Life Extension Magazine July 2006
As We See It
Eating Ourselves to Death
By William Faloon
A fascinating article published in Scientific American shows how caloric restriction favorably affects the genes that cause us to age and die.1
According to Scientific American, restricting food intake is the only longevity strategy “absolutely proven to work”! The article went further to state that reducing food consumption by only 30-40% can result in not just a longer life, but also a far healthier one.
As Life Extension members know, a huge body of evidence indicates that common diseases—including cancer,2-10 diabetes,11-13 cardiovascular,14-19 and neurological disorders20-26—can be forestalled if we could only eat less. Studies funded by the Life Extension Foundation and others have identified specific longevity genes that are favorably altered when food consumption is reduced.27-30
Can You Obtain the Benefits of Caloric Restriction from a Pill?
As we discover how caloric restriction prolongs healthy longevity, it is tantalizing to think that future medicines will be developed to emulate the beneficial gene-expression changes that occur when fewer calories are consumed.
Back in 2002, Life Extension researchers discovered that the drug metformin produces gene-expression changes similar to many of those caused by caloric restriction in mice.31-33 In 2004, Life Extension scientists expanded on research showing that grape extract with resveratrol also causes many of the gene-expression changes that occur in response to reduced food intake in mice.34,35
Previous studies have found that feeding resveratrol to yeast, worms, or flies—or placing them on calorie-restricted diets—extends their life span by about 30-70%.36-47
It is tempting to speculate that humans could achieve some of the benefits of caloric restriction merely by taking grape extract with resveratrol. While a myriad of health benefits are associated with resveratrol consumption, it is not yet proven that resveratrol by itself provides humans with the remarkable benefits of caloric restriction.
Even if resveratrol or metformin prove effective in extending human longevity, there are still pathological consequences to overeating that can result in premature disease and death.48,49 In other words, those seeking to maintain optimal health may always want to avoid over-consumption of calories.
A Novel Method to Suppress Appetite
In the recent Scientific American article that discussed our longevity genes, the prospect of humans radically reducing their food intake was not considered feasible. According to the authors:
“Yet if humans are ever to reap the health benefits of caloric restriction, radical dieting is not a reasonable option.” 1
When this statement was made, the authors were probably unaware that a natural compound had just been developed that suppresses the desire to eat by 29% and reduces food intake in humans by an astounding 36% compared to placebo.50-56
What is even more exciting about this novel compound is that is has been scientifically demonstrated to suppress hunger mechanisms in a way that enables people to reduce their meal portion size and not feel hungry.
The Most Significant Longevity Enhancer Yet Developed!
Based on the data we have reviewed, this appetite-suppressing supplement may become the hottest weight-loss product of all time. We at Life Extension, however, view it somewhat differently.
It is well known that being overweight or obese predisposes humans to a plethora of degenerative diseases. The conventional and alternative medical communities are unanimous in believing that Americans would be healthier if they reduced their body fat. No one disagrees with this fact.
Life Extension scientists, however, believe that even those who eat a normal diet are adversely affecting their longevity genes in a way that shortens both the average and maximum life span.
While most people will use this new appetite-suppressing supplement to achieve cosmetic weight loss, we at Life Extension urge all members (not suffering from malnutrition) to consider using it as a way to achieve some degree of caloric restriction without feeling hungry.
We know that many will enjoy seeing their weight drop, but the real benefit is that by enabling people to consistently eat less, this non-stimulating, natural appetite suppressant could add many years to our healthy life spans.
Be the First to Know
In this month’s issue, we feature an in-depth scientific report on this new appetite-suppressing compound. Members will be impressed by the meticulous human research that has been conducted to document its hunger-controlling effects.
As scientists long ago discovered, our bodies have evolved in a way to protect us against famine by inducing us to overeat whenever food is plentiful. In today’s world, food is widely available, thus stimulating multiple biological pathways in our bodies that tempt us to consume far too many calories. This novel compound safely turns down these hunger mechanisms, thus enabling humans to enjoy satiety while consuming fewer calories.
Members of the Life Extension Foundation are the first to learn about this natural method of reducing calorie intake, which should result in steady weight reduction while favorably affecting longevity genes in a way that increases healthy life span.
1. Available at: www.sciam.com/ article.cfm?articleID=000B73EB-3380-13F6-B38083414B7F0000&sc=I100322. Accessed May 1, 2006.
2. Politi MC, Rabin C, Pinto B. Biologically based complementary and alternative medicine use among breast cancer survivors: relationship to dietary fat consumption and exercise. Support Care Cancer. 2006 Apr 19.
3. Yoshida K, Hirabayashi Y, Watanabe F, Sado T, Inoue T. Caloric restriction prevents radiation-induced myeloid leukemia in C3H/HeMs mice and inversely increases incidence of tumor-free death: implications in changes in number of hemopoietic progenitor cells. Exp Hematol. 2006 Mar;34(3):274-83.
4. van Noord PA. Breast cancer and the brain: a neurodevelopmental hypothesis to explain the opposing effects of caloric deprivation during the Dutch famine of 1944-1945 on breast cancer and its risk factors. J Nutr. 2004 Dec;134(12 Suppl):3399S-406S.
5. Kritchevsky D. Caloric restriction and cancer. J Nutr Sci Vitaminol (Tokyo). 2001 Feb;47(1):13-9.
6. Kritchevsky D. Caloric restriction and experimental mammary carcinogenesis. Breast Cancer Res Treat. 1997 Nov;46(2-3):161-7.
7. Grasl-Kraupp B, Bursch W, Ruttkay-Nedecky B, et al. Food restriction eliminates preneoplastic cells through apoptosis and antagonizes carcinogenesis in rat liver. Proc Natl Acad Sci USA. 1994 Oct 11;91(21):9995-9.
8. Albanes D. Caloric intake, body weight, and cancer: a review. Nutr Cancer. 1987;9(4):199-217.
9. Kritchevsky D, Klurfeld DM. Influence of caloric intake on experimental carcinogenesis: a review. Adv Exp Med Biol. 1986;206:55-68.
10. Weindruch R, Walford RL. Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence. Science. 1982 Mar 12;215(4538):1415-8.
11. Ugochukwu NH, Mukes JD, Figgers CL. Ameliorative effects of dietary caloric restriction on oxidative stress and inflammation in the brain of streptozotocin-induced diabetic rats. Clin Chim Acta. 2006 Feb 28.
12. Heller RF, Heller RF. Hyperinsulinemic obesity and carbohydrate addiction: the missing link is the carbohydrate frequency factor. Med Hypotheses. 1994 May;42(5):307-12.
13. Haffner SM, Stern MP, Mitchell BD, Hazuda HP, Patterson JK. Incidence of type II diabetes in Mexican Americans predicted by fasting insulin and glucose levels, obesity, and body-fat distribution. Diabetes. 1990 Mar;39(3):283-8.
14. Avogaro A. Insulin resistance: trigger or concomitant factor in the metabolic syndrome. Panminerva Med. 2006 Mar;48(1):3-12.
15. Butler MG, Bittel DC, Kibiryeva N, Garg U. C-reactive protein levels in subjects with Prader-Willi syndrome and obesity. Genet Med. 2006 Apr;8(4):243-8.
16. Reaven GM. Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. Panminerva Med. 2005 Dec;47(4):201-10.
17. Petrie JR, Cleland SJ, Small M. The metabolic syndrome: overeating, inactivity, poor compliance or ‘dud’ advice? Diabet Med. 1998 Nov;15 Suppl 3S29-S31.
18. Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci USA. 2004 Apr 27;101(17):6659-63.
19. Fan AZ. Metabolic syndrome and progression of atherosclerosis among middle-aged US adults. J Atheroscler Thromb. 2006 Feb;13(1):46-54.
20. Mattson MP. Neuroprotective signaling and the aging brain: take away my food and let me run. Brain Res. 2000 Dec 15;886(1-2):47-53.
21. Boden-Albala B. Current understanding of multiple risk factors as the metabolic syndrome: distillation or deconstruction. Semin Neurol. 2006 Feb;26(1):108-16.
22. Luchsinger JA, Tang MX, Shea S, Mayeux R. Hyperinsulinemia and risk of Alzheimer disease. Neurology. 2004 Oct 12;63(7):1187-92.
23. Yaffe K, Kanaya A, Lindquist K, et al. The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA. 2004 Nov 10;292(18):2237-42.
24. Rosengren A, Skoog I, Gustafson D, Wilhelmsen L. Body mass index, other cardiovascular risk factors, and hospitalization for dementia. Arch Intern Med. 2005 Feb 14;165(3):321-6.
25. McElroy SL, Kotwal R, Malhotra S, et al. Are mood disorders and obesity related? A review for the mental health professional. J Clin Psychiatry. 2004 May;65(5):634-51.
26. Raikkonen K, Matthews KA, Kuller LH. The relationship between psychological risk attributes and the metabolic syndrome in healthy women: antecedent or consequence? Metabolism. 2002 Dec;51(12):1573-7.
27. Available at: http://www.lef.org/magazine/mag2001/sep2001_report_conference_01.html. Accessed April 26, 2006.
28. Available at: http://www.lef.org/magazine/mag2001/dec2001_report_reprint_01.html. Accessed April 26, 2006.
29. Available at: http://www.lef.org/magazine/mag2002/jun2002_report_kenyon_01.html. Accessed April 26, 2006.
30. Available at: http://www.lef.org/magazine/mag2006/jan2006_cover_lef_01.htm. Accessed April 26, 2006.
31. Available at: http://www.lef.org/magazine/mag2003/2003_preprint_bio_01.html. Accessed April 26, 2006.
32. Available at: http://www.lef.org/magazine/mag2004/jun2004_awsi_01.htm. Accessed April 26, 2006.
33. Dhahbi JM, Mote PL, Wingo J, et al. Caloric restriction alters the feeding response of key metabolic enzyme genes. Mech Ageing Dev. 2001 Jul 31;122(10):1033-48.
34. Available at: http://www.lef.org/magazine/mag2006/jan2006_awsi_01.htm. Accessed May 4, 2006.
35. Hsieh TC, Burfeind P, Laud K, et al. Cell cycle effects and control of gene expression by resveratrol in human breast carcinoma cell lines with different metastatic potentials. Int J Oncol. 1999 Aug;15(2):245-52.
36. Ingram DK, Zhu M, Mamczarz J, et al. Calorie restriction mimetics: an emerging research field. Aging Cell. 2006 Apr;5(2):97-108.
37. Labinskyy N, Csiszar A, Veress G, et al. Vascular dysfunction in aging: potential effects of resveratrol, an anti-inflammatory phytoestrogen. Curr Med Chem. 2006;13(9):989-96.
38. Valenzano DR, Terzibasi E, Genade T, et al. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol. 2006 Feb 7;16(3):296-300.
39. Heilbronn LK, de JL, Frisard MI, et al. Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. JAMA. 2006 Apr 5;295(13):1539-48.
40. Zhang J. Resveratrol inhibits insulin responses in a SirT1-independent pathway. Biochem J. 2006 Apr 21.
41. de la Lastra CA, Villegas I. Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications. Mol Nutr Food Res. 2005 May;49(5):405-30.
42. Gredilla R, Barja G. Minireview: the role of oxidative stress in relation to caloric restriction and longevity. Endocrinology. 2005 Sep;146(9):3713-7.
43. Kloting N, Bluher M. Extended longevity and insulin signaling in adipose tissue. Exp Gerontol. 2005 Nov;40(11):878-83.
44. Wood JG, Rogina B, Lavu S, et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004 Aug 5;430(7000):686-9.
45. Howitz KT, Bitterman KJ, Cohen HY, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae life span. Nature. 2003 Sep 11;425(6954):191-6.
46. Roth GS, Handy AM, Mattison JA, et al. Effects of dietary caloric restriction and aging on thyroid hormones of rhesus monkeys. Horm Metab Res. 2002 Jul;34(7):378-82.
47. Lane MA, Tilmont EM, De AH, et al. Short-term calorie restriction improves disease-related markers in older male rhesus monkeys (Macaca mulatta). Mech Ageing Dev. 2000 Jan 10;112(3):185-96.
48. Vaag A, Brons C, Appel JS, Toubro S. Metabolic consequences of overeating. Ugeskr Laeger. 2006 Jan 9;168(2):183-7.
49. Scheurink AJ, Balkan B, Strubbe JH, van DG, Steffens AB. Overfeeding, autonomic regulation and metabolic consequences. Cardiovasc Drugs Ther. 1996 Jun;10 Suppl 1263-73.
50. Available at: http://www.sciencedaily.com/releases/2006/04/060404085953.htm. Accessed May 1, 2006.
51. Meier JJ, Gethmann A, Gotze O, et al. Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans. Diabetologia. 2006 Mar;49(3):452-8.
52. Paquot N, Tappy L. Adipocytokines: link between obesity, type 2 diabetes and atherosclerosis. Rev Med Liege. 2005 May;60(5-6):369-73.
53. Lee JW, Lee KW, Lee SW, Kim IH, Rhee C. Selective increase in pinolenic acid (all-cis-5,9,12-18:3) in Korean pine nut oil by crystallization and its effect on LDL-receptor activity. Lipids. 2004 Apr;39(4):383-7.
54. Christophe J. Is there appetite after GLP-1 and PACAP? Ann NY Acad Sci. 1998 Dec 11;865:323-35.
55. Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest. 1998 Feb 1;101(3):515-20.
56. Sugano M, Ikeda I, Wakamatsu K, Oka T. Influence of Korean pine (Pinus koraiensis)-seed oil containing cis-5,cis-9,cis-12-octadecatrienoic acid on polyunsaturated fatty acid metabolism, eicosanoid production and blood pressure of rats. Br J Nutr. 1994 Nov;72(5):775-83.
57. Dhahbi JM, Tsuchiya T, Kim HY, Mote PL, Spindler SR. Gene expression and physiologic responses of the heart to the initiation and withdrawal of caloric restriction. J Gerontol A Biol Sci Med Sci. 2006 Mar;61(3):218-31.
58. Spindler SR. Use of microarray biomarkers to identify longevity therapeutics. Aging Cell. 2006 Feb;5(1):39-50.
59. Dhahbi JM, Mote PL, Fahy GM, Spindler SR. Identification of potential caloric restriction mimetics by microarray profiling. Physiol Genomics. 2005 Nov 17;23(3):343-50.