For anyone taking Acetyl L-Carnitine (ALCAR), make sure you include Alpha Lipoic Acid (ALA). The reason being that ALCAR can generate free radicals by increased interaction with the mitochondria of cells. In fact, ALA is a good idea to take when supplementing with any anti-oxidant, because when Vitamins C, E and ubiquinone neutralize a free radical, the antioxidant molecule itself becomes a free radical unless it is properly "recycled", which is what ALA apparently does.
Chomsky,
Good information...I take R-ALA daily, do you any studies or info as to whether R-ALA or ALA work in the same fashion when taken with ALCAR?
storm
The studies showing the prevention of ALCAR-induced increases in mitochondrial free radical production with lipoic acid were performed by Drs. Bruce Ames and Tory Hagen. In fact,
all of their studies have used R(+)-lipoic acid, rather than the racemate. See:
"®-alpha-Lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate"
http://www.fasebj.or...t/full/13/2/411"The ®-form of lipoic acid used in this study is the naturally occurring enantiomer in mammalian cells (24) . Only the ®-form is used by mitochondrial -keto acid dehydrogenases and specifically reduced to dihydrolipoic acid, a powerful antioxidant, via mitochondrial lipoamide dehydrogenase. There is evidence that ®-lipoic acid supplementation may be more potent than either the racemic mixture (the form sold commercially as alpha-lipoic acid) or (S)-enantiomer, and thus a more relevant supplement for this study. Addition of ®-lipoic acid increases ATP synthesis and aortic blood flow during reoxygenation after hypoxia in a working heart model (25) . The (S)-enantiomer had no effect on ATP synthesis and improved blood flow at only 10-fold the effective dose of ®-lipoic acid. Packer and colleagues (26) also showed that ®-lipoic acid significantly reduced buthionine-S,R- sulfoximine-induced cataract formation, but (S)-lipoic acid had little effect at the same concentration. ®-Lipoic acid increased glucose uptake and the number of glucose transporters in muscle tissue much more effectively than (S)-lipoic acid (27) . The ®-enantiomer more effectively chelated copper and prevented copper-induced lipid peroxidation (28) .
"Other critical metabolites that become limiting due to age-associated metabolic changes may also be beneficial as dietary supplements. A number of studies report that administration of acetyl-L-carnitine (ALCAR), a derivative of carnitine involved in fatty acid transport into mitochondria, enhanced mitochondrial function in aged tissue 38-42) . We previously found (43) that ALCAR fed to old rats restores decayed mitochondria for cardiolipin content, membrane potential, and oxygen consumption and restores ambulatory activity of the rats. However, ALCAR supplementation also increased the rate of oxidant production, oxidative damage, and decreased cellular antioxidant levels (43) . This indicated that ALCAR supplementation improved mitochondrial electron flux but did not reverse the increased inefficiency of electron transport. In a separate study (T. M. Hagen et al., unpublished results), we find that feeding ALCAR in combination with lipoic acid to old rats effectively increases mitochondrial metabolism without an increase in oxidative stress."See also:
"Feeding acetyl-L-carnitine and [R-alpha]-lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress."
http://www.pnas.org/.../full/99/4/1870"To address whether the dietary addition of acetyl-L-carnitine [ALCAR, 1.5% (wt/vol) in the drinking water] and/or ®-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."
"We previously observed that feeding 1.5% (wt/vol) ALCAR alone to old rats, although markedly increasing metabolic activity through improved mitochondrial function, also resulted in heightened oxidant production and decreased low molecular weight antioxidant status. This finding was presumably caused by increased formation of ROS/reactive nitrogen species as by-products of heightened metabolic activity. To understand whether feeding ALCAR+LA could ameliorate this potential increase in oxidative stress, we measured ascorbic acid status, overall oxidant production, and markers of oxidative damage in freshly isolated hepatocytes taken from young and old rats fed with or without ALCAR+LA."
"Hepatocytes from old rats had significantly lower ascorbate levels as compared with young rats (7.29 ± 2.97 versus 3.38 ± 0.67; P = 0.003) (Fig. 2), suggesting that liver antioxidant status may be compromised with age. We observed, as previously, that ALCAR supplementation at 1.5% (wt/vol) resulted in a further and significant decline in ascorbate levels beyond the observed age-related loss in this key antioxidant. However, ALCAR+LA supplementation reversed the ALCAR-induced and age-related loss of ascorbate such that there was no longer a significant difference (P = 0.3) in hepatocellular ascorbate values between ALCAR+LA-treated old rats and that of untreated young animals (Fig. 2)."
"To further assess whether ALCAR+LA modulated age-related and ALCAR-induced oxidative stress, we also measured steady-state levels of MDA, a marker of lipid peroxidation (Fig. 4). Hepatocellular MDA levels in old untreated rats were more than 4-fold higher than the levels seen in young rats, a significant increase (P = 0.0001). Similar to results shown for oxidant production, we observed a small, but significant, increase in steady-state MDA levels in liver tissue from old rats fed ALCAR alone (Fig. 4); on average, a similar increase in young rats was not significant. These results again suggest that high ALCAR alone, although improving metabolism and cognitive function, also increased oxidative stress in the liver. When LA was given along with ALCAR, we observed that there was a significant decline in MDA levels (Fig. 4). Most importantly, hepatic MDA concentrations in old ALCAR+LA fed rats no longer statistically differed from those found in young untreated animals."See further details in these reports:
"Mitochondrial decay in the aging rat heart: evidence for improvement by dietary supplementation with acetyl-L-carnitine and/or lipoic acid."
http://www.ncbi.nlm....t_uids=11976222"Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites."
http://www.ncbi.nlm....t_uids=11976193It is unfortunate that many supplement companies use research on R(+)-LA to market their racemic pills.
AOR is proud to have been the first in the world to put pharmaceutical-grade R(+)-lipoic acid supplements into the hands of life extensionists.
To your health!
AOR
