Supplements for Weight Loss

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Supplements for Weight Loss

• Lecture 24

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Overview of Gastrointestinal System
Esophagus
Stomach
Blood stream
nutrients
Small intestine
Absorption
Large intestine
Cells
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• 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

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• 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.

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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

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• 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

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• 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
• 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
• gt11mg/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 EC 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
  EC observed 6.6 decrease in body fat with no
  side effects.
• Greenway et al. EC 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
• Restricting calories
• 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)