Ameliorating Hypertension and Insulin Resistance in Subjects at Increased Cardiovascular Risk

Abstract

Abstract-Insulin resistance, a key component of the metabolic syndrome, is a risk factor for diabetes mellitus and cardiovascular disease. Acetyl-L-carnitine infusion acutely ameliorated insulin sensitivity in type 2 diabetics with insulin resistance. In this sequential off-on-off pilot study, we prospectively evaluated the effects of 24-week oral acetyl-L-carnitine (1 g twice daily) therapy on the glucose disposal rate (GDR), assessed by hyperinsulinemic euglycemic clamps, and components of the metabolic syndrome in nondiabetic subjects at increased cardiovascular risk a priori segregated into 2 groups with GDR Յ7.9 (nϭ16) or Ͼ7.9 (nϭ16) mg/kg per minute, respectively. Baseline GDR and systolic blood pressure were negatively correlated (nϭ32; Pϭ0.001; rϭϪ0.545), and patients with GDR Յ7.9 mg/kg per minute had higher systolic/diastolic blood pressure than those with higher GDR. Acetyl-L-carnitine increased GDR from 4.89Ϯ1.47 to 6.72Ϯ3.12 mg/kg per minute (Pϭ0.003, Bonferroni-adjusted) and improved glucose tolerance in patients with GDR Յ7.9 mg/kg per minute, whereas it had no effects in those with higher GDRs. Changes in GDR were significantly different between groups (Pϭ0.017, ANCOVA). Systolic blood pressure decreased from 144.0Ϯ13.6 to 135.1Ϯ8.4 mm Hg and from 130.8Ϯ12.4 to 123.8Ϯ10.8 mm Hg in the lower and higher GDR groups, respectively (PϽ0.05 for both; PϽ0.001 overall) and progressively recovered toward baseline over 8 weeks posttreatment. Total and high molecular weight adiponectin levels followed specular trends. Diastolic blood pressure significantly decreased only in those with higher GDRs. Treatment was well tolerated in all of the patients. Acetyl-L-carnitine safely ameliorated arterial hypertension, insulin resistance, impaired glucose tolerance, and hypoadiponectinemia in subjects at increased cardiovascular risk. Whether these effects may translate into long-term cardioprotection is worth investigating. (Hypertension. 2009;54:567-574.)

Oral Acetyl- l -Carnitine Therapy and Insulin Resistance

“…1 These findings led us to suggest that acetyl-L-carnitine treatment corrects a relative carnitine deficiency in this population. However, in a recent letter to the editor, Muniyappa 2 states that oral L-carnitine supplementation cannot achieve the plasma carnitine levels required to increase skeletal muscle carnitine concentration and improve insulin sensitivity.…”

“…Moreover, 3 of 4 patients who regained normal glucose tolerance on acetyl-L-carnitine supplementation returned to their previous state of impaired glucose tolerance after acetyl-L-carnitine withdrawal. 1 As stated in our article, 1 we performed a pilot study aimed to explore the hypothesis that chronic acetyl-L-carnitine supplementation may have beneficial hemodynamic and metabolic effects in subjects at increased cardiovascular risk. The results confirmed the hypothesis and provided the background for a randomized, double-blind clinical trial, which we are currently running (identifier NCT00984750), to formally test the effects of acetyl-L-carnitine compared with placebo on blood pressure, lipid and metabolic profile, and kidney function in type 2 diabetes mellitus hypertensive patients.…”

Oxidative stress: New insights on the association of non-alcoholic fatty liver disease and atherosclerosis

“…In a recent study, l-carnitine supplementation reduced tumor necrosis factor (TNF)-α, liver function parameters, plasma glucose levels and histological scores in NASH [121] . However, even if a majority of studies have shown that l-carnitine supplementation can improve factors associated with MetS and CVD [122][123][124][125] , recent evidences suggested that dietary l-carnitine may accelerate atherosclerosis via gut microbiota metabolites [126] .…”

The role of nutrition and nutraceutical supplements in the treatment of hypertension

“…Endothelial function, NO and oxidative defense are improved while oxidative stress and BP are reduced [144][145][146][147] . Human studies on the effects of L-carnitine and acetyl-L-carnitine are limited, with minimal to no change in BP [148][149][150][151][152][153] . In patients with MS, acetyl-L-carnitine at one gram bid over 8 wk, improved dysglycemia and reduced SBP by 7-9 mmHg, but diastolic BP was significantly decreased only in those with higher glucose [151] .…”

“…Human studies on the effects of L-carnitine and acetyl-L-carnitine are limited, with minimal to no change in BP [148][149][150][151][152][153] . In patients with MS, acetyl-L-carnitine at one gram bid over 8 wk, improved dysglycemia and reduced SBP by 7-9 mmHg, but diastolic BP was significantly decreased only in those with higher glucose [151] . Low carnitine levels are associated with a nondipping BP pattern in Type 2 DM [153] .…”