LONGECITY

I am not sure if it is a good decision to put ALCAR in the same package. ALCAR has IMO question marks attached to it i.e. slightly increased mortality in the LEF lifespan study, and it appears to be of help mostly to the old animals with more damaged mitochondria. Subjectively, alcar appears to make me somewhat anxious.

Olli: I would not be at all surprised if ALCAR alone increased mortality. Who takes ALCAR without R-lipoic acid? These two only really work together as team in the mitochondria.

- is the natural form and S[-]- is an unnatural one ... And in our hands R[+]- works and S[-]- doesn't." 86

Astonishing results. Results that force us to ask daring, even radical questions about the role of this orthomolecule in the fundamental processes of life and death.

Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid

Jiankang Liu*,dagger , Elizabeth HeadDagger , Afshin M. Gharib*,dagger , Wenjun Yuan*, Russell T. Ingersoll*, Tory M. Hagen§, Carl W. CotmanDagger , and Bruce N. Ames*,dagger ,¶

* Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720; dagger Children's Hospital Oakland Research Institute, 5700 Martin Luther King, Jr., Way, Oakland, CA 94609; Dagger Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697-4540; and § Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331

Contributed by Bruce N. Ames, December 29, 2001

Abstract

Accumulation of oxidative damage to mitochondria, protein, and nucleic acid in the brain may lead to neuronal and cognitive dysfunction. The effects on cognitive function, brain mitochondrial structure, and biomarkers of oxidative damage were studied after feeding old rats two mitochondrial metabolites, acetyl-L-carnitine (ALCAR) [0.5% or 0.2% (wt/vol) in drinking water], and/or R-alpha -lipoic acid (LA) [0.2% or 0.1% (wt/wt) in diet] . Spatial memory was assessed by using the Morris water maze; temporal memory was tested by using the peak procedure (a time-discrimination procedure). Dietary supplementation with ALCAR and/or LA improved memory, the combination being the most effective for two different tests of spatial memory (P < 0.05; P < 0.01) and for temporal memory (P < 0.05). Immunohistochemical analysis showed that oxidative damage to nucleic acids (8-hydroxyguanosine and 8-hydroxy-2'-deoxyguanosine) increased with age in the hippocampus, a region important for memory. Oxidative damage to nucleic acids occurred predominantly in RNA. Dietary administration of ALCAR and/or LA significantly reduced the extent of oxidized RNA, the combination being the most effective. Electron microscopic studies in the hippocampus showed that ALCAR and/or LA reversed age-associated mitochondrial structural decay. These results suggest that feeding ALCAR and LA to old rats improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function.

PNAS | February 19, 2002 | vol. 99 | no. 4 | 1870-1875

Biochemistry
Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress
Tory M. Hagen*, Jiankang Liudagger ,Dagger , Jens Lykkesfeldt§, Carol M. Wehrdagger , Russell T. IngersollDagger , Vladimir Vinarskydagger , James C. Bartholomew¶, and Bruce N. Amesdagger ,Dagger ,||

* Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331; dagger Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; Dagger Children's Hospital Oakland Research Institute, Oakland, CA 94609; § Department of Pharmacology and Pathobiology, Royal Veterinary and Agricultural University, Copenhagen DK-1870, Denmark; and ¶ Lawrence Berkeley National Laboratory, Berkeley, CA 94720

Contributed by Bruce N. Ames, December 28, 2001

Abstract

Mitochondrial-supported bioenergetics decline and oxidative stress increases during aging. To address whether the dietary addition of acetyl-L-carnitine [ALCAR, 1.5% (wt/vol) in the drinking water] and/or (R+)-alpha -lipoic acid [LA, 0.5% (wt/wt) in the chow] improved these endpoints, young (2-4 mo) and old (24-28 mo) F344 rats were supplemented for up to 1 mo before death and hepatocyte isolation. ALCAR+LA partially reversed the age-related decline in average mitochondrial membrane potential and significantly increased (P = 0.02) hepatocellular O2 consumption, indicating that mitochondrial-supported cellular metabolism was markedly improved by this feeding regimen. ALCAR+LA also increased ambulatory activity in both young and old rats; moreover, the improvement was significantly greater (P = 0.03) in old versus young animals and also greater when compared with old rats fed ALCAR or LA alone. To determine whether ALCAR+LA also affected indices of oxidative stress, ascorbic acid and markers of lipid peroxidation (malondialdehyde) were monitored. The hepatocellular ascorbate level markedly declined with age (P = 0.003) but was restored to the level seen in young rats when ALCAR+LA was given. The level of malondialdehyde, which was significantly higher (P = 0.0001) in old versus young rats, also declined after ALCAR+LA supplementation and was not significantly different from that of young unsupplemented rats. Feeding ALCAR in combination with LA increased metabolism and lowered oxidative stress more than either compound alone.

Re: ALCAR, If I took 1.5-3G of this (used in most studies), I'd get over-stimulated, -- so I take 500mg, and get perhaps a minor effect, but I'm fine with that, also considering my age. ALCAR does have *numerous* effects on acetylcholine/dopamine, these 2 studies show it may even help you SEE better as the years pass by: it may inhibit cell loss in the occipital cortex (the area that is primary for vision). At least for rats. Perhaps it's working for me, too. [lol] But, this is one compound where I see many PREVENTIVE qualities.

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.

Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10. Ophthalmologica. 2005 May-Jun;219(3):154-66.