Its a bit like a scene from a movie: the elderly scientist, working late in the lab, takes a sip of potion from a bubbling flask and undergoes a miraculous transformation as his body regains its youth and vigour. Pure fantasy? Maybe not because thats pretty much what happened to elderly laboratory rats when they were fed two dietary supplements in a recent landmark study. According to the professor in charge of the study, the old rats became so full of energy, they got up and did the Macarena!
Over the last 18 months, scientific interest in alpha lipoic acid (ALA) and acetyl L-carnitine (ALC), the two supplements used in the studies, has exploded and a large number of studies are now under way with humans. Initial results look encouraging, but what are the implications for athletes and can these nutrients be harnessed to improve performance?
Some readers may be familiar with the amino acid carnitine, which carries fatty acids into the mitochondria (the cellular furnaces), where they are oxidised for energy. As its name suggests, acetyl L-carnitine (ALC) is very similar, consisting of the same basic amino acid structure, with an acetyl group attached. In the body, acetyl L-carnitine is synthesised from L-carnitine by the enzyme carnitine acetyltransferase. Although levels tend to decrease after the age of 40, acetyl L-carnitine (ALC) is not normally considered an essential nutrient because the body can manufacture all it needs.
One of the main roles of acetyl L-carnitine (ALC) is to carry fatty acids from the cytosol (the main body of the cell) into the mitochondria (the energy-producing furnaces within cells) so that these fats can be oxidised for energy. Although L-carnitine carries out this role too, acetyl L-carnitine (ALC) also provides acetyl groups, from which acetyl-coenzyme A (a key metabolic intermediate) can be regenerated, thereby facilitating the transport of metabolic energy and boosting mitochondrial activity.
The addition of the acetyl group also endows acetyl L-carnitine (ALC) with a greater solubility in water, which enables it not only to diffuse easily across the inner wall of the mitochondria and into the cell cytosol, but also cross cell membranes in general more easily. In plain English, acetyl L-carnitine (ALC) reaches parts of the body that L-carnitine just cant reach! In addition to its role in mitochondrial activity, acetyl L-carnitine (ALC) is involved in the production of the key brain neurotransmitter acetylcholine and is also able to donate its acetyl group in a number of other biochemical reactions.
Alpha lipoic acid (ALA) is a sulphur-containing antioxidant, which occurs naturally, in small amounts, in such foods as spinach, broccoli, beef, yeast, kidney, and heart. alpha lipoic acid (ALA) is readily soluble in water and fat, enabling it to exert an antioxidant effect in almost any part of the body, including the brain. In the mitochondria, alpha lipoic acid (ALA) can act both as an antioxidant, capable of recycling other antioxidant nutrients such as vitamin C and vitamin E, and as a coenzyme for key metabolic enzymes involved in energy production. In addition to its role as an antioxidant, alpha lipoic acid (ALA) also raises the levels within cells of a substance called glutathione, which is critical for neural function, and aids in glycolysis, the first stages of breaking down carbohydrates for energy.
The initial excitement about ALC/alpha lipoic acid (ALA) supplementation began when a team of researchers in California fed elderly rats both nutrients for a period of seven weeks and then compared them with young rats(1). They were testing the theory that mitochondrial decline is caused by free radical damage (see panel opposite). There was already evidence that supplementation with acetyl L-carnitine (ALC) could reverse the age-related decline in mitochondrial activity in rats, increase fatty acid oxidation and boost general metabolic activity(2). However the down side to this increased mitochondrial function was that more oxidative damage occurred(3), so the researchers decided to add the powerful mitochondrial antioxidant alpha lipoic acid (ALA) to the mix to see if they could get the best of both worlds: increased mitochondrial energy output, with reduced mitochondrial damage.
This two-pronged punch to ageing cells seemed to work, with the two supplements together producing better results than either one alone. After a month on the supplements, elderly (24-month-old) and lethargic rats had more energy and did better on memory tests, while their mitochondria worked better. The decline in overall activity typical of aged rats was reversed to the level of young-to-middle-aged adult rats, aged 7-10 months. The researchers likened this result to a group of 80-year-old humans throwing away their walking sticks and starting to act 35 years younger!
The implications for human health
These studies on rats caused a huge stir within the scientific community. Here was evidence that some of the processes of ageing could be slowed or even reversed, and the implications for human health and performance were enormous. In the months that followed, a number of human studies were started, many of which are still under way.
However, the question of whether the benefits observed in rats might also apply to humans will not be easy to determine. For one thing, the ageing process in humans is much slower than in rats, so the seven-week supplementation period used in the rat studies would equate to around five years of supplementation in humans! Secondly, the amounts of acetyl L-carnitine (ALC)/alpha lipoic acid (ALA) used in the rat studies were very high equivalent to 50g per day of acetyl L-carnitine (ALC) and 5g of alpha lipoic acid (ALA) for an 11-stone adult. Thats around 50 times more than is typically available in acetyl L-carnitine (ALC)/ALA supplements found on the shelves of most health food stores!
One of the earliest studies examining the effect of acetyl L-carnitine (ALC) and alpha lipoic acid (ALA) in humans was carried out at San Francisco State University in 2001. In a double-blind, placebo-controlled study lasting 17 weeks, 18 healthy sedentary men aged 60-71 were randomised to one of two treatment régimes: a placebo tablet twice a day or 1,000mgs of acetyl L-carnitine (ALC) and 400mgs of alpha lipoic acid (ALA) in two divided doses. Both groups were then asked to perform a demanding sequence of exercises, after which blood was drawn and analysed for signs of exercise-induced oxidative stress (a potentially damaging by-product of energy production). To measure oxidative stress, the study evaluated nine different biomarkers: ammonia, beta-carotene, glutamine, glutathione, malondialdehyde, total antioxidant status (TAS), vitamin C, vitamin E-alpha tocopherol, and vitamin E-gamma tocopherol. For eight of these nine biomarkers, a majority of subjects in the treatment group recorded values indicating that levels of oxidative stress had fallen. By contrast, no such benefits were reported in the placebo group.
If an acetyl L-carnitine (ALC)/alpha lipoic acid (ALA) combination can reduce exercise-induced oxidative stress, that would be good news for athletes, who are particularly vulnerable to such stress. However, because the small scale of this study made it difficult to reach statistically significant conclusions, the results were not submitted for scientific publication, which means they should be interpreted with caution.
Other human studies are also currently under way, but so far there are no published human studies available, although positive studies in animals continue to proliferate. Last year, for example, American researchers demonstrated that alpha lipoic acid (ALA) supplementation in older racehorses reduced the oxidative stress burden even under light training loads (4), while a number of other animal studies have shown that acetyl L-carnitine (ALC)/ALA supplementation reduces oxidative stress and improves mitochondrial function in a number of tissues, including brain, muscle and heart.
In one of these studies, researchers examined the effects of acetyl L-carnitine
(ALC)/alpha lipoic acid (ALA) therapy on ageing and hearing in rats, and found
that it reduced the normal age-associated deterioration in auditory sensitivity
and improved inner ear function (5). They concluded that these improvements were
related to the acetyl L-carnitine (ALC)/ALA combinations ability to protect
and repair age-induced mitochondrial DNA damage, thereby boosting mitochondrial
function and improving energy turnover. However, while the initial evidence from
animal studies looks extremely promising, the jury is still out as far as humans
THE THEORY OF MITOCHONDRIAL DECLINE AND AGEING
The free radical theory of ageing is based on the idea that our cells and DNA (the latter containing the code for proper cell division and replication) eventually become irreversibly damaged by the onslaught of highly-reactive chemical species called free radicals. These transient species are generated unavoidably as a by-product of aerobic (oxygen) metabolism. In other words, while oxygen provides us with the energy for life, its also responsible for generating highly damaging chemical species that cause biochemical havoc within the cells of our bodies. The mitochondrial decline theory of ageing takes this process one step further. Mitochondria are the energy-producing furnaces in the body, whose job is to make adenosine triphosphate (ATP), the energy currency of life, by burning fuel in the presence of oxygen. But this process inevitably leaves the mitochondria themselves subject to very high levels of damaging free radical attack by reactive oxygen species. Mitochondria lack many of the defence systems found in other parts of the body, so they decline in number and efficiency with age, leading to a corresponding decline in ATP production. Reduced ATP means less energy to fuel the vital life-sustaining processes of the body, which can result in the onset of a number of disease states and processes.
For athletes in hard training, the prospect of preventing or even reversing some of the age-related decline in physical performance is enticing, holding out the promise of longer careers, including more sustained levels of peak performance. However, as is so often the case with new and unfolding nutritional research, it is difficult to make hard and fast recommendations about the benefits of supplementation.
The first thing to point out is that dietary manipulation to boost these nutrients is not an option. Although alpha lipoic acid (ALA) and acetyl L-carnitine (ALC) are present in some foods, the amounts are very small by comparison with those used in human studies. To boost these nutrients, therefore, it is necessary to take supplements.
Secondly, its important to realise that even if the ALA/ALC combination is eventually proven to slow down or reverse mitochondrial decline, the evidence suggests this will not lead to sudden and dramatic improvements in performance. Like the antioxidant phytochemicals in fruit and vegetables and the antioxidant vitamins and minerals, alpha lipoic acid (ALA)/acetyl L-carnitine (ALC) is most likely to offer a long-term investment for your health.
If you are tempted to jump the scientific gun and supplement these nutrients anyway, the good news is that they appear to be relatively non-toxic, even at very high doses. The only caveat is that alpha lipoic acid (ALA) in high doses is known to enhance sensitivity to insulin, which could lead to a drop in blood sugar. For this reason, it should be taken with food.
The bad news is that alpha lipoic acid (ALA) and acetyl L-carnitine (ALC) are not particularly cheap, and athletes need to ask themselves whether that expenditure could be more effectively allocated to improving the basic quality of their diet. As yet, there is no clear guidance on what the optimum or most cost-effective intake of alpha lipoic acid (ALA)/acetyl L-carnitine (ALC) might be. The altitude sickness study (7) used 600mgs of alpha lipoic acid (ALA) per day, while studies showing that acetyl L-carnitine (ALC) improves brain function in Alzheimers patients (10) have used between 1,500 and 3,000mgs per day. However, the human study carried out in San Francisco, which used 400mgs of alpha lipoic acid (ALA) and 1,000mgs of acetyl L-carnitine (ALC) per day, was overseen by the same team that carried out the initial rat studies, so that might be a good place to start.
One final point: dont confuse acetyl L-carnitine (ALC) with L-carnitine. While it is considerably cheaper, L-carnitine does not have the same bioavailability as acetyl L-carnitine (ALC) and has not been used in studies on mitochondrial decline. And while L-carnitine has often been promoted as a popular fat burning and endurance supplement, there is actually very little evidence for this in the scientific literature. But thats another story!
1. Proceedings of the National Academy of Sciences, 99; 1876-1881, 2002
2. Proceedings of the National Academy of Sciences, 94; 3064-3069, 1997
3. Proceedings of the National Academy of Sciences, 95; 9562-9566, 1998
4. J Nutr, 132(6 Suppl 2): 1628S-31S, 2002
5. Am J Otol, 21(2): 161-7, 2000
6. Med Hypotheses, 56(5): 610-13, 2001
7. High Alt Med Biol, 2(1): 21-29, 2001
8. Exp Gerontol, 37(2-3): 401-410, 2002
9. Bipolar Disord, 4(1): 61-66, 2002
10. Int Clin Psychopharmacol, 18(2): 61-71, 2003