The use of Thioctic or Alpha-Lipoic acid (A.L.A.) as a dietary supplement has recently received tremendous online media attention. Abundant claims have been made that it is effective in the treatment of a number of serious illnesses including diabetes, diabetic neuropathy (nerve disease), Multiple Sclerosis, cognitive decline (dementia), H.I.V. infection, cancer, etc. In the World of Fitness, A.L.A. has been widely promoted for weight loss, energy boosting, and enhanced athletic performance due to prevention of exercise-related damage and stress to skeletal muscles. In our current segment, Spanking FIT examines carefully the latter fitness-related claims; but, first we explain what A.L.A. is and how it is believed to work in the human body:
What is Alpha Lipoic Acid and how does it function in the human body?
Alpha lipoic acid is a naturally occurring antioxidant compound synthesized within the human body in small amounts only. Antioxidants are substances that limit damage to body cells caused by the free radicals created by our normal metabolic processes. A.L.A. comes bound to specific proteins that function as cofactors (helper molecules) for mitochondrial enzymes. Enzymes are biological catalysts which speed up chemical reactions. Mitochondria are the little “energy factories” within our cells that produce Adenosine Triphosphate (A.T.P.). Finally, A.T.P. transports chemical energy within our cells for metabolism and is required for the biochemical reactions involved in exercise-related muscular contraction.
The theory goes that since A.L.A. plays an important role in energy production, it may be possible to increase energy metabolism through oral supplementation with this substance. The logical consequences would be enhanced athletic performance and a healthful distribution of both lean muscle and fat tissue within the human body. This theory is further bolstered by pharmacokinetic research indicating that higher oral doses result in increases, albeit transient, in measured quantities of free A.L.A. in blood plasma and in body cells. (See:”Enantioselective pharmacokinetics and bioavailability of racemic alpha-lipoic acid” by R. Hermann; Eur. J. Pharm. Sci ; 1996,4: 167-174) It should be noted here that although a form of this substance occurs naturally in food, “recommended” dietary supplement doses in the range of 200-600 mg. are orders of magnitude greater than what can be obtained from diet alone.
All scientific theories, however appealing, must be verified experimentally by collecting and analyzing data. In order to ascertain whether or not adequate experimentation has been performed to confirm the current claims made about A.L.A., Spanking FIT conducted a comprehensive evaluation of published research results. It should be noted that dietary supplementation with A.L.A. is not without critics. For example, the Linus Pauling Institute, well-regarded for its biochemical research, warns against it by stating that under certain chemical conditions, antioxidants may turn pro-oxidant! Consequently, it is imperative that theory be experimentally validated. Here are the main results of our review:
(1) “The combination of A.L.A. intake with eccentric exercise modulates erythropoietin release” by B. Morawin, et al., pub. in Biology of Sport; Aug. 2014; 31(3): 179-185
This biochemically detailed study conducted at a major Polish University is the one, perhaps, most frequently cited by popular health publications on the subject of A.L.A benefits. Sixteen young males were randomly assigned to either a control (placebo) or a treatment group consisting of 1.2 grams per day of A.L.A. for ten days. They were next subjected to a 90 minute run, followed by 15 minutes of an “eccentric” exercise phase ( 65% VO2 max with -10% gradient). The researchers inferred from data that serum Erythropoietin (E.P.O.) levels were significantly higher in the A.L.A. treated group versus control group, both pre- & post-exercise. Readers may recall from “Why Not Allow Lance Armstrong to Dope?” Spanking FIT , Nov. 2014, that E.P.O. is a hormone produced in the kidneys that controls red blood cell production and that has the ability to enhance athletic performance by improving oxygen delivery to muscles. Physiologists also believe that it exerts direct and indirect muscle-protecting properties during intense exercise, and stimulates proliferation of myoblasts, thereby playing a role in muscle mass maintenance. Myoblasts are undifferentiated cells capable of giving rise to muscle cells. The researchers also claim that their results supported the hypothesis that A.L.A. supplementation lessens oxidative damage to muscle cells as evidenced by lower levels of pro-oxidants such as 8-isoprostanes (8-iso) in the treatment group both before and after the exercise period. (Elevated levels of 8-iso are found in heavy smokers and in asthma patients. See:”Increased 8-iso, a marker of oxidative stress in exhaled condensate of asthma patients” by P. Montuschi, pub. in American Journal of Respiratory Critical Care Medicine, 1999 July; 160 (1): 216-20.) Lastly, the researchers reported lower levels of creatine kinase (C.K.) in the group treated with AL.A. 24 hrs. after exercise. C.K. is an enzyme found in skeletal muscle that is in a damaged condition, and hence can serve as a marker for muscle damage.
Regardless of how elaborate this study is from a biomedical perspective, annoying problems exist from a statistical one. Researchers used the technique of 2-way repeated measures ANOVA. The latter is a so-called parametric test more appropriate with larger sample sizes. (Parametric tests require that certain assumptions be made regarding the shape of the population data when it’s graphed.) Since sample sizes were small, non-parametric tests such Kruskal-Wallis should have been employed. At the very least, ANCOVA instead of ANOVA should have been used to account for potential disparities in the control versus treatment group prior to the experimentation. Such disparities are common whenever the sample sizes are small, even when randomization is employed.
From an economy perspective, the daily doses of A.L.A. given were quite high, and could easily cost over $100 per month on an average retail basis.
(2)”Assessment of the antioxidant effectiveness of A.L.A. in healthy men exposed to muscle-damaging exercise” by A. Zembron-Lacny pub. in Journal of Physiology & Pharmacology; July 2009, 60(2):n139-43.
This equally elaborate Polish University study was quite similar to the previous one in terms of design and purpose. 13 trained subjects were randomly assigned to control or 8 day treatment with A.L.A. (600 mg. per day) They subsequently performed isometric/ isokinetic exercise of their quadricep muscles. Data was acquired pre-exercise, immediately post-exercise, and after a 24 hour rest period. The chemical method known as T.B.A.R.S. was used to measure plasma lipid peroxidation product levels. Such products are formed when muscle tissue is subjected to oxidative stress. The researchers reported lower levels in the A.L.A. treatment group. They also reported that total thiol (T.T.), a measure of levels of antioxidants that protect against reactive oxygen species (R.O.S.), was elevated in the treatment group. The level of plasma protein carbonyls (P.C.), another biomarker of oxidative stress, was also reported lower in the treatment group. Finally, researchers reported 5-17% higher total work performed on average during 60 deg. 1/s angular velocity exercise by the treatment group compared to control.
The technique known as 2-way ANOVA was used on the data. Unfortunately, exactly the same objections may be raised as in the previously cited study from a statistical perspective.
(3) “Effects of A.L.A. on Body Weight in Obese Subjects” by E.H. Koh, et al. pub. in The American Journal of Medicine; Jan. 2011 v. 124 (1): 85
This study is unique in so far as sample sizes actually large enough to meet the requirements of the employed statistical A.N.O.V.A tests were used. Also, before treatment measurements were made and used as a baseline. 360 obese subjects were randomized into one of three groups: control (placebo), 1.2 grams per day of A.L.A. for 20 weeks (treatment 1), or 1.8 grams of A.L.A. for 20 weeks (treatment 2). All subjects received instructions to follow the same dietary guidelines with the goal of reducing daily calorie intake.
The percentage of subjects who lost 5% or more body weight was significantly higher in the group treated with 1.8 grams per day than in the others (21.6% versus 10% control). The results are encouraging for those who advocate A.L.A. supplementation specifically for purposes of weight reduction. However, an appearance of conflict of interest exists with this work, because it was sponsored by Dalim BioTech Co.. Spanking FIT confirmed that it is a manufacturer of A.L.A. Also, keep in mind that a dosage costing retail over $150 a month for five months was required for an average weight loss of only about 2%.
(4) “Alpha-lipoic acid increases energy expenditure by enhancing AMPK-PGC-1α signaling in the skeletal muscle of aged mice” by Y. Wang et al. pub. in Metabolism, July 2010, 59(7): 967-76
Physiologists and biochemists postulate that the enzyme A.M.P.K. plays an important role in energy homeostasis or energy balance in the body through metabolism. They characterize it as an intracellular energy sensor or “fuel gauge” that is activated during exercise as a result of increased cellular demand for A.T.P.. A.M.P.K. activation results in increased levels of cellular energy by increasing PGC-1α, a protein that also induces cells to synthesize mitochondria. You may recall that mitochondria are those tiny cellular “energy factories”. A.L.A. is believed to act as a stimulant for A.M.P.K. activity in skeletal muscle cells so that supplementation with it may provide an energy boost needed for enhancing normal and athletic activity. It may also yield desirable changes in body composition including reduced fat storage.
In order to test the hypotheses, researchers in Beijing China with funding from the U.S.D.A. and U.S.N.I.H. randomly assigned 20 mice (all 24 months old) to either a control group or a treatment group that consisted of unlimited access to 0.75% A.L.A. treated drinking water, for one month. The researchers reported a significantly higher level of A.M.P.K. activity in the muscle cells of the treated group. Differences in the body composition of the treated mice were also reported: Although the absolute quantity of lean mass was less, their overall body weight was also less resulting in a higher relative percentage of lean mass to total mass. Similarly, the relative percentage of bone mass was higher and both the absolute quantity and relative percentage of fat lower in the A.L.A. treated mice. Energy expenditure was also reported to be greater in the treated mice. PGC-1α was reportedly activated with resulting mitochondrial biogenesis in muscle cells.
From a statistical perspective familiar objections may be raised. The researchers used the technique of repeated measures A.N.O.V.A.. Since sample sizes were small, non-parametric tests such as Kruskal-Wallis would have been more appropriate. At the very least, A.N.C.O.V.A. in lieu of A.N.O.V.A. should have been performed to take into account potential disparities in the control versus the treatment group prior to experimentation. As I explained in reference no. 1 above, such disparities are common whenever the sample sizes are small, even when randomization is employed.
From an economy perspective, the mice received an estimated average daily dosage of 550 mg. per kilogram of body weight. That’s the equivalent of about 40 grams per day of A.L.A. for a 160 lb. individual at an average retail cost of about $120 per day!
(5) “Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic A.M.P.-activated protein kinase” by M.S. Kim pub. in Nature Medicine 2004; 10: 727-733
Referenced in no. 4 above, and published in the prestigious journal of the Nature Society, researchers reported lower body weight and food intake in a group of six mice treated with 230 mg. per day of A.L.A. for two weeks, as opposed to an untreated group of the same number. Also, energy expenditure was reported to be higher in the treatment group. Their “findings” immediately reverberated throughout the media. Unfortunately, this work suffers from exactly the same statistical flaws as the previous ones.
Can Alpha Lipoic transform the human body and enhance athletic performance?
Inadequate experimental sample sizes, inappropriately applied statistical techniques, conflicts of interest, and results based on rodents doused with mega doses of A.H.A.- what do we conclude from this? Although there appears to be a good biochemical case for A.L.A. supplementation, the theory has not been adequately verified experimentally. In their eagerness to achieve a plethora of results, researchers have been sacrificing statistical rigor. This may sound familiar to you if you read:”Does CoQ10 Enhance Athletic Performance?” Spanking FIT, Sept. 2015. Given the important implications of the theory to human health and well being, we suggest that future medical researchers slow down and perhaps focus on fewer physiological parameters while paying greater attention to the important statistical requirements of the data. By the way, include some females in your studies, also! Not just mice and men.
In the meantime, I do continue to consume 200 mg. of A.L.A. in R-isomer form daily. I believe that it enhances my energy levels and exercise performance. So do my good friends pictured above. Nevertheless, case example evidence can never substitute for well-designed clinical trial outcomes. As usual, I am looking forward to your feedback. Dr. Garrett