Alpha Lipoic Acid

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Alpha-lipoic acid is one of the most powerful antioxidants ever discovered. It is a vitamin-like sulfur-containing compound that is synthesized naturally in the human body. Sometimes it is referred to as alpha-lipoate, thioctic acid, or just lipoic acid. One of its most important characteristics is that it is both fat-soluble and water-soluble. This enables it to provide antioxidant protection in a much wider range of physiological environments throughout the body, which has resulted in some scientists referring to alpha-lipoic acid as the “universal” antioxidant.

In the body, alpha-lipoic acid is converted to dihydrolipoic acid (DHLA), which also functions as a strong antioxidant. Lipoic acid is part of two enzyme systems: PDH (pyruvate dehydrogenase) and alpha-ketoglutarate dehydrogenase. These enzymes are part of the Krebs cycle and are essential in the production of energy.


Alpha Lipoic Acid Articles

The Prediabetic Epidemic
Nutrition Science News ~ March 2001

Syndrome X, characterized by insulin resistance, is a prediabetic condition gaining increased scrutiny as America's obesity rates soar. Learn how to recognize its telltale signs and mitigate its symptoms through diet and supplements.


Alpha Lipoic Acid Research

Alpha-lipoic Acid Improves Vascular Endothelial Function in Patients
with Type 2 Diabetes: A Placebo-controlled Randomized Trial

Eur J Clin Invest. 2010 (Feb);   40 (2):   148–154

Intravenous Alpha-lipoic Acid treatment improves endothelium-dependent vasodilatation in patients with type 2 diabetes, in the absence of effects on forearm vasomotor function. If this salutary action translates into vascular risk reduction remains to be established.

The Effect of Acetyl-L-carnitine and R-alpha-lipoic acid Treatment in
ApoE4 Mouse as a Model of Human Alzheimer's Disease

J Neurol Sci 2009 (Mar 31)   [Epub ahead of print]

We measured age-dependent effects of human ApoE4 on cerebral blood flow (CBF) using ApoE4 transgenic mice compared to age-matched wild-type (WT) mice by use of [(14)C] iodoantipyrene autoradiography. Transmission electron microscopy with colloidal gold immunocytochemistry showed structural damage in young and aged microvessel endothelium of ApoE4 animals extended to the cytoplasm of perivascular cells, perivascular nerve terminals and hippocampal neurons and glial cells. These abnormalities coexist with mitochondrial structural alteration and mitochondrial DNA overproliferation and/or deletion in all brain cellular compartments. Spatial memory and temporal memory tests showed a trend in improving cognitive function in ApoE4 mice fed selective mitochondrial antioxidants acetyl-l-carnitine and R-alpha-lipoic acid. Our findings indicate that ApoE4 genotype-induced mitochondrial changes and associated structural damage may explain age-dependent pathology seen in AD, indicating potential for novel treatment strategies in the near future.

Peripheral Neuropathy:
Pathogenic Mechanisms and Alternative Therapies

Alternative Medicine Review 2006 (Dec);   11 (4):   294-329 ~ FULL TEXT

Peripheral neuropathy (PN), associated with diabetes, neurotoxic chemotherapy, human immunodeficiency virus (HIV)/antiretroviral drugs, alcoholism, nutrient deficiencies, heavy metal toxicity, and other etiologies, results in significant morbidity. Conventional pain medications primarily mask symptoms and have significant side effects and addiction profiles. However, a widening body of research indicates alternative medicine may offer significant benefit to this patient population. Alpha-lipoic acid, acetyl-L-carnitine, benfotiamine, methylcobalamin, and topical capsaicin are among the most well-researched alternative options for the treatment of PN. Other potential nutrient or botanical therapies include vitamin E, glutathione, folate, pyridoxine, biotin, myo-inositol, omega-3 and -6 fatty acids, L-arginine, L-glutamine, taurine, N-acetylcysteine, zinc, magnesium, chromium, and St. John's wort. In the realm of physical medicine, acupuncture, magnetic therapy, and yoga have been found to provide benefit. New cutting-edge conventional therapies, including dual-action peptides, may also hold promise.

Alpha Lipoic Acid Monograph
Alternative Medicine Review 2006 (Sep); 11 (3): 232–237 ~ FULL TEXT

Alpha-lipoic acid (ALA – also known as thioctic acid) was discovered in 1951 as a molecule that assists in acyl-group transfer and as a coenzyme in the Krebs cycle. In the 1980s, the scientific community realized alpha-lipoic acid is a powerful antioxidant. Several qualities distinguish alpha-lipoic acid from other antioxidants: ALA can be synthesized by animals and humans; [1] it neutralizes free radicals in both the fatty and watery regions of cells, in contrast to vitamin C (water soluble) and vitamin E (fat soluble); and, ALA functions as an antioxidant in both its reduced and oxidized forms. [2]

Alternative Therapies for Type 2 Diabetes
Alternative Medicine Review 2002 (Feb);   7 (1):   45–58 ~ FULL TEXT

Type 2 diabetes is a chronic metabolic disease that has a significant impact on the health, quality of life, and life expectancy of patients, as well as on the health care system. Exercise, diet, and weight control continue to be essential and effective means of improving glucose homeostasis. However, lifestyle management measures may be insufficient or patient compliance difficult, rendering conventional drug therapies (i.e., oral glucose-lowering agents and insulin injection) necessary in many patients. In addition to adverse effects, drug treatments are not always satisfactory in maintaining euglycemia and avoiding late stage diabetic complications. As an alternative approach, medicinal herbs with antihyperglycemic activities are increasingly sought by diabetic patients and health care professionals. Commonly used herbs and other alternative therapies, less likely to have the side effects of conventional approaches for type 2 diabetes, are reviewed.

Prevention of Hypertension, Insulin Resistance,
and Oxidative Stress by Alpha-lipoic Acid

Hypertension 2002 (Feb);   39 (2):   303–307

Increases in blood pressure, insulin resistance, and aorta superoxide production observed in glucose-fed rats were prevented by the supplementation of the diet with lipoic acid. Positive correlations were found between aortic superoxide production and blood pressure, between insulin resistance and blood pressure, or between superoxide production and insulin resistance. Moreover, a decrease in the activity of plasma glutathione peroxidase observed in the glucose-fed rats was prevented by lipoic acid treatment.

Effects of Alpha-lipoic Acid on Microcirculation in Patients
with Peripheral Diabetic Neuropathy

Diabetes Obes Metab 2002 (Jan);   4 (1):  29–35

The results suggest that alpha-lipoic acid can increase glucose uptake by a range of normal muscle types and improve the response to insulin by insulin-resistant skeletal muscles of ob/ob mice.

Chronic Fatigue Syndrome: Oxidative Stress and Dietary Modifications
Alternative Medicine Review 2001 (Oct);   6 (5):   450–459 ~ FULL TEXT

Chronic fatigue syndrome (CFS) is an illness characterized by persistent and relapsing fatigue, often accompanied by numerous symptoms involving various body systems. The etiology of CFS remains unclear; however, a number of recent studies have shown oxidative stress may be involved in its pathogenesis. The role of oxidative stress in CFS is an important area for current and future research as it suggests the use of antioxidants in the management of CFS.

Molecular Aspects of Lipoic Acid in the Prevention
of Diabetes Complications

Nutrition 2001 (Oct);   17 (10):   888–895

In experimental and clinical studies, LA markedly reduced the symptoms of diabetic pathologies, including cataract formation, vascular damage, and polyneuropathy. To develop a better understanding of the preventative and therapeutic potentials of LA, much of the current interest is focused on elucidating its molecular mechanisms in redox dependent gene expression.

Interactions of Exercise Training and Lipoic Acid on Skeletal Muscle
Glucose Transport in Obese Zucker Rats

J Appl Physiol 2001 (Jul);   91 (1):   145–153

These results indicate that Exercise Training and Alpha Lipoic Acid interact in an additive fashion to improve insulin action in insulin-resistant skeletal muscle. Because the further improvement in muscle glucose transport in the combined group was not associated with additional upregulation of GLUT-4 protein or a further reduction in oxidative stress, the mechanism for this interaction must be due to additional, as yet unidentified, factors.

Effect of Alpha-lipoic Acid on the Progression of Endothelial Cell
Damage and Albuminuria in Patients with Diabetes Mellitus:
An Exploratory Study

Diabetes Res Clin Pract 2001 (Jun);   52 (3):   175–183

Oxidative stress plays a central role in the pathogenesis and progression of late microangiopathic complications (diabetic nephropathy) in diabetes mellitus. Previous studies suggested that treatment of diabetic patients with the antioxidant alpha-lipoic acid reduce oxidative stress and urinary albumin excretion. In this prospective, open and non-randomized study, the effect of alpha-lipoic acid on the progression of endothelial cell damage and the course of diabetic nephropathy, as assessed by measurement of plasma thrombomodulin and urinary albumin concentration (UAC), was evaluated in 84 patients with diabetes mellitus over 18 months.

Alpha-lipoic Acid: A Multifunctional Antioxidant That Improves
Insulin Sensitivity in Patients with Type 2 Diabetes

Diabetes Technol Ther 2000 (Autumn);   2 (3):   401–413

LA has been used in Germany for over 30 years for the treatment of diabetes-induced neuropathy. In patients with type 2 diabetes, recent studies have reported that intravenous (i.v.) infusion of LA increases insulin-mediated glucose disposal, whereas oral administration of LA has only marginal effects. If the limitations of oral therapy can be overcome, LA could emerge as a safe and effective adjunctive antidiabetic agent with insulin sensitizing activity.

Engagement of the Insulin-sensitive Pathway in the Stimulation of Glucose
Transport by Alpha-lipoic Acid in 3T3-L1 Adipocytes

Diabetologia 2000 (Mar);   43 (3):   294–303

These results indicate that R (+) alpha-lipoic acid directly activates lipid, tyrosine and serine/threonine kinases in target cells, which could lead to the stimulation of glucose uptake induced by this natural cofactor. These properties are unique among all agents currently used to lower glycaemia in animals and humans with diabetes.

Effects of Alpha-lipoic Acid on Microcirculation in Patients with
Peripheral Diabetic Neuropathy

Exp Clin Endocrinol Diabetes 2000;   108 (3):   168–174

These results demonstrate that in patients with diabetic polyneuropathy ALA improves microcirculation as indicated by an increased perfusion reserve on demand. The observed effects are apparently acute effects. With the restriction of the pilot character of this investigation the findings support the assumption that ALA might exert its beneficial effects at least partially by improving microcirculation which is likely to occur also at the level of the vasa nervorum.

Oral Administration of RAC-alpha-lipoic Acid Modulates Insulin
Sensitivity in Patients with Type-2 diabetes Mellitus:
A Placebo-controlled Pilot Trial

Free Radic Biol Med 1999 (Aug);   27 (3-4):   309–314

This placebo-controlled explorative study confirms previous observations of an increase of insulin sensitivity in type-2 diabetes after acute and chronic intravenous administration of ALA. The results suggest that oral administration of alpha-lipoic acid can improve insulin sensitivity in patients with type-2 diabetes. The encouraging findings of this pilot trial need to be substantiated by further investigations.

Alpha-lipoic Acid in the Treatment of Diabetic Polyneuropathy in Germany:
Current Evidence From Clinical Trials

Exp Clin Endocrinol Diabetes 1999;   107 (7):   421–430

Diabetic neuropathy represents a major health problem, as it is responsible for substantial morbidity, increased mortality, and impaired quality of life. Near-normoglycaemia is now generally accepted as the primary approach to prevention of diabetic neuropathy, but is not achievable in a considerable number of patients. In the past two decades several medical treatments that exert their effects despite hyperglycaemia have been derived from the experimental pathogenetic concepts of diabetic neuropathy. Such compounds have been designed to improve or slow the progression of the neuropathic process and are being evaluated in clinical trials, but with the exception of alpha-lipoic acid (thioctic acid) which is available in Germany, none of these drugs is currently available in clinical practice.

Alpha Lipoic Acid Monograph
Alternative Medicine Review 1998 (Aug); 3 (4): 308–311 ~ FULL TEXT

Acting as a potent antioxidant, DHLA was found to protect rat pancreatic islet cells from destruction by reactive oxygen species.10 In vitro, lipoic acid was found to stimulate glucose uptake by muscle cells in a manner similar to insulin. Type 2 diabetics, given 1000 mg intravenously (I.V.), experienced a 50 percent improvement in insulin-stimulated glucose uptake.


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Vanadium (Vanadyl Sulfate) - Monograph
Alternative Medicine Review 2009 (Jun);   14 (2):   177–180 ~ FULL TEXT

Nutritionally, vanadium is thought to be a cofactor in various enzymatic reactions. Data from animal and human studies suggest vanadium mimics the action of insulin. Consequently, it may serve a beneficial role in promoting healthy glucose metabolism in individuals with diabetes or dysglycemia. Dietary sources for vanadium include mushrooms, shellfish, black pepper, parsley, dill seed, and grains.

Effect of Long-term Treatment with Vanadate in Drinking Water
on KK Mice with Genetic Non-insulin-dependent Diabetes Mellitus

Biol Trace Elem Res 2001 (May);   80 (2):   159–174

The glucose tolerance in the vanadate-treated mice with 10 and 100 microg V/mL was remarkably improved compared with the control group. Biochemical analyses at the end of experiments demonstrated that a distinct tendency for the glucose and hemoglobin A1c (HbA1c) levels to decrease with vanadate treatment in the blood was also observed.

Vanadyl Sulfate Improves Hepatic and Muscle Insulin Sensitivity
in Type 2 Diabetes

J Clin Endocrinol Metab 2001 (Mar);   86 (3):   1410–1417

Vanadyl sulfate (VOSO(4)) is an oxidative form of vanadium that in vitro and in animal models of diabetes has been shown to reduce hyperglycemia and insulin resistance. Small clinical studies of 2- to 4-week duration in type 2 diabetes (T2DM) have led to inconsistent results.


Mitochondrial Factors in the Pathogenesis of Diabetes:
A Hypothesis for Treatment

Alternative Medicine Review 2002 (Apr);   7 (2):   94–111 ~ FULL TEXT

A growing body of evidence has demonstrated a link between various disturbances in mitochondrial functioning and type 2 diabetes. This basic research into the pathogenesis of diabetes has led to the awareness of natural therapeutics (such as coenzyme Q10) that increase mitochondrial functioning and avoidance of trans-fatty acids that decrease mitochondrial functioning.

Toward Practical Prevention of Type 2 Diabetes
Med Hypotheses 2000 (May);   54 (5):   786–793

Other nutrients that might prove to aid diabetic glycemic control, and thus have potential for prevention, include coenzyme Q and conjugated linoleic acids (CLA). Since the nutrients cited here - including ethanol in moderation - appear to be quite safe and (with the exception of CLA) quite affordable, supplementation with these nutrients may prove to be a practical strategy for diabetes prevention.

Insulin Resistance: Lifestyle and Nutritional Interventions
Alternative Medicine Review 2000 (Apr); 5 (2): 109–132 ~ FULL TEXT

Insulin resistance appears to be a common feature and a possible contributing factor to several frequent health problems, including type 2 diabetes mellitus, polycystic ovary disease, dyslipidemia, hypertension, cardiovascular disease, sleep apnea, certain hormone-sensitive cancers, and obesity. The role of nutritional and botanical substances in the management of insulin resistance requires further elaboration; however, available information suggests some substances are capable of positively influencing insulin resistance. Minerals such as magnesium, calcium, potassium, zinc, chromium, and vanadium appear to have associations with insulin resistance or its management. Amino acids, including L-carnitine, taurine, and L-arginine, might also play a role in the reversal of insulin resistance.

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