A good article for anyone who is unfamiliar with ALA:




1. What is ALA?

ALA (alpha lipoic acid) is an enzyme found throughout the body and a key component of mitochondria, which produce energy for cells. It is involved in a variety of reactions, such as the conversion of pyruvate and other alpha-keto acids in the Krebs cycle. It is also a potent antioxidant that has been used to treat a variety of conditions, including diabetes, AIDS, cancer, hypertension, neurological degeneration, cataracts, kidney and liver disorders, and coronary heart disease.

2. What application does ALA have?

ALA has a variety of applications for the athlete, as it will enhance both performance and general health. In addition to its antioxidant properties, it may also increase eNOS activity, stabilize blood sugar, chelate heavy metals, and improve cognitive function.

Exercise can increase mitochondrial superoxide production, ischaemia-reperfusion, and auto-oxidation of catecholamines (1). Research has found that exercise may result in a 10- to 20-fold increase in whole-body oxygen uptake, with oxygen flux increasing by a magnitude of 100-200 in muscle fibers. According to a recent article in Sports Medicine, "Studies during the past 2 decades suggest that during strenuous exercise, generation of reactive oxygen species (ROS) is elevated to a level that overwhelms tissue antioxidant defence systems. The result is oxidative stress. The magnitude of the stress depends on the ability of the tissues to detoxify ROS, that is, antioxidant defences.... Efforts to determine individual needs of athletes and a balanced diet rich in antioxidant supplements are highly recommended (2)." Studies have shown orally supplemented ALA to specifically protect against exercise-induced oxidative stress, and shown it to be superior to other antioxidants in this respect (8, 9).

3. How does ALA work?

Many have called ALA the "perfect antioxidant." This is because ALA does not exhibit many of the weaknesses found in many common antioxidants, such as Vitamin C, Vitamin E, beta carotene, cartenoids, and others, and has many added advantages.

First of all, most antioxidants only defend against one or a few varieties of ROS. ALA removes peroxyl, peroxynitrite, hydroxyl, alkoxyl, and superoxide radicals, among many others. Secondly, most antioxidants are tissue specific. For example, many are either fat soluble (such as Vitamin E) or water soluble (such as Vitamin C). Alpha lipoic acid is fat soluble, and it's metabolite, dihydrolipoic acid - which is another potent antioxidant - is water soluble. Third, the small size of the ALA molecule allows it to prevent oxidation in areas where others cannot, such as oxidation within the cell nucleus. Fourth, research has shown ALA to be readily absorped (3), whereas many other antioxidants are readily excreted or have low bioavailability. Fifth, ALA recycles itself, while many other antioxidants are rapidly oxidized (4). Finally, ALA operates synergistically with three other important antioxidants, glutathione, Vitamin C, and Vitamin E. It allows Vitamin C to be recycled (4), a synergistic effect has been shown with Vitamin E (5), and both Vitamin E and Vitamin C recycle ALA by donating electrons to ALA cations (6). The fact that ALA increases production of glutathione (7) is especially important. Glutathione is one of the body's primary antioxidants. However, exogenously administered glutathione does not cross cell membranes, but ALA does.

4. What are some further benefits of ALA use?
  • Stabilizes blood sugar - ALA has been used in the treatment of diabetes and the prevention of Type 2 diabetes (10). It modulates glucose uptake by changing the intracellular redox status, thus improving insulin sensitivity (11, 12). Insulin resistance decreases blood flow, oxygen availability, and glucose uptake in muscle during exercise (14, 15). Additionally, ALA may have an additive effect on improving insulin sensitivity when combined with exercise (13).
  • Hemodilation - A new line of supplements known as "hemodilators," which usually contain arginine alpha-ketoglutarate (A-AKG), increase the levels of nitric oxide (NO) in the bloodstream, thus causing vasodilation, lowering blood pressure, and increasing blood flow to the muscles. Unfortunately, there are issues which these products do not address, the first being that increasing NO levels often causes an increase in free radical (namely, peroxynitrite) formation (16), and the second being that excesses of arginine will cause methionine deficiency (17).

    It has been shown that ALA directly stimulates the production of NO by increasing the activity of eNOS (endothelial nitric oxide synthase) (4, 18). Also, ALA does this while simultaneously increasing the antioxidant defenses of endothelial cells (4). In other words, it has all of the good properties of A-AKG with none of the bad. This is why many users of ALA report increased pumps both in and out of the gym.
  • Improves cognitive function - ALA has been shown to improve cognitive function in many ways, some of which may be independent of it's antioxidant properties. It exhibits a concentration-dependant upregulation of Phase II detoxification enzymes, especially NAD(P)H:quinone oxidoreductase (NQO1) and glutathione-S-transferase (GST), both of which are potent neuroprotectants (19). It decreases all three indices of oxidative stress in the brain, which in turn reverses memory impairment and improves cognition (20). It also improves nerve conduction and neural blood flow (21), and improves mitochondrial function and decreases DNA/RNA oxidation in the brain, both of which prevent memory loss (22). Because of this, it has been used to treat a variety of ailments, including Alzheimer's (23).
  • Other benefits - ALA is highly concentrated in the eye and can prevent visual impairment. It reduces advanced glycation end products (AGEs) (24), which may play a role in macular degeneration and diabetic retinopathy (25). It also protects the retina against ischemia-reperfusion injury (26).

    Because of its effect on NO production, ALA can also aid in the prevention of hypertension (12). In addition, ALA protects the heart by increasing mitochondrial function and decreasing superoxide anion production, as well as reducing plasma lipid levels, reduces the risk of coronary heart disease (27).

    As a general antioxidant, ALA has also been used in the treatment of many other ailments, including impaired kidney function, impaired liver function, and cancer.
5. Are there any side effects?

ALA has no serious side effects. Some users are allergic and have a mild rash; if this happens you should discontinue use or consult a doctor. Also, some users report nausea with high doses. If you have low blood pressure or are hypoglycemic, you should consult a doctor before taking ALA as it may possibly exacerbate these conditions.

6. What form of ALA is best?

There are two forms of ALA in popular usage. ALA is a mixture of 50% R-ALA and 50% S-ALA while R-ALA is the stereoisomer that naturally occurs in the body, hence supplemental R-ALA is much more potent (30). In some areas, such as prevention of cataracts, R-ALA works while S-ALA has no effect at all (29). In addition, there is evidence that S-ALA may negate some of the beneficial effects of R-ALA (28). R-ALA is clearly a better choice, although one can get some of the beneficial effects from regular ALA.

7. How should I take ALA?

As a general antioxidant, dosages of 100 mg a day are effective. For increased pumps or increased insulin response, 100-200 mg 2-3 times daily with food are recommended. Keep in mind that the effects of ALA are largely dose-dependent, but long-term studies with dosages over 600 mg/day (of R-ALA) have not been done. Also, the dosage one requires for R-ALA will be significantly lower than with regular ALA.

8. What are some good supplements to take along with ALA?

Although ALA functions excellently on its own, taking some supplements in conjunction may increase its benefits. It works well in tandem with many other antioxidants, such as vitamin C, vitamin E, and N-acetyl cysteine. It also has an additive effect with acetyl-L-carnitine in improving brain function (22).