Life Extension Magazine
LE Magazine Special Edition, Winter 2004/2005
New Brain Regeneration Nutrient Grows Neurites

Brain cells communicate with each other because they are connected by neurites (dendrites and axons). Neurites are long filament-like terminal branches of nerve cells that grow much like branches of a tree. Neurites function to provide the communication circuitry pathways between the nerve cells.

As we age, there is a loss of neurites, which results in slowed thinking as neural-connection pathways are reduced from many in number to only a few. The effect of the age-related neurite loss is that thought processing pathways, thinking time, and reaction times are all significantly diminished.

Acetyl-l-carnitine-arginate is a patented form of carnitine that stimulates the growth of neurites in the brain.* Studies show that acetyl-l-carnitine-arginate stimulates the growth of new neurites by an astounding 19.5% (as much as Nerve Growth Factor itself). Acetyl-l-carnitine-arginate acts together with acetyl-l-carnitine to increase neurite outgrowth.1

Acetyl-l-carnitine by itself stimulates neurite growth after 5 days by 5.6%. Acetyl-l-carnitine-arginate, on the other hand, stimulates neurite outgrowth in the same time period by 19.5%…a more than three-fold increase!1

An equally impressive finding was the average length of the neurites produced by the acetyl-carnitine-arginate—21% longer than in the acetyl-l-carnitine-only group.1

When scientists compared the effects of acetyl-l-carnitine and arginine, the mixture gave the same growth results as acetyl carnitine by itself, i.e. 5.2%. This study showed that acetyl-l-carntine-arginate induced 3.48 times more neurite growth compared to acetyl-l-carnitine mixed with arginine.1

Acetyl carnitine arginate protects brain cells against the toxicity caused by the presence of B-amyloid, which is found in older and Alzheimer’s brains and which causes disruptions in healthy cellular calcium 2+ balance.2 Acetyl carnitine arginate also increases the neurotransmitter content of brain cells, maintains their proper structure (morphology) in terms of size and shape, and keeps them in their proper state of differentiation (specialization).3

Multiple Neurological Effects of Acetyl-L-Carnitine
The acetylated form of L-carnitine (acetyl-l-carnitine) facilitates the release and synthesis of acetylcholine by donating its acetyl group towards the production of acetylcholine, an important neurotransmitter. Acetyl-l-carnitine also enhances the release of dopamine from neurons and helps it bind to dopamine receptors.4-8 Numerous human and animal studies validate the multiple beneficial mechanisms that acetyl-l-carnitine exerts in the brain.9-28

The amino acid acetyl-l-carnitine boosts mitochondrial energy production through its ability to facilitate fatty acid transport and oxidation within the cell.29-31

Each capsule of the new
Acetyl-L-Carnitine-Arginate formula provides:

Acetyl-l-carnitine
arginate DHCl ...........250 mg

Acetyl-l-carnitine
HCl ..........................350 mg

New Acetyl-L-Carnitine Arginate Supplement
Since 1995, Life Extension members have been supplementing with acetyl-l-carnitine and deriving the many benefits this form of carnitine has shown in published scientific studies. With the discovery of acetyl-l-carnitine-arginate, the benefits of acetyl-l-carnitine can now be greatly augmented.

Acetyl-l-carnitine arginate has been added to the new Mitochondrial Energy Optimizer described in this special edition of Life Extension. For those who prefer to take additional acetyl-l-carnitine- arginate, or are not taking the Mitochondrial Energy Optimizer, a new formula has been designed to replace the previous acetyl-l-carnitine stand alone supplement.

The suggested dose is three to four capsules per day.

References

1. Taglialatela G, Navarra D, Olivi A, et al. Neurite outgrowth in PC12 cells stimulated by acetyl-L-carnitine arginine amide. Neurochem Res. 1995 Jan;20(1):1-9.

2. Scorziello A, Meucci O, Calvani M, et al. Acetyl-L-carnitine arginine amide prevents beta 25-35-induced neurotoxicity in cerebellar granule cells. Neurochem Res. 1997 Mar;22(3):257-65

3. Westlund KN, Lu Y, Werrbach-Perez K, et al. Effects of nerve growth factor and acetyl-L-carnitine arginyl amide on the human neuronal line HCN-1A. Int J Dev Neurosci. 1992 Oct;10(5):361-73.

4. Tolu P, Masi F, Leggio B, et al. Effects of long-term acetyl-L-carnitine administration in rats: I. increased dopamine output in mesocorticolimbic areas and protection toward acute stress exposure. Neuropsychopharmacology. 2002 Sep;27(3):410-20.

5. Sershen H, Harsing LG Jr, Banay-Schwartz M, et al. Effect of acetyl-L-carnitine on the dopaminergic system in aging brain. J Neurosci Res. 1991 Nov;30(3):555-9.

6. Harsing LG Jr, Sershen H, Toth E, et al. Acetyl-L-carnitine releases dopamine in rat corpus striatum: an in vivo microdialysis study. Eur J Pharmacol. 1992 Jul 21;218(1):117-21.

7. Toth E, Harsing LG Jr, Sershen H, et al. Effect of acetyl-L-carnitine on extracellular amino acid levels in vivo in rat brain regions. Neurochem Res. 1993 May;18(5):573-8.

8. Florio T, Meucci O, Grimaldi M, et al. Effect of acetyl-L-carnitine treatment on brain adenylate cyclase activity in young and aged rats. Eur Neuropsychopharmacol. 1993 Jun;3(2):95-101.

9. Ando S, Tadenuma T, Tanaka Y, et al. Enhancement of learning capacity and cholinergic synaptic function by carnitine in aging rats. J Neurosci Res. 2001 Oct 15;66(2):266-71.

10. Sorbi S, Forleo P, Fani C, Piacentini S. Double-blind, crossover, placebo-controlled clinical trial with L-acetylcarnitine in patients with degenerative cerebellar ataxia. Clin Neuropharmacol. 2000 Mar-Apr;23(2):114-8.

11. Anonymous. Acetyl-L-carnitine. Altern Med Rev. 1999 Dec;4(6):438-41.

12. Passeri M, Cucinotta D, Bonati PA, et al. Acetyl-L-carnitine in the treatment of mildly demented elderly patients. Int J Clin Pharmacol Res. 1990;10(1-2):75-9.

13. Kalaria RN, Harik SI. Carnitine acetyltransferase activity in the human brain and its microvessels is decreased in Alzheimer’s disease. Ann Neurol. 1992 Oct;32(4):583-6.

14. Napoleone P, Ferrante F, Ghirardi O, et al. Age-dependent nerve cell loss in the brain of Sprague-Dawley rats: effect of long term acetyl-L-carnitine treatment. Arch Gerontol Geriatr. 1990 Mar-Apr;10(2):173-85.

15. Virmani A, Binienda Z. Role of carnitine esters in brain neuropathology. Mol Aspects Med. 2004 Oct-Dec;25(5-6):533-49.

16. Hagen T, Wehr C, Ames B. Mitochondrial decay in aging—Reversal through supplementation of Acetyl-L-Carnitine and N-tert-Butyl-alpha-phenyl-nitrone. Ann N Y Acad Sci. 1998 Nov 20;854:214-23.

17. Mazzio E, Yoon KJ, Soliman KF. Acetyl-L-carnitine cytoprotection against 1-methyl-4-phenylpyridinium toxicity in neuroblastoma cells. Biochem Pharmacol. 2003 Jul 15;66(2):297-306.

18. Pettegrew JW, Klunk WE, Panchalingam K, et al. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer’s disease. Neurobiol Aging. 1995 Jan-Feb;16(1):1-4.

19. Spagnoli A, Lucca U, Menasce G, et al. Long-term acetyl-L-carnitine treatment in Alzheimer’s disease. Neurology. 1991 Nov;41(11):1726-32.

20. Carta A, Calvani M, Bravi D, Bhuachalla SN. Acetyl-L-carnitine and Alzheimer’s disease: Pharmacological considerations beyond the cholinergic sphere. Ann N Y Acad Sci. 1993 Sep 24;695:324-6.

21. Rai G, Wright G, Scott L, et al. Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer’s dementia. Curr Med Res Opin 1990;11:638-647.

22. Bonavita E. Study of the efficacy and tolerability of L-acetylcarnitine therapy in the senile brain. Int J Clin Pharmacol Ther Toxicol. 1986 Sep;24(9):511-6.

23. Cucinotta D, Passeri M, Ventura S, et al. Multicenter clinical placebo-controlled study with acetyl-L-carnitine (LAC) in the treatment of mildly demented elderly patients. Drug Development Res 1988;14:213-6.

24. Tempesta E, Casella L, Pirrongelli C, et al. L-acetylcarnitine in depressed elderly subjects. A crossover study vs placebo. Drugs Exp Clin Res 1987 13:417-23.

25. Garzya G, Corallo D, Fiore A, et al. Evaluation of the effects of L-acetylcarnitine on senile patients suffering from depression. Drugs Exp Clin Res 1990;16:101-106.

26. Di Giulio AM, Gorio A, Bertelli A, et al. Acetyl-L-carnitine prevents substance P loss in the sciatic nerve and lumbar spinal cord of diabetic animals. Int J Clin Pharmacol Res. 1992;12(5-6):243-6.

27. Gorio A, Di Giulio AM, Tenconi B, et al. Peptide alterations in autonomic diabetic neuropathy prevented by acetyl-L-carnitine. Int J Clin Pharmacol Res 1992 12(5-6):225-30.

28. Cavallini G, Caracciolo S, Vitali G, Cavallini G, Caracciolo S, Vitali G, et al. Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Urology. 2004 Apr;63(4):641-6.

29. Aureli T, Miccheli A, Ricciolini R, et al. Aging brain: effect of acetyl-L-carnitine treatment on rat brain energy and phospholipid metabolism. A study by 31P and 1H NMR spectroscopy. Brain Res. 1990 Aug 27;526(1):108-12.

30. Ebeling P, Tuominen JA, Arenas J, et al. The association of acetyl-L-carnitine with glucose and lipid metabolism in human muscle in vivo: the effect of hyperinsulinemia. Metabolism. 1997 Dec;46(12):1454-7.

31. Paradies G, Ruggiero FM, Petrosillo G, et al. Carnitine-acylcarnitine translocase activity in cardiac mitochondria from aged rats: the effect of acetyl-L-carnitine. Mech Ageing Dev. 1995 Oct 13;84(2):103-12.


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