The following Study is done by the US National Library of Medicine,
Mitochondria produce reactive oxygen species that may contribute to vascular dysfunction. Alpha-lipoic acid and acetyl-L-carnitine reduce oxidative stress and improve mitochondrial function. In a double blind, crossover study, we examined the effects of combined alpha-lipoic acid /acetyl-L-carnitine treatment and placebo (eight weeks per treatment) on vasodilator function and blood pressure in 36 subjects with coronary artery disease. Active treatment increased brachial artery diameter by 2.3% (P=0.008), consistent with reduced arterial tone. Active treatment tended to decrease systolic blood pressure for the whole group (P=0.07) and had a significantly effect in the subgroup with blood pressure above the median (151±20 to 142±18 mmHg, P=0.03) and in the subgroup with the metabolic syndrome (139±21 to 130±18 mmHg, P=0.03). Thus, mitochondrial dysfunction may contribute to the regulation of blood pressure and vascular tone. Further studies are needed to confirm these findings and determine the clinical utility of alpha-lipoic acid/acetyl-L-carnitine as antihypertensive therapy.
In addition to serving as the site of oxidative phosphorylation, it is now clear that mitochondria regulate many cellular functions, in part, by producing reactive oxygen species that signal the adaptive response to environmental stress and injury.1 Excess production of mitochondria-derived oxidants, however, may have maladaptive effects.2,3 There is growing evidence that disturbances of mitochondrial function, including increased oxidant production and altered mitochondria-dependent signaling contribute to the pathogenesis of vascular disease in atherosclerosis and cardiovascular risk factors.1,4,5
On the basis of these observations, we hypothesized that an intervention designed to improve mitochondrial function would have beneficial vascular effects in patients with cardiovascular disease. Recent experimental studies have shown that administration of alpha-lipoic acid and/or acetyl-L-carnitine can reduce oxidant production and improve mitochondrial function in models of aging6,7 Furthermore, these compounds reduce blood pressure and improve endothelial function in animal models of hypertension8-12 and diabetes13-16 The present study was designed to examine the effects of combined alpha-lipoic acid/acetyl-L-carnitine treatment on vascular function and blood pressure in patients with coronary artery disease.
This randomized, placebo-controlled, double blind crossover study demonstrated that combined alpha-lipoic acid/acetyl-L-carnitine treatment was associated with an increase in baseline brachial artery diameter. Furthermore, we observed a non significant trend for a blood pressure lowering effect of alpha lipoic acid/acetyl-L-carnitine in all subjects and a significant reduction in systolic blood pressure in subjects with systolic blood pressures above the median and in subjects with the metabolic syndrome. These findings suggest the possibility that these mitochondria-directed antioxidants reduce basal arterial tone, particularly in two clinically relevant subgroups. In contrast, we observed no effect of treatment on the dilator responses to increased flow, nitroglycerin, or ischemia (reactive hyperemia).
A prior study demonstrated a decrease in systolic blood pressure and a direct vasodilator effect in nailfold capillaries after treatment with oral L-carnitine (3g/d for 20days) in patients with digital vasospastic disease.29An open-label study of patients with diabetic nephropathy, reported that long-term alpha lipoic acid treatment (600 mg/d for 18 months) prevented the increases in blood pressure and urine albumin concentration observed in control patients.30 Experimental studies have consistently demonstrated an anti-hypertensive effect of alpha-lipoic acid or L-carnitine in various rat models of hypertension, including spontaneously hypertensive rats,8,9 uninephrectomized deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats10and salt-loaded Dahl and Wistar-Kyoto rats.11,12
Our study differs from several previous human studies that examined the effects of lipoic acid or carnitine on endothelial function. For example, Heitzer and colleagues observed an acute improvement in endothelium-dependent dilation of forearm microvessels following an intra-arterial infusion of lipoic acid (final concentration 0.2 mmoles/L) in patients with diabetes mellitus.26 Sola and colleagues recently reported improved brachial artery flow-mediated dilation following treatment with lipoic acid 300 mg/d for four weeks in young patients with the metabolic syndrome (mean age 46 years).27 Intravenous administration of L-carnitine (3 gram bolus) enhanced reactive hyperemia in patients with peripheral arterial disease.31 The apparent discrepancies between the results of those prior studies and the present study likely relate to the marked differences in dose, route of administration, vascular bed studied and/or patient population.
The mechanisms accounting for the increased brachial artery diameter and suggestive anti-hypertensive effects of alpha-lipoic acid and acetyl-L-carnitine in our study remain undefined. We observed no effect of treatment on serum lipids, glucose, and insulin, which might have influenced endothelial function or arterial diameter. Experimental studies indicate that alpha-lipoic acid and acetyl-L-carnitine play important and potentially synergistic roles in normal mitochondrial function, and that reduced levels of these compounds are associated with increased mitochondrial oxidant production.6,25,32 In addition, lipoic acid supplementation has favorable effects on cellular redox state and has been shown to decrease lipid peroxidation and cellular production of reactive oxygen species.6,7,32,33 The effects of alpha-lipoic acid and acetyl-L-carnitine on oxidative stress which contributes to the pathogenesis and cardiovascular complications of hypertension suggests that these compounds may be useful adjuncts in treatment.34 In the present study, we investigated the possibility that these compounds reduced oxidative stress and inflammation, but observed no effect of treatment on urinary F2 isoprostanes or serum C-reactive protein. It is important to point out, however, that these systemic markers may not accurately reflect events in the vascular wall.
Despite the effects on blood pressure and basal diameter, it is notable that we only observed a trend for increased total serum carnitine following treatment. It is known that acetyl-L-carnitine and alpha-lipoic acid are rapidly metabolized in human subjects with plasma half lives of 4.2 hours35 and 30 minutes,36respectively. Thus, it is likely that acetyl-L-carnitine and lipoic acid metabolites and/or tissue levels may be more relevant for the observed effects. Similarly, the lack of effect of treatment on urine F2 isoprostanes does not rule out an effect of active treatment on oxidative stress at the tissue level.
We observed a particular benefit of alpha-lipoic acid/acetyl-L-carnitine in patients with the metabolic syndrome. This syndrome of insulin resistance is associated with hypertension; improvement of insulin sensitivity could have an anti-hypertensive effect. Consistent with our findings, several experimental studies suggest a blood pressure-lowering effect in models of diabetes mellitus or insulin resistance.13-16 Those results and our findings are consistent with the growing evidence linking insulin resistance to mitochondrial dysfunction
Read more at the following link http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734271/