[Viva] Fwd: CATIE News - Combination of niacin, fenofibrate, exercise and low-fat diet significantly improves blood lipid levels

[Tami Starlight]

---------- Forwarded message ----------
From: <mailing at mercury.catie.ca>
Date: Tue, Jul 19, 2011 at 7:03 AM
Subject: CATIE News - Combination of niacin, fenofibrate, exercise and
low-fat diet significantly improves blood lipid levels
To: cosmictami at shaw.ca


*CATIE News - Combination of niacin, fenofibrate, exercise and low-fat diet
significantly improves blood lipid levels
*

In addition to weakening the immune system, HIV infection appears to affect
the health of many other organ-systems, including the heart and circulatory
system. The reasons for this are not certain but there may be several
possibilities. For instance, some studies have found unfavourable changes to
levels of lipids (fatty substances) in the blood in untreated HIV
infection—specifically, increased levels of bad cholesterol (LDL-C) and
triglycerides, together with decreased levels of good cholesterol (HDL-C).
Over the long term, such changes can increase the risk for cardiovascular
disease (CVD). But there may be other factors that play a role in
intensifying the risk for CVD, such as the following:

   - HIV infection causes the immune system to produce chemical signals that
   increase inflammation. Prolonged inflammation appears to weaken blood
   vessels.
   - Proteins produced by HIV-infected cells not only affect the immune
   system but can be absorbed by other organ-systems such as the liver. A
   dysfunctional liver may contribute to excessive levels of triglycerides and
   cholesterol in the blood.
   - Experiments with simian immunodeficiency virus (SIV), which causes an
   AIDS-like disease in susceptible monkeys, suggests that this virus
   accelerates the development of cardiovascular disease, particularly in
   monkeys fed an unhealthy diet.
   - Some therapies for HIV infection can cause unfavourable changes to
   lipid levels.

The need for improvement

At least one study has found that improvement to the diet alone is not
enough to fully reverse the unfavourable changes to lipids brought about by
HIV. And despite the use of lipid-lowering therapy, some HIV-positive people
may not have the same degree of improvement seen in HIV-negative people on
the same therapy.
An intensive combination

Researchers at the Baylor College of Medicine and at several clinics in
Houston, Texas, conducted a randomized placebo-controlled study to assess
the impact of a comprehensive approach to lipid health in HIV-positive
people. The Heart Positive study compared different interventions, including
the following:

   - increasing doses of the B-vitamin niacin
   - the lipid-lowering drug fenofibrate
   - a diet low in saturated fat (30% of calories came from fat and 7% or
   less calories came from saturated fat)
   - regular supervised exercise
   - a combination of all of the above

After six months, researchers found significant improvements in lipid
levels. Also, the use of niacin appeared to increase levels of the hormone
adiponectin. Less-than-normal levels of this hormone have been associated
with an increased risk for pre-diabetes, diabetes and obesity.

Researchers screened 441 HIV-positive people and found 221 that they could
recruit and randomly assign to receive one of five interventions in the
following groups:

   - Group 1: standard of care and general advice about a heart-healthy diet
   - Group 2: changes to the diet along with a supervised exercise regimen
   and two placebos (fake niacin and fake fenofibrate)
   - Group 3: changes to the diet along with a supervised exercise regimen,
   fenofibrate and niacin placebo
   - Group 4: changes to the diet along with a supervised exercise regimen,
   niacin and fenofibrate placebo
   - Group 5: changes to the diet along with a supervised exercise regimen,
   niacin and fenofibrate

Food

Participants in Groups 2 through 5 were taught how to maintain their weight
by keeping track of their food intake, assessing the number of calories in
foods, learning how to reduce their intake of saturated fat and how to
select and prepare different types of food. For the first two weeks of the
study, participants received pre-packaged meals from the study centre’s
kitchens to help reinforce their training about healthy eating habits.
Throughout the six months of the study, participants kept diaries to log the
foods that they ate, which a dietician assessed from time to time.
Exercise

Participants in Groups 2 through 5 engaged in supervised exercise regimens—a
mix of aerobics and weight lifting at the study’s gym for between 75 and 90
minutes, three times weekly. Participants who were unable to go to the
study’s gym were given a membership at a more conveniently located gym and
fitness instructors monitored their exercise regimens.
Niacin

Participants in Groups 4 and 5 received an extended-release formulation of
niacin (Niaspan) at an initial dose of 500 mg at bedtime every night. They
increased the dose at two-week intervals until they reached a total daily
dose of 2,000 mg per night.
Fenofibrate

Participants in Groups 3 and 5 took fenofibrate (145 mg) at bedtime.

At the start of the study, the average profile of participants was as
follows:

   - 87% men, 13% women
   - age – 44 years
   - CD4+ count – 500 cells
   - 75% had a viral load less than 400 copies/ml because of the use of
   anti-HIV therapy
   - hepatitis B virus co-infection – 5%
   - hepatitis C virus co-infection – 3%

At least 50% of participants had a history of smoking tobacco and 10% had a
history of substance use. About 37% of participants had a family history of
diabetes and many were impoverished.
Results

In total, 127 participants completed the study. The best results were seen
among people in Group 5, where all interventions were implemented. Compared
to people in Group 1, who received no major intervention, participants in
Group 5 experienced the following changes:

   - 52% decrease in triglycerides
   - 12% increase in good cholesterol (HDL-C)
   - 19% decrease in non-HDL-C (this term describes several types of
   cholesterol that are not heart friendly, such as LDL-C, among others)

At the end of the study, these changes were so significant that on average
participants in Group 5 had levels of triglycerides and HDL-C that were
within the normal range.

In theory, when taken together, the changes seen with participants in Group
5 have the potential to greatly reduce the risk for cardiovascular disease
events, such as a heart attack. However, to prove such benefits, a larger
and longer study is needed.

The ratio of total cholesterol to HDL-C has been validated in previous
studies as having a high predictive value for future cardiovascular risk.
This ratio was reduced (a favourable change) in Groups 3, 4 and 5 and was
lowest in Group 5.
Managing blood sugar

Insulin is a hormone produced by the pancreas gland. This hormone helps
control the amount of sugar (or glucose) in the blood. Cells use sugar as a
source of energy.

In cases of pre-diabetes, cells become gradually resistant to the effect of
insulin. So the pancreas gland is forced to produce ever-higher amounts of
this hormone. Although this can initially help, insulin resistance continues
to develop and blood sugar levels gradually rise. If left untreated, insulin
resistance can lead to diabetes.
Niacin and blood sugar

In previous clinical trials with HIV-negative and HIV-positive people,
exposure to niacin has, in some cases, increased the risk for insulin
resistance. So, in the Heart Positive study, researchers paid special
attention to insulin resistance and the body’s ability to manage blood
sugar.

In general, the researchers found that the use of niacin resulted in “mild”
increases in the following:

   - glucose levels in the blood
   - insulin levels in the blood
   - assessments of insulin resistance

Furthermore, when such changes occurred they were generally within the
normal range, according to the researchers.
Considerations arising from Aim-High

A Canadian-U.S. study called Aim-High was recently halted prematurely in
part because of a relatively small increase in strokes among participants
who received the lipid-lowering agent simvastatin (Zocor) and niacin
(Niaspan). However, in analysing the preliminary data from Aim-High,
investigators have not found evidence that niacin was linked to the small
increase in strokes seen in that study. Moreover, previous controlled
clinical trials did not find any association between the use of niacin and
an increased risk of stroke. Indeed, niacin has been used safely over the
past 50 years to help normalize lipid levels. For further details about
Aim-High, see “Is there a link between niacin and stroke?” available here:

www.catie.ca/catienews.nsf/news/76740A600BD77937852578C600553114?OpenDocument
Focus on adiponectin

Adiponectin, a hormone produced mostly by fat cells, increases the body’s
sensitivity to insulin. Normal levels of adiponectin in the blood range
between 5 and 30 micrograms/mL depending on the test used. Women tend to
have greater adiponectin concentrations than men. Less-than-normal levels of
adiponectin have been found in HIV-negative people with certain conditions,
some of which include the following: obesity, insulin resistance, type 2
diabetes, inflammation and perhaps certain cancers such as those of the
breast, colon and prostate. Factors such as eating a diet high in fat,
smoking tobacco and not getting enough exercise have also been linked to low
adiponectin levels.

The following activities have been associated with increased adiponectin
levels in the blood, which reduces the risk for developing insulin
resistance, diabetes and cardiovascular disease:

   - regular exercise
   - eating a Mediterranean-type diet (including whole gains)
   - losing excess body weight
   - eating nuts

Adiponectin and HIV

Research suggests that HIV infection may affect the body’s regulation of
adiponectin (though precisely how this happens is not yet clear). As in
HIV-negative people, associations between reduced adiponectin levels and
abnormal lipid levels in the blood and higher-than-normal blood pressure
have been found in HIV-positive people. It is possible that reduced
adiponectin levels place HIV-positive people at increased risk for
cardiovascular disease.

In the present study, the use of niacin doubled adiponectin levels in the
blood from about 5 micrograms/mL at the start of the study to 10
micrograms/mL by the end. Among participants who did not receive niacin,
adiponectin levels remained stable. This difference in adiponectin levels
between participants who received niacin and those who did not was
statistically significant.

However, while adiponectin levels increased in niacin users, over the
short-term this increase did not apparently result in improved control of
blood sugar. So the overall improvement in cardiovascular health because of
increased adiponectin levels is not known from this study.
A very useful study

The Heart Positive study provided some very valuable information. Not only
did it demonstrate that a combination of interventions is effective in
managing abnormal lipid levels, but it also showed that this combination,
which included high doses of the B-vitamin niacin, is safe and effective.
Moreover, the unexpected impact of niacin on adiponectin levels in this
placebo-controlled clinical trial may pave the way for further studies of
adiponectin and other hormones produced by fat cells and their impact on
human health. Future studies also need to explore the possibility of
interactions between the combination of niacin and fenofibrate together with
multiple anti-HIV drugs. Such possible interactions were only partially
explored in the present study.
Exercise—easy to prescribe, hard to implement and maintain

The combination of modified diet, supervised exercise and a fibrate and
niacin as described in this study was undoubtedly an intensive regimen for
many participants. By the end of the study, only about 60% of the original
participants remained enrolled. Also, adherence to the diet and exercise
portions of the regimen was achieved by just 55% of participants. Perhaps
the study’s results would have been strengthened had adherence to diet and
exercise been greater.

In the everyday world outside of a clinical trial, it may be difficult for
some people living with HIV (like other people with complex chronic health
conditions) to sustain improvements in diet, intensive exercise and
medication management unless they are given support. Additionally, some
HIV-positive people can experience bouts of unexpected fatigue from time to
time or may have complications and disabilities that make rigorous exercise
difficult.

Regular exercise has many health benefits. It not only helps strengthen the
heart and circulatory system, but it can also improve mood and the ability
to cope with stress. So, in the future, researchers need to test a variety
of interventions, including, at least initially, less intensive exercise
regimens to assess what can help HIV-positive people improve and maintain
their heart and overall health.

To find out about keeping your heart healthy, please see the CATIE in-depth
fact sheet on "HIV and cardiovascular disease":

www.catie.ca/facts.nsf/9a83231f2055bda9852566b90004b064/78ab93dc461831ea85257680006d5d24!OpenDocument<http://www.catie.ca/facts.nsf/9a83231f2055bda9852566b90004b064/78ab93dc461831ea85257680006d5d24%21OpenDocument>


            *—Sean R. Hosein*

REFERENCES:

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   2. Armstrong C, Liu E, Okuma J, et al. Dyslipidemia in an HIV-positive,
   antiretroviral treatment-naïve population in Dar es Salaam,
Tanzania. *Journal
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   3. Riddler SA, Li X, Otvos J, et al. Antiretroviral therapy is associated
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   4. Balasubramanyam A, Coraza I, Smith EO, et al. Combination of niacin
   and fenofibrate with lifestyle changes improves dyslipidemia and
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   7. Côté M, Cartier A, Reuwer AQ, et al. Adiponectin and risk of coronary
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   8. Tsai JS, Guo FR, Chen SC, et al. Smokers show reduced circulating
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   10. Plaisance EP, Mestek ML, Mahurin AJ, et al. Postprandial triglyceride
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   ahead of print].



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-- 
Meegwetch/Thank you/Merci
*Tami M. Starlight*
Vancouver, Canada
tamistarlight at gmail.com
tami.cosmic (facebook)
tami_starlight (twitter)
cosmictami (skype)
604-200-2445home
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