This document contains partial reference to clinical studies for some of the ingredient utilized in Lean Optimizer™. For additional references, including hard-copy files, please send requests to:

HFL, Inc. Dept: Lean Optimizer/Clinicals 3635 South Fort Apache Road Suite 200-41 Las Vegas NV 89147

Advantra-Z Efficacy Jan 2012 The naturally occurring p-synephrine in Advantra Z will exhibit at least twice the

physiological activity compared to an equal weight of synthetic p-synephrine. Stereochemical and Physiological Differences between Naturally Occurring p-Synephrine and Synthetic p-Synephrine - Stohs and Preuss, Journal of Functional Foods

Mar 2011 Ingestion of a multi-ingredient weight management supplement containing Advantra Z, caffeine and green tea extract increased resting metabolic rate, but did not lead to increased cardiovascular stress. Effect of Acute Administration of an Herbal Preparation on Blood Pressure and Heart Rate in Humans - Seifert, International Journal of Medical Sciences †

Mar 2008 Exercise was easier 83% of the time - and no significant adverse events occurred - following use of a performance-enhancing dietary supplement containing Advantra Z. Human Pharmacology of a Performance-Enhancing Dietary Supplement Under Resting and Exercise Conditions - Haller, University of California, San Francisco, British Journal of Clinical Pharmacology †

May 2006 Consuming an enriched coffee beverage containing bitter orange (e.g. Advantra Z) increased resting energy expenditures. No differences in average heart rate and blood pressure were observed. Thermogenic Effect from Nutritionally Enriched Coffee Consumption - Hoffman, Journal of the International Society of Sports Nutrition

2006 A multi-ingredient supplement containing Advantra Z increased energy production and fat oxidation. Metabolic and Physiological Effects of Ingesting Extracts of Bitter Orange, Green Tea and Guarana at Rest and During Treadmill Walking in Overweight Males - Sale,

University of Chichester, International Journal of Obesity

Jul 2005 A three-part study conducted over a period of six years supports the efficacy of Advantra Z - Gougeon, McGill University, Obesity Research

• Increase in the Thermic Effect of Food by Adrenergic Amines Extracted from Citrus aurantium Increase in the Thermic Effect of Food by Adrenergic Amines Extracted from Citrus aurantium - Gougeon

• Advantra Z caused a measurable increase in the metabolic rate in obese subjects. Thermic Effect of Citrus aurantium in Obese Subjects - Pathak

• Advantra Z increased the thermic effect of food in lean subjects after consumption of a meal, resulting in a measurable increase in metabolic rate without heart rate or blood pressure irregularities. Thermic Effect of Beta-Sympathicomimetic Compounds Extracted from Citrus aurantium in Humans - Hedrei

2005 A multi-ingredient supplement containing Advantra Z was more effective in inducing weight loss than diet and exercise alone. Effect of a Multi-Ingredient Weight-Loss Product on Body Composition in Overweight Adult Men and Women - Zenk †

May 2004 A multi-ingredient supplement containing Advantra Z reversed the decrease in resting metabolic rate associated with calorie restriction in overweight adults without serious adverse events. Effect of Multi-Ingredient Weight-Loss Product on Metabolic Rate and Body Composition - Zenk, Journal Nutrition †

2003 A multi-ingredient supplement containing Advantra Z significantly enhanced metabolism without negatively affecting blood pressure. Efficacy of a Commercial Green Tea Extract/Caffeine-Based Product to Increase Basal Metabolism in Healthy Adults - Kalman

2003 A multi-ingredient product containing Advantra Z reduced fatigue and curbed appetite in overweight adults without serious adverse events. An Acute Clinical Trial to Evaluate the Safety and Efficacy of a Popular Weight Loss Supplement When Used with Exercise - Kalman †

2002 Citrus aurantium (e.g., Advantra Z) may be the best thermogenic substitute for ephedra. Citrus aurantium as a Thermogenic, Weight Reduction Replacement for Ephedra: An Overview - Preuss, Journal of Medicine

Sep 2000 A multi-ingredient supplement containing Advantra Z aided weight loss - particularly during the first, frustrating weeks of dieting - without causing serious adverse events.

Study on the Effectiveness of a Multi-Ingredient Supplement for the Reduction of Body Weight - Kendall-Reed

Mar 1999 A multi-ingredient supplement containing Advantra Z was effective in promoting weight and fat loss - without significant changes in blood pressure and heart rate - when combined with diet and exercise. Effects of Citrus aurantium Extract, Caffeine and St. John's Wort on Body Fat Loss, Lipid Levels, and Mood States in Overweight Healthy Adults - Colker, Current Therapeutic Research †

Mechanism of Action Jun 2011 p-Synephrine - the dominant amine in Advantra Z - binds to beta-3 adrenergic

receptors that trigger lipolysis. p-Synephrine exhibits little or no binding to alpha-, beta -1 and beta-2 adrenergic receptors, which are associated with increases in heart rate and blood pressure. A Review of the Receptor-Binding Properties of p-Synephrine as Related to Its Pharmacological Effects - Stohs, Oxidative Medicine and Cellular Longevity

Apr 2007 Synephrine-rich orange peel induced lipolysis in fat cells. Lipolysis Induced by Segment Wall Extract from Satsuma Mandarin Orange - Tsujita, Ehime University, Journal of Nutritional Science and Vitaminology

Aug 2003 The alkaloids in Advantra Z are biologically and physiologically distinct from those found in ephedra, due to differences in pharmacokinetics and pharmacodynamics. The most obvious difference is that Advantra Z, unlike ephedra, does not readily pass into the brain. The Difference between Citrus aurantium Extract (Advantra Z) and Ephedra Extract - Jones

Jun 2002 Advantra Z primarily stimulates beta 3 receptors, which are responsible for triggering thermogenesis. It does not cross the blood/brain barrier, making minimal contact with the excitatory receptors that cause negative cardiovascular and central nervous systems side effects. Advantra Z: Observation on its Effects and Mechanism of Action - Jones

Apr 1998 Activation of beta-3 adrenergic receptors stimulates lipolysis. A Selective Human Beta-3 Adrenergic Receptor Agonist Increases Metabolic Rate in Rhesus Monkeys - Fisher, Journal of Clinical Investigation

Safety/Toxicity April 2013 A single one-time dose, up to 70 mg p-synephrine alone or 40 mg in combination

with 320 mg of caffeine is not likely to cause adverse effects. If taken as divided doses spaced out over the course of a day, 100 mg of p-synephrine alone (e.g., 50 mg twice a day or 33 mg three times daily) or 70 mg in combination with 400 mg of caffeine is unlikely to be associated with adverse effects. Review of the Safety Data Available on p-Synephrine, Caffeine, and p-Synephrine-Caffeine Containing Combination Products. - Intertek Cantox

May 2011 1 to 50 mg of p-synephrine, the dominant amine in Advantra Z, per day for healthy

adults is not likely to cause adverse health consequences - nor are products providing up to 40 mg of p synephrine in combination with a maximum of 320 mg of caffeine per day. Synephrine, Octopamine and Caffeine Health Risk Assessment Report, Marles, Health Canada Natural Health Products Directorate, File No. 172091

May 2011 High dosages of bitter orange (e.g., Advantra Z) and its primary amine, p synephrine,

did not produce maternal or fetal toxicity in rats - even when combined with caffeine. Developmental Toxicity of Citrus aurantium in Rats - Hansen, Birth Defects Research Part B: Developmental and Reproductive Toxicology

Apr 2011 An analysis of the chemistry and safety of bitter orange (e.g., Advantra Z) drawn from more than 50 research studies and reference sources concluded that bitter orange - alone or in combination with caffeine and other ingredients - has no effect on blood pressure or heart rate. The Safety of Citrus aurantium (Bitter Orange) and its Primary Protoalkaloid p-Synephrine - Stohs and Preuss, Phytotherapy Research

Feb 2011 Based on current research and the extensive ingestion of products containing bitter orange (e.g., Advantra Z), bitter orange extract is safe for human consumption, and challenges to the safety of this ingredient are without scientific basis. The Safety of Bitter Orange (Citrus aurantium) and p-Synephrine - Stohs and Preuss, HerbalGram

Nov 2010 Bitter orange, the source of Advantra Z, was not linked to adverse events presented in the 22 reports received between April 2004 and October 2009. Assessment of the Adverse Event Reports (AERS) Associated with Citrus aurantium (bitter orange) from April 2004 to October 2009, Stohs, Journal of Functional Foods

Oct 2010 Advantra Z contains only p-synephrine, a stable isomer of the synephrine alkaloid; it does not contain m-synephrine, which has the potential for raising blood pressure. Sani-Pure Food Laboratories

2009 Researchers observed a reduction in body weight gain, but no effects on organ weights or biochemical/hematological parameters when low to high doses of bitter orange (e.g., Advantra Z) and p-synephrine were administered to mice. Subchronic Toxicity of Citrus aurantium L. (Rutaceae) Extract and p Synephrine in Mice - Arbo, Regulatory Toxicology and Pharmacology

2007 Daily supplementation with Advantra Z did not produce any cardiovascular risks in healthy adults. Citrus aurantium Extract has No Effect on Blood Pressure or Heart Rate in Healthy Adults - Talbott, Experimental Biology

Apr 2006 A single-dose bitter orange (e.g., Advantra Z) did not cause a false-positive response to the CEDIAs amphetamines assay. Response of CEDIAs Amphetamines Assay after a Single Dose of Bitter Orange - Nguyen, University of California, San Francisco, Therapeutic Drug Monitoring

Nov 2005 Advantra Z had virtually no impact on blood pressure or heart rate. Absence of QTc Interval-Prolonging or Hemodynamic Effects of a Single Dose of Bitter-Orange Extract in Healthy Subjects - Min, University of Connecticut, Pharmacotherapy †

Sep 2005 Advantra Z had little or no effect on the central nervous system and did not cause any increase in blood pressure in doses relevant to dietary supplements on the market. Hemodynamic Effects of Ephedra Free Weight Loss Supplements in Humans - Haller, University of California, San Francisco, American Journal of Medicine †

Sep 2004 Analysis of 147 adverse event reports could not establish bitter orange as the cause of the adverse events. Review and Assessment of the Adverse Event Reports citing Bitter Orange from 1969 to March 2004 - American Herbal Products Association, AHPA Report

Jun 2004 Bitter orange (e.g., Advantra Z) does not have ephedra�s negative cardiovascular and central nervous system side effects. National Toxicology Study on Bitter Orange - National Institute of Health

2004 Long-term, daily administration of bitter orange extract (e.g., Advantra Z) does not cause negative herb drug interactions. Pharmokenetics and Drug Disposition - Gurley, American Society of Clinical Pharmacology and Therapeutics

2001 Cardiovascular indices were not significantly altered by Seville orange juice ingestion, even though the juice contained marked amounts of synephrine. Seville (sour) Orange Juice: Synephrine Content and Cardiovascular Effects in Normotensive Adults - Penzak, Journal of Clinical Pharmacology

Jul 1997 The acute oral LD50 toxicity test of Advantra Z was greater than 10,000 mg per kilogram. An Acute Oral Toxicity Study in Rats with Advantra Z - Douds

Hoodia Gordonii • Zimmerman HJ. Unconventional drugs. Miscellaneous drugs and diagnostic chemicals. In,

Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott,1999: pp. 731-4. (Expert review of hepatotoxicity published in 1999; hoodia is not discussed).

• Liu LU, Schiano TD. Hepatotoxicity of herbal medicines, vitamins and natural hepatotoxins. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 2nd ed. New York: Informa Healthcare USA, 2007, pp. 733-54. (Review of hepatotoxicity of herbal and dietary supplements [HDS] published in 2007; hoodia is not discussed).

• No authors listed. Hoodia. In, PDR for Herbal Medicines. 4th ed. Montvale, New Jersey: Thomson Healthcare Inc. 2007: pp. 453-7. (Compilation of short monographs on herbal medications and dietary supplements).

• van Heerden FR, Marthinus Horak R, Maharaj VJ, Vleggaar R, Senabe JV, Gunning PJ. An appetite suppressant from Hoodia species. Phytochemistry 2007; 68: 2545-53. PubMed Citation (Extracts of Hoodia gordonii have appetite suppressant activity in a rat model, found largely in fractions with pregnane glycosides).

• Avula B, Wang YH, Pawar RS, Shukla YJ, Smillie TJ, Khan IA. A rapid method for chemical fingerprint analysis of Hoodia species, related genera, and dietary supplements using UPLC-UV-MS. J Pharm Biomed Anal 2008; 48: 722-31. PubMed Citation (The demand for Hoodia gordonii has resulted in use of other species which may not have appetite suppressant activity; using chromatography and mass spectrometry, it is possible to identify the fingerprint of the 12 hoodigosides and correctly identify products from H. gordonii).

• van Heerden FR. Hoodia gordonii: a natural appetite suppressant. J Ethnopharmacol 2008; 119: 434-7. PubMed Citation (Hoodia is a multistemmed succulent which is classified as a stapeliad [and not related to the cactus family], which is found in South Africa and was used by native people as food and to quench thirst, but has been marketed and become popular as an appetite suppressant, the clinical bases for the claims being weak; hoodia contains multiple pregnane glycosides which are being evaluated for appetite suppressant activity).

• Whelan AM, Jurgens TM, Szeto V. Case report. Efficacy of Hoodia for weight loss: is there evidence to support the efficacy claims? J Clin Pharm Ther 2010; 35: 609-12 PubMed Citation (Review of literature on hoodia found no prospective control trials of its efficacy; open label studies reported that its appetite suppressing activity was promising and that it had no adverse events).

• Blom WA, Abrahamse SL, Bradford R, Duchateau GS, Theis W, Orsi A, Ward CL, Mela DJ. Effects of 15-d repeated consumption of Hoodia gordonii purified extract on safety, ad libitum energy intake, and body weight in healthy, overweight women: a randomized controlled trial. Am J Clin Nutr 2011; 94: 1171-81. PubMed Citation (In a controlled trial of 15 days of hoodia vs placebo in 49 overweight women, hoodia was associated with abnormal skin sensitivity, nausea, vomiting, increases in blood pressure and elevations in total [indirect] bilirubin and Alk P without a change in ALT levels, clinically apparent liver injury or decrease in caloric intake).

5-HTP • Angst J, Woggon B, Schoepf J. The treatment of depression with L-5-hydroxytryptophan versus

imipramine. Results of two open and one double-blind study. Arch Psychiatr Nervenkr. 1977;224:175–186.

• Attele AS, Xie JT, Yuan CS. Treatment of insomnia: an alternative approach.Altern Med Rev. 2000;5(3):249-259.

• Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998;3:271–280.

• Byerley WF, et al. 5-Hydroxytryptophan: a review of its antidepressant efficacy and adverse effects. J Clin Psychopharmacol. 1987;7:127-137.

• Cangiano C, et al. Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients. Int J Obes Relat Metab Disord. 1998; 22:648-654.

• Cangiano C, Ceci F, Cascino A, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. J Clin Nutr. 1992;56:863-867.

• Caruso I, Sarzi Puttini P, Cazzola M, et al. Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. J Int Med Res. 1990;18:201-209.

• Cauffield JS, Forbes HJ. Dietary supplements used in the treatment of depression, anxiety, and sleep disorders. Lippincotts Prim Care Pract. 1999; 3(3):290-304.

• Ceci F, Cangiano C, Cairella M, Cascino A, et al. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm. 1989;76:109-117.

• Curcio JJ, Kim LS, Wollner D, Pockaj BA. The potential of 5-hydryxtryptophan for hot flash reduction: a hypothesis. Altern Med Rev. 2005;10(3):216-21.

• DeBenedittis G, Massei R. Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. J Neurosurg Sci. 1985; 29:239-248.

• Elko CJ, Burgess JL, Robertson WO. Zolpidem-associated hallucinations and serotonin reuptake inhibition: a possible interaction. J Toxicol Clin Toxicol. 1998;36(3):195-203.

• Freedman RR. Treatment of menopausal hot flashes with 5-hydroxytryptophan. Maturitas. 2010 Apr;65(4):383-5.

• Gardner DM, Lynd LD. Sumatriptan contraindications and the serotonin syndrome. Ann Pharmacother. 1998;32(1):33-38.

• Iovieno N, Dalton ED, Fava M, Mischoulon D. Second-tier natural antidepressants: Review and critique. J Affect Disord. 2010 Jun 24.

• Joffe RT, Sokolov ST. Co-administration of fluoxetine and sumatriptan: the Canadian experience. Acta Psychiatr Scand. 1997;95(6):551-552.

• Joly P, Lampert A, Thomine E, Lauret P. Development of pseudobullous morphea and sclero-derma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. J Am Acad Dermatol. 1991;25(2):332-333.

• Juhl JH. Primary fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90-day open study. Altern Med Rev. 1998;3:367-375.

• Mason BJ, Blackburn KH. Possible serotonin syndrome associated with tramadol and sertraline coadministration. Ann Pharmacother. 1997;31(2):175-177.

• Meyers S. Use of neurotransmitter precursors for treatment of depression. Altern Med Rev. 2000;5(1):64-71.

• Perry NK. Venlafaxine-induced serotonin syndrome with relapse following amitripyline. Postgrad Med J. 2000;76(894):254.

• Puttini PS, Caruso I. Primary fibromyalgia and 5-hydroxy-L-tryptophan: a 90-day open study. J Int Med Res. 1992;20:182-189.

• Rakel D. Rakel Integrative Medicine, 2nd ed. Philadelphia, PA: Saunders; 2008;47. • Reibring L, Agren H, Hartvig P, et al. Uptake and utilization of [beta-11c] 5-hydroxytryptophan

(5-HTP) in human brain studied by positron emission tomography. Psychiatry Research. 1992;45:215-225.

• Ribeiro CA. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. Headache. 2000 Jun;40(6):451-6.

• Shaw K, Turner J, Del Mar C. Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis. Aust N Z J Psychiatry. 2002 Aug;36(4):488-91.

• Sternberg EM, Van Woert MH, Young SN, et al. Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. New Eng J Med. 1980;303:782-787.

• Toner LC, Tsambiras BM, Catalano G, et al. Central nervous system side effects associated with zolpidem treatment. Clin Neuropharmacol. 2000;23(1):54-58.

• Van Praag HM. Management of depression with serotonin precursors. Biol Psychiatry. 1981;16:291-310.

• Zmilacher K, et al. L-5-hydroxytryptophan alone and in combination with a peripheral decarboxylase inhibitor in the treatment of depression. Neuropsychobiology. 1988;20:28–33.

7-Keto • National Institutes of Health. Weight Control Information Network. Available at: www. niddk. nih. gov/ health/ nutrit/ pubs/ health. htm. Accessed on May 30, 2001.

• National Center for Health Statistics. Prevalence of overweight and obesity among adults: United States, 1999. Available at: www. cdc. gov/ nchs/ products/ pubs/ pubd/ hestats/ obese/ obse99. htm. Accessed June 5, 2001.

• Pi-Sunyer FX. The fattening of America. JAMA. 1994; 272: 238-239.

• Colker CM, Torina GC, Swain MA, et al. Double-blind study evaluating the effects of exercise plus 3-acetyl-7-oxo-dehydroepiandrosterone on body composition and the endocrine system in overweight adults. J Exerc Physiol (online). 1999; 2: 1-2. Available at: www. css. edu/ users/ tboone2/ asep/ abstractROB. html.

• Lardy H, Kneer N, Wei Y, Partridge B, Marwah P. Ergosteroids. II: Biologically active metabolites and synthetic derivatives of dehydroepiandrosterone. Steroids. 1998; 63: 158-165.

• Lardy H, Partridge B, Kneer N et al. Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone. Proc Natl Acad Sci USA. 1995; 92: 6617-6619.

• Lardy H, Kneer N, Bellei M, Bobyleva V. Induction of thermogenic enzymes by DHEA and its metabolites. Ann N Y Acad Sci. 1995; 774: 171-179.

• Davidson M, Marwah A, Sawchuk RJ, et al. Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers. Clin Invest Med. 2000; 23: 300-310.

• Obesity and physical health. In: Grodner M, Anderson SL, DeYoung S. Foundations and Clinical Applications of Nutrition: A Nursing Approach. St. Louis, Mo: Mosby; 2000: 284-287.

• Pleuss J. Overnutrition and obesity. In: Porth CM. Pathophysiology: Concepts of Altered Health States. 5th ed. Philadelphia, Pa: Lippincott; 1998: 1254-1258.

• Obesity. In: Guyton AC, Hall JE. Textbook of Medical Physiology. Philadelphia, Pa: W. B. Saunders Company; 1998: 893-894.

• American Diabetes Association. What is type II diabetes? Available at: navigation. helper. realnames. com/ framer/ 1/ 112/ default. asp? realname= American+ Diabetes +Association. Accessed: June 6, 2001.

• Guven S, Kuenzi J. Diabetes mellitus. In: Porth CM. Pathophysiology: Concepts of Altered Health States. 5th ed. Philadelphia, Pa: Lippincott; 1998: 805.

• American Heart Association. Questions and answers about obesity. Available at: women. americanheart. org/ self_ care/ fs_ reduce_ risk2. html. Accessed June 6, 2001.

• American Cancer Society. The importance of nutrition in cancer prevention. Available at: www2. cancer. org/ prevention/ NutritionandPrevention. cfm. Accessed June 6, 2001.

• Sturmer T, Gunther KP, Brenner H. Obesity, overweight and patterns of osteoarthritis: the Ulm Osteoarthritis Study. J Clin Epidemiol. 2000; 53: 307-313.

• Takahashi S, Moriwaki Y, Tsutsumi Z, Yamakita J, Yamamoto T, Hada T. Increased visceral fat accumulation further aggravates the risks of insulin resistance in gout. Metabolism. 2001; 50: 393-398.

• Bender R, J?l KH, Trautner C, Spraul M, Berger M. Effect of age on excess mortality in obesity. JAMA. 1999; 281: 1498-1504.

• Weisburger JH. Eat to live, not live to eat. Nutrition. 2000; 16: 767-773.

• Volatier JL, Verger P. Recent national French food and nutrient intake data. Br J Nutr 1999; 81( Suppl) 2: S57-S59

• Krauss RM, Eckel RH, Howard B, et al.. Revision 2000: a statement for healthcare professionals from the Nutrition Committee of the American Heart Association. J Nutr. 2001; 131: 132-146.

• Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995; 332: 621-628.

• Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997; 387: 903-908.

• Heymsfeld SB, Greenburg AS, Fujioka K, et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA. 1999; 282: 1568-1575.

• Components of total energy expenditure. In: Grodner M, Anderson SL, DeYoung S. Foundations and Clinical Applications of Nutrition: A Nursing Approach. St. Louis, Mo: Mosby; 2000: 254-255.

• Schwartz AG, Pashko LL. Cancer chemoprevention with the adrenocortical steroid dehydroepiandrosterone and structural analogs. J Cell Biochem Suppl. 1993; 17: 73-79.

• Cleary MP, Zisk JF. Anti-obesity effect of two different levels of dehydroepiandro-sterone in lean and obese middle-aged female Zucker rats. Int J Obes. 1986; 10: 193-204.

• United States patents for 7-Keto DHEA. Patent number 5,296,481, May 22, 1994; 5,424,463, June 13, 1995.

• Williamson DF, Thompson TJ, Thun M, Flanders D, Pamuk E, Byers T. Intentional weight loss and mortality among overweight individuals with diabetes. Diabetes Care. 2000; 23: 1499-1504.

Guggulsterones • Agarwal RC, Clinical trial of gugulipid--a new hypolipidemic agent of plant origin in primary

hyperlipidemia. Indian J Med Res. 84:626-34. 1986 • Antonio J., et al. The effects of a standardized guggulsterone-phosphate supplement on body

composition in overweight adults. Curr Ther Res. 60 (4): 220-227. 1999 • Burris TP, et al. The Hypolipidemic Natural Product Guggulsterone is a Promiscuous Steroid

Receptor Ligand. Mol Pharmacol. 67(3): 948-954. 2005 • Dalvi SS. Effect of gugulipid on bioavailability of diltiazem and propranolol. Dept of

Pharmacology, Seth GS Medical College, Parel, Bombay. J Assoc Physicians India. 42(6):454-5. 1994

• Francis JA, et al. Bioactive terpenoids and guggulusteroids from Commiphora mukul gum resin of potential anti-inflammatory interest.Chem Biodivers. (11):1842-53. 2004. Michigan State University, East Lansing, Michigan, USA.

• Heymsfield, S. et al. Garcinia cambogia (Hydroxycitric Acid) as a Potential Antiobesity Agent: A Randomized Controlled Trial. JAMA. 280: 1596-1600. 1998.

• Katzeff HL, Selgrad C. Maintenance of thyroid hormone production during exercise-induced weight loss. Am J Physiol. 261:E382-8. 1991. Department of Medicine, North Shore University Hospital, Manhasset, New York.

• Kaciuba-Uscilko H, et al. Effect of phosphate supplementation on metabolic and neuroendocrine responses to exercise and oral glucose load in obese women during weight reduction. J Physiol Pharmacol. 44(4):425-40. 1993.Department of Applied Physiology, Polish Academy of Sciences, Warsaw.

• Lehnert H, Wurtman RJ. Amino acid control of neurotransmitter synthesis and release: physiological and clinical implications. Psychother Psychosom. 1993;60(1):18-32.

• Melamed E, et al. Plasma tyrosine in normal humans: effects of oral tyrosine and protein-containing meals. J Neural Transm. 1980;47(4):299-306.

• Nazar K. et al. Phosphate supplementation prevents a decrease of triiodothyronine and increases resting metabolic rate during low energy diet. Physiol Pharmacol. 47(2): 373-83 1996. Department of Applied Physiology, Polish Academy of Sciences, Warsaw, Poland

• Nityanand S., Clinical trials with guggulipid, a new hypolipidaemic agent. J Assoc Physicians India. 37(5): 323-328. 1989

• Owasoyo, J O et al. Tyrosine and its potential use as a countermeasure to performance decrement in military sustained operations. Aviat-Space-Environ-Med. 63(5): 364-9. 1992.

• Panda S, Kar A. Life Sci. Guggulu (Commiphora mukul) induces triiodothyronine production: possible involvement of lipid peroxidation. 65(12):PL137-41. 1999. School of Life Sciences, Devi Ahilya University, Vigyan Bhawan, Indore, India.

• Panda S, Kar A. Guggulu (Commiphora mukul) potentially ameliorates hypothyroidism in female mice.. Phytother Res. 19(1):78-80. 2005. Thyroid Research Unit, School of Life Sciences, D. A. University, Indore, India.

• Rosenbaum M, et al. Effects of changes in body weight on carbohydrate metabolism, catecholamine excretion, and thyroid function. Am J Clin Nutr. 71(6):1421-32. 2000.

• Singh BB, et al. The effectiveness of Commiphora mukul for osteoarthritis of the knee: an outcomes study. Altern Ther Health Med. 9(3):74-9. 2003. Southern California University of Health Sciences, USA.

• Szapary PO, et al, Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trialJAMA. 13;290(6):765-72. 2003. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6021, USA.

• Tripathi YB, et al. Thyroid-stimulating action of Z-gugglesterone obtained from comminphora mukul. Planta Medica. 50(1): 78-80. 1984. Department of Kayachikitsa, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, India.

• Tripathi YB, et al. Thyroid stimulating action of Z-guggulsterone obtained from Commiphora mukul.Planta Medica. 50(1):78-80.1988.

• Ulbricht C, etl al, Guggul for hyperlipidemia: a review by the Natural Standard Research Collaboration. Natural Standard Research Collaboration. Complement Ther Med. 2005 Dec;13(4):279-90. 2005. Massachusetts General Hospital, USA

• Van der Heyden JT, et al. Effects of caloric deprivation on thyroid hormone tissue uptake and generation of low-T3 syndrome. Am J Physiol. 251(2 Pt 1):E156-63. 1986

• Visser TJ, et al. Serum thyroid hormone concentrations during prolonged reduction of dietary intake. Metabolism. 27(4):405-9. 1978.

• Wilson JH, Lamberts SW. The effect of obesity and drastic caloric restriction on serum prolactin and thyroid stimulating hormone. Int J Obes. 5(3):275-8. 1981

Chromium • Mertz W. Chromium occurrence and function in biological systems. Physiol Rev 1969;49:163-239.

• Mertz W. Chromium in human nutrition: a review. J Nutr 1993;123:626-33.

• Mertz W. Interaction of chromium with insulin: a progress report. Nutr Rev 1998;56:174-7.

• Porte Jr. D, Sherwin RS, Baron A (editors). Ellengerg & Rifkin's Diabetes Mellitus, 6th Edition. McGraw-Hill, New York, 2003.

• Schwarz K, Mertz W. Chromium(III) and the glucose tolerance factor. Arch Biochem Biophys 1959;85:292-5.

• Hopkins Jr. LL, Ransome-Kuti O, Majaj AS. Improvement of impaired carbohydrate metabolism by chromium(III) in malnourished infants. Am J Clin Nutr 1968;21:203-11.

• Jeejeebhoy KN, Chu RC, Marliss EB, Greenberg GR, Bruce-Robertson A. Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation in a patient receiving long-term total parenteral nutrition. Am J Clin Nutr 1977;30:531-8.

• Anderson R. Chromium. In: Trace Elements in Human and Animal Nutrition (edited by Mertz M). Academic Press, San Diego, CA, 1987, pp. 225-244.

• Lukaski HC. Chromium as a supplement. Annu Rev Nutr 1999;19:279-302.

• Stoecker BJ. Chromium. In: Present Knowledge in Nutrition, 8th Edition (edited by Bowman B, Russell R). ILSI Press, Washington, DC, 2001, pp. 366-372.

• Vincent JB. The potential value and toxicity of chromium picolinate as a nutritional supplement, weight loss agent and muscle development agent. Sports Med 2003;33:213-30.

• Anderson RA, Bryden NA, Polansky MM. Dietary chromium intake: freely chosen diets, institutional diets and individual foods. Biol Trace Elem Res 1992;32:117-21.

• Kozlovsky AS, Moser PB, Reiser S, Anderson RA. Effects of diets high in simple sugars on urinary chromium losses. Metabolism 1986;35:515-8.

• Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001.

• Cabrera-Vique C, Teissedre P-L, Cabanis M-T, Cabinis J-C. Determination and levels of chromium in French wine and grapes by graphite furnace atomic absorption spectrometry. J Agric Food Chem 1997;45:1808-11.

• Dattilo AM, Miguel SG. Chromium in health and disease. Nutr Today 2003;38:121-33.

• National Research Council, Food and Nutrition Board. Recommended Dietary Allowances, 10th Edition. National Academy Press, Washington, DC, 1989.

• Cocho JA, Cervilla JR, Rey-Goldar ML, Fdez-Lorenzo JR, Fraga JM. Chromium content in human milk, cow's milk, and infant formulas. Biol Trace Elem Res 1992;32:105-7.

• Doisy RJ, Streeten DHP, Souma ML, Kalafer ME, Rekant SL, Dalakos TG. Metabolism of 51chromium in human subjects. In: Newer Trace Elements in Nutrition (edited by Mertz W, Cornatzer WE). Dekker, New York, 1971, pp. 155-68.

• Anderson RA, Polansky MM, Bryden NA, Patterson KY, Veillon C, Glinsmann WH. Effects of chromium supplementation on urinary Cr excretion of human subjects and correlation of Cr excretion with selected clinical parameters. J Nutr 1983;113:276-81.

• Bunker VW, Lawson MS, Delves HT, Clayton BE. The uptake and excretion of chromium by the elderly. Am J Clin Nutr 1984;39:797-802.

• Anderson RA, Kolovsky AS. Chromium intake, absorption and excretion of subjects consuming self-selected diets. Am J Clin Nutr 1985;41:1177-83.

• Offenbacher EG, Spencer H, Dowling HJ, Pi-Sunyer FX. Metabolic chromium balances in men. Am J Clin Nutr 1986;44:77-82.

• Anderson RA, Polansky MM, Bryden NA, Canary JJ. Supplemental-chromium effects on glucose, insulin, glucagon, and urinary chromium losses in subjects consuming controlled low-chromium diets. Am J Clin Nutr 1991;54:909-16.

• Anderson RA, Bryden NA, Patterson KY, Veillon C, Andon MB, Moser-Veillon PB. Breast milk chromium and its association with chromium intake, chromium excretion, and serum chromium. Am J Clin Nutr 1993;57:419-23.

• Offenbacher E. Promotion of chromium absorption by ascorbic acid. Trace Elem Elect 1994;11:178-81.

• Lim TH, Sargent T 3rd, Kusubov N. Kinetics of trace element chromium(III) in the human body. Am J Physiol 1983;244:R445-54.

• Anderson R. Stress Effects on Chromium Nutrition in Humans and Animals, 10th Edition. Nottingham University Press, England, 1994.

• Lukaski HC, Bolonchuk WW, Siders WA, Milne DB. Chromium supplementation and resistance training: effects on body composition, strength and trace element status of men. Am J Clin Nutr 1996;63:954-65.

• Freund H, Atamian S, Fischer JE. Chromium deficiency during total parenteral nutrition. JAMA 1979;241:496-8.

• Brown RO, Forloines-Lynn S, Cross RE, Heizer WD. Chromium deficiency after long-term total parenteral nutrition. Dig Dis Sci 1986;31:661-4.

• Davies S, Howard JM, Hunnisett A, Howard M. Age-related decreases in chromium levels in 51,665 hair, sweat, and serum samples from 40,872 patients — implications for the prevention of cardiovascular disease and type II diabetes mellitus. Metabolism 1997;46:469-73.

• Gibson RS. Principles of Nutritional Assessment, 2nd Edition. Oxford University Press, New York, 2005.

• Stoecker BJ. Chromium. In: Modern Nutrition in Health and Disease, 9th Edition (edited by Shils ME, Olson JA, Shike M, Ross AC.) Lippincott Williams and Wilkins, New York, 1999, pp. 277-282.

• Althuis MD, Jordan NE, Ludington EA, Wittes JT. Glucose and insulin responses to dietary chromium supplements: a meta-analysis. Am J Clin Nutr 2002;76:148-55.

• Cefalu WT, Hu FB. Role of chromium in human health and in diabetes. Diabetes Care 2004;27:2741-51.

• Offenbacher E, Pi-Sunyer F. Chromium. In: Handbook of Nutritionally Essential Mineral Elements (edited by O'Dell B, Sunde R). Marcel Dekker, New York, 1997, pp. 389-411.

• Roeback Jr. JR, Hla KM, Chambless LE, Fletcher RH. Effects of chromium supplementation on serum high-density lipoprotein cholesterol levels in men taking beta-blockers. A randomized, controlled trial. Ann Intern Med 1991;115:917-24.

• Abraham AS, Brooks BA, Eylath U. The effects of chromium supplementation on serum glucose and lipids in patients with and without non-insulin-dependent diabetes. Metabolism 1992;41:768-71.

• Hermann J, Arquitt A. Effect of chromium supplementation on plasma lipids, apolipoproteins, and glucose in elderly subjects. Nutr Res 1994;14: 671-4.

• Doisy RJ, Streeten DHP, Freiberg JM, Schneider AJ. Chromium metabolism in man and biochemical effects. In: Trace Elements in Human Health and Disease, Volume 2: Essential and Toxic Elements (edited by Prasad A, Oberleas D). Academic Press, New York, 1976, pp. 79-104.

• Lifschitz ML, Wallach S, Peabody RA, Verch RL, Agrawal R. Radiochromium distribution in thyroid and parathyroid deficiency. Am J Clin Nutr 1980:33:57-62.

• Riales R, Albrink MJ. Effect of chromium chloride supplementation on glucose tolerance and serum lipids including high-density lipoprotein of adult men. Am J Clin Nutr 1981;34:2670-8.

• Mossop RT. Effects of chromium III on fasting blood glucose, cholesterol and cholesterol HDL levels in diabetics. Cent Afr J Med 1983;29:80-2.

• Anderson RA, Polansky MM, Bryden NA, Roginski EE, Mertz W, Glinsmann W. Chromium supplementation of human subjects: effects on glucose, insulin, and lipid variables. Metabolism 1983;32:894-9.

• Rabinowitz MB, Gonick HC, Levin SR, Davidson MB. Effects of chromium and yeast supplements on carbohydrate and lipid metabolism in diabetic men. Diabetes Care 1983;6:319-27.

• Uusitupa MI, Kumpulainen JT, Voutilainen E, Hersio K, Sarlund H, Pyorala KP, Koivistoinen PE, Lehto JT. Effect of inorganic chromium supplementation on glucose tolerance, insulin response, and serum lipids in noninsulin-dependent diabetics. Am J Clin Nutr 1983;38:404-10.

• Offenbacher EG, Rinko CJ, Pi-Sunyer FX. The effects of inorganic chromium and brewer's yeast on glucose tolerance, plasma lipids, and plasma chromium in elderly subjects. Am J Clin Nutr 1985;42:454-61.

• Potter JF, Levin P, Anderson RA, Freiberg JM, Andres R, Elahi D. Glucose metabolism in glucose-intolerant older people during chromium supplementation. Metabolism 1985;34:199-204.

• Uusitupa MI, Mykkanen L, Siitonen O, Laakso M, Sarlund H, Kolehmainen P, Rasanen T, Kumpulainen J, Pyorala K. Chromium supplementation in impaired glucose tolerance of elderly: effects on blood glucose, plasma insulin, C-peptide and lipid levels. Br J Nutr 1992;68:209-16.

• Pittler MH, Stevinson C, Ernst E. Chromium picolinate for reducing body weight: meta-analysis of randomized trials. Int J Obes Relat Metab Disord 2003;27:522-9.

• Davis ML, Seaborn CD, Stoecker BJ. Effects of over-the-counter drugs on 51chromium retention and urinary excretion in rats. Nutr Res 1995;15:201-10.

• Kamath SM, Stoecker BJ, Davis-Whitenack ML, Smith MM, Adeleye BO, Sangiah S. Absorption, retention and urinary excretion of chromium-51 in rats pretreated with indomethacin and dosed with dimethylprostaglandin E2, misoprostol or prostacyclin. J Nutr 1997;127:478-82.

• Chromium. In: Natural Medicines Comprehensive Database, 2005. http://www.naturalmedicines.com.

• Nutrition Business Journal. NBJ's Supplement Business Report 2003. Penton Media Inc., San Diego, CA, 2003.

Alpha Lipoic Acid • α-lipoic acid can improve endothelial dysfunction in subjects with impaired fasting glucose • Lipoic Acid Biosynthesis:  LipA Is an Iron−Sulfur Protein • Akiba S, et al. Assay of protein-bound lipoic acid in tissues by a new enzymatic method. Anal

Biochem. (1998) • Wollin SD, Jones PJ. Alpha-lipoic acid and cardiovascular disease. J Nutr. (2003) • Moini H, Packer L, Saris NE. Antioxidant and prooxidant activities of alpha-lipoic acid and

dihydrolipoic acid. Toxicol Appl Pharmacol. (2002) • Merry BJ, Kirk AJ, Goyns MH. Dietary lipoic acid supplementation can mimic or block the effect

of dietary restriction on life span. Mech Ageing Dev. (2008) • Satoh S, et al. Selective and sensitive determination of lipoyllysine (protein-bound alpha-lipoic

acid) in biological specimens by high-performance liquid chromatography with fluorescence detection. Anal Chim Acta. (2008)

• Backman-Gullers B, et al. Studies on lipoamidase: characterization of the enzyme in human serum and breast milk. Clin Chim Acta. (1990)

• Hiltunen JK, et al. Mitochondrial fatty acid synthesis type II: more than just fatty acids. J Biol Chem. (2009)

• Shay KP, et al. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. (2009)

• Reed LJ. From lipoic acid to multi-enzyme complexes. Protein Sci. (1998) • Park CH, et al. Improved efficacy of appetite suppression by lipoic acid particles prepared by

nanocomminution. Drug Dev Ind Pharm. (2009) • The Chemistry of 1,2-Dithiolane (Trimethylene Disulfide) As a Model for the Primary Quantum

Conversion Act in Photosynthesis • Kinetics of the thiol-disulfide exchange. II. Oxygen-promoted free-radical exchange between

aromatic thiols and disulfides • Saito G, Swanson JA, Lee KD. Drug delivery strategy utilizing conjugation via reversible disulfide

linkages: role and site of cellular reducing activities. Adv Drug Deliv Rev. (2003) • Interrelationships of Lipoic Acids • Jones W, et al. Uptake, recycling, and antioxidant actions of alpha-lipoic acid in endothelial cells.

Free Radic Biol Med. (2002) • Preparation and use of salts of the pure enantiomers of alpha-lipoic acid • Dosage forms containing thioctic acid or solid salts of thioctic acid with improved release and

bioavailability • Takaishi N, et al. Transepithelial transport of alpha-lipoic acid across human intestinal Caco-2

cell monolayers. J Agric Food Chem. (2007) • Prasad PD, et al. Cloning and functional expression of a cDNA encoding a mammalian sodium-

dependent vitamin transporter mediating the uptake of pantothenate, biotin, and lipoate. J Biol Chem. (1998)

• Balamurugan K, Vaziri ND, Said HM. Biotin uptake by human proximal tubular epithelial cells: cellular and molecular aspects. Am J Physiol Renal Physiol. (2005)

• Teichert J, et al. Investigations on the pharmacokinetics of alpha-lipoic acid in healthy volunteers. Int J Clin Pharmacol Ther. (1998)

• Teichert J, et al. Plasma kinetics, metabolism, and urinary excretion of alpha-lipoic acid following oral administration in healthy volunteers. J Clin Pharmacol. (2003)

• Carlson DA, et al. The plasma pharmacokinetics of R-(+)-lipoic acid administered as sodium R-(+)-lipoate to healthy human subjects. Altern Med Rev. (2007)

• Breithaupt-Grögler K, et al. Dose-proportionality of oral thioctic acid--coincidence of assessments via pooled plasma and individual data. Eur J Pharm Sci. (1999)

• Harrison EH, McCormick DB. The metabolism of dl-(1,6-14C)lipoic acid in the rat. Arch Biochem Biophys. (1974)

• Panigrahi M, et al. alpha-Lipoic acid protects against reperfusion injury following cerebral ischemia in rats. Brain Res. (1996)

• Arivazhagan P, et al. Effect of DL-alpha-lipoic acid on the status of lipid peroxidation and antioxidant enzymes in various brain regions of aged rats. Exp Gerontol. (2002)

• Mignini F, et al. Single dose bioavailability and pharmacokinetic study of a innovative formulation of α-lipoic acid (ALA600) in healthy volunteers. Minerva Med. (2011)

• Schupke H, et al. New metabolic pathways of alpha-lipoic acid. Drug Metab Dispos. (2001) • Ou P, Tritschler HJ, Wolff SP. Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant.

Biochem Pharmacol. (1995) • Cakatay U, et al. Postmitotic tissue selenium and manganese levels in alpha-lipoic acid-

supplemented aged rats. Chem Biol Interact. (2008) • Suh JH, et al. Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related

accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Rep. (2005) • Bush AI. Metal complexing agents as therapies for Alzheimer's disease. Neurobiol Aging. (2002) • McCarty MF, Barroso-Aranda J, Contreras F. The "rejuvenatory" impact of lipoic acid on

mitochondrial function in aging rats may reflect induction and activation of PPAR-gamma coactivator-1alpha. Med Hypotheses. (2009)

• Hagen TM, et al. (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB J. (1999)

• Liu J, et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A. (2002)

• Liu J, Killilea DW, Ames BN. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A. (2002)

• Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress

• Arivazhagan P, Ramanathan K, Panneerselvam C. Effect of DL-alpha-lipoic acid on the status of lipid peroxidation and antioxidants in mitochondria of aged rats. J Nutr Biochem. (2001)

• Arivazhagan P, Ramanathan K, Panneerselvam C. Effect of DL-alpha-lipoic acid on mitochondrial enzymes in aged rats. Chem Biol Interact. (2001)

• Freisleben HJ, et al. Influence of selegiline and lipoic acid on the life expectancy of immunosuppressed mice. Arzneimittelforschung. (1997)

• Kim MS, et al. Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. Nat Med. (2004)

• Cheng PY, et al. Reciprocal effects of α-lipoic acid on adenosine monophosphate-activated protein kinase activity in obesity induced by ovariectomy in rats. Menopause. (2011)

• Wang Y, et al. alpha-Lipoic acid increases energy expenditure by enhancing adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling in the skeletal muscle of aged mice. Metabolism. (2010)

• Timmers S, et al. Prevention of high-fat diet-induced muscular lipid accumulation in rats by alpha lipoic acid is not mediated by AMPK activation. J Lipid Res. (2010)

• Fernández-Galilea M, et al. Effects of lipoic acid on apelin in 3T3-L1 adipocytes and in high-fat fed rats. J Physiol Biochem. (2011)

• El Midaoui A, et al. Impact of α-lipoic acid on liver peroxisome proliferator-activated receptor-α, vascular remodeling, and oxidative stress in insulin-resistant rats. Can J Physiol Pharmacol. (2011)

• Prieto-Hontoria PL, et al. Lipoic acid prevents body weight gain induced by a high fat diet in rats: effects on intestinal sugar transport. J Physiol Biochem. (2009)

• Seo EY, Ha AW, Kim WK. α-Lipoic acid reduced weight gain and improved the lipid profile in rats fed with high fat diet. Nutr Res Pract. (2012)

• Prieto-Hontoria PL, et al. Lipoic acid inhibits leptin secretion and Sp1 activity in adipocytes. Mol Nutr Food Res. (2011)

• Gupte AA, et al. Lipoic acid increases heat shock protein expression and inhibits stress kinase activation to improve insulin signaling in skeletal muscle from high-fat-fed rats. J Appl Physiol. (2009)

• Butler JA, Hagen TM, Moreau R. Lipoic acid improves hypertriglyceridemia by stimulating triacylglycerol clearance and downregulating liver triacylglycerol secretion. Arch Biochem Biophys. (2009)

• Prieto-Hontoria PL, et al. Effects of lipoic acid on AMPK and adiponectin in adipose tissue of low- and high-fat-fed rats. Eur J Nutr. (2012)

• Valdecantos MP, et al. Lipoic acid administration prevents nonalcoholic steatosis linked to long-term high-fat feeding by modulating mitochondrial function. J Nutr Biochem. (2012)

• Valdecantos MP, et al. Lipoic Acid Improves Mitochondrial Function in Nonalcoholic Steatosis Through the Stimulation of Sirtuin 1 and Sirtuin 3. Obesity (Silver Spring). (2012)

• Kim E, et al. A preliminary investigation of alpha-lipoic acid treatment of antipsychotic drug-induced weight gain in patients with schizophrenia. J Clin Psychopharmacol. (2008)

• Freitas RM, Jordán J, Feng D. Lipoic acid effects on monoaminergic system after pilocarpine-induced seizures. Neurosci Lett. (2010)

• Santos IM, et al. Alterations on monoamines concentration in rat hippocampus produced by lipoic acid. Arq Neuropsiquiatr. (2010)

• Ferreira PM, Militão GC, Freitas RM. Lipoic acid effects on lipid peroxidation level, superoxide dismutase activity and monoamines concentration in rat hippocampus. Neurosci Lett. (2009)

• Ranieri M, et al. The use of alpha-lipoic acid (ALA), gamma linolenic acid (GLA) and rehabilitation in the treatment of back pain: effect on health-related quality of life. Int J Immunopathol Pharmacol. (2009)

• Di Geronimo G, et al. Treatment of carpal tunnel syndrome with alpha-lipoic acid. Eur Rev Med Pharmacol Sci. (2009)

• Bertolotto F, Massone A. Combination of alpha lipoic acid and superoxide dismutase leads to physiological and symptomatic improvements in diabetic neuropathy. Drugs R D. (2012)

• Ziegler D, et al. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. (2011)

• Zechner R, et al. Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. J Lipid Res. (2009)

• Kuo YT, et al. Alpha-lipoic acid induces adipose triglyceride lipase expression and decreases intracellular lipid accumulation in HepG2 cells. Eur J Pharmacol. (2012)

• Park KG, et al. Alpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. Hepatology. (2008)

• Koh EH, et al. Effects of alpha-lipoic Acid on body weight in obese subjects. Am J Med. (2011) • Park HS, et al. Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase. EMBO

J. (2001) • Park KJ, Gaynor RB, Kwak YT. Heat shock protein 27 association with the I kappa B kinase

complex regulates tumor necrosis factor alpha-induced NF-kappa B activation. J Biol Chem. (2003)

• Antioxidants preserve redox balance and inhibit c-Jun-N-terminal kinase pathway while improving insulin signaling in fat-fed rats: evidence for the role of oxidative stress on IRS-1 serine phosphorylation and insulin resistance

• Chen WL, et al. α-Lipoic acid regulates lipid metabolism through induction of sirtuin 1 (SIRT1) and activation of AMP-activated protein kinase. Diabetologia. (2012)

• Shen QW, et al. Ca2+/calmodulin-dependent protein kinase kinase is involved in AMP-activated protein kinase activation by alpha-lipoic acid in C2C12 myotubes. Am J Physiol Cell Physiol. (2007)

• Chou TC, Shih CY, Chen YT. Inhibitory effect of α-lipoic acid on platelet aggregation is mediated by PPARs. J Agric Food Chem. (2011)

Green Tea Extract • Belza A, Toubro S, Astrup A. The effect of caffeine, green tea and tyrosine on thermogenesis and

energy intake. Eur J Clin Nutr. 2007; [Epub ahead of print]. • Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, Corti A. Chemoprevention of human

prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res. 2006;66(2):1234-40.

• Borrelli F, Capasso R, Russo A, Ernst E. Systematic review: green tea and gastrointestinal cancer risk. Aliment Pharmacol Ther Mar 1, 2004;19(5):497-510.

• Boschmann M, Thielecke F. The effects of epigallocatechin-3-gallate on thermogenesis and fat oxidation in obese men: a pilot study. J Am Coll Nutr. 2007;26(4):389S-395S.

• Brown AL, Lane J, Holyoak C, Nicol B, Mayes AE, Dadd T. Health effects of green tea catechins in overweight and obese men: a randomised controlled cross-over trial. Br J Nutr. 2011 Jun 7:1-10. [Epub ahead of print]

• Cooper R, Morre DJ, Morre DM. Medicinal benefits of green tea: Part I. Review of noncancer health benefits. J Altern Complement Med. 2005;11(3):521-8.

• Diepvens K, Westerterp KR, Westerterp-Plantenga MS. Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin and green tea. Am J Physiol Regul Integr Comp Physiol. 2007;292(1):R77-85.

• Fujita H, Yamagami T. Antihypercholesterolemic effect of Chinese black tea extract in human subjects with borderline hypercholesterolemia. Nutr Res. 2008;28(7):450-6.

• Fukino Y, Ikeda A, Maruyama K, Aoki N, Okubo T, Iso H. Randomized controlled trial for an effect of green tea-extract powder supplementation on glucose abnormalities. Eur J Clin Nutr. 2007; [Epub ahead of print].

• Gross G, Meyer KG, Pres H, Thielert C, Tawfik H, Mescheder A. A randomized, double-blind, four-arm parallel-group, placebo-controlled Phase II/III study to investigate the clinical efficacy of two galenic formulations of Polyphenon(R) E in the treatment of external genital warts. J Eur Acad DermatolVenereol. 2007;21(10):1404-12.

• Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. [review]. Am J Health Syst Pharm. 2000 Jul 1;57(13):1221-1227.

• Hsu CH, Liao YL, Lin SC, Tsai TH, Huang CJ, Chou P. Does supplementation with green tea extract improve insulin resistance in obese type 2 diabetics? A randomized, double-blind, and placebo-controlled clinical trial. Altern Med Rev. 2011 Jun;16(2):157-63.

• Inoue M, Tajima K, Mizutani M, et al. Regular consumption of green tea and the risk of breast cancer recurrence: follow-up study from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. Cancer Lett. 2001;167(2):175-182.

• Jian L, Xie LP, Lee AH, Binns CW. Protective effect of green tea against prostate cancer: a case-control study in southeast China. Int J Cancer Jan 1, 2004;108(1):130-135.

• Jin X, Zheng RH, Li YM. Green tea consumption and liver disease: a systematic review. Liver Int. 2008;28(7):990-6.

• Katiyar SK, Ahmad N, Mukhtar H. Green tea and skin. Arch Dermatol. 2000;136(8):989-94. • Kato A, Minoshima Y, Yamamoto J, Adachi I, Watson AA, Nash RJ. Protective effects of dietary

chamomile tea on diabetic complications. J Agric Food Chem. 2008;56(17):8206-11. • Kimura K, Ozeki M, Juneja LR, Ohira H. L-Theanine reduces psychological and physiological stress

responses. Biol Psychol. 2007;74(1):39-45. • Koo SI, Noh SK. Green tea as inhibitor of the intestinal absorption of lipids: potential mechanism

for its lipid-lowering effect. J Nutr Biochem. 2007;18(3):179-83. • Kovacs EM, Lejeune MP, Nijs I, Westerterp-Plantenga MS. Effects of green tea on weight

maintenance after body-weight loss. Br J Nutr Mar 1, 2004;91(3):431-437. • Kuriyama S, Shimazu T, Ohmori K, Kikuchi N, Nakaya N, Nishino Y, Tsubono Y, Tsuji I. Green tea

consumption and mortality due to cardiovascular disease, cancer and all causes in Japan: the Ohsaki study. JAMA. 2006;296(10):1255-65.

• Lee W, Min WK, Chun S, Lee YW, Park H, Lee do H, Lee YK, Son JE. Long-term effects of green tea ingestion on atherosclerotic biological markers in smokers. Clin Biochem. Jan 1, 2005;38(1):84-87.

• Low Dog T, Riley D, Carter T. Traditional and alternative therapies for breast cancer. Alt Ther. 2001;7(3):36-47.

• McKenna DJ, Hughes K, Jones K. Green tea monograph. Alt Ther. 2000;6(3):61-84. • Miura Y, Chiba T, Tomita I, et al. Tea catechins prevent the development of atherosclerosis in

apoprotein E-deficient mice. J Nutr. 2001;131(1):27-32. • Nagao T, Hase T, Tokimitsu I. A green tea extract high in catechins reduces body fat and

cardiovascular risks in humans. Obesity (Silver Spring). 2007;15(6):1473-83. • Peters U, Poole C, Arab L. Does tea affect cardiovascular disease? A meta-analysis. Am J

Epidemiol. 2001;154(6):495-503. • Pianetti S, Guo S, Kavanagh KT, Sonenshein GE. Green tea polyphenol epigallocatechin-3 gallate

inhibits Her-2/neu signaling, proliferation, and transformed phenotype of breast cancer cells. Cancer Res. 2002;62(3):652-655.

• Rowe CA, Nantz MP, Bukowski JF, Percival SS. Specific formulation of Camellia sinensis prevents cold and flu symptoms and enhances gammadelta T cell function: a randomized, double-blind, placebo-controlled study. J Am Coll Nutr. 2007;26(5):445-52.

• Ryu OH, Lee J, Lee KW, et al. Effects of green tea consumption on inflammation, insulin resistance and pulse wave velocity in type 2 diabetes patients. Diabetes Res Clin Pract. 2006;71(3):356-8.

• Sano T, Sasako M. Green tea and gastric cancer. N Engl J Med. 2001;344(9):675-676. • Sasazuki S, Kodama H, Yoshimasu K et al. Relation between green tea consumption and the

severity of coronary atherosclerosis among Japanese men and women. Ann Epidemiol. 2000;10:401-408.

• Setiawan VW, Zhang ZF, Yu GP, et al. Protective effect of green tea on the risks of chronic gastritis and stomach cancer. Int J Cancer. 2001;92(4):600-604.

• Shankar S, Ganapathy S, Hingorani SR, Srivastava RK. EGCG inhibits growth, invasion, angiogenesis and metastasis of pancreatic cancer. Front Biosci. 2008;13:440-52.

• Steptoe A, Gibson EL, Vuonovirta R, Hamer M, Wardle J, Rycroft JA, Martin JF, Erusalimsky JD. The effects of chronic tea intake on platelet activation and inflammation: a double-blind placebo controlled trial. Atherosclerosis. 2007;193(2):277-82.

• Suzuki Y, Tsubono Y, Nakaya N, Suzuki Y, Koizumi Y, Tsuji I. Green tea and the risk of breast cancer: pooled analysis of two prospective studies in Japan. Br J Cancer. Apr 5, 2004;90(7)1361-1363.

• Thatte U, Bagadey S, Dahanukar S. Modulation of programmed cell death by medicinal plants. [Review]. Cell Mol Biol. 2000;46(1):199-214.

• Thavanesan N. The putative effects of green tea on body fat: an evaluation of the evidence and a review of the potential mechanisms. Br J Nutr. 2011 Aug 3:1-13. [Epub ahead of print]

• Tsubono Y, Nishino Y, Komatsu S, et al. Green tea and the risk of gastric cancer in Japan. N Engl J Med. 2001;344(9):632-636.

• Vinson JA, Teufel K, Wu N. Green and black teas inhibit atherosclerosis by lipid, antioxidant, and fibrinolytic mechanisms. J Agric Food Chem. 2004;52(11):3661-5.

• Wargovich MJ, Woods C, Hollis DM, Zander ME. Herbals, cancer prevention and health. [Review]. J Nutr. 2001;131(11 Suppl):3034S-3036S.

• Westerterp-Plantenga MS, Lejeune MP, Kovacs EM. Body weight and weight maintenance in relation to habitual caffeine intake and green tea. Obes Res Jul 2005;13(7):1195-1204.

• Wu AH, Butler LM. Green tea and breast cancer. Mol Nutr Food Res. 2011 Jun;55(6):921-30. • Yang G, Shu XO, Li H, Chow WH, Ji BT, Zhang X, Gao YT, Zheng W. Prospective cohort study of

green tea consumption and colorectal cancer risk in women. Cancer Epidemiol Biomarkers Prev. 2007;16(6):1219-23.

• Yang G, Zheng W, Xiang YB, Gao J, Li HL, Zhang X, Gao YT, Shu XO. Green tea consumption and colorectal cancer risk: a report from the Shanghai Men's Health Study. Carcinogenesis. 2011 Sep 8. [Epub ahead of print]

• Yuan JM. Green tea and prevention of esophageal and lung cancers. Mol Nutr Food Res. 2011 Jun;55(6):886-904.

• Zhang M, Lee AH, Binns CW, Xie X. Green tea consumption enhances survival of epithelial ovarian cancer. Int J Cancer Nov 10, 2004;112(3):465-469.

• Zheng J, Yang B, Huang T, Yu Y, Yang J, Li D. Green tea and black tea consumption and prostate cancer risk: an exploratory meta-analysis of observational studies. Nutr Cancer. 2011;63(5):663-72. Epub 2011 Jun 11.

• Zhou B, Yang L, Wang L, Shi Y, Zhu H, Tang N, Wang B. The association of tea consumption with ovarian cancer risk: a meta-analysis. Am J Obstet Gynecol. 2007;197(6):594.e1-6.