Supplements for Weight Loss

Lecture 24

Overview of Gastrointestinal System

Esophagus

Stomach

Blood stream

nutrients
Small intestine

Absorption

Large intestine
Cells

First, where in the process from digestion to

storage would a weight loss supplement act?
Increasing adipose tissue lipolysis (and use)
*caffeine & ephedra, conjugated linoleic acid
Blocks fatty acid synthesis
*hydroxycitric acid (HCA)
Reduce fat absorption from the small intestine
*chitosan

Many of the common actions of epinephrine

(adrenaline) are mediated by the cAMP system.
In response to a sudden stress (fear, surprise)
epinephrine is released from the adrenal medulla
and binds to target cells in the heart, arteriole
smooth muscle, adipose tissue, muscle and liver.
Rise in cAMP and activation of protein kinases
cause HR, BP, mobilization of fatty acids from
TG, breakdown of glycogen to glucose.

Similar process causes glycogen to be mobilized to

individual glucose molecules.
Because cAMP is rapidly broken down, protein kinases
quickly revert back to their less active state.
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Effects of epinephrine do not last more than 15

minutes or so.
Ephedrine (synthetic or extracted from ephedra
plant as a component of ma huang) mimics
the action of epinephrine but with a more
sustained response.
* non-drowsy cold medicines
* diet drugs, herbal ecstasy

No dietary supplement illustrates the promise and

perils of dietary supplement use, (lack of)
regulation, and manufacturing more than ephedra.
In 2000, sales of ephedra were $1.05 billion, up
from $800 million in 1999 (according to Nutr. Bus.
J.).
In their natural form, some species of ephedra
plants contain a mixture of alkaloid compounds
including ephedrine, pseudoephedrine, etc.
ma huang: powdered extract

Generally marketed to increase energy, burn fat,

increase metabolic rate (thermogenesis), lose
weight, elevate mood.
Some claim enhanced athletic performance.
Every careful study in which the effects of ma
huang or ephedrine alone on athletic
performance (time to exhaustion, strength,
power, lactate, fat/carbohydrate oxidation) has
shown no effect.
Caffeine + ephedrine improved cycling time to
exhaustion (EJAP)
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Products reputed to contain ma huang include

Ripped Fuel, Energel, Diet Fuel, Diet-Herb,
Metabolife 356, Ultimate Orange, Herbal
Ecstasy, herbal Phen-Fen, Diet Pep, Diet
Phen, Escalation, Excel ..
Usually claim to contain about 150-350 grams
of ephedra herb or ma huang per dosage and
often recommend 2-3 doses/day.
Most do not make a label claim for ephedrine
content. Most also contain 100-400mg of
caffeine, usually in the form of guarana.
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Metabolife International, one of the largest distributors of

ephedra in the United States, says many of the people in
the FDA reports who died may have been taking the
supplement, but it didn't kill them.
"There are reports where someone was shot and killed in a
grocery store, and they happened to be taking ephedra,"
said Metabolife's Dr. Randy Smith.
Still, University of Arkansas pharmacologist Bill Gurley said
he is worried about people who take ephedra for many
weeks or who take more than the recommended dosage.
"You have to realize that these things are potent cardiac
stimulants, and when you are exercising and lifting heavy
weights, you are already taxing your cardiovascular
system, and ephedra makes it work harder.
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Gurley analyzed approximately 20 ephedra

products and found great variability in the
amount of active ingredient, not only between
products but often within the same brand.
"If a conventional pharmaceutical company had
this kind of quality control, the FDA would shut
them down in a heartbeat," Gurley said.
Though it did not appear on the label, the FDA
recommended that pregnant women, people
with high blood pressure, heart conditions or
neurological disorders avoid ephedra products.
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Gurley et al. studied the actual alkaloid

content of popular ephedra-containing products
and compared it with product labels.
They found that:
1. most products contained ephedra alkaloids in
markedly different quantities than labels indicate.
e.g. Ephedra label indicates 375mg ephedra but
contains only 5.04mg total alkaloids.
2. many products did not contain natural ephedra.
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Natural ephedra sources contain a mixture of all

the alkaloids. Many products contain only
ephedrine and pseudoephedrine.
e.g. Herbal Ecstasy, Diet Pep, Diet Phen,
Energel, Herbal Phen-Fen (only EPH).
Suggests products are spiked with synthetic
sources of EPH, PEPH.
Few products report EPH content on label even
when they contain substantial quantities.
e.g. Diet Pep makes no EPH claim but contains
>11mg/tablet
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Since 1994, the FDA has had more than 800 reports of side
effects from ephedrine, including heart palpitations,
psychosis, heart attacks and strokes. But the GAO said the
FDA needed to provide better evidence to support the
proposed restrictions.
"FDA needs to provide stronger evidence on the
relationship between the intake of dietary supplements
containing ephedrine alkaloids and the occurrence of
adverse reactions," the GAO said.
FDA relied heavily on Adverse Events Reports without
providing its usual follow-up investigation, the GAO said.
The GAO report is considered a victory for dietary
supplements.
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How strong is the evidence that ephedra products

were dangerous?
1993-1999, FDA collected more than 1400 reports
of adverse events, 80 fatal, that were associated
with use of ephedra.
Industry claimed association does not prove
cause-and-effect. If use of ephedra products
reduces obesity (which causes premature
death), what if it saves more lives than it causes?
This is a reasonable point so the FDA hired
Haller and Benowitz to review 140 adverse event
reports submitted to the FDA 1997-99
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They found that of those cases, 31% were

definitely or probably related to ephedra, 31%
were possibly related, and 17% were unrelated
(21% no way to judge).
Found that common theme in most serious
adverse events was combination of ephedra,
caffeine and exercise.
Most events were cardiovascular and usually
involved cerebral hemorrhage, stroke, or MI.
Typical culprit was elevated blood pressure.
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Evidence has also shown ephedra plus caffeine to be

somewhat effective and (maybe) safe for promoting weight
loss in clinical trials.
Boozer et al.: 8 weeks of E+C supplementation promoted
2.1% loss in body fat with minor side effects.
Boozer et al.: also reported a 6-month clinical trial with no
significant adverse events.
Molnar et al.: overweight children, 20 weeks with E+C
observed 6.6% decrease in body fat with no side effects.
Greenway et al.: E+C was more cost effective treatment
for reducing weight, cardiac risk, and LDL cholesterol
than several weight loss drugs.
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In 2000, 3 college football players died under

circumstances that suggested a link with ephedra.
The most highly-publicized case
was death of Baltimore pitcher
Steve Bechler in spring training
2002. It stoked the fires in call for
banning of ephedra-containing
products.
Ephedra was banned in
minor-league baseball
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Experts, Senator Criticize Ephedra, 10/9/02

WASHINGTON (AP) -- A senator chided the FDA for
not taking some action to block the sales of diet
supplements containing ephedra, an herb that has
been linked in many reports with heart attacks, high
blood pressure and even death.
Sen. Richard Durbin, D-Ill., chairing a Senate
subcommittee hearing, said Tuesday that even
though there have been thousands of reports linking
ephedra with serious medical complications,
companies continue to sell it to children and the
FDA has taken little action.
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In the spring of 2004, the FDA (finally) banned

the sale of ephedra-containing dietary
supplements in the U.S. market.

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So caffeine + ephedra has some efficacy but safety is

an issue. Exercise + EC is potentially lethal.
What other supplements promote fat reduction?
Stimulates lipolysis
* caffeine, ephedra and conjugated linoleic acid
Blocks fatty acid synthesis
*hydroxycitric acid (HCA)
Reduce fat absorption from the small intestine
*chitosan
Also grouped into the fat reduction category is
chromium (III) picolinate, a supplement involved in
glucose control.
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Conjugated linoleic acid (CLA): Isomers of linoleic

acid that contain conjugated double bonds
Primarily meat and dairy products (and vegetable oil)
Marketed as a weight-loss and muscle building
supplement.
CLA seems to reduce body fat in mice (Park et al.)
* May be through a reduction in energy intake;

however the results were also correlated with a

reduction in growth rate and total body protein.

* On the other hand a different study (Delany et al.)

found fat accumulation and higher protein content
with CLA supplementation.
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In humans...CLA:
There are few studies, they have not been
published in peer-reviewed journals.
Some studies have shown CLA may modestly
increase lean body mass and promote fat loss
Others show that CLA has no effect on body
composition in trained or untrained individuals
Suggested that the discrepancy in the findings is
due to the differences in purity and ratio of
isomers... Call for more research.
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*Hydroxycitric acid (HCA): Blocks fatty acid

synthesis may suppress appetite
Theory:
Conversion of CHO to fat requires pyruvate to be
converted to acetyl-CoA (inside the mitochondria)
Fatty acid synthesis requires the acetyl group to
be transported from mitochondria to cytosol
Acetyl group is transported as citrate
ATP-citrate lyase cleaves citrate into acetyl-CoA
and oxaloacetate (acetyl group enters synthesis
pathway)
HCA inhibits ATP-citrate lyase: prevents the
conversion of CHO to fatty acids
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HCA is obtained from extracts of the herbs Garcinia

cambogia and Garcina indica, both native to India.
Animal studies: HCA administered orally or
intravenously inhibits fatty acid synthesis in the liver
and significantly reduced total body fat.
Also lowered food intake (appetite suppressant??).
Human studies: well controlled studies are lacking...
Studies have been done with HCA in conjunction
with other ingredients, which could be active
ingredients.
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*Chitosan: Decreases fat absorption from the

intestine
Is a fiber supplement in the form of chitin:
extracted from the shells of crustaceans.
Functions in one of two ways:
By binding to bile acids and reducing their
recycling back to liver
Binding to the fat in the small intestine and
delaying digestion/absorption
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Chitosan...contd.
Animal studies: In seven studies conducted in
rats, all seven report that chitosan reduced blood
cholesterol levels.
Yet to be determined if there is an effect on body fat

One human study: Girola et al. (1996) divided

obese subjects into treatment (chitosan, HCA and
chromium) or placebo and had them consume a
hypocaloric diet (1000 kcal)

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Girola et al. found that the treatment group lost

more weight than the placebo and that the effect
was dose dependent. Subjects also saw a
reduction in total cholesterol and LDL.
When fat absorption is inhibited, fat is eliminated in
the feces.
Diarrhea
Reduction in calcium absorption and fat soluble
vitamins (especially vitamin E)
Recommend supplementation of nutrients lost in
feces.

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Chromium (III) picolinate

Active ingredient in over 55 supplements (as of
2001)... It is the second largest-selling mineral
(Calcium is #1) in the USA.
Numerous claims have been made that chromium
aids in body development (for athletes) and in
losing weight (obese individuals)
Studies have failed to demonstrate chromium helps
with muscle growth or fat loss.

Chromium deficiency is linked to improper glucose

metabolism by making insulin less effective. Thus
chromium supplementation MAY help with glucose
control in people with Type-2 diabetes
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Chromium (III) piccolinate

Meta-Analysis in 2002 found no association
between chromium and glucose/insulin
concentrations for non-diabetics and inconclusive
results in diabetics.
This study was challenged by Kalman in 2003 that
it did not include some significant positive findings.
In addition, chromium (III) piccolinate may cause
DNA mutations. It has also been associated with
decreased iron transport in the blood, kidney failure
and when combined with vitamin C the risk for
adverse side effects may be greater.
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Summary
Weight loss is dependent on creating an energy
deficit. This can be done two ways:
1. Restricting calories
2. Exercise
Supplements are designed to mimic exercise
(increase metabolism, promote fat use) as well as
restrict nutrients from entering the cell for storage.
The old adage of no pain, no gain usually applies
to weight loss strategies with the most effective one
being a modest reduction in total energy intake in
conjunction with exercise (aerobic + resistance)
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