Food additive may one day help control blood lipids and reduce
disease
risk
Science Centric | 31 July 2009 08:10 GMT

Scientists at Washington University School of Medicine in St. Louis
have identified a substance in the liver that helps process fat and
glucose. That substance is a component of the common food additive
lecithin, and researchers speculate it may one day be possible to use
lecithin products to control blood lipids and reduce risk for
diabetes, hypertension or cardiovascular disease using treatments
delivered in food rather than medication.

'Currently, doctors use drugs called fibrates to treat problems with
cholesterol and triglycerides,' says the study's co-first author
Irfan
J. Lodhi, Ph.D., a post-doctoral fellow in endocrinology and
metabolism. 'By identifying this substance that occurs naturally in
the body - and also happens to be used as a food additive - it may be
possible to improve the treatment of lipid disorders and minimise
drug
side effects by adding particular varieties of lecithin to food.'

Lecithin is found at high concentrations in egg whites. It also is in
soybeans, grains, fish, legumes, yeast and peanuts. Most commercially
used lecithin comes from soybeans. Lecithin can alter food taste and
texture and also can be mixed with water to disperse fats, making it
a
common additive in margarine, mayonnaise, chocolate and baked goods.
Lecithin is a mixture of fatty compounds called phosphatidylcholines.
Various types of phosphatidylcholines house different kinds of fatty
molecules linked to a common core.

This new study demonstrates that in the liver, a specific type of
lecithin binds with a protein called PPAR-alpha, allowing PPAR-alpha
to regulate fat metabolism. Scientists long have known that PPAR-
alpha
is involved in lipid and glucose metabolism. When doctors prescribe
fibrate drugs to lower triglycerides and elevate good cholesterol in
the blood, those drugs work by activating PPAR-alpha.

Although fibrates activate the protein, no one previously had
identified any naturally occurring substance that could perform that
task. Reporting in the Aug. 7 issue of the journal Cell, the
Washington University research team describes how it found the link
between lecithin and PPAR-alpha.

They first created a strain of mice that could not make fatty acid
synthase in the liver. When humans or animals eat, we take in sugars.
Fatty acid synthase converts those sugars to fatty acids in the
liver,
where they play important roles in energy metabolism.

'To our surprise, animals missing fatty acid synthase in the liver
were just like animals that couldn't make PPAR-alpha. They had lower
fasting insulin levels, and they were prone to develop fatty liver
disease,' says senior investigator Clay F. Semenkovich, M.D., the
Herbert S. Gasser Professor and chief of the Division of
Endocrinology, Metabolism and Lipid Research. 'When we gave the
animals fibrate drugs that activated PPAR-alpha, the mice returned to
normal, leading us to suspect that fatty acid synthase also was
involved in the activation of PPAR-alpha. Although we knew that
fibrate drugs would regulate PPAR-alpha, we also knew that our
ability
to regulate the metabolism of fats and sugars was in place long
before
humans started making drugs. But until now, no one had identified how
it worked.'

Semenkovich, Lodhi, John Turk, M.D. Ph.D., professor of medicine and
of pathology, and the rest of the team used mass spectrometry and
gene
expression studies to isolate the phosphatidylcholine, or lecithin
compound, that activated PPAR-alpha in the liver.

One reason fatty acid synthase had never been connected to PPAR-alpha
function was the distance of the two proteins from each other,
according to Semenkovich. PPAR-alpha is a nuclear receptor. That is,
it's housed in the nucleus of the cell. Fatty acid synthase, on the
other hand, lives out in the cell body, or cytoplasm.

'The neighbourhoods where PPAR-alpha and fatty acid synthase live
aren't very close together,' says Semenkovich. 'The synthase is way
out in the cytoplasm - that's like being in the suburbs - whereas the
PPAR-alpha lives right in the middle of the 'city.' These are all
microscopic distances, but to the cell, they're worlds apart, so it's
amazing that the two are linked.'

It's also fortunate, he says, that an extremely common compound like
lecithin binds to a key drug target like PPAR-alpha.

'That information could be used to make better drugs or even to
develop what people sometimes refer to as nutriceuticals - nutrients
that have pharmaceutical-like properties,' Semenkovich says.

Source: Washington University School of Medicine

---------------

Omega-3 fatty acids better than statins in reducing death

There are a number of strategies that have been used over the years
in
the attempt to reduce the risk of death from heart disease and
increase life expectancy. These strategies usually entail attempting
to improve blood cholesterol and/or fat levels. A study in the April
2005 issue of Archives of Internal Medicine examines all randomized,
controlled trials published between 1965 and 2003 that compared a
lipid lowering strategy with a placebo or usual care. The authors
determined that 97 studies met their eligibility criteria. Combining
all these studies they were able to examine over 130,000 people in
treatment groups compared with an almost equal number of people in
control groups.

The authors found that compared with the control groups the risk
ratio
for death was reduced by 23% for omega-3 (or n-3) fatty acids, 16%
for
resins, 13% for statins, 4% for niacin, 3% for diet, and 0% for
fibrates. “Our study confirms the benefit of statins in reducing the
risk of overall cardiac mortality in patients with or without CHD
[Coronary Heart Disease] and additionally shows that n-3 fatty acids
reduce overall and cardiac mortality in patients with CHD.”

They note that in the class of medications, fibrates, there was “no
reduction in overall mortality and an increased risk of death from
noncardiovascular causes in individuals taking fibrates compared with
individuals in placebo or control groups.”

If used at a correct dosage, omega-3 fatty acids are just as
effective
as fibrates at reducing triglyceride levels, but unlike fibrates they
are associated with an overall reduction in mortality. However,
omega-3 fatty acids only slightly lower cholesterol, which means that
their benefit is also through other mechanisms. “Studies suggest that
n-3 fatty acids may have antiarrhythmic properties with membrane
bilizing effects in addition to an antithrombotic and anti-
inflammatory properties on the endothelial level.”

Omega-3 fatty acids include eicosapentaenoic acid (EPA) and
docosahexanoic acid (DHA), both found primarily in oily cold-water
fish such as mackerel, salmon, and tuna. Apart from seaweed, plant
foods rarely contain EPA or DHA. Alpha-linolenic acid (ALA), is found
primarily in dark green leafy vegetables, flaxseed oils, pumpkin
seeds, walnuts, and certain vegetable oils. There are no known side
effects associated with increasing your intake of omega-3 fatty acids
through foods, although fish oil capsules do pose the risk of an
unpleasant, fishy aftertaste that occurs with some brands of fish oil
capsules. In addition, omega-3 fatty acids may increase the blood-
thinning effects of warfarin or aspirin.

The liver makes bile out of cholesterol and secretes it into the
intestine. Resin medications bind bile and prevent it from being
reabsorbed. This class of medications include cholestyramine
(Questran
and Questran Light), colestipol (Colestid), and colesevelam
(WelChol).
Since these medications cause the body to lose bile, the liver then
takes cholesterol out of the blood stream and converts it to bile,
thus lowering the serum cholesterol level. These medications
primarily
lower LDL-cholesterol but not the triglycerides. The major side
effects of resins are gastrointestinal, mainly constipation.

Statins are a group of drugs that reduce the amount of cholesterol
and
certain fatty substances in the blood by inhibiting a key enzyme that
helps produce cholesterol. There are currently 6 statins on the
market: atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin
(Mevacor), pravastatin (Pravachol), simvastatin (Zocor), and
rosuvastatin (Crestor). A seventh statin, cerivastatin (Baycol) was
removed from the market in 2001 because of potentially serious side
effects and a number of deaths. Although generally well tolerated,
the
most common side effects are nausea, diarrhea, constipation, and
muscle aches. The two potentially serious side effects are elevated
liver enzymes and statin myopathy, which is muscle pain and
tenderness. In severe cases, muscle cells can break down
(rhabdomyolysis) and release a protein called myoglobin into the
bloodstream. Myoglobin can impair kidney function and lead to kidney
failure.

Niacin, or nicotinic acid, is a water-soluble B vitamin, which is
essential for energy production in cells. It improves circulation and
reduces the cholesterol level in the blood, maintains the nervous
system, helps metabolize protein, sugar and fat, reduces high blood
pressure, increases energy through proper utilization of food,
prevents pellagra, and helps maintain a healthy skin, tongue and
digestive system. There are side effects associated with niacin and
these side effects seem to correlate with dosage and may be reduced
if
you are taking a time-released form of niacin. Symptoms typically
disappear over a week or so, as your body is adjusting to the
medication and include, flushing (redness, itching, warmth, redness),
night sweats, palpitations, cardiac fibrillations, or other
arrhythmias, decreased glucose tolerance, and migraines.

Fibrates are a group of cholesterol-moderating drugs in use since the
early 1960s that includes clofibrate (Atromid), gemfibrozil (Lopid),
and fenofibrate (Tricor). Fibrates are used primarily to treat high
triglyceride levels and they can also help to increase HDL levels.
Side effects of Fibrates include, increased effect of blood thinners
or other cholesterol lowering medications, upset stomach or diarrhea,
anemia and lower white blood cell count, bile to become more
concentrated, thus increasing the likelihood of gallstone formation,
temporary dizziness, and temporary blurred vision.

Source: Archives of Internal Medicine, April 2005

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