Supplement research


Acetyl L-Carnitine

What is Acetyl L-Carnitine?

Carnitine is a non-essential nutrient that has several roles in intermediary metabolism. It can be manufactured in the liver and kidneys. Dietary sources are provided from animal foods. Carnitine that is ingested or synthesised is in the L-isoform. L-carnitine is stored primarily in the heart and skeletal muscle. Acetyl L-carnitine is derived from acetyl-CoA units and carnitine.

Proposed Benefits of Acetyl L-Carnitine

It is proposed that acetyl carnitine might enhance high intensity exercise performance in situations that might otherwise be limited by excess lactate and hydrogen ion accumulation.

It is proposed that acetyl-L-carnitine may be of benefit in treating diseases such as Alzheimer's dementia, depression in the elderly, HIV infection, diabetic neuropathies, ischemia and reperfusion of the brain, and cognitive impairment of alcoholism.

Mechanism of Action of Acetyl L-Carnitine

Exercise Performance

One of the roles of carnitine is to act as sink for acetyl-CoA units which are produced during high intensity exercise. By converting acetyl CoA to acetyl carnitine and CoA, carnitine could help maintain CoA availability which could increase the flux through the citric acid cycle. Furthermore, by reducing levels of acetyl CoA (by generating acetylcarnitine), the oxidative metabolism of glucose may be increased because of the enhanced activity of the enzyme pyruvate dehydrogenase (PDH). This could result in lower lactate production which might enhance exercise performance in situations that might otherwise be limited by high lactate levels and increased muscle acidity.

Dementia and Neural Properties

Acetyl-L-carnitine contains carnitine and acetyl moieties, both of which have neurobiological properties. Carnitine is important for the oxidation of fat and the acetyl moiety can be used to maintain acetyl-CoA levels. Other neurobiological effects of acetyl-L-carnitine may include modulation of brain energy and phospholipid metabolism, neurohormones, and neurotransmitters.

Various pathological processes, particularly affecting the cholinergic neurotransmitter system, are linked to memory impairment in dementia. Acetyl-L-carnitine is described as having several properties that may be beneficial in dementia. These include, activity at cholinergic neurons, membrane stabilisation and enhancing mitochondrial function. Acetyl-L-carnitine facilitates the uptake of acetyl CoA into the mitochondria, enhances acetylcholine production (a hormone of the parasympathetic nervous system), and stimulates protein and membrane phospholipid synthesis.

Mitochondria decay with age due to the oxidation of lipids, protein, RNA and DNA. It is thought that feeding the mitochondrial metabolite acetylcarnitine may reverse some of this decay.

Research on Acetyl L-Carnitine

Exercise Performance

Research suggests that the enzyme PDH is maximally active within a few seconds of high intensity exercise and additional carnitine is unlikely to further stimulate this activity (1). Carnitine content of skeletal muscle does fall during exercise, as acetylcarnitine accumulates, but to date there is little data supporting the postulate that lowered carnitine levels are rate limiting.

Two earlier studies do show that acute supplementation with 2g of carnitine 1 hour before exercise reduced the exercise-induced increase in blood lactate levels and have increased time to exhaustion (2,3). It is difficult to know if 90 minutes provides sufficient time for carnitine to be absorbed through the gut and into the bloodstream and taken up by the muscle. Hultman et al have shown that it is unlikely that carnitine supplementation over a period of days to weeks will change muscle total carnitine content in humans (4). Also note that these studies used L-carnitine. Further studies have failed to show an effect of carnitine supplementation on performance (5-7).

Dementia

Some animal research suggests that feeding acetyl-L-carnitine in old rats improves age-associated decline in ambulatory activity and memory, and partially restores mitochondrial structure and function (8).

Some early studies suggested a beneficial effect of acetyl-L-carnitine on cognition and behaviour in aging subjects. More recent large studies have failed to support these earlier findings. Much of the differences in results are because of variations in study design.

A 1-year clinical trial was carried out to determine the efficacy of acetyl-L-carnitine on the rate of decline in early onset Alzheimer's disease patients (9). There were 229 patients in total with 117 receiving a placebo and 112 acetyl-L-carnitine. Overall, acetyl-L-carnitine failed to show decline in these patients.

Two meta-analyses (a statistical combination of clinical trials) have been performed on acetyl-L-carnitine (10,11). One of the meta-analyses investigated the efficacy of acetyl-L-carnitine in mild cognitive impairment and mild (early) Alzheimer's disease (11). The meta-analysis included studies of at least 3 months duration with a daily dose varying from 1.5-3.0g/day. Results showed a significant advantage of acetyl-L-carnitine compared to the placebo. Beneficial effects were seen on both the clinical scales and the psychometric tests.

A second meta-analysis investigated whether acetyl-L-carnitine was effective at treating patients with Alzheimer's disease (10). Eleven trials were included in the analysis. There were significant treatment effects in favour of acetyl-L-carnitine for the numbers showing improvement as determined by Clinical Global Impression. However there was no evidence of benefit for acetyl-L-carnitine in the areas of cognition, severity of dementia, functional ability or Clinical Global Impression as a continuous measure. It was concluded that there was evidence for benefit of as determined by clinical global impression, but there was no evidence using objective assessments in any other area of outcome.

These two meta-analyses obviously contribute conflicting findings. This may be due to the fact that Montgomery et al studied the effects of acetyl-L-carnitine in those with mild cognitive impairment and early Alzheimer's disease. Results may be more promising if treatment with acetyl-L-carnitine is started earlier in the disease process?

Rating of Efficacy for Acetyl L-Carnitine

Research on acetyl carnitine has produced mixed results. Acetyl-L-carnitine at present is not recommended routinely for use in clinical practice.

6/10

References

  1. Heinonen O.J. Carnitine and physical exercise. Sports Med. 22:109-132, 1996.
  2. Siliprandi N., Di Lisa F. and Pieralisi G. Metabolic changes induced by maximal exercise in human subjects following L-carnitine administration. Biochimica et Biophysica Acta. 1034:17-21, 1990.
  3. Vecchiet L., Di Lisa F. and Pieralisi G. Influence of L-carnitine administration on maximal physical exercise. Eur J Appl Physiol. 61:486-490, 1990.
  4. Hultman E., Cederblad G. and Harper P. Carnitine administration as a tool to modify energy metabolism during exercise. Eur J Appl Physiol. 6, 1991.
  5. Greig C., Finch K.M., Jones D.A., Cooper M., Sargeant A.J. and Forte C.A. The effect of oral supplementation with L-carnitine on maximum and submaximum exercise capacity. Eur J Appl Physiol. 56:457-460, 1987.
  6. Trappe S.W., Costill D.L., Goodpaster M.D. and Fink W.J. The effects of L-carnitine supplementation on performance during interval swimming. In J Sport Med. 15:181-185, 1994.
  7. Wyss V., Ganzit G.P. and Rienzi A. Effects of L-carnitine administration on VO2max and the aerobic-anaerobic threshold in normoxia and acute hypoxia. Eur J Appl Physiol. 60:1-6, 1990.
  8. Liu J., Atamna H., Kuratsune H. and Ames B.N. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Ann NY Acad Sci. 959:133-166, 2002.
  9. Thal L.J., Calvani M., Amato A. and Carta A. A 1-year controlled trial of acetyl-L-carnitine in early-onset AD. Neurology. 55:805-810, 2000.
  10. Hudson S. and Tabet N. Acetyl-L-carnitine for dementia. Cochrane Database of Systematic Reviews. 2:CD003158, 2003.
  11. Montgomery S.A., Thal L.J. and Amrein R. Meta-analysis of double blind randomized controlled trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. Int Clin Psychopharm. 18:61-71, 2003.