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Carbohydrate's effect on hunger and obesity: Commentary on Geiselman and Novin (1982)
Appetite, 1985 , 6, 60-63
Carbohydrate's Effect on Hunger and Obesity: Commentary on Geiselman and Novin (1982)
NORIGEARY Department of Psychology, Columbia University
Human obesity is a syndrome defined by similarity of appearance, not a pathophysiological state with an understood causal mechanism. Although several types of obesity have been distinguished (Bray, 1976; Bray & York, 1979;Garrow, 1976; Salans, 1979; Sims, 1979; Stunkard , 1980), the greatest number of cases of obesity are idiopathic and remain resistant to therapy. The field awaits not just a single breakthrough, but several. Gei selman and N ovin (1 982) have hypothesized a mech an ism that may explain some obesity. The basic idea is a hoary one-that carbohydrate ingestion leads to o vereating and obesity. But Geiselman and Novin (1982) propose a new mechanism for this old idea . They suggest th at carbohydrate-related (especially sugar-rela ted) food stimuli elicit hyperinsulinemia, that this hyperinsulinemia elicits hypogl ycemia , and that the hypoglycemia elicits hunger, increased food int ake, and obesity in susceptible individuals. Gei selman and Novin (1982) offer more than enough data to make their enthusiasm for this hypothesis infectious, and, given the high stakes, their review will certainly stimulate research. I believe, howe ver, that progress in this direction ma y be facilitated by bringing some issues into clearer focus than the author s ha ve done. One crucial question th at Geiselman and Novin (1982) do not address is how indi viduals who are susceptible to what might be termed carbohydrate obesity differ from those who are not. There appea r to be three pos sibilities. First, ind ividuals may be a t risk because carbohydrate has the hypothesized effects only in them. Second, risk may occur if carbohydrate, although eliciting hunger in all individuals, elicits hunger more strongly in some than in others. Third, carbohydrate may have a uniform effect on hunger but some other factor, such as, for example, the degree to which individuals are exposed to carbohydrate, may characterize susceptible individuals. Geiselman and Novin (1982) dr aw much of their data from studies of non-obese individuals. This impl ies th at their hypothesis is that carbohydrate usually stimulates hunger, but onl y occasionally causes obesity. This in turn suggests that either the seco nd or the third pos sibilit y hold s, but that the first do es no t. These a re very different alternatives. Only the second form of the hypothesis posits a distinct type of obesity cau sed by a pathophysiology of moti vation. The third form, in contrast, posits that an environment too rich in carbohydrate is sufficient for obesity. Gei selman and Novin (1982) do not make clear which of these alternatives they favor , and review eviden ce relevant to each . Gi ven the very different directions that research following the se alternatives is likel y to take, guid ance here would be most helpful. Req uests for repr ints sho uld be sent to No ri Gea ry, Department of Psychology, Box 28, Schermerhorn Hall, Columbia University, New Yo rk, NY 10027, U.S.A. OI65- 6663/85/0 l0060 +04 $OJOO/O
C9
1985 Academic Press Inc. (London) Limited
C AR BOH YDRATE, H U NG ER AND OBESIT Y
61
Can a case be made that some obesity is caused by a pathophysiology of carbohydrate's effect on hunger? The deepest well of relevant data tapped by G eiselman and Novin (1982) is the literature of the control of feeding in laboratory animals. Even here, howe ver, the evidence is at best suggestive. One problem is that support for the indi vidu al links of the hypothesized chain are evalu ated individually. Thi s is understandable, because appropriate tests of the entire seq uence are not available. But is it likely that the whole will be merely the sum of the parts? A related problem is that many of the findings used to support the hypothesis in volve manipulations that move the relevant ph ysiological variables far out side the normal range. Whether mechanisms revealed in such studies operate during normal feeding is an open and crucial que stion . For example, while carbohydr ate certainly can elicit a robust insulin response in both normal weight and obese rat s (Louis-Sylvestre, 1978; Steffens, 1970; Strubbe & Steffens, 1975; Woods & Porte, 1978), it is not clear that prandial hyperinsulinemia ever elicits the dose-related decreases in blood glucose that exogenous insulin treatment does (Brandes, 1977). One reason for this is that, in addition to stimul at ing insulin secretion, food intake also promotes incre ases in glycemic levels. In additio n to glucose deri ved from the absorption of ingested carbohyd rates, there are entero-insular responses that increa se endogenous glucose production during and after feeding. For example, food int ake, even sucros e intake , can stimulate the release of glucose from hepatic glycogen or other stores into the blood (Langhans, Geary & Scharrer, 1982; Rupe & Mayer, 1967). Thus, until carbohydrateinduced changes in endogenous insulin levels that are stimulated by carbohydrate ingestion can be relat ed to glycemic effects, the hypoglycemic and feeding effects of exogenous insulin in rats th at Geiselman a nd N avin (1982) review remain of uncertain relevance to their hypothesis. Whether the feeding respon se to hypoglycemia reflects a normally acting con trol of feeding is similarly uncertain. Administration of ins ulin or of glucose antimeta bolites elicits glucoprivation and food intake, but this invariably appears to require doses producing effects beyond the range normally encountered before spontaneous meals (Brande s, 1977; Epstein, Nicolaide s & Miselis, 1975; Sclafani, 1982; Smith, Gibbs, Strohmaycr & Stokes, 1972; Woods & Ma cKay, 1978). Geiselman and No vin (1982) cite Lou is-Sylvestre and Le Magnen's (1 980) demonstr at ion tha t rats' femoral vein blood glucose drops 6 mg/IOO ml from 92 mg/100 ml at 5 min before meal initiation to 86 mg/IOO ml at 2 min after meal onset as evidence that hypoglycemia and glucoprivation may be important stimuli in normal meal initiation. I disagree . What has been demonstrat ed is a corr elation between a slight drop in blood glucose and meal initi ati on, not decreased gluco se utilization and meal initiation. The change is simply not large enough to affect cellular glucose utilization (Crone , 1965; Siegel, Albers, Agranoff & Kat zman , 1981). A typical criterion for biochemical hypogl ycemia is 40 mg/l00 ml (Hofeldt, 1975). Such hypoglycemia is yet to be demonstrated at the site of any proposed glucoreceptors during spontaneous meal s. Differentiat ion of lowered blood glucose from biochemical hypoglycemia would certainly aid the evaluation of a hypothesized role of glucose metaboli sm in meal initiation. Finally, I emph asize that Geiselman and Novin's (1982) hypothe sis is not crucially tested by any of the points I have tried to make. Rather , I hope to illustrate the kind of support th at their hypothesis requires. The crucial issue, whether carbohydrate's effects on hunger ever cause obesity, remains open. It ma y pro ve easier, and would be an equally useful beginning, to demonstrate this mechanism in a more limited model situation. Geiselman and No vin (1982) discus s, for example, rat s made ob ese by
62
N. GEARY
exposure to sugar solutions in addition to chow, and several workers have illustrated how accessible this phenomenon is to analysis (Castonguay, Hirsch & Collier, 1981; Kanarek & Marks-Kaufman, 1979; Sclafani, Aravich & Landman, 1981). Another potentially useful model is the transient, five-fold increase in feeding rate displayed by mice at dusk (Peterson, 1978). Hyperinsulinemia and marked reductions in blood glucose accompany this hyperphagia. If food is withheld, however, no glycemic or insulinemic effects occur. Thus, as Peterson (1978) suggests, feeding may induce metabolic changes in this situation that hasten the re-onset of hunger. If Geiselman and Novin's (1982) hypothesized causal chain could be demonstrated in any such setting, it might represent the first step in understanding and developing a therapy for a possibly substantial proportion of human obesity. REFERENCES
Brandes, J. S. Insulin induced overeating in the rat. Physiology and Behavior, 1977,18,1095-1102. Bray, G. A. The obese patient. Philadelphia: Saunders, 1976. Bray, G. A., & York, D. A. Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis. Physiological Reviews, 1979, 59, 719-807. Castonguay, T. W., Hirsch, E., & Collier, G. Palatability of sugar solutions and dietary selection? Physiology and Behavior, 1981,27, 7-12. Crone, C. Facilitated transfer of glucose from blood into brain tissue. Journal ofPhysiology, 1965, 181.103-113. Epstein, A. N., Nicolaides, S., & Miselis, R. The glucoprivic control of food intake and the glucostatic theory of feeding behavior. In G. 1. Mogenson & F. R. Calaresu (Eds.), Neural integration of physiological mechanisms and behavior. Pp.148-168. Toronto: University of Toronto Press, 1975. Garrow,1. Energy balance and obesity in man. New York: Elsevier-North Holland, 1976. Geiselman, P. 1., & Novin, D. The role of carbohydrate in appetite, hunger and obesity. Appetite, 1982,3,203-223. HofeJdt, F. D. Reactive hypoglycemia. Metabolism, 1975,24,1193-1208. Kanarek, R. B., & Marks-Kaufman, R. Developmental aspects of sucrose-induced obesity in rats. Physiology and Behavior, 1979,23,881-885. Langhans, W., Geary, N., & Scharrer, E. Liver glycogen decreases during meals in rats. American Journal of Physiology, 1982,243, R450-R453. Louis-Sylvestre, 1. Relationship between two stages of prandial insulin release in rats. American Journal of Physiology, 1978,235, E103-Ell1. Louis-Sylvestre, J., & Le Magnen, 1. A fall in blood glucose level precedes meal onset in free feeding rats. Neuroscience and Biobehavioral Reviews, 1980, 4 (Supp\. 1), 13-15. Peterson, S. Feeding, blood glucose and plasma insulin of mice at dusk. Nature, 1978, 275, 647-649. Rupe, B. D., & Mayer, J. Endogenous glucose release stimulated by oral sucrose administration in rats. Experientia, 1967,23, 1009-1010. Salans, 1. B. Natural history of obesity. In G. A. Bray (Ed.), Obesity in America. Pp.69-94. Washington, D.C.: N.I.H. Publication No. 79-359, 1979. Sclafani, A. On the role of hypoglycemia in carbohydrate appetite. Appetite, 1982,3, 227-228. Sclafani, A., Aravich, P. F., & Landman, M. Vagotomy blocks hypothalamic hyperphagia in rats on a chow diet and sucrose solution, but not a palatable mixed diet. Journal ofComparative and Physiological Psychology, 1981,95,720-734. Siegel, G. J., Albers, R. W., Agranoff, B. W., & Katzman, R. Basic neurochemistry (3rd ed.). Boston: Little Brown, 1981. Sims, E. A. H. Definitions, criteria, and prevalence of obesity. In G. A. Bray (Ed.), Obesity in America. Pp.20-36. Washington, D.C.: N.I.H. Publication No. 79-359, 1979. Smith, G. P., Gibbs, 1., Strohmayer, A., & Stokes, P. Threshold doses of 2-deoxY-D-glucose for hyperglycemia and feeding in rats and monkeys. American Journal ofPhysiology, 1972,222, 77-81.
CARBOHYDRATE, HUNGER AND OBESITY
63
Steffens, A. B. Plasma insulin content in relation to blood glucose level and meal pattern in the normal and hypothalamic hyperphagic rat. Physiology and Behavior, 1970,5, 147-151. Strubbe, 1. H., & Steffens, A. B. Rapid insulin release after ingestion of a meal in the unanesthetized rat. American Journal of Physiology, 1975,229, 1019-1022. Stunkard, A. 1. Obesity. Philadelphia: Saunders, 1980. Woods, S. C, & MacKay, C D. Intraventricular alloxan eliminates feeding elicited by 2-deoxyglucose. Science, 1978,202,1209-1211. Woods, S. C, & Porte, D., Jr. The central nervous system, pancreatic hormones, feeding, and obesity. Advances in Metabolic Disorders, 1978,9,283-312. Received 6 February, 1984; revised form 28 February, 1984
Carbohydrate's Effect on Hunger and Obesity: Commentary on Geiselman and Novin (1982)
NORIGEARY Department of Psychology, Columbia University
Human obesity is a syndrome defined by similarity of appearance, not a pathophysiological state with an understood causal mechanism. Although several types of obesity have been distinguished (Bray, 1976; Bray & York, 1979;Garrow, 1976; Salans, 1979; Sims, 1979; Stunkard , 1980), the greatest number of cases of obesity are idiopathic and remain resistant to therapy. The field awaits not just a single breakthrough, but several. Gei selman and N ovin (1 982) have hypothesized a mech an ism that may explain some obesity. The basic idea is a hoary one-that carbohydrate ingestion leads to o vereating and obesity. But Geiselman and Novin (1982) propose a new mechanism for this old idea . They suggest th at carbohydrate-related (especially sugar-rela ted) food stimuli elicit hyperinsulinemia, that this hyperinsulinemia elicits hypogl ycemia , and that the hypoglycemia elicits hunger, increased food int ake, and obesity in susceptible individuals. Gei selman and Novin (1982) offer more than enough data to make their enthusiasm for this hypothesis infectious, and, given the high stakes, their review will certainly stimulate research. I believe, howe ver, that progress in this direction ma y be facilitated by bringing some issues into clearer focus than the author s ha ve done. One crucial question th at Geiselman and Novin (1982) do not address is how indi viduals who are susceptible to what might be termed carbohydrate obesity differ from those who are not. There appea r to be three pos sibilities. First, ind ividuals may be a t risk because carbohydrate has the hypothesized effects only in them. Second, risk may occur if carbohydrate, although eliciting hunger in all individuals, elicits hunger more strongly in some than in others. Third, carbohydrate may have a uniform effect on hunger but some other factor, such as, for example, the degree to which individuals are exposed to carbohydrate, may characterize susceptible individuals. Geiselman and Novin (1982) dr aw much of their data from studies of non-obese individuals. This impl ies th at their hypothesis is that carbohydrate usually stimulates hunger, but onl y occasionally causes obesity. This in turn suggests that either the seco nd or the third pos sibilit y hold s, but that the first do es no t. These a re very different alternatives. Only the second form of the hypothesis posits a distinct type of obesity cau sed by a pathophysiology of moti vation. The third form, in contrast, posits that an environment too rich in carbohydrate is sufficient for obesity. Gei selman and Novin (1982) do not make clear which of these alternatives they favor , and review eviden ce relevant to each . Gi ven the very different directions that research following the se alternatives is likel y to take, guid ance here would be most helpful. Req uests for repr ints sho uld be sent to No ri Gea ry, Department of Psychology, Box 28, Schermerhorn Hall, Columbia University, New Yo rk, NY 10027, U.S.A. OI65- 6663/85/0 l0060 +04 $OJOO/O
C9
1985 Academic Press Inc. (London) Limited
C AR BOH YDRATE, H U NG ER AND OBESIT Y
61
Can a case be made that some obesity is caused by a pathophysiology of carbohydrate's effect on hunger? The deepest well of relevant data tapped by G eiselman and Novin (1982) is the literature of the control of feeding in laboratory animals. Even here, howe ver, the evidence is at best suggestive. One problem is that support for the indi vidu al links of the hypothesized chain are evalu ated individually. Thi s is understandable, because appropriate tests of the entire seq uence are not available. But is it likely that the whole will be merely the sum of the parts? A related problem is that many of the findings used to support the hypothesis in volve manipulations that move the relevant ph ysiological variables far out side the normal range. Whether mechanisms revealed in such studies operate during normal feeding is an open and crucial que stion . For example, while carbohydr ate certainly can elicit a robust insulin response in both normal weight and obese rat s (Louis-Sylvestre, 1978; Steffens, 1970; Strubbe & Steffens, 1975; Woods & Porte, 1978), it is not clear that prandial hyperinsulinemia ever elicits the dose-related decreases in blood glucose that exogenous insulin treatment does (Brandes, 1977). One reason for this is that, in addition to stimul at ing insulin secretion, food intake also promotes incre ases in glycemic levels. In additio n to glucose deri ved from the absorption of ingested carbohyd rates, there are entero-insular responses that increa se endogenous glucose production during and after feeding. For example, food int ake, even sucros e intake , can stimulate the release of glucose from hepatic glycogen or other stores into the blood (Langhans, Geary & Scharrer, 1982; Rupe & Mayer, 1967). Thus, until carbohydrateinduced changes in endogenous insulin levels that are stimulated by carbohydrate ingestion can be relat ed to glycemic effects, the hypoglycemic and feeding effects of exogenous insulin in rats th at Geiselman a nd N avin (1982) review remain of uncertain relevance to their hypothesis. Whether the feeding respon se to hypoglycemia reflects a normally acting con trol of feeding is similarly uncertain. Administration of ins ulin or of glucose antimeta bolites elicits glucoprivation and food intake, but this invariably appears to require doses producing effects beyond the range normally encountered before spontaneous meals (Brande s, 1977; Epstein, Nicolaide s & Miselis, 1975; Sclafani, 1982; Smith, Gibbs, Strohmaycr & Stokes, 1972; Woods & Ma cKay, 1978). Geiselman and No vin (1982) cite Lou is-Sylvestre and Le Magnen's (1 980) demonstr at ion tha t rats' femoral vein blood glucose drops 6 mg/IOO ml from 92 mg/100 ml at 5 min before meal initiation to 86 mg/IOO ml at 2 min after meal onset as evidence that hypoglycemia and glucoprivation may be important stimuli in normal meal initiation. I disagree . What has been demonstrat ed is a corr elation between a slight drop in blood glucose and meal initi ati on, not decreased gluco se utilization and meal initiation. The change is simply not large enough to affect cellular glucose utilization (Crone , 1965; Siegel, Albers, Agranoff & Kat zman , 1981). A typical criterion for biochemical hypogl ycemia is 40 mg/l00 ml (Hofeldt, 1975). Such hypoglycemia is yet to be demonstrated at the site of any proposed glucoreceptors during spontaneous meal s. Differentiat ion of lowered blood glucose from biochemical hypoglycemia would certainly aid the evaluation of a hypothesized role of glucose metaboli sm in meal initiation. Finally, I emph asize that Geiselman and Novin's (1982) hypothe sis is not crucially tested by any of the points I have tried to make. Rather , I hope to illustrate the kind of support th at their hypothesis requires. The crucial issue, whether carbohydrate's effects on hunger ever cause obesity, remains open. It ma y pro ve easier, and would be an equally useful beginning, to demonstrate this mechanism in a more limited model situation. Geiselman and No vin (1982) discus s, for example, rat s made ob ese by
62
N. GEARY
exposure to sugar solutions in addition to chow, and several workers have illustrated how accessible this phenomenon is to analysis (Castonguay, Hirsch & Collier, 1981; Kanarek & Marks-Kaufman, 1979; Sclafani, Aravich & Landman, 1981). Another potentially useful model is the transient, five-fold increase in feeding rate displayed by mice at dusk (Peterson, 1978). Hyperinsulinemia and marked reductions in blood glucose accompany this hyperphagia. If food is withheld, however, no glycemic or insulinemic effects occur. Thus, as Peterson (1978) suggests, feeding may induce metabolic changes in this situation that hasten the re-onset of hunger. If Geiselman and Novin's (1982) hypothesized causal chain could be demonstrated in any such setting, it might represent the first step in understanding and developing a therapy for a possibly substantial proportion of human obesity. REFERENCES
Brandes, J. S. Insulin induced overeating in the rat. Physiology and Behavior, 1977,18,1095-1102. Bray, G. A. The obese patient. Philadelphia: Saunders, 1976. Bray, G. A., & York, D. A. Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis. Physiological Reviews, 1979, 59, 719-807. Castonguay, T. W., Hirsch, E., & Collier, G. Palatability of sugar solutions and dietary selection? Physiology and Behavior, 1981,27, 7-12. Crone, C. Facilitated transfer of glucose from blood into brain tissue. Journal ofPhysiology, 1965, 181.103-113. Epstein, A. N., Nicolaides, S., & Miselis, R. The glucoprivic control of food intake and the glucostatic theory of feeding behavior. In G. 1. Mogenson & F. R. Calaresu (Eds.), Neural integration of physiological mechanisms and behavior. Pp.148-168. Toronto: University of Toronto Press, 1975. Garrow,1. Energy balance and obesity in man. New York: Elsevier-North Holland, 1976. Geiselman, P. 1., & Novin, D. The role of carbohydrate in appetite, hunger and obesity. Appetite, 1982,3,203-223. HofeJdt, F. D. Reactive hypoglycemia. Metabolism, 1975,24,1193-1208. Kanarek, R. B., & Marks-Kaufman, R. Developmental aspects of sucrose-induced obesity in rats. Physiology and Behavior, 1979,23,881-885. Langhans, W., Geary, N., & Scharrer, E. Liver glycogen decreases during meals in rats. American Journal of Physiology, 1982,243, R450-R453. Louis-Sylvestre, 1. Relationship between two stages of prandial insulin release in rats. American Journal of Physiology, 1978,235, E103-Ell1. Louis-Sylvestre, J., & Le Magnen, 1. A fall in blood glucose level precedes meal onset in free feeding rats. Neuroscience and Biobehavioral Reviews, 1980, 4 (Supp\. 1), 13-15. Peterson, S. Feeding, blood glucose and plasma insulin of mice at dusk. Nature, 1978, 275, 647-649. Rupe, B. D., & Mayer, J. Endogenous glucose release stimulated by oral sucrose administration in rats. Experientia, 1967,23, 1009-1010. Salans, 1. B. Natural history of obesity. In G. A. Bray (Ed.), Obesity in America. Pp.69-94. Washington, D.C.: N.I.H. Publication No. 79-359, 1979. Sclafani, A. On the role of hypoglycemia in carbohydrate appetite. Appetite, 1982,3, 227-228. Sclafani, A., Aravich, P. F., & Landman, M. Vagotomy blocks hypothalamic hyperphagia in rats on a chow diet and sucrose solution, but not a palatable mixed diet. Journal ofComparative and Physiological Psychology, 1981,95,720-734. Siegel, G. J., Albers, R. W., Agranoff, B. W., & Katzman, R. Basic neurochemistry (3rd ed.). Boston: Little Brown, 1981. Sims, E. A. H. Definitions, criteria, and prevalence of obesity. In G. A. Bray (Ed.), Obesity in America. Pp.20-36. Washington, D.C.: N.I.H. Publication No. 79-359, 1979. Smith, G. P., Gibbs, 1., Strohmayer, A., & Stokes, P. Threshold doses of 2-deoxY-D-glucose for hyperglycemia and feeding in rats and monkeys. American Journal ofPhysiology, 1972,222, 77-81.
CARBOHYDRATE, HUNGER AND OBESITY
63
Steffens, A. B. Plasma insulin content in relation to blood glucose level and meal pattern in the normal and hypothalamic hyperphagic rat. Physiology and Behavior, 1970,5, 147-151. Strubbe, 1. H., & Steffens, A. B. Rapid insulin release after ingestion of a meal in the unanesthetized rat. American Journal of Physiology, 1975,229, 1019-1022. Stunkard, A. 1. Obesity. Philadelphia: Saunders, 1980. Woods, S. C, & MacKay, C D. Intraventricular alloxan eliminates feeding elicited by 2-deoxyglucose. Science, 1978,202,1209-1211. Woods, S. C, & Porte, D., Jr. The central nervous system, pancreatic hormones, feeding, and obesity. Advances in Metabolic Disorders, 1978,9,283-312. Received 6 February, 1984; revised form 28 February, 1984