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Acetyl-l-Carnitine/Alpha Lipoic Acid Abstracts
10-19-2003
Link to Linus
Pauling Institute Micronutrient Information Center.
(R)-alpha-lipoic acid-supplemented old rats
have improved mitochondrial function, decreased oxidative damage, and increased
metabolic rate.
Hagen TM, Ingersoll RT, Lykkesfeldt J, Liu J, Wehr CM, Vinarsky V,
Bartholomew JC, Ames AB.
Department of Molecular and Cell Biology, University of California at Berkeley,
Berkeley, California 94720, USA.
A diet supplemented with (R)-lipoic acid, a mitochondrial coenzyme, was fed to
old rats to determine its efficacy in reversing the decline in metabolism seen
with age. Young (3 to 5 months) and old (24 to 26 months) rats were fed an
AIN-93M diet with or without (R)-lipoic acid (0.5% w/w) for 2 wk, killed, and
their liver parenchymal cells were isolated. Hepatocytes from untreated old rats
vs. young controls had significantly lower oxygen consumption (P<0. 03) and
mitochondrial membrane potential. (R)-Lipoic acid supplementation reversed the
age-related decline in O2 consumption and increased (P<0.03) mitochondrial
membrane potential. Ambulatory activity, a measure of general metabolic
activity, was almost threefold lower in untreated old rats vs. controls, but
this decline was reversed (P<0.005) in old rats fed (R)-lipoic acid. The
increase of oxidants with age, as measured by the fluorescence produced on
oxidizing 2',7'-dichlorofluorescin, was significantly lowered in (R)-lipoic acid
supplemented old rats (P<0.01). Malondialdehyde (MDA) levels, an indicator of
lipid peroxidation, were increased fivefold with age in cells from
unsupplemented rats. Feeding rats the (R)-lipoic acid diet reduced MDA levels
markedly (P<0.01). Both glutathione and ascorbic acid levels declined in
hepatocytes with age, but their loss was completely reversed with (R)-lipoic
acid supplementation. Thus, (R)-lipoic acid supplementation improves indices of
metabolic activity as well as lowers oxidative stress and damage evident in
aging.
PMID: 9973329 [PubMed - indexed for MEDLINE]
Full Text
Feeding acetyl-L-carnitine and lipoic acid to
old rats significantly improves metabolic function while decreasing oxidative
stress.
Hagen TM, Liu J, Lykkesfeldt J, Wehr CM, Ingersoll RT, Vinarsky V,
Bartholomew JC, Ames BN.
Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State
University, Corvallis, OR 97331, USA.
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 O(2) 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.
PMID: 11854487 [PubMed - indexed for MEDLINE]
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Text
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.
Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, Cotman CW, Ames BN.
Division of Biochemistry and Molecular Biology, University of California,
Berkeley, CA 94720, USA.
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.
PMID: 11854529 [PubMed - indexed for MEDLINE]
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