Life Extension Magazine

Life Extension Magazine August 2012


Block Food Cravings At Their Molecular Root

By Michael Downey


1. Noury J, Bourges C. Enquête sur l'impact du complément alimentaire SATIEREAL chez des femmes ayant une tendance à l'hyperphagie réflexe non pathologique. Nutraveris. 2006; unpublished study.

2. Gout B, Bourges C, Paineau-Dubreuil S. Satiereal, a Crocus sativus L extract, reduces snacking and increases satiety in a randomized placebo-controlled study of mildly overweight, healthy women. Nutr Res. 2010 May;30(5):305-13.

3. Greeno CG, Wing RR. Stress-induced eating. Psychol Bull. 1994 May;115(3):444-64.

4. Lattimore P, Caswell N. Differential effects of active and passive stress on food intake in restrained and unrestrained eaters. Appetite. 2004 Apr;42(2):167-73.

5. Polivy J, Herman CP. Distress and eating: why do dieters overeat? Int J Eat Disord. 1999 Sep;26(2):153-64.

6. Laitinen J, Ek E, Sovio U. Stress-related eating and drinking behavior and body mass index and predictors of this behavior. Prev Med. 2002 Jan;34(1):29-39.

7. Pecoraro N, Reyes F, Gomez F, Bhargava A, Dallman MF. Chronic stress promotes palatable feeding, which reduces signs of stress: feedforward and feedback effects of chronic stress. Endocrinology. 2004 Aug;145(8):3754-62.

8. Adam TC, Epel ES. Stress, eating and the reward system. Physiol Behav. 2007;91:449-58.

9. Warne JP. Shaping the stress response: interplay of palatable food choices, glucocorticoids, insulin and abdominal obesity. Mol Cell Endocrinol. 2009 Mar 5;300(1-2):137-46.

10. Johnson PM, Kenny, PJ. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010 May;13(5):635-41.

11. Dallman MF, Pecoraro N, Akana SF, et al. Chronic stress and obesity: a new view of "comfort food." PNAS USA. 2003;100: 11696-701.

12. Bjorntorp P, Rossner S, Udden J. "Consolatory eating" is not a myth. Stress-induced increased cortisol levels result in leptin-resistant obesity. Lakartidningen. 2001;98:5458-61.

13. Alsiö J, Olszewski PK, Levine AS, Schiöth HB. Feed-forward mechanisms: Addiction-like behavioral and molecular adaptations in overeating. Front Neuroendocrinol. Epub 2012 Jan 28.

14. Available at: Accessed March 21, 2012.

15. Centers for Disease Control and Prevention (CDC). Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: U.S. Department of Health and Human Services interim public health recommendations, November 1997. MMWR. Morbidity and mortality weekly report 46. 1997;(45):1061-6.

16. Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine-phentermine. NEJM. 1997 Aug 28;337(9):581-8.

17. Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and the risk of hemorrhagic stroke.NEJM. 2000 Dec;343(25): 1826-32.

18. Berthoud HR, Lenard NR, Shin AC. Food reward, hyperphagia, and obesity. Am J Physiol Regul Integr Comp Physiol. 2011 Jun;300(6):R1266-77.

19. Hosseinzadeh H, Noraei NB. Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice. Phytother Res. 2009 Jun;23(6):768-74.

20. Rodgers RJ, Holch P, Tallett AJ. Behavioural satiety sequence (BSS): Separating wheat from chaff in the behavioural pharmacology of appetite. Pharmacol Biochem Behav. 2010 Nov;97(1):3-14.

21. Connolly HM, Crary JL, McGoon MD,et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med. 1997 Aug 28;337(9):581-8.

22. Dye L, Blundell JE. Menstrual cycle and appetite control: implications for weight regulation. Hum Reprod. 1997 Jun;12(6):1142-51.

23. Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi AH, Khalighi-Cigaroudi F. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816]. BMC Complement Altern Med. 2004 Sep 2;4:12.

24. Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N, Jamshidi AH. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial. J Ethnopharmacol. 2005 Feb 28;97(2):281-4.

25. Akhondzadeh Basti A, Moshiri E, Noorbala AA, Jamshidi AH, Abbasi SH, Akhondzadeh S. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):439-42.

26. Cascade E, Kalali AH, Kennedy SH. Real-world data on SSRI antidepressant side effects. Psychiatry (Edgmont). 2009 Feb;6 (2):16-8.

27. Zimmerman M, Galione JN, Attiullah N, et al. Underrecognition of clinically significant side effects in depressed outpatients. J Clin Psychiatry. 2010 Apr;71(4):484-90.

28. Lee KU, Lee YM, Nam JM, et al. Antidepressant-induced sexual dysfunction among newer antidepressants in a naturalistic setting. Psychiatry Investig. 2010 Mar;7(1):55-9.

29. Spencer RL, Hutchinson KE. Alcohol, Aging, and the Stress Response. Alcohol Res & Health. Winter 1999.

30. O'Rourke DA, Wurtman JJ, Wurtman RJ, et al. Aberrant snacking patterns and eating disorders in patients with obsessive compulsive disorder. J Clin Psychiatry. 1994 Oct;55(10):445-7.

31. Slotkin TA, McCook EC, Ritchie JC, Seidler FJ. Do glucocorticoids contribute to the abnormalities in serotonin transporter expression and function seen in depression? An animal model. Biol Psychiatry. 1996 Oct1;40(7):576-84.

32. Hosseinzadeh H, Noraei NB. Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice. Phytother Res. 2009 Jun;23(6):768-74.

33. Wang Y, Han T, Zhu Y, et al. Antidepressant properties of bioactive fractions from the extract of Crocus sativus L. J Nat Med. 2010 Jan;64(1):24-30.

34. Moshiri E, Basti AA, Noorbala AA, Jamshidi AH, Hesameddin Abbasi S, Akhondzadeh S. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trial. Phytomedicine. 2006 Nov;13(9-10):607-11.

35. Pitsikas N, Boultadakis A, Georgiadou G, Tarantilis PA, Sakellaridis N. Effects of the active constituents of Crocus sativus L., crocins, in an animal model of anxiety. Phytomedicine. 2008 Dec;15(12):1135-9.

36. Vinson JA, Burnham BR, Nagendran MV. Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects. Diabetes Metab Syndr Obes. 2012;5:21-7.

37. Available at: Accessed May 1, 2012.

38. Abdullaev FI. Plant-derived agents against cancer. In: Gupta SK, ed. Pharmacology and Therapeutics in the New Millennium. New Delhi: Narosa Publishing House; 2001:345-54.

39. Escribano J, Alonso GL, Coca-Prados M, Fernandez JA. Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro. Cancer Lett. 1996;100(1-2):22-30.

40. Chryssanthi DG, Lamari FN, Iatrou G, Pylara A, Karamanos NK, Cordopatis P. Inhibition of breast cancer cell proliferation by style constituents of different Crocus species. Anticancer Res. 2007;27(1A):357-62.

41. Abdullaev JF, Caballero-Ortega H, Riverón-Negrete L, et al. In vitro evaluation of the chemopreventive potential of saffron. Rev. Invest. Clin. 2002;54(5):430-6.

42. Abdullaev FI. Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.). Exp Biol Med. 2002;227:20-5.

43. Nair SC, Salomi MJ, Pannikar. B, Pannikar KR. Modulatory effects of the extracts of saffron and Nigela sativa against cisplatinum induced toxicity in mice. J Ethnopharmacol. 1991;31:75-83.

44. el Daly ES. Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats. J Pharm Belg. 1998 Mar-Apr;53(2):87-93; discussion 93-5.

45. Hosseinzadeh H, Sadeghnia HR. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. Jour Pharm Pharmaceut Sci. 2005;8(3):394-9.

46. Assimopoulou AN, Sinakos Z, Papageorgiou VP. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res. 2005 Nov;19(11):997-1000.

47. Papandreou MA, Tsachaki M, Efthimiopoulos S, Cordopatis P, Lamari FN, Margarity M. Memory enhancing effects of saffron in aged mice are correlated with antioxidant protection. Behav Brain Res. 2011 Jun 1;219(2):197-204.

48. Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, et al. Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial. Phytother Res. 2005 Feb;19(2):148-51.

49. Fetissov SO, Meguid MM. Serotonin delivery into the ventromedial nucleus of the hypothalamus affects differently feeding pattern and body weight in obese and lean Zucker rats. Appetite. 2010 Apr;54(2):346-53.

50. Yamauchi M, Tsuruma K, Imai S, et al. Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase activity. Eur J Pharmacol. 2011 Jan 10;650(1):110-9.

51. Maccarone R, Di Marco S, Bisti, S. Saffron supplement maintains morphology and function after exposure to damaging light in mammalian retina. Invest Ophth Visual. 2008 Mar;49(3):1254-61.

52. Falsini B, Piccardi M, Minnella A, et al. Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration. Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6118-24.

53. Moghaddasi MS. Saffron chemicals and medicine usage. Jour Med Plants Res. 2010 Mar;4(6):427-30.

54. Winterhalter P, Straubinger M. Saffron-renewed interest in an ancient spice. Food Rev Int. 2000;16(1):39-59.

55. Verma RS, Middha D. Analysis of saffron (Crocus sativus L. stigma) components by LC–MS–MS. Chromatographia. 2010;71 (1-2):117-23.

56. Pfander H, Schurtenberge H. Biosynthesis of C20-carotenoids in Crocus sativus. Phytochemistry. 1982;21:1039-42.

57. Himeno H, Sano K. Synthesis of crocin, picrocrocin and safranal by saffron stigma-like structures proliferated in vitro. Agric Biol Chem. 1987;51(9):2395-400.

58. Rödel W, Petrzika M. Analysis of the volatile components of saffron. J High Res Chromatogr. 1991;14:771-4.

59. Iborra JL, Castellar MR, Cánovas M, Manjón A. TLC preparative purification of picrocrocin, HTCC and crocin from saffron. J Food Sci. 1992;3:714-6.

60. Iborra JL, Castellar MR, Cánovas M, Manjón A. Picrocrocin hydrolysis by immobilized-glucosidase. Biotechnol Lett. 1992;14(6):475-80.

61. Narasimhan H, Chand H, Rajalakshmi D. Saffron, quality evaluation by sensory profile and gas chromatography. J Food Qual. 1992;15:303-14.

62. Sujata V, Ravishankar GA, Venkataraman LV. Methods for the analysis of the saffron metabolites crocin, crocetind, picrocrocin and safranal for the determination of the quality of spice using thin-layer chromatography, HPLC and GC. J Chromatogr. 1992;624(1-2):497-502.

63. Iborra JL, Castellar MR, Cánovas M, Manjón A. Analysis of a packed-bed reactor for hydrolysis of picrocrocin by immobilized β-glucosidase. Enzyme Microb Technol. 1993;15:780-4.

64. Castellar MR, Montijano H, Manjón A, Iborra JL. Preparative high-performance liquid chromatographic purification of saffron secondary metabolites. J Chromatogr. 1993;648:187-90.

65. Tarantilis PA, Polissiou M, Mentzafos D, Terzis A, Manfait M. The structure of dimethylcrocetin. J Chem Crystallogr. 1994;24(11):739-42.

66. Tarantilis PA, Polissiou M, Manfait M. Separation of picrocrocin, cis-trans-crocins and safranal of saffron using high-performance liquid chromatography with photodiode-array detection. J Chromatogr A. 1994;664:55-61.

67. Tarantilis PA, Tsoupras G, Polissiou M. Determination of saffron (Crocus sativus L.) components in crude plant extract using high-performance liquid chromatography-UV-visible photodiode-array detection-mass spectrometry. J Chromatogr A. 1995;699(1-2):107-18.

68. Corti P, Mazzei E, Ferri S, Franchi GG, Dreassi E. High-performance thin layer chromatographic quantitative analysis of picrocrocin and crocetin, active principles of saffron (Crocus sativus L.-Iridaceae): a new method. Phytochem Anal. 1996;7:201-3.

69. Saito K, Utsumi Y. Enhancing effect of UV light on accumulation of carthamine in dyer's saffron florets. Z Naturfosch [C]. 1996;51 (9-10):667-70.

70. Straubinger M, Jezussek M, Waibel R, Winterhalter P. Novel glucosidic constituents from saffron. J Agric Food Chem. 1997;45(5):1678-81.

71. Straubinger M, Bau B. Eckstein S, Fink M, Winterhalter P. Identification of novel glycosidic aroma precursors in saffron (Crocus sativus L.). J Agric Food Chem. 1998;46(8):3238-43.

72. Alonso GL, Salinas MR, Esteban-Infantes FJ, Sánchez-Fernández MA. Determination of safranal from saffron (Crocus sativus L.) by thermal desorption-gas chromatography. J Agric Food Chem. 1996;44:185-88.

73. Alonso GL, Salinas MR, Garijo J. Method to determine the authenticity of aroma of saffron (Crocus sativus L.). J Food Prot. 1998;61(11):1525-8.

74. Tarantilis PA, Polissiou M. Isolation and identification of the aroma components from saffron (Crocus sativus L.). J Agric Food Chem. 1997;45:459-62.

75. Li N, Lin G, Kwan YW, Min D. Simultaneous quantification of five major biologically active ingredients of saffron by high-performance liquid chromatography. J Chromatogr A. 1999;849(2):349-55.

76. Lozano P, Castellar MJ, Simancas MJ, Iborra JL. Quantitative high-performance liquid chromatographic method to analyze commercial saffron (Crocus sativus L.) products. J Chromatogr A. 1999;830:477-83.

77. Lozano P, Delgado D, Gomez D, Rubio M, Iborra JL. A non-destructive method to determine the safranal content of saffron (Crocus sativus L.) by supercritical carbon dioxide extraction combined with high-performance liquid chromatography and gas chromatography. J Biochem Biophys Methods. 2000;4328513-N(1-3):367-78.

78. Bhargava V. Medicinal uses and pharmacological properties of Crocus sativus Linn (Saffron). Int J Pharm Pharm Sci. 2011;3(Suppl 3):22-6.