Its use in weight management, metabolic syndrome, and diabetes
Alpha-lipoic acid (ALA), also known simply as lipoic acid, is a naturally-occurring substance that is an essential cofactor for several enzymes.[1] ALA, synthesized in the body from a medium-chain fatty acid known as octanoic acid,[2] plays a key role in mitochondrial metabolism and energy production.[3],[4]
ALA is also a potent antioxidant with anti-inflammatory activity.[5] It neutralizes reactive oxygen and nitrogen species, and helps regenerate the active forms of vitamin E, coenzyme Q10, and glutathione.[6],[7],[8],[9] ALA is one of several nutrients that support the nuclear factor E2-related factor 2 (Nrf2) pathway, a master regulator of antioxidant defenses, including glutathione.[10],[11]
Some foods contain ALA, including organ meats, red meat, spinach, broccoli, and tomatoes.[12] However, because dietary ALA is bound to proteins, the consumption of high-ALA foods does not increase free ALA in human plasma or cells.[13],[14] By contrast, oral supplementation with ALA has been shown to significantly increase the concentration of free ALA in the body.[15],[16]
Multiple studies now show that ALA helps maintain healthy body weight and blood glucose levels, which may reduce the risk of type 2 diabetes (T2DM) and attenuate its effects. We’ll touch on each of these key findings in this article.
Effect of lipoic acid on metabolic syndrome and diabetes
Metabolic syndrome is a condition associated with abdominal obesity, increased blood pressure, high cholesterol and/or triglycerides, inflammation, insulin resistance or full-blown diabetes, and a heightened risk of cardiovascular disease.[17] Obesity is the major determinant of metabolic syndrome, both of which are all-too-common clinical and public health challenges.[18]
Insulin resistance is typified by a reduced cellular sensitivity to the signaling molecule insulin, which leads to decreased cellular uptake and utilization of glucose in response to insulin binding receptors on the cell membrane. Because of the reduced sensitivity to insulin, the body simply increases insulin production to try to overcome this problem. With time, insulin resistance leads to elevated blood glucose levels (hyperglycemia), which causes oxidative stress and ultimately damages the heart, nerves, blood vessels, and many organs.[19] Antioxidants that can enhance insulin sensitivity and reduce oxidative stress are of great interest, as they may protect against the damaging effects of hyperglycemia.[13] Laboratory, animal, and human studies suggest that ALA has these important properties.[20],[21]
In laboratory studies, ALA was shown to increase glucose uptake in adipose and muscle cells.[20],[22] In animal models of metabolic syndrome or T2DM, the administration of ALA attenuated insulin resistance.[23],[24],[25],[26] In animals, ALA also reduces the metabolic effects of high-fructose diets, which are known to contribute to obesity and T2DM.[27],[28] (Fructose is a component of sucrose, a major contributor to the obesity epidemic.)[29]
Numerous clinical trials have shown that oral supplementation with ALA improves insulin sensitivity in individuals with T2DM.[30],[31],[32] A 2018 systematic review of 20 randomized controlled trials, involving over 1000 subjects with metabolic disorders (not limited to T2DM), showed that the administration of lipoic acid (200 to 1800 mg per day, for two weeks to one year) helped lower fasting blood glucose and insulin concentrations, insulin resistance, and blood hemoglobin A1c (HbA1c) levels, a marker of long-term glycemic control.[33] In various studies, ALA supplementation also lowered serum total cholesterol and low density lipoprotein (LDL)-cholesterol levels, which are risk factors for cardiovascular disease.[34]
ALA not only helps regulate blood glucose and cholesterol, but it may directly impact obesity, which is a major contributor to diabetes, cancer, and cardiovascular disease.
ALA not only helps regulate blood glucose and cholesterol, but it may directly impact obesity, which is a major contributor to diabetes, cancer, and cardiovascular disease.[35] Multiple randomized, placebo-controlled trials have found that ALA supplementation in individuals with high body mass index (BMI) produced a modest but significant reduction in body weight compared to placebo.[36],[37],[38],[39] Other clinical studies suggest that ALA supports cardiovascular health in overweight or obese individuals.[40],[41]
Effects of lipoic acid on peripheral neuropathy
Up to 50% of diabetic patients develop peripheral neuropathy (PN), a type of nerve damage associated with pain, loss of sensation, and weakness in the lower extremities.[42] Oxidative stress is one of the main contributors to the development of PN.[43],[44] Due to its antioxidant properties, ALA has been studied as a supplement to potentially reduce the risk of PN.[45],[46]
In laboratory studies, ALA was shown to attenuate the neurotoxicity induced by high glucose levels, improve nerve conduction parameters, and promote nerve fiber regeneration.[47],[48] In an animal model of PN, ALA improved glucose uptake into nerves,[49] and increased the velocity and amplitude of the signal conducted through them.[50] A combination of ALA and coenzyme Q10, both of which are mitochondrial antioxidants, was particularly effective in animal studies.[51]
In human clinical trials, ALA also has been shown to reduce the risk and/or signs of PN.[52],[53],[54] In medically-supervised trials, in which ALA is often administered by intravenous infusion, diabetic patients with PN experienced a reduction in pain, paresthesia (burning or prickling sensation), and numbness after several weeks of ALA treatment.[53],[55] A meta-analysis of 20 randomized controlled trials concludes that ALA may be useful as an adjunct to common drug treatments for PN.[56]
At a dosage of only 600 mg per day (taken for 40 days), ALA was shown to lead to symptom ratings of ‘very much better’ or ‘much better’ in half of all participants.
Several studies also suggest that oral supplementation of ALA may help improve PN.[57],[58],[59] In one clinical trial, 45 patients with T2DM and PN were supplemented with ALA (600 mg orally three times daily) for four weeks.[60] During this phase of the trial, ALA reduced the total symptom score (TSS) by 61% on average. The responders were then randomized to receive ALA (600 mg once daily) or to ALA withdrawal for 16 weeks. TSS was further reduced by 32% in those who continued on ALA, and the use of analgesics for neuropathic pain was 50% lower in the ALA group compared with the withdrawal group. In a 2018 study of patients with painful diabetic neuropathy, at a dosage of only 600 mg per day (taken for 40 days), ALA was shown to lead to symptom ratings of ‘very much better’ or ‘much better’ in half of all participants.[61]
One clinical trial with 181 diabetic individuals with PN showed that ALA supplementation (either 600, 1200, or 1800 mg per day for five weeks) significantly improved neuropathic symptoms and quality of life.57 The 600 mg/day dose was as effective as the higher doses. However, another placebo-controlled study by the same researchers found no effect of ALA on the total neuropathy score after four years.[62] Post-hoc analysis of these data revealed that the long-term efficacy of ALA depends on individual patient characteristics.[63] Somewhat surprisingly, those having a longer duration of diabetes and peripheral neuropathy were more responsive to ALA.
In an outpatient study, 443 diabetic patients with PN were supplemented with 600 mg of ALA daily for a mean period of five years.[64] They were then withdrawn from ALA altogether, or switched to a common medication used for nerve pain. In the group withdrawn from ALA, 73% of the patients developed neuropathic symptoms, which began as soon as two weeks after ALA was discontinued. These results suggest that ALA is a useful supplemental option for individuals with PN, with the impact becoming even more apparent when the supplement was withdrawn. Interestingly, in the group that switched from ALA to the analgesic drug, 45% of the patients had to stop taking the drug due to its side effects. This compares to the side effect rate of only 3% in patients receiving ALA, with side effects being mainly nausea and postprandial fullness.
A 2018 review article concludes, “Studies analyzing the effects of ALA have shown significant reduction of neuropathy symptoms in diabetic patients. In addition, ALA exhibits activity in weight management and insulin sensitivity.” And: “Current data provides evidence for the benefits of lipoic acid at a dose of 600 mg per day, either intravenously or orally, for a duration of at least 3 weeks with minimal side effects.”[65]
“Lipoic acid supplementation is an achievable adjunct therapy to help prevent vision loss in diabetic patients.”
Finally, various studies suggest that ALA supplementation may be beneficial for individuals with diabetic retinopathy,[66],[67],[68] a serious condition that can impair vision. A recent review article states, “Lipoic acid supplementation is an achievable adjunct therapy to help prevent vision loss in diabetic patients.”[69]
Summary
Lipoic acid is an important player in an armamentarium of natural approaches that can assist in the management of metabolic syndrome and/or diabetes. Since taking lipoic acid with food can potentially decrease its bioavailability, it is generally recommended that lipoic acid be taken 30 minutes before or two hours after eating.[70] As always, individuals with signs or symptoms of metabolic syndrome or diabetes should seek care from a qualified health professional when taking a supplement that can potentially impact blood glucose, insulin, and other markers.
For more information on natural approaches to metabolic syndrome and diabetes, also see:
Beating Metabolic Syndrome Before It Beats You
Banaba’s Powerful Effects in Diabetes
Defeating Diabetes: Keeping Your Sugars in Check through the Holidays
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