Taking high-dose multivitamins has no
health benefits for people starting antiretroviral therapy, but causes
serious disturbances in liver function, according to the results of a large
randomised trial published in the Journal
of the American Medical Association.
The study was stopped early after interim
results showed that high-dose multivitamins were associated with a more than
fivefold increase in ALT levels, a key marker of liver function. The interim
results also showed that multivitamins did not reduce the risk of HIV disease
progression; nor did they improve CD4 cell count or viral load.
“We found that high-dose multivitamin
supplementation provided no benefit to patients with HIV initiating HAART
[highly active antiretroviral therapy] compared with standard-dose multivitamin
supplementation,” comment the authors. “The study was stopped early due to an
increase in the risk of ALT elevations with high-dose multivitamin
Results of previous studies had shown that
treatment with high-dose multivitamins reduced the risk of HIV disease
progression and death in people who were not taking antiretroviral therapy.
Since then, access to antiretrovirals has
increased in resource-limited settings, but the risks and benefits of high-dose
multivitamins for individuals taking HIV therapy are far from clear.
Investigators therefore designed a study
involving people starting HIV treatment in Tanzania. Recruitment
took place between late 2006 and late 2008. The double-blind study involved over 3418
people and the participants were randomised to take
either high-dose multivitamins or standard-dose multivitamins. The study was intended to last 24
high-dose supplement contained between two and 21 times the recommended daily
intake of B vitamins, twice the recommended dose of vitamin E and six times the
daily allowance of vitamin C.
The investigators compared rates of HIV
disease progression and death between the two study arms; changes in CD4 cell
count and viral load; the risk of blood disorders such as anaemia and
neutropenia; and changes in liver function.
Participants had been followed for a median of
15 months when the study was stopped early in March 2009. At this point there
had been 2374 HIV progression events and 453 deaths.
Rates of disease progression and death were
identical between the participants taking the high-dose supplements and those
taking standard-dose multivitamins (72 vs 72%).
There was no difference between the two
treatment groups in terms of all-cause mortality (13 vs 13%) or AIDS-related
mortality (4 vs 4%).
In a subsidiary analysis, the investigators
looked at the impact of multivitamin dose on the outcomes of the most severely
malnourished participants (with a body mass index below 16). They found that high-dose
multivitamins were associated with a modest increase in the risk of death
compared with standard-dose supplements (38 vs 28%).
Changes in CD4 cell count and viral load
were similar between the high-dose and standard treatment, and therapy with
high-dose supplements had no impact on the risk of anaemia.
The only benefit associated with high-dose multivitamin
therapy was a 19% reduction in the risk of neutropenia (IRR = 0.81; 95% CI,
However, high-dose therapy was associated
with serious safety issues.
An increase in ALT levels of five or more
times the upper limit of normal was observed in 38% of participants receiving
high-dose supplements, compared to just 2% of those taking standard-dose
treatment. This finding, coupled with the lack of any benefit from high-dose
treatment, led to the study being stopped early.
“Although the provision of high-dose
vitamin supplements has been safe among patients infected with HIV not
receiving HAART, safety cannot be presumed in the context of potent combination
therapies due to the potential negative interactions among nutrients and
antiretrovirals,” comment the authors. “In the absence of clear evidence of the
benefit of high-dose micronutrient supplementation on morbidity and mortality in
adults receiving HAART, it is prudent to follow current recommendations to
promote and support dietary intake of micronutrients at recommended daily