbaric oxygen (HBO) therapy [5, 6, 7].
Skin Damage & Aging
Applied directly to the skin, lipoic acid increased the thickness [8] and decreased the roughness and sun damage of skin in older women [9].
Topical lipoic acid also reversed skin damage caused by cigarette smoke [10].
2) Diabetes
Lipoic acid appears to have possible beneficial effects in the prevention of diabetes. In some countries, it is approved as part of a treatment plan for diabetic patients [11].
Lipoic acid has insulin-mimetic activity [11], in that it improves glucose handling/utilization [4].
In patients with type-2 diabetes, lipoic acid decreases blood glucose and improves insulin sensitivity [12, 13, 14], including in overweight adults with type 2 diabetes [15].
Glutathione, an important antioxidant, is usually decreased in diabetics. In children and adolescents with asymptomatic type 1 diabetes, lipoic acid increased glutathione (GSH) levels [16].
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 [17].
Diabetes-Associated Complications
People with diabetes are more prone to oxidative stress, and oxidative damage plays a key role in the development of diabetes-associated disorders and diseases [18, 19].
Lipoic acid has drawn considerable attention as an antioxidant for use in managing diabetic complications such as retinopathy, neuropathy and other vascular diseases [11].
Neuropathies
In Europe, alpha-lipoic acid is approved for the treatment of diabetic neuropathy (nerve damages due to high blood sugar in diabetics). It is believed to enhance insulin sensitivity, improve microcirculation and reduce neuropathic symptoms [1, 20].
Studies show that lipoic acid improves these nerve damage symptoms such as stabbing and burning pain, asleep numbness, and prickling sensations [21, 22, 23, 24]. Lipoic acid also improves the function of motor nerves and reduced blood glucose [25].
Lipoic acid is a well-tolerated and effective long-term intervention for diabetic neuropathy. In mild-to-moderate cases, lipoic acid supplementation for four years improved symptoms and prevented progression of neuropathic impairments [26].
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 [27].
In diabetics, lipoic acid also improved cardiac autonomic neuropathy [28].
Cardiovascular Complications
People with impaired glucose metabolism often have blood vessel damage and impaired blood vessel function. Lipoic acid can improve blood vessel function by decreasing oxygen-derived free radicals [29].
In adolescents with type 1 diabetes, lipoic acid improved blood vessel function [20].
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) [16].
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 [30].
Elevated asymmetric dimethylarginine (ADMA) concentrations predict cardiovascular events in patients with type 2 diabetes. In patients with T2D, lipoic acid reduced ADMA [31].
In patients with type 2 diabetes, lipoic acid increased vasodilatation (widening of blood vessels) in response to ACh [32].
3) Weight Management
In healthy overweight/obese women on a calorie-restricted diet, those who were given lipoic acid supplements lost a little more weight than those who didn’t. The authors concluded that ALA could be a helpful addition to a weight loss program, but that ALA by itself won’t trigger weight loss [33].
Even without dieting, lipoic acid can 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 [34].
In several other studies with overweight or obese subjects, lipoic acid was associated with slight weight loss accompanied by a reduction in waist circumference [35, 36, 37].
In obese patients with type 2 diabetes, people given lipoic acid lost significantly more weight and had lower triglyceride levels [38].
Lipoic acid inhibits the production of chemerin, a molecule that is associated with obesity and metabolic syndrome. This may be how lipoic acid helps to combat obesity and diabetes [39].
Insufficient Evidence For
The following purported benefits are only supported by limited, low-quality clinical studies. There is insufficient evidence to support the use of lipoic acid for any of the below-listed uses. Remember to speak with a doctor before taking lipoic acid supplements, and never use them in place of something your doctor recommends or prescribes.
5) Brain Health & Neurological Disorders
In all, lipoic acid has produced promising results in various neurological disorders, but further research is still required in order to determine the role of ALA in human brain health and whether it can be used in any therapies.
Because of its antioxidant properties, lipoic acid may act as a neuroprotective agent. It promoted neuronal regeneration in rats [40] and prevented the degeneration of neurons in a cell study [41].
In rats, lipoic acid given immediately after stroke restored damaged neurons and promoted long-term functional recovery through enhanced anti-inflammatory and antioxidant actions [40].
Another study in rats showed that lipoic acid reduced brain damage and increased survival rate after a stroke [42].
In cell studies, ALA exposure increased glutathione (GSH), which in theory could help improve brain function, but this effect has not been investigated in animals or humans [43].
Alzheimer’s
Oxidative stress, inflammation, and increased cholesterol levels have been associated with Alzheimer‘s disease (AD) pathology [44]. Lipoic acid could help with all of these.
When lipoic acid was given daily to 9 patients with AD (receiving a standard treatment with cholinesterase inhibitors), their cognitive symptoms appeared to stabilize. The patients did not improve, but their disease progressed much more slowly [45].
In another study, in 43 AD patients with dementia, lipoic acid slowed down the progression of the disease [45].
Similarly, a combination of omega-3 fatty acids and lipoic acid slowed the cognitive and functional decline in 39 people with AD [44].
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 [46].
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 [47].
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 proinflammatory molecules [48].
Lipoic acid reduces neuronal death in laboratory models of Parkinson’s disease [49].
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 [50].
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 [51].
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) [52].
Multiple Sclerosis
Lipoic acid was shown to have an anti-inflammatory effect in subjects with multiple sclerosis (MS) [53] and to improve their total antioxidant capacity [54].
Lipoic acid may prove useful in people with MS as it inhibits MMP-9 activity, interfering with T-cell migration into the brain/spinal cord [55], and reducing both Th1 and Th2 cytokines [53].
In a Russian study, lipoic acid reduced relapse frequency in multiple sclerosis patients and decreased corticosteroid use [56]. Effects were further magnified by adding other antioxidants to the regimen.
Lipoic acid suppressed the symptoms of MS in a mouse model [57].
6) Exercise Recovery
Further clinical studies are required to determine whether ALA supplements improves exercise recovery in humans. Short-term lipoic acid supplementation protected DNA and cells against exercise-induced oxidative stress [58]. It also improved muscle regeneration in 16 physically active men [59].
Lipoic acid supplementation decreased oxidative damage in the muscles in men who perform muscle-damaging exercises, regardless of whether they are trained or untrained [60, 58].
By increasing blood total antioxidant capacity, lipoic acid protected DNA and fatty acids from oxidative stress due to exercise [58].
Lipoic acid appeared to shift the internal chemistry of cells, promoting 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 [59].
Lipoic acid, when co-ingested with creatine, enhanced muscle total creatine content [61].
7) Inflammation
A diet rich in lipoic acid could reduce markers of inflammation over time, but more studies on the effect of supplements are required.
Abnormal inflammatory responses contribute to diseases such as diabetes, Alzheimer’s disease and multiple sclerosis [53]. Lipoic acid was shown to have an anti-inflammatory effect in subjects with multiple sclerosis [53], metabolic syndrome [62], and diabetes [63].
Lipoic acid can reduce inflammatory markers in subjects with organ transplants [64].
Lipoic acid alleviates acute inflammatory responses in animal models [65, 66].
In overweight and obese women, lipoic acid caused a greater reduction in the marker of chronic inflammation CRP [67].
8) Heart Health
Dietary lipoic acid may help support heart health, but more research into the effects of supplements on the human heart is required.
Cholesterol
In clinical trials, lipoic acid supplementation reduced LDL cholesterol and triglycerides, but increased HDL (good) cholesterol [68].
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 [20].
Lipoic acid improves blood vessel structure and function [1, 68]. Lipoic promotes anti-inflammatory and antithrombotic (blood clot-reducing) pathways and increases nitric oxide-mediated vasodilatation (blood vessel widening) [20].
Lipoic acid may also decrease atherosclerotic plaque burden [68].
Lipoic acid reduced circulating inflammatory risk markers, such as CRP and leukocyte (white blood cell) count in healthy overweight or obese women independently of weight loss [67].
Lipoic acid counteracted oxidative stress, normalized NADPH oxidase activity, and prevented angiotensin II-induced macrophage, monocyte, and T cell infiltration [68].
Lipoic acid reduced NF-κB-mediated inflammatory responses [68].
Lipoic acid may also prevent LDL oxidation [68]. Oxidized LDL is more detrimental to cardiovascular health.
One study indicates that lipoic acid may increase the atherogenicity of LDL, but when it’s combined with exercise, this atherogenic effect is abolished [69].
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 [68].
In multiple clinical trials, lipoic acid inhibited the overproduction of endothelin I, the main vasoconstrictor (narrower of blood vessels) [68]. Furthermore, lipoic acid significantly increased the synthesis of NO, the main vasodilator (widener of blood vessels) [68].
Lipoic acid may improve the function of the cells making up the blood vessel walls [68].
However, clinical studies have also shown that lipoic acid is not very effective in lowering blood pressure on its own. Its effectiveness at reducing blood pressure is limited without the use of other strategies [68].
A combination of lipoic acid with acetyl-L-carnitine reduced blood pressure and improved the function of various arteries [70].
9) Metabolic Syndrome
People who eat a diet rich in ALA seem to be less likely to develop the markers of metabolic syndrome, but the relationship is unclear and more human research is required.
In animal studies, lipoic acid reduced blood pressure and insulin resistance, improved cholesterol, and reduced body weight. These are all components of metabolic syndrome [71].
In 58 patients with metabolic syndrome, lipoic acid improved blood vessel cell function and reduced proinflammatory markers [62].
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 [72].
Lipoic acid significantly reduced ROS and improved HDL cholesterol in men with metabolic syndrome, especially those treated with blood sugar-reducing drugs [73].
10) Eye Health
Further research will be required to determine the role of lipoic acid in human eye health.
Oxidative stress increases with aging and conditions such as diabetes, and it can have detrimental effects on vision. According to a few studies, lipoic acid may help by counteracting oxidative stress in the eyes.
In one study, lipoic acid improved vision and other symptoms in 45 patients with glaucoma [74].
Lipoic acid also improved the vision-related quality of life in patients with age-related macular degeneration (AMD) [75].
Lipoic acid inhibited diabetic cataract formation in animals [76, 77].
Lipoic acid reduced retinal cell death in mice with retinitis pigmentosa, an inherited, degenerative eye disease [78].
11) Migraines
Migraines are poorly understood, and much more research will be needed to determine the role of lipoic acid in their prevention and treatment.
Migraines have been linked to mitochondrial disorders [79] and oxidative stress [80]. Lipoic acid helps with both.
In 44 patients with migraines, lipoic acid reduced the frequency, duration, and intensity of migraines [81].
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 [82].
12) Pain
While lipoic acid is not as effective as conventional painkillers, it may reduce the quantity of pharmaceutical drugs required to manage pain. Much more research will be required to determine its role in pain management.
Lipoic acid improved 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 [83].
Lipoic acid reduced the postoperative incidence of pain in patients with carpal tunnel syndrome [84].
Lipoic acid decreased sciatic pain caused by a herniated disc. Patients on lipoic acid reported a decreased need for analgesia [85].
In patients with chronic neck pain, a combination of lipoic acid and superoxide dismutase (SOD) improved pain control and the efficacy of physiotherapy [86].
Lipoic acid administered together with gamma-linolenic acid (GLA) reduced symptoms and functional impairment in patients with carpal tunnel syndrome [87].
13) Sperm Quality
While promising, these results are limited to a single study which has not yet been repeated. Much more research will be required to determine the effect of ALA on male fertility. However, eating a healthy, ALA-rich diet wouldn’t hurt.
In a study of 44 infertile men, 600 mg of lipoic acid significantly increased total sperm count, sperm concentration, and motility levels after 12 weeks [88].
14) High-Risk Pregnancies
More human studies will be required to determine the full extent of ALA’s role in pregnancy and birth. While ALA-rich foods should be safe, talk to your doctor before supplementing with lipoic acid if you are expecting.
In high-risk pregnancies, lipoic acid may facilitate the return to normal pregnancy conditions and improve the condition of both the mother and the fetus [89]. Additionally, smaller numbers of miscarriages were recorded with lipoic acid supplementation [90].
Lipoic acid decreases inflammation in women with gestational diabetes [63].
Lipoic acid reduced cervical inflammation after a preterm labor episode [91].
15) Bone Health
Osteoporosis
In postmenopausal women with osteopenia (low bone density), lipoic acid slightly increased bone mineral density (BMD) [92].
Several laboratory studies showed that lipoic acid inhibits inflammation-induced bone loss [93, 94, 95].
In female rats with osteopenia, lipoic acid not only stopped the bone resorption but stimulated its formation [96].
Osteoarthritis
Lipoic acid decreased inflammation and ameliorated cartilage degeneration in rats with osteoarthritis [97].
Animal & Cell Research (Lacking Evidence)
No clinical evidence supports the use of lipoic acid for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
16) Ulcers and IBD
There have, as of yet, been no studies on the effect of ALA in humans with ulcers or IBD.
In rats, lipoic acid protected against alcohol-induced stomach ulcers [98].
In mouse models of IBD, lipoic acid suppresses diarrhea, inflammation, and reduced colon lining injuries [99].
Other studies also showed that lipoic acid effectively attenuates ulcerative colitis in mice [100, 101]. However, in one study in mice with mild ulcerative colitis, lipoic acid actually increased oxidative damage to the colon and liver [102].
17) Detox
While these results may seem promising, they have not been repeated in human trials. Many ALA-rich foods are generally considered healthy, but it’s important to talk to your doctor if you think you’ve been exposed to heavy metals or other toxic compounds.
Heavy Metals
Lipoic acid can chelate (bind to) toxic metals and neutralize them [103, 104]. This may protect the liver, the kidneys, and the nervous system.
Lipoic acid protected cells from cadmium (Cd)-induced toxicity by activating Nrf2 and regenerating GSH [105].
Lipoic acid protected against Cd-induced oxidative stress and kidney cell death in rats [106].
Lipoic acid attenuated liver damage caused by copper nanoparticles in rats [107].
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 [108].
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 [109].
Lipoic acid protected against polychlorinated biphenyl (PCB)-induced testicular toxicity in male rats [110].
Lipoic acid reduced methylmercury-induced brain injury in rats [111].
Lipoic acid reduced nicotine-induced lung and liver damage in rats [112].
Lipoic acid attenuated antimycin A-induced cell toxicity [113].
19) Longevity Research
Longevity research is contentious and controversial, and the extent to which lifespan can be extended with diet and supplements is unknown. Furthermore, ALA has not been correlated with longevity in humans. However, many ALA-rich foods are part of a healthy diet, and lipoic acid consumption may be linked to lifespan in this way.
Lipoic acid extends the lifespan of adult flies [114] and worms [115].
The situation in mice is more complex, as the conclusions from the literature are mixed. Lipoic acid may decrease [116], increase [117], or have no impact on the lifespan [118].
A study showed that while lower doses of lipoic acid increased the total lifespan in mice, high doses decreased it [117].
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 [119].
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 [114].
- 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 [120].
- Increasing telomerase. Lipoic acid may increase telomerase [121], thereby increasing telomere length and reversing the aging process.
Further Reading
Takeaway
Lipoic acid is an antioxidant and important nutrient that plays a role in skin health, inflammation, fat metabolism, and heart and brain function. It is found in every cell in the body and seems to be essential for mitochondrial function.
Supplementing with lipoic acid has shown promising results for skin health, diabetes, and obesity, while diets rich in lipoic acid are associated with better health outcomes in a number of other categories. The best dietary sources of lipoic acid include plant oils, fish, seafood, nuts, and seeds.
