By Christopher Tack | Clinical Specialist Physiotherapist
Alpha-Lipoic Acid. The name is quite appropriate. In ethology (the study of animals) “alpha” is indicative of the highest ranking animal in a group. That’s where the term “alpha male” comes from. The alpha is the strongest, smartest, most respected or most deferred to- indicating superiority and status.
Alpha-lipoic acid (ALA) could certainly be considered the alpha of the group of supplements which act similarly to it. As a non-vitamin coenzyme, ALA’s metabolic and anti-oxidant functions need to be explained in detail to be believed.
So sit back and let me explain, exactly why ALA is worthy of the prefix “Alpha”.
What is Alpha Lipoic Acid?
ALA (also known as thiotic acid) is a naturally occurring compound involved in energy metabolism which was originally identified in the 1950s as a component of the Kreb’s cycle (a series of chemical reactions which allows aerobic organisms to create energy through cellular respiration).
However, since the 1980s more research has been done to explore the variable qualities of this compound, which distinguish it from other compounds with similar functions.
This coenzyme is a powerful anti-oxidant and has an essential role in the metabolism of the macronutrients (carbohydrates, proteins and fats). It is synthesised by animals and humans (1) and importantly is both fat and water soluble. This is unlike other anti-oxidants such as vitamin C which is only water soluble or vitamin E which is fat soluble.
This characteristic means that ALA can deliver its effect to any cell or tissue type, and transiently accumulate in many of the bodies tissues, ready for use as required (2-3). This benefit is even further extended by the fact that its works in both its oxidised (lipoic acid) and reduced (dihydrolipoic acid) forms (4-5).
It therefore goes without saying that ALA is a substance that should be considered for dietary supplementation for anyone concerned with anti-oxidant defence for general health, and those wanting to maintain proper glucose metabolism.
How does ALA work?
The first distinct trait of ALA is its absorbability. As mentioned ALA can be transferred and accumulated in the tissues of our bodies, however it is also important to note that it is readily taken up through oral supplementation and converted to its reduced form dihydrolipoic acid (DHLA) in most of the body’s tissues (6). This is a key feature as it is not only easily ingested and absorbed, but also converted for immediate use where ever in the body it is required.
ALA can provide anti-oxidant benefits in two distinct ways: directly or indirectly.
ALA can directly inactivate reactive oxygen species (7-8) (free radicals) which are responsible not only a plethora of health complaints, but also implicated in the physical process of aging (9-10).
This leads to a reduction in the levels of oxidative stress through body tissues (11) whether in fat or water soluble mediums, and as such any health condition which involves oxidation can expect to benefit from ALA supplementation (12).
ALA can orchestrate and facilitate the optimal function of other anti-oxidants to enhance its benefit against oxidative stress.
For example, ALA can assist the increase in concentration of other anti-oxidant vitamins, namely vitamin C and vitamin E. Increased levels of ALA can regenerate vitamin C (ascorbic acid) from its oxidised form (dehydroascorbic acid) (13) and therefore increase the levels of cellular vitamin C (14). Likewise, ALA can regenerate vitamin E from its oxidised form in a similar way (13).
However, vitamin C and E are not the only anti-oxidants which are stimulated by ALA ingestion. Additionally, the tripeptide glutathione (15-16) and the coenzyme Q10 (which is a fat soluble substance which resembles a vitamin) (17) are both increased by ALA.
✓ In fact, ALA increases glutathione concentrations by up to 70% (18), by both regenerating glutathione from its oxidised form and providing cysteine for the synthesis of this anti-oxidant.
These anti-oxidant functions occur alongside an anti-inflammatory effect to acute injuries, which has been demonstrated in animal models (8). This further highlights the health benefits of this compound.
The role of ALA in energy metabolism, as stated previously, centres round the citric acid cycle (Krebs cycle). Notably, ALA works within the mitochondria of our cells to recharge specific enzymes and increase their availability to produce energy (23).
✓ Two specific enzymes to note are PDH (pyruvate dehydrogenase) and alpha-KGDH (alpha-ketoglutarate dehydrogenase) which have an important role in the mitochondria for energy production.
✓ Additionally, enzyme complex which is facilitated by ALA is BCKADH (branch chain keto acid dehydrogenase) which has a role in creating energy from the branched chain amino acids: leucine, isoleucine and valine (24).
Alpha Lipoic Acid | Health Benefits
With its significant absorbability, anti-oxidant, anti-inflammatory, metal chelation and energy production functions, it goes without saying that ALA is able to provide benefits for a number of health conditions.
Below we shall summarise some, if not all of these benefits.
A similar benefit for pain is seen in individuals with low back pain (57). This study examined the effect of supplementation of ALA with those with chronic low back pain, and found a 65.5% reduction in subjects needing to take pain killers, and significantly improved pain and disability scores.
Studies have shown supplementation of ALA can assist various brain functions including improvements in long term memory in aged mice (28), depression (29), and Alzheimer’s related memory dysfunction in humans (4).
Similar to the metal chelation properties of ALA, it can also reduce chemical toxicity in tissues and counteract subsequent oxidative stress changes (in keeping with ALA’s anti-oxidant benefits). This has been shown with the chemicals cyanate (30) and the chemotherapy drug, ifosfamide (31); as well as toxic mushroom poisoning (32); and lead poisoning (33).
The heart and cardiovascular system related benefits of ALA include the ability to reduce the size of myocardial infarcts (heart attacks) whilst also providing a degree of heart tissue protection (46). This is particularly true in the case of diabetic cardiomyopathy (47), where a heart disorder is apparent in those with diabetes without coronary heart disease. ALA also helps to reduce high blood pressure (48).
ALA can assist in reducing the degree of bone loss in osteoporosis following the menopause (49-50).
In experimental models of nerve injury due to exposure to light (51) and spinal cord direct pressure (52), ALA was seen to provide a degree of nerve protection against injury. Additionally, a series of trials on individuals with diabetic neuropathy, have shown that ALA supplementation helped reduce symptoms of neuropathy (54); improve nerve conduction (53); and improved nerve function generally (55). A further study showed a reduction in neuropathic pain in this patient group (56).
ALA & Insulin Resistance
ALA has been found to have effectiveness in handling some of the physical consequences of diabetes and metabolic syndrome (58-59).
Interestingly, ALA has been found to stimulate glucose uptake by muscle similarly to insulin (60) indicating that it may have a distinctive role in managing insulin resistance and hyperinsulinaemia (61).
✓ Insulin resistance is the reduced ability of the hormone insulin to stimulate glucose transport and metabolism in our body’s tissues (namely muscle but sporadically fat), or to reduce the production of glucose by the liver.
As a characteristic of metabolic disease it is often associate d with other problems, such as high blood pressure, weight gain and cardiovascular issues (e.g. atherosclerosis) (62-64). There is even a mix of various risk factors related to metabolism and cardiovascular health leading this issue to be designated with its own diagnostic label “syndrome X” (62,64). Although, sometimes it is just called “insulin resistance syndrome” (63).
Insulin resistance is often mentioned interchangeably with “insulin sensitivity”. In essence if you are insulin resistant, then you have low insulin sensitivity (or visa versa). Insulin resistance is a bad thing, as it means that your cells do not respond well to the presence of insulin, meaning higher levels of this hormone in your blood. This has a strong association with weight gain and obesity as you will struggle to metabolise fuel for energy as efficiently. It also can make you feel tired and crave sugar.
✓ However, you will be happy to know that ALA (along with its other myriad of functions) has also been seen to contribute to the prevention of obesity and weight gain, even in those fed a high fat diet (65-66).
…The question is, how does ALA do this?
Studies indicate that ALA has a specific role in managing glucose metabolism and insulin levels to prevent weight gain.
For example, one study found that a dosage of 600mg of ALA twice per day for 4 weeks increased insulin sensitivity and the effectiveness of the response to glucose in both lean and obese subjects (67).
ALA + Exercise IS BETTER
Perhaps, in light of both exercise and ALA supplementation having corresponding effects on GLUT4 recruitment, it may be obvious that the combination leads to more benefit than the sum of its parts.
Certainly exercise training leads to changes in glucose control and insulin action in muscle glucose metabolism in those with insulin resistance or diabetes (70,72-73).
However, as in many health intervention scenarios, the complexity of the problem means it is difficult for one solution to be sufficient to adequately normalise insulin control.
Therefore, it makes sense to combine both interventions (exercise and ALA) to increase the effect on insulin resistance.
Our bodies are in fact capable of producing ALA from fatty acids and cystein, however the amounts are too small to be sufficient (1).
As such it is suggested that ALA needs to be ingested from external sources (76) and as the typical Western diet does not typically contain enough ALA, the burden falls to dietary supplementation to fill this gap (14).
Even supplementation can have difficulty increasing our ALA levels with only 20-40% absorption into plasma seen following a 200mg dose (77). Lowest levels of absorption interestingly are seen when consumed with food, indicating that there is a degree of competition for the carrier proteins required to allow adequate absorption (77).
Recommended dosages of oral supplementation of ALA range from 600-1800mg per day with lower doses exclusively met by R-ALA to ensure effectiveness (78).
However, it has been suggested that even lower ranges (between 200mg-600mg) can provide 1000 times the amount of ALA consumed by most diets (79).
ALA Side Effects
There has not been a defined upper limit of ALA consumption in humans, despite evidence that animals do suffer toxicity at very high levels of ingestion. To some extent some of the benefits of ALA (e.g. chemical binding to metals) can lead to problems, meaning it is always better to individualise the dosage for each specific person.
The specific dose taken of course should be based upon the experience of the individual following ingestion, and in light of how each person feels during supplementation. Certainly, if a positive response (effectiveness) is not apparent during the early stages of a supplementation regime then ingestion should be stopped (80).
In animal studies
>>> It has been found that a dose comparable to 100,000mg-200,000mg in a human, is the lethal dose where 50% of animals died following consumption (2000mg/kg) (4). However, it is difficult to truly extrapolate these findings to a human model.
Large scale human trials
>>> Found that dosages up to 2400mg per day caused no adverse effects (53), and long term dosages of 1800mg-2400mg orally over 6 months also showed no adverse effects (5,55).
It is certainly apparent that we would benefit from more research regarding both the safety and optimal dose of ALA (14).
Take Home Message
ALA is obviously an intriguing compound worthy of your consideration to add to your health supplement regime. Its vast benefits for a myriad of health issues and its ability to assist with increasing insulin sensitivity/ reducing insulin resistance, means that it is even worth considering if all you need to do is lose stubborn fatty deposits.
Best used alongside a proper training regime, it is likely that ALA can use its anti-oxidant benefits to improve your health and help you shed some body fat.