Effects of L-Carnitine on Postprandial Clearance of Triglyceride-rich Lipoproteins in HIV Patients on HAART

The postprandial state is a proinflammatory and proatherogenic condition. Increasing evidence support the contention the elevated triglyceride (TG)-rich lipoproteins (TGRL) are atherogenic. Hypertriglyceridemia is a characteristic of the metabolic complications during human immunodeficiency virus/highly active antiretroviral therapy (HIV/HAART) and the increased postprandial lipemia commonly seen in this situation may convey an increased cardiovascular risk. A possible contribution to the hypertriglyceridemia in HIV/HAART may be a decrease in mitochondrial function, resulting in a decreased fatty acid oxidation. A decrease in mitochondrial function may also contribute to insulin resistance. L- Carnitine plays an important role in the transfer of long-chain acyl groups into the mitochondrial matrix and potentially improves energy metabolism. L- Carnitine has been shown to reduce hypertriglyceridemia during HAART in HIV-positive subjects, but virtually nothing is known about its effect in the postprandial state. We have experience from postprandial studies in HAART-treated HIV-positive African American and Hispanic subjects, where we have focused on the relationship between lipids, fatty acids, insulin and adipokines. This is of particular relevance among African Americans, where key metabolic components differ substantially from levels in Caucasians. Further, the relationship between metabolic parameters and HIV/HAART is far less explored in this ethnic group. We recently found a proportional relationship between insulin and non-esterified fatty acids (NEFA) in response to food among African American HIV-positive subjects. Further, we showed a relationship between fasting insulin and postprandial adipokine levels.

In this randomized, double blind placebo-controlled pilot study, we will explore whether L- Carnitine affects TGRL metabolism in the fasting and the postprandial states among African American and Hispanic HIV-positive subjects undergoing antiretroviral therapy.

We hypothesize: (1) that L- Carnitine supplementation will improve both fasting TGRL levels and the postprandial response, and (2) that L- Carnitine will impact on the relationship between insulin and NEFA or adipokines in the postprandial state.

In our specific aims, we will test the effect of L- Carnitine supplementation on:

• Baseline TGRL metabolism and insulin, NEFA and adipokine levels
• Postprandial TGRL responses and the postprandial relationship between insulin and non-esterified fatty acids (NEFA) and adipokines We believe that the results generated from the proposed studies will help to evaluate effects of L- Carnitine supplementation on postprandial TGRL-associated cardiovascular risks.

Inclusion criteria

• Men and Women Ages 18-70,
• Stable HAART regimen x 6 mo,
• PI or NNRTI based regimens,
• Caucasian, African American or Hispanic patients

Exclusion criteria

• Diabetes Mellitus,
• Liver Disease,uncontrolled
• Pregnant or nursing mothers,
• BMI> 35,
• Hemoglobin <11 g/dl,
• Conditions known to lower seizure threshold (ie. brain tumor) or taking medications that lower seizure threshold,
• Patients taking: Warfarin, ValproicAcid or Zidovudine,Wellbutrin or Effexor
• Chronic Kidney Disease Stage 3-5,
• Untreated Thyroid Disease,
• Hormone replacement therapy,
• Triglycerides >500 mg/dl (fasting)