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Supplements for Weight Loss

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?

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Supplements for Weight Loss

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  1. Supplements for Weight Loss Lecture 24

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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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)

  9. 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.

  10. 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”.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. In the spring of 2004, the FDA (finally) banned • the sale of ephedra-containing dietary • supplements in the U.S. market.

  21. 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.

  22. 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.

  23. 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.

  24. *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

  25. 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.

  26. *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

  27. Chitosan...cont’d. • 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)

  28. 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.

  29. 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

  30. 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.

  31. 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)

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