The Nine Pillars of Successful Weight LossJune 2009
By William Faloon
Pillar Number 7: Restore Healthy Adipocyte Signaling
The adipocyte (fat cell) is the primary site for fat storage. Adipocytes of obese individuals are bloated with triglycerides, which is the form that most fat exists in the body. Fat storage and release is tightly regulated by adipocyte command signals.
Weight gain occurs when adipocytes (fat cells) enlarge with large amounts of triglycerides. Adipocytes accumulate excess triglycerides due to overeating, nutrient deficiencies, excessive stress, and other causes. These factors, however, fail to address the reason why aging individuals put on fat pounds despite eating less, taking dietary supplements, and following other practices that should in theory lead to weight loss.
The aging process adversely affects the adipocyte command signal network, which helps explain the difficulty maturing individuals have in controlling their weight.
Adipocytes regulate their size and number by secreting command signals. The three command signals that regulate adipocytes are:
A West African medicinal food called Irvingia gabonensis has been shown to favorably affect the three adipocyte command centers in the following ways:
Released by adipocytes, leptin travels to the brain to perform two critical functions. First it signals the brain that enough food has been ingested and shuts down appetite. It then depletes bloated adipocytes by promoting the burning of stored triglycerides. Leptin is much more abundant in the blood of obese individuals, yet leptin functions to turn off appetite while promoting the burning of triglycerides that bloat our adipocytes. The reason why obese people have higher blood levels of leptin is that leptin receptor sites on cell membranes are inactivated by inflammatory factors in the body. Irvingia helps unblock “leptin resistance”.
The second command signal released by adipocytes is adiponectin. The transcription factors associated with adiponectin help determine the amount of triglycerides stored in adipocytes and number of adipocytes formed in the body. Higher levels of adiponectin enhance insulin sensitivity, which is a long established method to induce weight loss. Gene transcriptional factors involved with adiponectin are directly involved in sequential expression of adipocyte-specific proteins. Irvingia suppresses transcriptional factors involved in the formation of new adipocytes, while enhancing cell membrane insulin sensitivity by increasing adiponectin. High circulating levels of adiponectin have been shown to protect against coronary artery disease, whereas low adiponectin levels are observed in overweight individuals.
An enzyme that facilitates the conversion of blood glucose into stored triglyceride fat is glycerol-3-phosphate dehydrogenase. The presence of this enzyme in the body reveals why low-fat diets alone fail to achieve sustained weight loss, i.e. the body will take ingested carbohydrates and convert them into stored triglyceride fat via the glycerol-3-phosphate dehydrogenase enzyme. Irvingia inhibits glycerol-3-phosphate dehydrogenase, thus reducing the amount of ingested sugars that are converted to body fat.
Clinical studies have demonstrated significant belly fat and total weight loss in response to taking a 150 mg Irvingia gabonensis extract twice daily. A mechanism for this weight loss reported by many Irvingia users is a reduction in appetite with a concomitant decrease in the number of ingested calories.
Pillar Number 8: Inhibiting the Lipase Enzyme
Orlistat is an inhibitor of pancreatic and gastric lipase. It decreases the intestinal absorption of ingested dietary triglycerides by 30%. By reducing the breakdown and absorption of dietary fat, orlistat enhances weight loss and lessens insulin resistance.
In studies of obese subjects, orlistat treatment improves insulin and glucose blood levels while significantly decreasing C-reactive protein, a marker for chronic inflammation. Orlistat treatment favorably influences other blood markers (such as leptin and adiponectin) that are involved with obesity.
In a one-year trial of overweight women, a group with metabolic syndrome treated with orlistat (120 mg three times a day) and lifestyle modification lost 20.5 pounds compared with only 0.44 pounds weight loss in the placebo control group. A group of overweight women without metabolic syndrome taking the same dose of orlistat + lifestyle modification lost 20.2 pounds more than the control group with metabolic syndrome.
In a three-month open-label trial of overweight patients without type 2 diabetes treated with orlistat (120 mg three times a day), men lost 17.4 pounds and women lost 12.3 pounds. In overweight patients with type 2 diabetes mellitus, men lost 18.7 pounds and women lost 12.5 pounds. In this study, leptin levels decreased by 51% in men with type 2 diabetes and 25% in women with type 2 diabetes mellitus. Leptin levels dropped by 48% in overweight men and 23% in overweight women without type 2 diabetes mellitus. A reduction in leptin blood levels is considered a favorable response as it indicates a reduction in the “leptin resistance” phenomenon that so often precludes successful weight loss.
Not all studies demonstrate this much weight loss in response to orlistat. Poor compliance is always a factor in the variability that exists among studies of the same compound. Another reason for these discrepancies is that orlistat users are warned to avoid excess ingestion of dietary fats, and are likely to switch to consuming more simple carbohydrates. Overweight individuals often suffer metabolic disturbances, meaning that ingested sugars more readily convert to stored (triglyceride) fats on the body. This is why taking carbohydrate-blocking agents (alpha-glucosidase and amylase inhibitors) in conjunction with orlistat for the first 60 days of a weight-loss program may be necessary to induce some immediate reduction of fat pounds that overweight and obese individuals expect.
Orlistat is available by prescription in 120 mg capsules as Xenical®, or over-the-counter under the trade name alli® in 60 mg capsules. The suggested dose for the 60-day initiation period is 120 mg before each meal (three times a day). Make sure to take fat-soluble nutrients such as omega-3 fish oil, vitamins D, E, and K, and carotenoids (like lutein and zeaxanthin) at the time of the day most removed from the last orlistat dose as its fat-blocking effects can interfere with absorption of these critical nutrients into the blood.
Pillar Number 9: Eat to Live a Long and Healthy Life
No one should embark on a weight-loss program by trying to follow a fad diet that cannot be adhered to over the long term. At the same time, aging individuals have to make choices as to what is more important, i.e., ingesting foods that are known to promote weight gain (and cause horrendous diseases) or selecting healthier foods that facilitate weight loss and protect against illness.
Six years ago, Life Extension® published an article about the dangers of eating foods cooked at high temperatures (over 250 degrees). Overcooked foods damage our body’s proteins, while foods cooked at lower temperatures have been shown to facilitate weight loss. So just changing how your foods are prepared could help you shed body fat and, at the same time, protect against age-related disease (see “Eating food cooked at high temperature accelerates aging,” Life Extension, May 2003).
Solid scientific evidence shows that excess calorie ingestion accelerates the onset of degenerative disease and the aging process itself—in addition to promoting the unsightly accumulation of body fat. With the help of the various elements described in this Nine Pillars of Successful Weight Loss, the reduction in body fat one may see should provide a strong motivational basis to initiate more sensible food intake patterns.
It’s never too late to change one’s lifestyle in a manner that promotes better health while melting away excess body fat.
Lifestyle changes are clearly critical to safe and responsible loss of weight and body fat and provide additional quality-of-life benefits that vastly exceed simple reduction in disease risk. Clinicians and patients who are truly committed to attaining a long and happy life will always include responsible diet and moderate exercise programs in their long-term plans.
If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370.
1. Available at: http://www.lef.org.magazine/mag96/aug_new_therapies.html. Accessed January 2, 2008.
2. Yamasa T, Ikeda S, Koga S, et al. Evaluation of glucose tolerance, post-prandial hyperglycemia and hyperinsulinemia influencing the incidence of coronary heart disease. Intern Med. 2007;46(9):543-6.
3. Rodriguez-Moran M, Guerrero-Romero F. Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial. Diabetes Care. 2003 Apr;26(4):1147-52.
4. Yasmin T, Shara M, Bagchi M, Preuss HG, Bagchi D. Toxicological assessment of a novel niacin-bound chromium, known to ameliorate the symptoms of metabolic syndromes. J Amer College Nutr. 45th Annual Meeting, Abs 77. (Long Beach, California.) 2004 Oct;76(2):272-5.
5. Anderson RA, Cheng N, Bryden NA, et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes. 1997 Nov;46(11):1786-91.
6. Grassi D, Necozione S, Lippi C, et al. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension. 2005 Aug;46(2):398-405.
7. Ebbesson SO, Risica PM, Ebbesson LO, Kennish JM, Tejero ME. Omega-3 fatty acids improve glucose tolerance and components of the metabolic syndrome in Alaskan Eskimos: the Alaska Siberia project. Int J Circumpolar Health. 2005 Sep;64(4):396-408.
8. Wilkins C, Long RC, Jr., Waldron M, Ferguson DC, Hoenig M. Assessment of the influence of fatty acids on indices of insulin sensitivity and myocellular lipid content by use of magnetic resonance spectroscopy in cats. Am J Vet Res. 2004 Aug;65(8):1090-9.
9. Emral R, Koseoglulari O, Tonyukuk V, et al. The effect of short-term glycemic regulation with gliclazide and metformin on postprandial lipemia. Exp Clin Endocrinol Diabetes. 2005 Feb;113(2):80-4.
10. Deutsch JC, Santhosh-Kumar CR, Kolhouse JF. Efficacy of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med. 1996 Jan 25;334(4):269-70.
11. Charles MA, Eschwege E. Prevention of type 2 diabetes: role of metformin. Drugs. 1999;58 Suppl 1:71-3.
12. Paolisso G, Amato L, Eccellente R, et al. Effect of metformin on food intake in obese subjects. Eur J Clin Invest. 1998 Jun;28(6):441-6.
13. Henry RR, Wiest-Kent TA, Scheaffer L, Kolterman OG, Olefsky JM. Metabolic consequences of very-low-calorie diet therapy in obese non-insulin-dependent diabetic and nondiabetic subjects. Diabetes. 1986 Feb;35(2):155-64.
14. Larson-Meyer DE, Heilbronn LK, Redman LM, et al. Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects. Diabetes Care. 2006 Jun;29(6):1337-44.
15. Bodkin NL, Ortmeyer HK, Hansen BC. Long-term dietary restriction in older-aged rhesus monkeys: effects on insulin resistance. J Gerontol A Biol Sci Med Sci. 1995 May;50(3):B142-7.
16. Gumbs AA, Modlin IM, Ballantyne GH. Changes in insulin resistance following bariatric surgery: role of caloric restriction and weight loss. Obes Surg. 2005 Apr;15(4):462-73.
17. Nakai Y, Taniguchi A, Fukushima M, et al. Insulin sensitivity during very-low-calorie diets assessed by minimal modeling. Am J Clin Nutr. 1992 Jul;56(1 Suppl):179S-81S.
18. Abate N, Haffner SM, Garg A, Peshock RM, Grundy SM. Sex steroid hormones, upper body obesity, and insulin resistance.J Clin Endocrinol Metab. 2002 Oct;87(10):4522-7.
19. Vermeulen A, Kaufman JM, Goemaere S, van Pottelberg I. Estradiol in elderly men. Aging Male. 2002 Jun;5(2):98-102.
20. Marin P, Krotkiewski M, Bjorntorp P. Androgen treatment of middle-aged, obese men: effects on metabolism, muscle and adipose tissues. Eur J Med. 1992 Oct;1(6):329-36.
21. Villareal DT, Holloszy JO. Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial. JAMA. 2004 Nov 10;292(18):2243-8.
22. Mayes JS, Watson GH. Direct effects of sex steroid hormones on adipose tissues and obesity. Obes Rev. 2004 Nov;5(4):197-216.
23. Björntorp, P. The regulation of adipose tissue distribution in humans. Int J Obes Relat Metab Disord. 1996 Apr;20(4):291-302.
24. Haffner SM. Abdominal adiposity and cardiometabolic risk: do we have all the answers? Am J Med. 2007 Sep;120(9 Suppl 1):S10-6.
25. Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006 Dec 14;444(7121):881-7.
26. Bergman RN, Kim SP, Hsu IR, et al. Abdominal obesity: role in the pathophysiology of metabolic disease and cardiovascular risk. Am J Med. 2007 Feb;120(2 Suppl 1):S3-S8.
27. Whitmer RA. The epidemiology of adiposity and dementia. Curr Alzheimer Res. 2007 Apr;4(2):117-22.
28. Lee CD, Jacobs DR Jr, Schreiner PJ, Iribarren C, Hankinson A. Abdominal obesity and coronary artery calcification in young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Am J Clin Nutr. 2007 Jul;86(1):48-54.
29. Botton J, Heude B, Kettaneh A, et al. Cardiovascular risk factor levels and their relationships with overweight and fat distribution in children: the Fleurbaix Laventie Ville Santé II study. Metabolism. 2007 May;56(5):614-22.
30. Connelly PW, Hanley AJ, Harris SB, Hegele RA, Zinman B. Relation of waist circumference and glycemic status to C-reactive protein in the Sandy Lake Oji-Cree. Int.J Obes Relat Metab Disord. 2003 Mar;27(3):347-54.
31. Arslan U, Türkoğlu S, Balcioğlu S, Tavil Y, Karakan T, Cengel A. Association between nonalcoholic fatty liver disease and coronary artery disease. Coron Artery Dis. 2007 Sep;18(6):433-6.
32. Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology. 2003 Jan;124(1):71-9.
33. Vozarova B, Stefan N, Lindsay RS, et al. High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes. Diabetes. 2002 Jun;51(6):1889-95.
34. McCarty MF. Glucomannan minimizes the postprandial insulin surge: a potential adjuvant for hepatothermic therapy. Med Hypotheses. 2002 Jun;58(6):487-90.
35. Available at: http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=181996. Accessed January 9, 2008.
36. Liu S, Willett WC, Manson JE, et al. Relation between changes in intakes of dietary fiber and grain products and changes in weight and development of obesity among middle-aged women. Am J Clin Nutr. 2003 Nov;78(5):920-7.
37. Appleby PN, Thorogood M, Mann JI, Key TJ. Low body mass index in non-meat eaters: the possible roles of animal fat, dietary fibre and alcohol. Int J Obesity Relat Metab Disord. 1998 May;22(5):454-60.
38. Ludwig DS, Pereira MA, Kroenke CH, et al. Dietary fiber, weight gain, and cardiovascular disease risk factors in young adults. JAMA. 1999 Oct 27;282(16):1539-46.
39. Kromhout D, Bloemberg B, Seidell JC, Nissinen A, Menotti A. Physical activity and dietary fiber determine population body fat levels: the Seven Countries Study. Int J ObeS Relat Metab Disord. 2001 Mar;25(3):301-6.
40. Reyna-Villasmil N, Bermudez-Pirela V, Mengual-Moreno E, et al. Oat-derived beta-glucan significantly improves HDLC and diminishes LDLC and non-HDL cholesterol in overweight individuals with mild hypercholesterolemia. Am J Ther. 2007 Mar;14(2):203-12.
41. Poppitt SD, van Drunen JD, McGill AT, Mulvey TB, Leahy FE. Supplementation of a high-carbohydrate breakfast with barley beta-glucan improves postprandial glycaemic response for meals but not beverages. Asia Pac J Clin Nutr. 2007;16(1):16-24.
42. Luo W, Cao J, Li J, He W. Adipose tissue-specific PPARgamma deficiency increases resistance to oxidative stress. Exp Gerontol. 2007 Nov 21.
43. Ziccardi P, Nappo F, Giugliano G, et al. Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation. 2002 Feb 19;105(7):804-9.
44. Hawley JA, Lessard SJ. Exercise training-induced improvements in insulin action. Acta Physiol (Oxf). 2008 Jan;192(1):127-35.
45. Bodary PF, Iglay HB, Eitzman DT. Strategies to reduce vascular risk associated with obesity. Curr Vasc Pharmacol. 2007 Oct;5(4):249-58.
46. Williams MJ, Williams SM, Milne BJ, Hancox RJ, Poulton R. Association between C-reactive protein, metabolic cardiovascular risk factors, obesity and oral contraceptive use in young adults. Int J Obes Relat Metab Disord. 2004 Aug;28(8):998-1003.
47. Kim YJ, Shin YO, Bae JS, et al. Beneficial effects of cardiac rehabilitation and exercise after percutaneous coronary intervention on hsCRP and inflammatory cytokines in CAD patients. Pflugers Arch. 2007 Sep 29.
48. Milani RV, Lavie CJ, Mehra MR. Reduction in C-reactive protein through cardiac rehabilitation and exercise training. J Am Coll Cardiol. 2004 Mar 17;43(6):1056-61.
49. Lee M, Aronne LJ. Weight management for type 2 diabetes mellitus: global cardiovascular risk reduction. Am J Cardiol. 2007 Feb 19;99(4A):68B-79B.
50. Leigh C. Serotonin and the Biology of Bingeing. Eating Disorders: A Reference Sourcebook. In: Lemberg R. Ed., Oryx Press; 1998:51.
51. Breum L, Rasmussen MH, Hilsted J, Fernstrom JD. Twenty-four-hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction. Am J Clin Nutr. 2003 May;77(5):1112-8.
52. Brandacher G, Hoeller E, Fuchs D, Weiss HG. Chronic immune activation underlies morbid obesity: is IDO a key player? Curr Drug Metab. 2007 Apr;8(3):289-95.
53. Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003 Dec;112(12):1821-30.
54. Cavaliere H, Medeiros-Neto G. The anorectic effect of increasing doses of L-tryptophan in obese patients. Eat Weight Disord. 1997 Dec;2(4):211-5.
55. Heraief E, Burckhardt P, Wurtman JJ, Wurtman RJ. Tryptophan administration may enhance weight loss by some moderately obese patients on a protein-sparing modified fast (PSMF) diet. Int J Eating Disord. 1985:4(3):281-92.
56. Abidov M, Roshen S. Effect of Fucoxanthin and Xanthigen™, a phytomedicine containing fucoxanthin and pomegranate seed oil, on energy expenditure rate in obese non-diabetic female volunteers with non-alcoholic fatty liver disease: a double-blind, randomized and placebo-controlled trial. Submitted for publication. Int J Obesity. 2008.
57. Abidov M, Siefulla R, Ramazanov Z. The effect of Xanthigen™, a phytomedicine containing fucoxanthin and pomegranate seed oil, on body weight and liver fat, serum triglycerides, C-reactive protein, and plasma aminotransferases in obese non-diabetic female volunteers: a double-blind, randomized and placebo-controlled trial. Submitted for publication. Int J Obesity. 2008.
58. Dulloo AG, Duret C, Rohrer D, et al. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr. 1999 Dec;70(6):1040-5.
59. Dulloo AG, Seydoux J, Girardier L, Chantre P, Vandermander J. Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity. Int J Obes Relat Metab Disord. 2000 Feb;24(2):252-8.
60. Li JJ, Huang CJ, Xie D. Anti-obesity effects of conjugated linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid. Mol Nutr Food Res. 2008 Jun;52(6):631-45.
61. Wang YW, Jones PJ. Conjugated linoleic acid and obesity control: efficacy and mechanisms. Int J Obes Relat Metab Disord. 2004 Aug;28(8):941-55.
62. Matsumoto T, Miyawaki C, Ue H, Yuasa T, Miyatsuji A, Moritani T. Effects of capsaicin-containing yellow curry sauce on sympathetic nervous system activity and diet-induced thermogenesis in lean and obese young women. J Nutr Sci Vitaminol (Tokyo). 2000 Dec;46(6):309-15.
63. Ohnuki K, Niwa S, Maeda S, Inoue N, Yazawa S, Fushiki T.CH-19 sweet, a non-pungent cultivar of red pepper, increased body temperature and oxygen consumption in humans. Biosci Biotechnol Biochem. 2001 Sep;65(9):2033-6.
64. Eldershaw TP, Colquhoun EQ, Dora KA, Peng ZC, Clark MG. Pungent principles of ginger (Zingiber officinale) are thermogenic in the perfused rat hindlimb. Int J Obes Relat Metab Disord. 1992 Oct;16(10):755-63.
65. Safar ME, Czernichow S, Blacher J. Obesity, arterial stiffness, and cardiovascular risk. J Am Soc Nephrol. 2006 Apr;17(4 Suppl 2):S109-11.
66. Rosa EC, Zanella MT, Ribeiro AB, Kohlmann JO. Visceral obesity, hypertension and cardio-renal risk: a review. Arq Bras Endocrinol Metabol. 2005 Apr;49(2):196-204.
67. Rush EC, Chandu V, Plank LD. Reduction of abdominal fat and chronic disease factors by lifestyle change in migrant Asian Indians older than 50 years. Asia Pac J Clin Nutr. 2007;16(4):671-6.
68. Rokling-Andersen MH, Reseland JE, Veierod MB, et al. Effects of long-term exercise and diet intervention on plasma adipokine concentrations. Am J Clin Nutr. 2007 Nov;86(5):1293-301.
69. 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 Jun;15(6):1473-83.
70. Slentz CA, Aiken LB, Houmard JA, et al. Inactivity, exercise, and visceral fat. STRRIDE: a randomized, controlled study of exercise intensity and amount. J Appl Physiol. 2005 Oct;99(4):1613-8.
71. Reeves GK, Pirie K, Beral V, et al. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. BMJ. 2007 Dec 1;335(7630):1134.
72. Setiawan VW, Stram DO, Nomura AM, Kolonel LN, Henderson BE. Risk factors for renal cell cancer: the multiethnic cohort. Am J Epidemiol. 2007 Oct 15;166(8):932-40.
73. Ahrens W, Timmer A, Vyberg M, et al. Risk factors for extrahepatic biliary tract carcinoma in men: medical conditions and lifestyle: results from a European multicentre case-control study. Eur J Gastroenterol Hepatol. 2007 Aug;19(8):623-30.
74. Campbell KL, McTiernan A. Exercise and biomarkers for cancer prevention studies. J Nutr. 2007 Jan;137(1 Suppl):161S-9.
75. Schapira DV, Kumar NB, Lyman GH. Estimate of breast cancer risk reduction with weight loss. Cancer. 1991 May 15;67(10):2622-5.
76. Khaitan L, Smith CD. Obesity in the United States: is there a quick fix? Pros and cons of bariatric surgery from the adult perspective. Curr Gastroenterol Rep. 2005 Dec;7(6):451-4.
77. Celio CI, Luce KH, Bryson SW, et al. Use of diet pills and other dieting aids in a college population with high weight and shape concerns. Int J Eat Disord. 2006 Sep;39(6):492-7.
78. Cohen PA, McCormick D, Casey C, Dawson GF, Hacker KA. Imported compounded diet pill use among Brazilian women immigrants in the United States. J Immigr Minor Health. 2007 Dec 9 [Epub ahead of print].
79. Fleming RM. The effect of ephedra and high fat dieting: a cause for concern! A case report. Angiology. 2007 Feb-Mar;58(1):102-5.
80. Rakovec P, Kozak M, Sebestjen M. Ventricular tachycardia induced by abuse of ephedrine in a young healthy woman. Wien Klin Wochenschr. 2006 Sep;118(17-18):558-61.
81. Blanck HM, Serdula MK, Gillespie C, et al. Use of nonprescription dietary supplements for weight loss is common among Americans. J Am Diet Assoc. 2007 Mar;107(3):441-7.