"Although it is unusual to see physicians prescribing vitamins in the hospital,
Acetyl l-Carnitine is routinely prescribed by kidney specialists for their patients,
since the kidney is a major site of carnitine synthesis."
(1) Urology. 2004 Apr;63(4):641-6.
Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging.
Cavallini G, Caracciolo S, Vitali G, Modenini F, Biagiotti G. Andrological Operative Unit, Headquarters of Societa Italiana di Studi di Medicina della Riproduzione, Bologna, Italy
Protective effect of alpha-lipoic acid against ischaemic acute renal failure in rats.
J Am Pharm Assoc (Wash) 2002 Mar-Apr;42(2):217-26
Takaoka M, Ohkita M, Kobayashi Y, Yuba M, Matsumura Y.
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
1. In the present study, we investigated whether treatment with alpha-lipoic acid (LA),
a powerful and universal anti-oxidant, has renal protective effects in rats with ischaemic acute renal failure (ARF).
2. Ischaemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion,
2 weeks after contralateral nephrectomy. Blood urea nitrogen (BUN), plasma concentrations of creatinine (Pcr) and
urinary osmolality (Uosm) were measured for the assessment of renal dysfunction. Creatinine clearance (Ccr) and
fractional excretion of Na+ (FENa) were used as indicators of glomerular and tubular function, respectively.
3. Renal function in ARF rats decreased markedly 24 h after reperfusion. Intraperitoneal injection of LA at a dose of
10 mg/kg before the occlusion tended to attenuate the deterioration of renal function. A higher dose of LA (100 mg/kg)
(P less than 0.01) attenuated the ischaemia/reperfusion-induced increases in
BUN (19.1 +/- 0.7 vs 7.2 +/- 0.7 mmol/L before and after treatment, respectively),
Pcr (290 +/- 36 vs 78.1 +/- 4.2 micromol/L before and after treatment, respectively)
and FENa (1.39 +/- 0.3 vs 0.33 +/- 0.09% before and after treatment, respectively).
Treatment with 100 mg/kg LA significantly (P less than 0.01) increased Ccr
(0.70 +/- 0.13 vs 2.98 +/- 0.27 mL/min per kg before and after treatment, respectively)
and Uosm (474 +/- 39 vs 1096 +/- 80 mOsmol/kg before and after treatment, respectively).
4. Histopathological examination of the kidney of ARF rats revealed severe lesions.
Tubular necrosis (P less than 0.01), proteinaceous casts in tubuli (P less than 0.01) and medullary congestion
(P less than 0.05) were significantly suppressed by the higher dose of LA. 5. A marked increase in endothelin
(ET)-1 content in the kidney after ischaemia/reperfusion was evident in ARF rats (0.43 +/- 0.02 ng/g tissue)
compared with findings in sham- operated rats (0.20 +/- 0.01 ng/g tissue). Significant attenuation
(P less than 0.01) of this increase occurred in ARF rats treated with the higher dose of LA (0.24 +/- 0.03 ng/g tissue).
6. These results suggest that administration of LA to rats prior to development of ischaemic
ARF prevents renal dysfunction and tissue injury, possibly through the suppression of overproduction of ET-1
in the postischaemic kidney.
PMID: 11906481 [PubMed - indexed for MEDLINE]
Mitochondrial decay in the aging rat heart: evidence for improvement by dietary supplementation with acetyl-L-carnitine and/or lipoic acid.
Ann N Y Acad Sci 2002 Apr;959:491-507
Hagen TM, Moreau R, Suh JH, Visioli F.
Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331, USA. firstname.lastname@example.org
Mitochondrial decay has been postulated to be a significant underlying part of the aging process. Decline in mitochondrial function may lead to cellular energy deficits, especially in times of greater energy demand, and compromise vital ATP-dependent cellular operations, including detoxification, repair systems, DNA replication, and osmotic balance. Mitochondrial decay may also lead to enhanced oxidant production and thus render the cell more prone to oxidative insult. In particular, the heart may be especially susceptible to mitochondrial dysfunction due to myocardial dependency on beta-oxidation of fatty acids for energy and the postmitotic nature of cardiac myocytes, which would allow for greater accumulation of mitochondrial mutations and deletions. Thus, maintenance of mitochondrial function may be important to maintain overall myocardial function. Herein, we review the major age-related changes that occur to mitochondria in the aging heart and the evidence that two such supplements, acetyl-l-carnitine (ALCAR) and (R)-alpha-lipoic acid, may improve myocardial bioenergetics and lower the increased oxidative stress associated with aging. We and others have shown that feeding old rats ALCAR reverses the age-related decline in carnitine levels and improves mitochondrial beta-oxidation in a number of tissues studied. However, ALCAR supplementation does not appear to reverse the age-related decline in cardiac antioxidant status and thus may not substantially alter indices of oxidative stress. Lipoic acid, a potent thiol antioxidant and mitochondrial metabolite, appears to increase low molecular weight antioxidant status and thereby decreases age-associated oxidative insult. Thus, ALCAR along with lipoic acid may be effective supplemental regimens to maintain myocardial function.
PMID: 11976222 [PubMed - indexed for MEDLINE]
Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)-(alpha)-lipoic acid.
FASEB J 2001 Mar;15(3):700-6
Suh JH, Shigeno ET, Morrow JD, Cox B, Rocha AE, Frei B, Hagen TM.
Linus Pauling Institute, Department of Biochemistry, Oregon State University, Corvallis, Oregon 97331, USA.
Oxidative stress has been implicated as a causal factor in the aging process of the heart and other tissues. To determine the extent of age-related myocardial oxidative stress, oxidant production, antioxidant status, and oxidative DNA damage were measured in hearts of young (2 months) and old (28 months) male Fischer 344 rats. Cardiac myocytes isolated from old rats showed a nearly threefold increase in the rate of oxidant production compared to young rats, as measured by the rates of 2,7-dichlorofluorescin diacetate oxidation. Determination of myocardial antioxidant status revealed a significant twofold decline in the levels of ascorbic acid (P = 0.03), but not alpha-tocopherol. A significant age-related increase (P = 0.05) in steady-state levels of oxidative DNA damage was observed, as monitored by 8-oxo-2'-deoxyguanosine levels. To investigate whether dietary supplementation with (R)-alpha-lipoic acid (LA) was effective at reducing oxidative stress, young and old rats were fed an AIN-93M diet with or without 0.2% (w/w) LA for 2 wk before death. Cardiac myocytes from old, LA-supplemented rats exhibited a markedly lower rate of oxidant production that was no longer significantly different from that in cells from unsupplemented, young rats. Lipoic acid supplementation also restored myocardial ascorbic acid levels and reduced oxidative DNA damage. Our data indicate that the aging rat heart is under increased mitochondrial-induced oxidative stress, which is significantly attenuated by lipoic acid supplementation.
PMID: 11259388 [PubMed - indexed for MEDLINE]
Acetyl-L-Carnitine is a substance which retains the well-known effects of L-Carnitine on muscle tissue; i.e., long-chain fatty acid transport for ATP production within the mitochondria. ALCÍs further impact on both skeletal muscle and the myocardium include antioxidant effects leading to less lipid peroxidation, thus protecting exercising muscle tissue from free-radical damage.38 Additionally, it may improve cardiolipin levels in the aged heart, a substance which maintains crucial membrane factors in cardiac mitochondria and thus ensures efficient phosphate transport for energy. In a rat mitochondrial model, it was shown that ALC administered to aged animals returned cardiolipin levels to that of young ones. 39
John H. Furlong N.D.
Protective effects of propionyl-L-carnitine during ischemia and reperfusion.
Cardiovasc Drugs Ther (UNITED STATES) Feb 1991, 5 Suppl 1 p77-83
When cardiac function in isolated rat hearts was impaired by subjecting them to ischemia, subsequent perfusion with propionyl-L-carnitine and related compounds increased their rate of recovery. Thus at 11 mM, both propionyl-L-carnitine and, to a lesser extent, its taurine amide, and also acetyl-L-carnitine, significantly restored cardiac function in 15 minutes after 90 minutes of either low-flow or intermittent no-flow ischemia. Carnitine itself was ineffective. Propionyl-L-carnitine also increased tissue ATP and creatine phosphate compared with controls, but did not affect the levels of long-chain acyl carnitine and coenzyme. These esters also depleted fatty acid peroxidation, as shown with malonaldehyde, and were more effective than carnitine in preventing the production of superoxide. In myocytes, propionyl-L-carnitine alone stimulated palmitate oxidation, but in rat heart homogenates, both L-carnitine and propionyl-L-carnitine did so, while acetyl-L-carnitine was actually inhibitory. Possible mechanisms for the protective action of propionyl-L-carnitine against ischemia include an increased rate of cellular transport, stimulation of fatty acid oxidation, and a reduction of free radical formation.
The effects of treatment with alpha-lipoic acid or evening primrose oil on vascular hemostatic and lipid risk factors, blood flow, and peripheral nerve conduction in the streptozotocin-diabetic rat.
Metabolism 2001 Aug;50(8):868-75
Ford I, Cotter MA, Cameron NE, Greaves M.
Departments of Medicine & Therapeutics, University of Aberdeen, Aberdeen, Scotland.
Oxidative stress and defective fatty acid metabolism in diabetes may lead to impaired
nerve perfusion and contribute to the development of peripheral neuropathy. We studied the
effects of 2-week treatments with evening primrose oil (EPO; n = 16) or the antioxidant alpha-lipoic acid
(ALA; n = 16) on endoneurial blood flow, nerve conduction parameters, lipids, coagulation, and endothelial
factors, in rats with streptozotocin-induced diabetes. Compared with their nondiabetic littermates, untreated
diabetic rats had impaired sciatic motor and saphenous sensory nerve-conduction velocity
(NCV; P less than .001), reduced endoneurial blood flow (P less than .001), and increased serum
triglycerides (P less than .01), cholesterol (P less than 0.01), plasma factor VII (P less than .0001), and
von Willebrand factor (vWF; P less than .0001). Plasma fibrinogen and serum high-density lipoprotein
concentrations were not significantly different. Treatment with either ALA or EPO effectively corrected the
deficits in NCV and endoneurial blood flow. ALA was associated with marked and statistically significant
decreases in fibrinogen, factor VII, vWF, and triglycerides (P less than .01, paired t tests before v
after treatment). In contrast, EPO was associated with significant (P less than .05) increases in fibrinogen,
factor VII, vWF, triglycerides, and cholesterol and a significant decrease in high-density lipoprotein. Changes
in levels of coagulation factors and lipids, qualitatively similar to those found with EPO, were obtained with a
diet containing sunflower oil (to control for calorific and lipid content) or with a normal diet alone. Blood glucose
and hematocrit levels were not significantly altered by treatments. These data suggest that although both ALA and
EPO improve blood flow and nerve function, their actions on vascular factors differ. The marked effects of ALA in
lowering lipid and hemostatic risk factors for cardiovascular disease indicate potential antithrombotic and
antiatherosclerotic actions that could be of benefit in human diabetes and merit further study.
Copyright 2001 by W.B. Saunders Company
PMID: 11474472 [PubMed - indexed for MEDLINE]
A study of the ameliorating effects of carnitine on hepatic steatosis induced by total parenteral nutrition in rats.
Liang LJ, Yin XY, Luo SM, Zheng JF, Lu MD, Huang JF.
1: World J Gastroenterol. 1999 Aug;5(4):312-315.
Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University of Medical Sciences, 56 Zhongshan Er Lu, Guangzhou 510080,China.
AIM:To investigate the effects of carnitine on ameliorating hepatic steatosis induced by total parenteral nutrition (TPN) in animal model.METHODS: Eighteen normal Wistar rats and 19 cirrhotic Wistar rats induced by carbon tetrachloride were randomly divided into three groups, i.e., free
access to food and drink (group A), TPN (group B) and TPN+carnitine (group C) for one week, respectively. Hepatic function, histology and its fat content were determined on the 7th day.RESULTS: Hepatic triglyceride (TG) and cholesterol (CHO) contents were significantly higher in groups B and C than in group A,and significantly lower in group C than in group B in both normal and cirrhotic rats
(all P less than 0.05). Histopathological examinations revealed that hepatic steatosis was more severe in group B than in group C in both normal and cirrhotic rats.CONCLUSION:Carnitine can ameliorate hepatic steatosis associated with TPN in both non-cirrhotic and cirrhotic rats.
PMID: 11819455 [PubMed - as supplied by publisher]
Acetyl-L-Carnitine and Ethanol
A number of interesting reports on the relationship between hepatic detoxification of ethanol and carnitines have been produced. It is observed that pretreatment of both rats and chickens with carnitines resulted in a prolonged half-life of ethanol in the blood.43,44 Additionally, a protective effect on prenatal ethanol damage to thalamic and cortical regions in rats was observed with administration of ALC.47 Two studies by Cha and Sachan with isolated rat hepatocytes harvested after pretreatment with ALC elucidate the mechanism of these interesting effects. An inhibition of alcohol dehydrogenase was present and significantly increased when the nicotinamide adenine dinucleotide:ALC ratio was low. It was also shown that L-Carnitine itself was much less effective at producing this inhibition.47,48 As a final addition to these findings of great therapeutic interest, oral administration of ALC was shown to improve the cognitive impairments of 55 chronic alcoholics.48
We may infer from this work that patients with high ethanol intake may have prolonged ethanol half-life if they are concurrently taking ALC supplementation. This effect may be due in part to low niacin levels and could be modified by niacin administration. ALCÍs cerebro-thalamic protection observed in rat pups exposed to ethanol prenatally and the apparent hepato-protective effects observed in models of chronic alcohol use provide exciting possibilities for preventing the intergenerational sequelae of high ethanol intake.
John H. Furlong N.D.