September 28, 2009
Inside each cell are tiny power plants called mitochondria. Inside mitochondria, fats are burned to release energy to power a cell. When mitochondria are damaged, cells do not get sufficient energy and can become dysfunctional and, in some cases, even die.
Carnitine is a nutrient found in food of animal origin. Carnitine helps to move fatty substances into mitochondria, where they can be used to produce energy.
Some studies have found less-than-normal levels of carnitine in the blood of HIV positive people. Other studies have found that regular supplementation with carnitine can help to reduce abnormal levels of triglycerides, a fatty substance in the blood. Most of the studies focused on a formulation of carnitine called L-carnitine.
Long-term studies of a different formulation of carnitine -- acetyl-L-carnitine -- suggest that this substance can help damaged nerves recover from the toxicity of certain anti-HIV drugs such as d4T (Zerit, stavudine) and ddI (Videx EC, didanosine).
Now researchers in Milan, Italy, have conducted a small study with HIV positive volunteers and carnitine, to assess its effects on body composition and other related metabolic parameters. The results from this study suggest the possibility of a decreased risk for diabetes. Furthermore, the research team claims that carnitine supplements increased the fat content in the legs of volunteers. We urge readers to exercise caution when interpreting the results of this small study and we provide critical details later in this CATIE News bulletin.
Researchers at San Raffaele Hospital in Milan recruited nine HIV positive volunteers for this study. Their average profile was as follows:
All participants were taking highly active antiretroviral therapy (HAART) and had stable CD4+ cell counts.
Researchers also enrolled nine healthy HIV negative volunteers of similar age and gender mix. This group was used for comparison.
No HIV positive participant had diabetes or serious heart, lung, liver or kidney dysfunction. All HIV positive participants had lost a moderate-to-severe degree of subcutaneous fat, the fatty layer just under the skin.
All participants ate a diet designed by the researchers that consisted of a similar amount of calories.
All participants received magnetic scans or MRIs (magnetic resonance imaging) of different parts of their body. They also received low-dose X-ray scans called DEXA (dual-energy x-ray absorptiometry) to assess changes in fat distribution.
HIV positive participants received carnitine formulated as L-acetyl-carnitine at a dose of 2 grams per day for eight consecutive months.
There was a trend for levels of fat in the upper body of participants to decrease. Perhaps this trend might have become statistically significant had the study continued for a longer period of time or had many more people participated. Still, according to a statistical analysis, there was no significant change in the fat content of the upper body or arms. However, according to the results of DEXA scans, the legs of HIV positive participants became a bit thicker as the amount of fat increased by about 500 grams (about a pound). This difference would probably not be noticed by participants as it likely happened gradually and was only detectable using high-tech instruments. Moreover, the increase in fat content of the legs of HIV positive people, although statistically significant, resulted in leg fat levels far below those seen in HIV negative people.
The hormone insulin helps cells absorb sugar from the blood. In cases of pre-diabetes, cells gradually lose their ability to respond to the effects of insulin. As a result, blood sugar levels can remain high for prolonged periods of time. The pancreas gland, which produces insulin, is forced to make ever-high amounts of this hormone to try to stimulate cells to reduce blood sugar. If this continues over a period of years, the pancreas gets exhausted and can eventually fail.
At the start of the study, the bodies of the HIV positive participants were somewhat insensitive to the effects of insulin. By the end of the study, insulin sensitivity improved among HIV positive people and reached the level detected in HIV negative people.
After eight months of carnitine supplementation, lipid -- cholesterol and triglyceride -- levels in the blood were only modestly affected, with small decreases in total cholesterol and "bad" (LDL-C) cholesterol and triglycerides.
In some previous studies, reduced levels of thyroid hormones were sometimes detected in carnitine users. However, in the present Italian study no reduction in thyroid hormone levels were seen.
Less-than-normal levels of growth hormone (GH) occur in HIV infection. At the start of the study, GH levels were about 67% below levels seen in HIV negative people. However, after eight months of carnitine supplementation, GH levels increased by 40% -- a significant difference.
Although the results of this study are promising, they should be viewed with caution for the following reasons:
The results from the present Italian study with HIV positive volunteers are interesting, particularly the impact on insulin sensitivity and GH production. Now a larger and longer study is needed to confirm and extend the results seen so far. At a minimum, such a trial should consider a strategy of randomization and also a placebo-controlled phase, perhaps for the first six or eight months. These steps may be helpful in reducing bias when interpreting the results of such a trial.
L-carnitine is a prescription drug in North America for the treatment of carnitine deficiency, sold under the brand name Carnitor. Not all provincial/territorial formularies in Canada will pay for Carnitor in cases of HIV infection.
Acetyl-L-carnitine is available over the counter in Italy and some health food stores in the United States.
The carnitine formulation used in the present study was made by Sigma-Tau SpA, Italy.
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