CATIE News

1 December 2006 

Colourful supplement may lengthen survival in some people with AIDS

One of the complications of HIV/AIDS is unintentional and prolonged weight loss, also known as wasting. If left untreated, this loss of body mass can become life threatening. Wasting can occur for a number of reasons, including the following:

• HIV damages the intestine, affecting its ability to break down, process and absorb food and nutrients.
• Weakened immunity makes some people with HIV/AIDS (PHAs) more susceptible to parasitic infections that can also damage the intestine.
• Energy cycles can change with the body “burning” up more energy than is eaten.
• Hormonal changes can occur, such as decreased levels of testosterone, reducing the body’s ability to build up and retain muscle mass.

Because HIV’s damage to the body is ongoing, there may be an increased need for nutrients that is not being met by dietary habits. For instance, in the face of a chronic infection such as HIV, the body may find its need for protein increased as it fights back against this virus. If the necessary amount of protein is not being consumed, then the body may tear down muscles to convert to protein and amino acids.

Because of the possible situations listed above, deficiencies of nutrients can occur in HIV disease, possibly affecting the functioning of the immune system.

One group of nutrients that can affect the immune system is called carotenoids. Examples of these include the following:

• alpha-carotene
• beta-carotene
• cryptoxanthin
• lutein
• lycopene
• zeaxanthin

Carotenoids are often red, orange or yellow and are found in fruit and vegetables; these compounds are responsible for the colour of these foods.

One carotenoid, beta-carotene, is converted into vitamin A by the body as needed. Vitamin A is essential for maintaining immunity and the health of mucous membranes. The precise role of the other carotenoids is not clear but they all tend to have antioxidant activity.

In the time before highly active antiretroviral therapy (HAART) was available in high-income countries, several studies suggested a link between low levels of vitamin A or beta-carotene and weakened immunity. In studies that analysed HIV positive people with different degrees of immune impairment, low levels of vitamin A or beta-carotene were associated with a faster breakdown of the immune system.

In lab experiments with cells of HIV negative people that were conducted in the late 1980s and early 1990s, high doses of carotenoids appeared to improve the functioning of the immune system. In experiments conducted in the same era among HIV positive people, high doses of beta-carotene did not significantly affect CD4+ cell counts or HIV replication.

Groups of vitamins
It is noteworthy that some nutrients perhaps work best as a group rather than on their own, such as B-complex vitamins. Another example is vitamin E. There are approximately eight compounds that belong to the vitamin E group. The mixed results from clinical trials of vitamin E in the past decade may be due to the use of only one form of this vitamin.

Studies in the 1980s and 1990s with just one carotenoid, beta-carotene, found little or no benefit when either HIV positive or negative people were given high doses of it alone. To try to avoid the pitfalls of using just one carotenoid, researchers in Canada conducted a randomized, placebo-controlled study of mixed carotenoids and micronutrients (vitamins and minerals) in people with AIDS in the late 1990s. Their findings suggest that supplements of these nutrients may significantly prolong survival in some people with AIDS.

Study details
Researchers across Canada affiliated with the Canadian HIV Trials Network and the Community Research Initiative Toronto (CRIT) recruited 331 PHAs between 1997 and 1999. Participants were divided into two groups as follows:

• carotenoid group
• control group

Both groups received a multivitamin and mineral supplement. People in the carotenoid group also received a supplement of mixed carotenoids equivalent to 120,000 IU (72 mg) of beta-carotene daily. The carotenoids and micronutrients were co-formulated into one caplet for those who received both. The control group received fake carotenoids (placebo).

The profile of participants at the start of the study was as follows:

• 10% female, 90% male
• average age – 40 years
• average CD4+ count – 67 cells
• average viral load – 46,000 copies
• 14% were not taking anti-HIV medications
• 70% were taking antibiotics to prevent pneumonia
• about 80% were taking HAART
• at least 37% had previously experienced a life-threatening infection

Results—Survival and CD4+ counts
According to the study team, the primary aim of the study was to assess the impact of supplementation on “new or recurring AIDS-defining events (infections, cancers) or death.” In this regard, no statistically significant differences occurred between the two groups.

However, another aim of the study was to assess the effect of carotenoid supplementation on the overall deaths in the study. To do this, the researchers adjusted their data, taking into account the CD4+ cell counts and other characteristics of participants. They then found that participants who used carotenoids had a significantly reduced risk of death. This benefit from mixed carotenoids was greatest on the following participants:

• PHAs who entered the study with more than 50 CD4+ cells
• PHAs who entered the study with low levels of beta-carotene in their blood

The impact of carotenoid supplementation on death/survival in this study was relatively large. Indeed, among participants who did not receive the supplement, the risk of death was three times greater than among participants who received carotenoids. Moreover, even though during the study the level of carotenoids in the supplement varied due to manufacturing issues, participants who received carotenoids showed a benefit from supplementation for at least 18 months.

Volunteers in the carotenoid group had an extra 40 CD4+ cells 12 to 18 months into the study compared to the control group.

Why did mixed carotenoids help?
The research team is not sure precisely why nutritional supplementation with carotenoids appeared to provide benefit(s) to study participants, but here are some possibilities:

• Perhaps the carotenoids helped provide vitamin A for participants who were deficient.
• Carotenoids have antioxidant activity, and this may have somehow helped participants’ immune systems.
• Carotenoids might have affected the processing of anti-HIV medications in the liver, increasing the concentration of these drugs in the blood.

The findings from this study suggest that supplements of micronutrients and mixed carotenoids may have a beneficial impact on some people with AIDS. Larger studies are needed to confirm this effect.

Sean R. Hosein


REFERENCES:

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