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Brief Communication: Sleep Curtailment in Healthy Young Men Is Associated with Decreased Leptin Levels, Elevated Ghrelin Levels, and Increased Hunger and Appetite

Karine Spiegel, PhD; Esra Tasali, MD; Plamen Penev, MD, PhD; and Eve Van Cauter, PhD
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From University of Chicago, Chicago, Illinois, and Université Libre de Bruxelles, Brussels, Belgium.

Acknowledgment: The authors thank Paul Rue for performing the leptin assays, Miho Yoshida for performing the ghrelin assays, and Kristen Knutson for providing statistical assistance. The authors also thank the volunteers for their participation in this demanding study and the nursing staff of the University of Chicago General Clinical Research Center for their expert assistance.

Grant Support: In part by grants from the National Institutes of Health (DK-41814, AG-11412, and HL-72694), from the European Sleep Research Society, from the Belgian Fonds de la Recherche Scientifique Médicale (FRSM-3.4583.02), from the University of Chicago Diabetes Research and Training Grant (NIH DK-20595), and from The University of Chicago General Clinical Research Center (NIH MO1-RR-00055).

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Eve Van Cauter, PhD, Department of Medicine, MC 1027, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637.

Current Author Addresses: Dr. Spiegel: Laboratoire de Physiologie, Centre d'Etude des Rythmes Biologiques (CERB), Université Libre de Bruxelles, Campus Hôpital Erasme–CPI 604, 808, Route de Lennik, B-1070 Brussels, Belgium.

Drs. Tasali, Penev, and Van Cauter: Department of Medicine, MC 1027, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637.

Author Contributions: Conception and design: K. Spiegel, E. Van Cauter.

Analysis and interpretation of the data: K. Spiegel, E. Tasali, P. Penev, E. Van Cauter.

Drafting of the article: K. Spiegel, E. Tasali, E. Van Cauter.

Critical revision of the article for important intellectual content: E. Tasali, P. Penev, E. Van Cauter.

Final approval of the article: K. Spiegel, E. Tasali, P. Penev, E. Van Cauter.

Provision of study materials or patients: E. Van Cauter.

Statistical expertise: E. Van Cauter.

Obtaining of funding: K. Spiegel, E. Van Cauter.

Administrative, technical, or logistic support: E. Van Cauter.

Collection and assembly of data: K. Spiegel, E. Tasali, E. Van Cauter.

Ann Intern Med. 2004;141(11):846-850. doi:10.7326/0003-4819-141-11-200412070-00008
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Leptin levels were stable across the daytime period under both sleep conditions, which was consistent with the fact that calories were exclusively delivered in the form of a constant glucose infusion. Average total sleep time was 9 hours and 8 minutes when the men spent 10 hours in bed and 3 hours and 53 minutes when the men spent 4 hours in bed (P < 0.01). When spending 4 hours in bed, the participants had mean leptin levels that were 18% lower (2.1 ng/mL vs. 2.6 ng/mL; P = 0.04) (Figure 1, part A) and mean ghrelin levels that were 28% higher (3.3 ng/mL vs. 2.6 ng/mL; P = 0.04) (Figure 1, part B) than when the participants spent 10 hours in bed. The ratio of the concentrations of orexigenic ghrelin to anorexigenic leptin increased by 71% (CI, 7% to 135%) with 4 hours in bed compared with 10 hours in bed. Sleep restriction relative to sleep extension was associated with a 24% increase in hunger ratings on the 10-cm visual analogue scale (P < 0.01) and a 23% increase in appetite ratings for all food categories combined (P = 0.01) (Figure 1, parts C and D, and Table 1). The increase in appetite tended to be greatest for calorie-dense foods with high carbohydrate content (sweets, salty foods, and starchy foods: increase, 33% to 45%; P = 0.06) (Table 1). The increase in appetite for fruits and vegetables was less consistent and of lesser magnitude (increase, 17% to 21%) (Table 1). Appetite for protein-rich nutrients (meat, poultry, fish, eggs, and dairy foods) was not significantly affected by sleep duration (Table 1). When we considered the changes in ghrelin and leptin in an integrated fashion by calculating the ghrelin-to-leptin ratio, the increase in hunger was proportional to the increase in ghrelin-to-leptin ratio (r = 0.87) (Figure 2). Almost 70% of the variance in increased hunger could be accounted for by the increase in the ghrelin-to-leptin ratio.

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Figure 1.
Effect of sleep duration on daytime leptin levels, ghrelin levels, hunger, and appetite.

A. Mean (±SE) daytime (9:00 a.m. to 9:00 p.m.) profiles of leptin after 2 days with 4 hours in bed or 2 days with 10 hours in bed. Mean leptin levels were 18% lower when sleep was restricted. B. Mean (±SE) daytime (9:00 a.m. to 9:00 p.m.) profiles of ghrelin from 9 of the 12 participants after 2 days with 4 hours in bed or 2 days with 10 hours in bed. Mean ghrelin levels were 28% higher in the afternoon and early evening (12:00 noon to 9:00 p.m.) when sleep was restricted. C and D. Ratings of hunger (C) (0- to 10-cm visual analogue scale) and overall appetite (D) (0- to 70-cm visual analogue scale) after 2 days with 4 hours in bed or 2 days with 10 hours in bed. When sleep was restricted, ratings of hunger and overall appetite increased by 24% and 23%, respectively.

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Figure 2.
Association between the change in hunger ratings and the change in ghrelin-to-leptin ratio during the 12:00 noon to 9:00 p.m. time period when sleep is restricted as compared with extended.

The changes in hunger ratings and in ghrelin-to-leptin ratio were calculated as the values obtained after 4 hours in bed minus the values obtained after 10 hours in bed. For each of these variables, negative values were obtained when the variable measured after 10 hours in bed was higher than when measured after 4 hours in bed. The Spearman coefficient was 0.87 and the p value was 0.01.

Grahic Jump Location




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Desperately Seeking Serotonin
Posted on December 14, 2004
Calvin Ezrin
Conflict of Interest: None Declared

The authors suggest other factors in addition to leptin and ghrelin may be involved in the change in appetite from sleep curtailment (1). Of special significance in this study was the craving for foods of high carbohydrate content (2). Serotonin deficiency has long been linked with carbohydrate craving (3). A good night's sleep produced by the sedative- hypnotic trazodone has been shown to curb carbohydrate craving and in my clinical experience facilitates significant weight loss (4). Trazodone (a serotonin modulator) appears to improve the depth and restorative quality of sleep which influences central autonomic functions that likely affect ghrelin and leptin (5). The SSRI's do not produce this effect.

Trazodone deserves to be considered for obese patients with disturbed sleep manifested by middle of the night awakening, snoring, sleep apnea and daytime fatigue. It should also be the subject of controlled studies to justify it's more general acceptance as therapy for stressed, carbohydrate craving, obese patients who are also likely sleep deprived but may not complain of it.

References 1. Flier,J.S.,Elmquist,J.K. A good night's sleep: future antidote to the obesity epidemic. Ann Intern Med 2004; 141 885-886 2. Speigel,K.,Tasali,E.,Penev,P.,Van Cauter,E.Brief Communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite Ann Intern Med 2004;141: 846-850 3. Wurtman,R.et al.-Carbohydrate craving in obese people: supression by treatments affecting serotoninergic neurotransmission. Int J Eating Dis 1981; 1:2-15 4. Ezrin,C.,Caron,K.L. Desperately seeking serotonin,pp 45-50 in Your Fat Can Make You Thin, New York; McGraw-Hill 2001 5. Ware,J.C..Pittard,J.T. Increased deep sleep after trazodone use: a double-blind placebo controlled study in healthy young adults. J. Clin Psychiatry 1990;51:9(suppl)18-22

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Summary for Patients

Sleep Duration and Levels of Hormones That Influence Hunger

The summary below is from the full report titled “Brief Communication: Sleep Curtailment in Healthy Young Men Is Associated with Decreased Leptin Levels, Elevated Ghrelin Levels, and Increased Hunger and Appetite.” It is in the 7 December 2004 issue of Annals of Internal Medicine (volume 141, pages 846-850). The authors are K. Spiegel, E. Tasali, P. Penev, and E. Van Cauter.


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