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Proposed Natural Treatments

Among the many proposed natural treatments for HIV, none has more than preliminary supporting evidence.

Inhibiting viral replication. No natural remedies rival the effectiveness of antiretroviral drugs for inhibiting HIV replication in the body. However, preliminary research suggests that an extract of the leaves and stems of the boxwood shrub may have at least some efficacy. Many other herbs and supplements have been proposed, but there is little evidence that they work.

Boxwood. In a double-blind, placebo-controlled study of 145 people with HIV, French researchers studied the effects of two doses of a preparation made from the evergreen boxwood (Buxus sempervirens). The preparation was given in doses of 990 milligrams (mg) and 1,980 mg per day for periods ranging from four to sixty-four weeks.

When participants started the study, they had no symptoms of HIV and had never taken antiretroviral drugs. They were kept off anti-HIV drugs during the study. (This was before the use of anti-HIV drugs became widespread.) At the end, researchers found that among those taking the lower dose, fewer people developed AIDS, symptomatic HIV, or CD4+ counts below 200 compared with those taking the higher dose or placebo. Additionally, by the end of their treatment period, fewer people in the low-dose group had a large increase in the amount of HIV they carried compared with the other two groups.

The researchers had originally planned the study to continue for eighteen months (seventy-eight weeks). However, as the study progressed, a review committee decided to halt the study early when the average participant had taken boxwood or placebo for only thirty-seven weeks. The review committee felt it was unethical to continue to have some people take placebo, given the positive results among those taking the extract. Nonetheless, further research is necessary to confirm the effectiveness of boxwood extract for HIV, particularly with proven antiviral drugs, which have now become the standard of care for HIV infection.

No severe side effects were reported in this study, and the people taking boxwood had the same overall rate of side effects as those taking placebo. However, there are some safety concerns with this herb. A substance called cycloprotobuxine is believed to be one of the active ingredients in boxwood. High doses of this substance can cause vomiting, diarrhea, muscular spasms, and paralysis. The herb should only be taken under medical supervision. Safety in pregnant or nursing women, young children, and people with liver or kidney disease has not been established. In addition, touching fresh boxwood leaves can occasionally cause skin irritation.

Only a special boxwood extract has been studied as a treatment for HIV infection. One should not try to use raw boxwood leaf because it might not be safe.

Other proposed natural treatments. One of the constituents of the
herb aloe, acemannan, has shown some promise in test-tube and animal studies for
stimulating immunity and inhibiting the growth of viruses. These findings have led
to trials of acemannan (or whole aloe) for the treatment of HIV
infection. However, a double-blind, placebo-controlled trial of acemannan failed
to find any benefits for people with severe HIV infection. (There is some question
whether the effects seen in these studies were actually caused by acemannan or by
a contaminant called aloeride.)

Other substances that have been investigated for possible HIV suppression include bacailin (Chinese skullcap), curcumin, elderberry, schisandra, spirulina, and reishi. However, as with aloe, the evidence that they work is primarily limited to test-tube and animal studies; whether these results translate into real improvement among people with HIV has not been determined.

The herb St.
John’s wort contains a substance called hypericin, which has
been investigated for possible anti-HIV effects. However, contrary to popular
belief, neither hypericin nor St. John’s wort is useful for treating HIV
infection. In addition, St. John’s wort seriously impairs the activity of standard
HIV medications and might lead to treatment failure.

Enhancing the immune system. In test-tube studies, a number of substances have been found to improve measures of immunity in HIV infection, for example, by elevating CD4+ counts, changing the ratio between CD4+ cells and other immune cells, increasing amounts of other immune chemicals, or enhancing the body’s ability to attack invading substances. However, there is relatively little information on whether they can actually help people with HIV infection.

N-acetylcysteine. One of the natural substances most widely used
by people with HIV in hopes of enhancing immune system function is the antioxidant
N-acetylcysteine (NAC), but evidence that it helps is
somewhat conflicting. NAC is a specially modified form of the dietary amino acid
cysteine. NAC supplements help the body make the important antioxidant enzyme
glutathione. Early human trials, including a double-blind
study of forty-five people, suggest that NAC may increase levels of CD4+ cells in
healthy people and slow CD4+ cell decline in people with HIV infection. Another
study of NAC combined with selenium had mixed results, affecting T-cell counts in
some people but not in others. However, preliminary results of another study found
that NAC had no effect on CD4+ counts or the amount of HIV in the blood. Whey
protein also contains cysteine and may increase glutathione levels, but there is
no evidence of any meaningful benefit.

Other proposed natural treatments. One study found evidence that the amino acid methionine taken at a dose of 2.4 g daily may mildly improve immune function in people with HIV infection. Other natural treatments that are sometimes recommended to boost immunity in HIV include andrographis, trichosanthin (compound Q), lipoic acid, coenzyme Q10, maitake, a component of licorice known as glycyrrhizin, Momordica charantia (an herb also called bitter melon), echinacea, ginseng, omega-6 fatty acids, carnitine, and proteolytic enzymes. However, there is no real evidence that these treatments actually work. Garlic is sometimes recommended too, but for safety reasons it should be avoided by persons with HIV infection.

Fish
oil is also sometimes recommended for enhancing immunity in
HIV infection. However, one six-month, double-blind study found that a combination
of the omega-3 fatty acids in fish oil plus the amino acid arginine was no more
effective than placebo in improving immune function in people with HIV infection.
Another study found that the hormone dehydroepiandrosterone (DHEA) does not
improve immunity in people with HIV infection.

Study results are mixed on whether massage therapy can improve measures of
immune function. A careful review of thirty-five randomized trials found that
relaxation
therapies may be generally helpful at improving the quality
of life of HIV-positive persons and in reducing their anxiety, depression, stress,
and fatigue. These interventions, though, had no significant effect on the growth
of the virus, nor did they influence immunologic or hormonal activity.
Subsequently, however, a small study involving forty-eight persons with HIV found
that mindfulness meditation, a popular method for inducing the relaxation
response, slowed the loss of the specific immune cells destroyed by the virus,
though more research needs to be done to confirm this result.

Treating other symptoms and opportunistic infections. In addition to the foregoing treatments, a number of natural remedies have been proposed for symptoms of HIV or common opportunistic infections. Bovine colostrum has been suggested as a treatment for the chronic diarrhea that commonly occurs in people with HIV or AIDS, but the evidence that it works is weak at best.

Tea tree oil and cinnamon have been suggested as treatments for thrush (oral candida infection). There is some evidence that capsaicin cream applied topically is beneficial for limb pain caused by peripheral neuropathy associated with HIV infection.

DHEA is a hormone that seems to decrease in people with AIDS, possibly because of malnutrition and stress. One small double-blind trial suggests that DHEA (50 mg per day) may improve mood and fatigue scores in people with HIV; another small trial found inconclusive results. A more substantial (145-participant) double-blind study found that DHEA at a dose of 100 to 400 mg daily improved symptoms of dysthymia (minor depression) in people with HIV, without significant adverse effects. DHEA does not appear to provide general benefits for people with HIV, such as improving immunity, suppressing virus levels, or aiding weight maintenance.

Chinese herbal combinations have been investigated for the treatment of HIV, but the results have not been very promising. In a twelve-week, double-blind, placebo-controlled trial, thirty HIV-infected adults with CD4+ counts of 200 to 500 were given a Chinese herbal formula containing thirty-one herbs. The results hint that the use of the herbal combination might have improved various symptoms compared with placebo, but none of the differences were statistically significant. People who believed they were taking the real treatment showed significant benefit regardless of whether they were in the placebo group or the real treatment group.

In another double-blind, placebo-controlled trial, sixty-eight HIV-positive adults were given either placebo or a preparation of thirty-five Chinese herbs for six months. The results indicate that the use of Chinese herbs did not improve symptoms or objective measurements of HIV severity. In fact, people using the herbs reported more digestive problems than those given placebo.

Fighting weight loss. Undesired weight loss is a frequent symptom
of HIV and AIDS. Weight loss can be so extreme that the person seems to “waste
away,” hence the name “AIDS wasting syndrome,” which is technically defined as the
loss of more than 10 percent of body weight combined with either chronic diarrhea
or weakness and fever. Many factors can contribute to this weight loss, including
loss of appetite, nausea, malabsorption of nutrients, and mouth sores.
Supplemental medium-chain triglycerides (MCTs), a particular type of fat,
and glutamine may be helpful for this symptom, although there is no definitive
evidence that they work.

MCTs. Fat malabsorption is particularly common in HIV infection and can lead to both diarrhea and weight loss. MCTs, which are more easily absorbed than ordinary fats (long-chain triglycerides), may help decrease diarrhea and wasting. Two small, double-blind studies have found that MCTs are more easily absorbed than long-chain triglycerides in people with HIV or AIDS. However, there is no direct evidence that MCTs actually help people gain weight. In both of these studies, participants consumed nothing but a special nutritional formula containing MCTs. Taking MCTs in this way requires medical supervision to determine the dose. People with HIV or diabetes should not use MCTs (or any other supplement) without a doctor’s supervision.

Glutamine. Another promising treatment for wasting is the amino
acid glutamine, a substance that plays a role in maintaining the
health of the immune system, digestive tract, and muscle cells. Although research
is still preliminary, one double-blind, placebo-controlled study found that a
combination of glutamine and antioxidants (vitamins C and E, beta-carotene,
selenium, and N-acetylcysteine) led to significant weight gain in people with HIV
who had lost weight. Another small, double-blind trial found that combination
treatment with glutamine, arginine, and beta-hydroxy beta-methylbutyrate could
increase muscle mass and possibly improve immune status.

Other natural treatments. Whey protein is sometimes recommended for weight gain in HIV, but evidence that it works is preliminary at best. One study found that while exercise improved weight gain, whey protein alone or with exercise offered no benefit. Fish oil might be helpful for weight gain, however.

Treating the side effects of medication. Several natural treatments have been proposed to treat side effects from various medications used in the treatment of HIV infection. Reverse transcriptase inhibitors, such as lamivudine and zidovudine, may damage mitochondria, the energy-producing subunits of cells. The supplement CoQ10 has been tried for minimizing side effects attributed to mitochondrial damage. In one study, the use of CoQ10 improved sense of well-being in asymptomatic people with HIV infection; however, it actually worsened pain symptoms in people with peripheral neuropathy.

Taking AZT (zidovudine, formerly called azidothymidine) can lead to
zinc deficiency, which may interfere with immune function. One partially blinded
study found that zinc supplements may benefit people on AZT. In the zinc-treated
group, body weight increased or stabilized, CD4+ count rose, and participants had
significantly fewer opportunistic infections.

Carnitine has also been proposed as a treatment for AZT side
effects, based on early evidence that it may keep AZT from damaging muscle cells.
Other weak evidence hints that the acetyl form of carnitine might reduce
nerve-related side effects caused by HIV drugs in general.

Based on preliminary evidence, vitamin B12 has been suggested as a preventive for blood abnormalities caused by AZT. In one well-designed, double-blind study, the use of the amino acid glutamine at a dose of 30 grams (g) daily significantly reduced the diarrhea caused by the protease inhibitor nelfinavir. Presumably, glutamine would be helpful for other protease inhibitors.

It has been suggested that the supplement NAC might help prevent side effects from the antibiotic TMP-SMX (trimethoprim-sulfamethoxazole). However, two controlled studies found that NAC did not significantly decrease adverse reactions to TMP-SMX. Note, however, that TMP-SMX is known to decrease folate levels in the body, and folate supplements might therefore be useful.

The herb milk thistle is sometimes recommended for preventing liver problems related to the use of HIV medications. While there is no direct evidence that it is helpful for this purpose, there is fairly good evidence that the use of milk thistle does not adversely affect blood levels of indinavir.

General nutrition support. People infected with HIV may be particularly vulnerable to malnutrition because of decreased appetite, poor absorption, or possibly increased requirements for specific nutrients. Studies have found deficiencies of vitamins A, B1, B6, B12, and E, beta-carotene, choline, folate, selenium, and zinc to be common among people with HIV infection. Many deficiencies become more common as the disease worsens. This suggests, but does not prove, that taking supplements of these nutrients may be helpful. One study evaluated whether the use of a multivitamin tablet might reduce infectivity of African women with HIV infection. Researchers unexpectedly found the opposite: Multivitamin tablets increase the levels of HIV in the genital area. The reason for this surprising finding is unknown. It is not clear whether the same response would occur among people living in developed countries who, presumably, have better underlying nutrition.

Vitamin A, beta-carotene, and mixed carotenoids.
Vitamin
A and beta-carotene are described together
here because the body uses beta-carotene to produce vitamin A. Substances called
carotenoids are closely related to vitamin A; this family includes lutein and
lycopene.

Vitamin A deficiency may be linked to lower CD4+ counts and to higher death rates among HIV-positive people. A few preliminary studies have raised hopes that beta-carotene supplements might increase or preserve immune function or decrease symptoms among HIV-positive persons. One small, double-blind study suggested that taking beta-carotene might raise white blood cell count in people with HIV infection. However, two subsequent larger controlled trials found no significant differences between those taking beta-carotene or placebo in white blood cell count, CD4+ count, or other measures of immune function.

Two observational studies lasting six to eight years suggest that higher intakes of vitamin A or beta-carotene may be helpful, but they also found that caution is in order with regard to dosage. This group of researchers generally linked higher intake of vitamin A or beta-carotene to lower risk of AIDS and lower death rates, with an important exception: People with the highest intake of either nutrient (more than 11,179 international units [IU] per day of beta-carotene, more than 20,268 IU per day of vitamin A) did worse than those who took somewhat less. Excessive dosages of vitamin A can be toxic to the liver. One should consult with a physician about the right dose.

At one point it was thought that vitamin A supplements might decrease the rate of transmission of HIV from a pregnant woman to her newborn. However, it now appears that the reverse may be true: Vitamin A may increase the chance of such transmission.

One double-blind study found statistically weak evidence that the use of mixed carotenoids by persons with AIDS might prolong life.

B vitamins. An observational study found that HIV-positive men with the highest intakes of vitamins B1, B2, and B6 and niacin had significantly longer survival rates, while a similar study found that those taking the most B1 or niacin had a significantly lower rate of developing AIDS.

Vitamin B12 deficiencies in people infected with HIV have been linked to neurologic symptoms, including slower processing of information in studies of cognitive functioning; early research suggests that restoring B12 levels to normal may decrease these symptoms. Vitamin B12 deficiency has also been linked to lower CD4+ counts and more rapid development of AIDS.

Vitamin B6 deficiency has been linked to impaired immune function in one study of people with HIV infection. Excessive intake of vitamin B6 can cause neurologic problems.

Vitamins C and E. Massive doses of vitamin C
have at times been popular among people with HIV based on preliminary evidence. An
observational study linked high doses of vitamin C with slower progression to
AIDS. High intake of vitamin E was also linked to decreased
risk of progression to AIDS in a different observational study.

However, a double-blind study of forty-nine people with HIV who took combined vitamins C and E or placebo for three months did not show any significant effects on the amount of HIV detected or the number of opportunistic infections. It has been suggested that vitamin E may enhance the antiviral effects of AZT, but evidence for this is minimal.

Choline. The substance choline has been newly added to the
list of essential nutrients. Evidence suggests that people with HIV who are low in
choline may experience more rapid disease progression.

Iron. A study of seventy-one HIV-positive children noted a high rate of iron deficiency. One observational study of 296 men with HIV infection linked high intake of iron to a decreased risk of AIDS six years later. One should not take iron supplements, however, unless one is iron deficient.

Selenium.
Selenium is required for a well-functioning immune system.
Observational studies have linked higher levels of selenium in the blood with
higher CD4+ counts and reduced risk of mortality from HIV disease. Selenium
deficiency may also increase the infectiousness of women who are HIV positive.

In a double-blind, placebo-controlled study of 450 people with HIV, the use of selenium supplementation at a dose of 200 micrograms (mcg) per day appeared to reduce measures of viral load. However, the statistical method used in this study is somewhat questionable. Previous smaller studies using more standard statistical methods failed to find such effects.

In one double-blind, placebo-controlled study, the use of selenium at a dose of 200 mcg decreased anxiety in patients undergoing HAART. Selenium has also been proposed as a preventive or treatment for cardiomyopathy, a disorder of the heart muscle that can affect people with AIDS. Evidence of its benefits is weak.

Zinc. Some studies have found that HIV-positive people tend to be
deficient in zinc, with levels dropping lower in more severe disease. It remains
unclear whether taking zinc will help.

Higher zinc levels have been linked to better immune function and higher CD4+ cell counts, whereas zinc deficiency has been linked to increased risk of dying from HIV infection. One preliminary study among people taking AZT found that thirty days of zinc supplementation led to decreased rates of opportunistic infection over the following two years.

Other research has linked higher zinc intake to more rapid development of AIDS. In another study of HIV-positive people, those with higher zinc intake or those taking zinc supplements in any dosage had a greater risk of death within the following eight years. However, one study found that the use of zinc supplements could reduce diarrhea symptoms in people with HIV infection.

Multivitamins. Because so many nutrients are affected by HIV infection and treatments, multivitamin supplements are a logical choice. A double-blind study of forty people on HAART found that the use of a multinutrient supplement improved CD4 counts and possibly improved neuropathy symptoms. As indicated by a foregoing study that evaluated whether the use of a multivitamin tablet might reduce infectivity of African women with HIV, multivitamin tablets actually increased the levels of HIV in the genital area.

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