Offices in Washington, D.C., New Jersey, England, Spain
THE ROLE OF SPECIFIC OLFACTORY STIMULATION IN APPETITE SUPPRESSION AND WEIGHT LOSS
Dr. S.N. Mayer, Dr. R.S. Davidson and Dr. C.B. Hensley
Human Neuro-Sensory Laboratory
A Division of BioTem Cytotechnologies
BIOTEM CYTOTECHNOLOGIES
c/o Mark Cohen, Ph.D.
PO Box 2602
Cherry Hill, NJ 08034
INTRODUCTION:
More than 30% of American adults age 20 and older are overweight (1, 2). Obesity is a serious, chronic disease of epidemic proportions in the United States and is second only to smoking as a risk factor for disease (3). Obesity increases the risk for a number of serious and often fatal comorbid diseases such as non-insulin dependent diabetes mellitus (NIDDM), dyslipidemias, cadiovascular disease, gallbladder disease, osteoarthritis and some forms of cancer such as colon and post menopausal breast cancer (4, 5). Approximately 300,000 deaths each year are attributed to obesity, with obesity and its related diseases costing the American health care system between 40 and 100 billion dollars annually (3, 4, 6). A recent estimate placed the direct economic costs of obesity at more than 5.5% of all medical expenditures (6).
Medical studies have shown that even a modest weight loss of only 10% can significantly reduce obesity-related diseases (7). Yet, despite the fact that over 40% of women and 24% of men in the United States are trying to lose weight, spending over 30 billion dollars annually on weight reduction products, services and programs, less than 5% are actually successful in achieving long-term weight loss. In the last decade or so, there has been a 30% increase in the number of overweight Americans, a greater increase than any past decade (1, 8). Obviously, the myriad of methods used to treat obesity, often involving complicated eating regimens, dietary restrictions and deprivation and even prescription medication, have been unsuccessful in the long term and sometimes even dangerous. Even so, Americans continue to fight the war against excess weight.
One method which seems promising is the role of olfaction in weight regulation. Specifically, the inhalation of positive hedonic (pleasant smelling) scents has been shown to have beneficial effects on appetite and hunger regulation (9, 10, 11). This idea stems from everyday observations of how food aromas affect appetite and from clinical observations of how patients with acute anosmia often gain weight. These observations suggest a breakdown in an olfactory-satiety feedback mechanism. Also, there are scientific EEG and brain mapping studies documenting the effects of the inhalation of particular food scents on brain wave activity (12, 13, 14, 15).
The hunger-satiety cycle is regulated by a variety of interacting factors. Psychological, social and environmental factors, nutrients and metabolic processes and gastric movements initiate hunger signals. Eating (along with associated sensory processes), in turn, activate inhibitory signals leading to satiety. Because of the inherent delay between the swallowing of food and the digestion of food, a short-term signal other than preabsorptive and postabsorptive humoral and neural mechanisms is required (16). It is not simply the digestion of food or physical stomach distention that allows the brain to determine a sense of fullness. Rather, it is a variety of factors which include the aromas of food detected by olfactory receptors that convey messages of how much food has been consumed to the appetite control center of the brain (9, 10, 17).
The anatomical/physiologic mechanisms of olfactory-induced satiety is complex. This olfactory-satiety feedback mechanism is a result of direct anatomical connections between the olfactory bulb and the ventromedial nucleus of the hypothalamus, the satiety center (18). Ambient scents are detected by olfactory receptor cells, bipolar neurons that can distinguish over 10,000 different volatile aroma molecules. The axons of these receptor cells synapse directly with neurons in the olfactory bulb (17, 19). The olfactory bulb is a unique structure because it is actually an outgrowth of the brain and contains almost all of the neurotransmitters found in the rest of the brain including cholecystokinin and somatostatin, gastrointestinal hormones known to control hunger and satiety (20). Recently, it has been demonstrated that the dorsmedial thalamus plays a role in the hedonic perception of food, and that lesions within this region of the brain result in alteration in appetite and loss of weight (21). In addition, anatomical and physiologic results clearly establish a functional/anatomical link between processing of olfactory and visual information in the orbitofrontal cortex of the brain and the control of feeding related behavior (22). These studies indicate that central processing of hedonic clues is important in the short-term regulation of food intake and thus long-term control of body weight.
These new insights into the mechanism of hunger and satiety provide a new approach to an old problem of weight regulation. It is clearly evident that the sense of olfaction via this olfactory-satiety feedback loop has a powerful and immediate effect on appetite regulation. A recent medical study investigated the hypothesis that intentionally inhaling specially formulated, positive-hedonic scents would facilitate weight loss in overweight subjects. In this study, simply inhaling specially formulated scents without any conscious changes in diet or lifestyle, subjects sustained an average weight loss of 2% of body weight per month (4.7 pounds per month) over a six month period (10).
The goals of this present study were to extend these observations and further test the association of the inhalation of the same, specially formulated scents and weight reduction in a double blind, randomized, controlled study to rule out any placebo effects that may have been at work in the above study. This study tests the hypothesis that inhalation of specially formulated, positive-hedonic scents can function in the acute regulation of appetite and contribute to satiety. We also test the hypothesis that the inhalation of positive hedonic scents can lead to sustained weight loss. Finally, this study was designed to delineate the time course and rate of weight loss.
MATERIALS AND METHODS:
Subjects:
Phase one: 80 subjects participated in phase one of the double blind study (36 male and 44 female; ages 18 – 43). Healthy adult volunteers who were at least ten pounds overweight, indicating a desire to lose weight, and with no history of asthma were enrolled in the study. Potential subjects responded to flyers posted at a local university, were screened for the above criteria and were assigned by prior computer randomization to receive either specially formulated scents or placebo scents. The average height and weight of the subjects was 5’3’’ and 136 lbs. (range 110-185) respectively for females and 5’10’’ and 189 lbs. (range 165-220) respectively for males.
Phase two: 30 healthy adult volunteers (9 male and 21 female) with no history of asthma participated in phase two of the study. Potential subjects responded to flyers posted at a local university, were screened for the above criteria and were assigned by prior computer randomization to receive either specially formulated scents or placebo scents.
Materials: The same specifically formulated scents, which have been shown in previous studies by Dr. Alan Hirsch to have an effect on appetite control (10), were provided to each subject in a convenient and practical vehicle (pens). It should be noted that humans are capable of discerning greater than 10,000 different scents and thus olfaction has the potential to provide a wide array of physiologically relevant stimuli. Placebo Scents were developed and supplied by Biotem Cytotechnologies Inc. The placebo pens were exact replicas of the pens containing the specially formulated scents but did not contain these scents and were impregnated with a detergent scent. Both pens containing the specially formulated scents and placebo scents were collected and evaluated for use (remaining scent and pen weight) as a measure of compliance.
Protocol:
Phase One: 80 subjects were provided with the Diet Pens (n=40) or placebo pens (n=40). Each set of test pens contained 3 different scents which were used in an alternate fashion. Each subject received 6 sets of pens and were instructed to change to a new set every three weeks or until the scents began to significantly diminish, which ever occurred first. Subjects were instructed to inhale the scents in each nostril three times for three repeating cycles, 5-6 minutes prior to eating and again within 5-6 minutes after eating. Subjects were instructed to use the pens containg the specially formulated scents or those containing placebo scents before meals, snacks, or whenever they felt the urge to eat. The investigators and subjects did not know which subjects received devices containing the active ingredients. The subjects were instructed not to overtly alter their normal routine of exercise or food selection. Subjects were weighed each week for a duration of sixteen weeks. Subjects were questioned at the end of the study regarding their impressions of the effects of the pens on appetite and food consumption.
Data were collected manually, reduced and analyzed for statistical significance by two tail Student’s t-test. An alpha level of P less than or equal to 0.05 was used for defining statistical significance of differences between treatment groups.
Phase two: 30 Subjects were recruited for phase two of the study. The subjects were provided with the pens containing specially formulated scents (n=15) or placebo scents (n=15). After subjects were presented with olfactory and visual stimuli (a slice of pizza), they were instructed to rank their appetite cravings on a 1-10 scale. Subjects were instructed to inhale the scents from one pen in each nostril three times for three repeating cycles. The subjects were again asked to rank their appetite cravings (1-10) 1 and 5 minutes after smelling the pens. The data were tabulated and the significance of the difference were determine by two tail Student’s t-test.
An alpha level of P less than or equal to 0.05 was used for defining statistical significance of differences between treatment groups.
RESULTS:
Subjects using the pens containing the specially formulated scents lost an average of 19.15 lbs. (11.68% of body weight) compared to placebo scents (3.85 lbs.; 2.43% of body weight) over the 16 week period (Tables 1-3; Figures 1-4). This translates to an effective weight loss of 15.4 lbs. (9.34% of body weight) in subjects using the pens containing the specially formulated scents which was significant at the 99% level of confidence (P less than 0.01). The rate of weight loss over time was slightly sigmoid showing the greatest amount of effectiveness during the middle third of the study (Tables 1-2; Figures 1-2).
Experiments designed to test the efficacy of the specially formulated scents as an acute appetite suppressant demonstrated that the use of the pens containing the specially formulated scents blunted the olfactory/visual stimulated appetite by 35.1% in 1 minute and 49.25% in 5 minutes and both results were significant at the 99.9% level of confidence (Table 4) (P less than 0.001) when compared with placebo ( no reduction in appetite after 1 and 5 minutes).
CONCLUSIONS:
This study confirms the results of a previous study "Weight reduction through Inhalation of Odorants" by Drs. Hirsch and Gomez (10), that the inhalation of certain aromas can aid in appetite control and weight loss and were not just a behavioral response or an effect of being in a study. This study conclusively proves in a randomized, controlled, double-blind fashion that the inhalation of specially formulated scents are effective in appetite reduction, squelching food cravings and weight loss without any conscious dieting or exercising.
Subjects using the pens containing the specially formulated scents as a weight loss tool were able to lose a significant amount of weight over the course of the study, while subjects using the placebo version did not see a significant degree of weight loss. Given that the only difference between the pen containing the specially formulated scents and the placebo was the presence of specific olfactory stimuli, the increased weight loss is attributable to the specially formulated scents themselves. The rate of weight loss was fairly consistent throughout the study demonstrating a lack of habituation to scents over time. This is an important consideration when dealing with olfactory/neural mechanisms.
In addition to affecting appetite and inducing weight loss, this study also shows that the specially formulated scents are very effective in blunting food cravings. Use of the pens containing the specially formulated scents decreased the cravings for food by 35% within one minute and 50% within five minutes. This effect was significantly greater than what was seen with the placebo scents indicating that the majority of the effect was attributable to the specially formulated scents. These results suggest that acute appetite suppression is, at least in part, a viable mechanism for the observed effects of the specially formulated scents on weight loss. This is supported by the fact that subjects using the pens containing the specially formulated scents reported an earlier and an increased sense of satiety while eating. The subjects also reported that they were eating less during the meal and were able to curb snaking by using the pens containing the specially formulated scents.
In conclusion, this study demonstrates that the inhalation of specially formulated scents harnesses the body’s internal appetite control mechanism, the olfactory-satiety feedback loop, by delivering specially formulated, positive hedonic (pleasant) scents triggering the satiety center of the brain without the actual consumption of food. The sense of smell enables the brain to determine a sense of fullness by translating the amount of smell that reaches the olfactory cells into a proportional amount of food one has presumably eaten before any digestion has taken place. Thus inhaling the specially formulated scents, in the absence of food, causes early satiety, squelches food cravings and decreases appetite by "fooling" the brain into thinking that one has eaten a proportional amount of food. In the end, this process turns off hunger, helps the user to stop eating sooner and thus controls the amount of food consumed - a direct link to caloric consumption. This study conclusively proves that inhaling these specially developed scents results in weight loss without any conscious changes in diet or exercise.
LITERATURE CITED
1. Kuczmarski RJ, Flegal KM, Campbell SM,et al: Increasing prevalence of overweight among US adults: The National Health and Nutrition Examination Surveys, 1960 to 1991. JAMA 1994; 272: 205-211.
2. Kurscheid T, Lauterbach K. The cost implications of obesity for health care and society. Int J Obes Relat Metab Disord 1998 Aug;22 Suppl 1:S3-5; discussion S6.
3. McGinnis, JM and Foege, WH. Actual causes of death in the US. Journal of American Medical Association 1993, 270: 2207-2212.
4. Colditz GA. Economic costs of obesity. Am J Clin Nutr 1992 Feb;55(2 Suppl):503S-507S.
5. Pi-Sunyer Fx. Medical Hazards of Obesity. Ann Intern Med 1993; 119: 655-660.
6. Martin LF, Hunter SM, Lauve RM, O'Leary JP. Severe obesity: expensive to society, frustrating to treat, but important to confront. South Med J 1995 Sep;88(9):895-902
7. Goldstein DJ. Beneficial Health Effects of Madest Weight Los. Int J. Obes Relat Metab Disord. 1992: 16: 397-414.
8. Methods of Voluntary weight loss and Control. National Institutes of Health Technology Assessment Conference Statement, March 30 - April 1 1992.
9. Hirsch AR and Dougherty, DD Inhalation of 2-acetylpyridine for weight reduction Vol 18(5) October 1993 pg 570 -572.
10. Hirsch AR, Gomez R. Weight reduction through inhalation of odorants. Journal of Neurological and Orthopedic Medicine and Surgery 1995 16: 26-31.
11. Warwick ZS, Hall WF, Pappas TN, Schiffman SS. Taste and smell sensations enhance the satiating effect of both a high-carbohydrate and high-fat meal in humans. Physiol Behavior 1993; 53-563.
12. Martin, GN The Effect of Food Odour on the human brain: 2 EEG Experiments. Cognition and Brain Sciences Research Centre School of Psychology Middlesex University Enfield EN 3 4 SF. A Summary paper to accompany oral presentation at the British Psychological Society’s London Conference, December 17-18, 1996.
13. Martin, GN. Olfactory influences on the human EEG. J Pyschophysiology Vol 9(2) 1995 page 183.
14. Martin, GN. Human neocortical EEG response to food odour. Chemical Senses 17, 862, 1992.
15. Martin, GN. Brain electrical activity mapping and the human sense of smell. J. Psychophysiol 7, 265, 1993.
16. Plata-Salaman CR. Regulation of hunger and satiety in man. Dig Dis 1991;9(5):253-68
17. Breer H. Odor recognition and second messenger signaling in olfactory receptor neurons. Semin Cell Biol. 1994, 5: 25-32.
18. Brodal A. Neurological anatomy in relation to clinical medicine. 3rd ed. New York: Oxford University Press, 1981; 653, 751.
19. Sullivan SL, Ressler KJ, Buck LB. Odorant receptor diversity and patterned gene expression in the mammalian olfactory epithelium. Prog Clin biol Res. 1994; 39: 75-84.
20. Greer CA. Structural organization fo the olfactory system. In: Getchell TV, Doty Tl, Bartoshuk LM, Snow JB, (eds). Smell and taste in health and disease. New York: Raven Press, 1991; 78.
21. Rousseaux M, Muller P, Gahide I, Mottin Y, Romon M. Disorders of smell, taste, and food intake in a patient with a dorsomedial thalamic infarct. Stroke 1996 Dec;27(12):2328-30
22. Critchley HD, Rolls ET. Hunger and satiety modify the responses of olfactory and visual neurons in the primate orbitofrontal cortex. J Neurophysiol 1996 Apr;75(4):1673-86 |
