- Email: [email protected]
OPIOID PEPTIDES AND OBESITY
905 and the bipolar depressed group (10-6±2-8 .U/ml, p>0.05) Both groups demonstrated group (10-3±2-6 U/ml, p>0.05). a A TSH that was slightly, but not significantly, lower than that of the controls (12-8±1-4 jjLU/ml). One unipolar and one bipolar depressed patient showed a clearly diminished TSH response to TRH (A TSH <5.0 U/ml). We recently reported a non-significant trend for a diminished A TSH in a larger group of thirty-four unipolar and bipolar depressed patients when compared with twenty-three normal controls.6 While a clinical neuroendocrine test that could differentiate between subgroups of depressed patients would be of considerable value, we have been unable to confirm the report of Gold et al. Additional studies on larger series are needed to validate this potentially interesting finding. This work
supported by grants
was
MH 14654, and RSDA-MH
00044, and V. A. Research Funds. University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; and Depression Research Unit, V. A. Hospital, Philadelphia, Pennsylvania 19104, U.S.A.
CEREAL
J. D. AMSTERDAM A. WINOKUR J. MENDELS P. SNYDER
FIBRE, TOTAL ENERGY INTAKE, AND OBESITY
hypothesis’I that diets depleted in unrefined carbohydrates are more likely to encourage overnutrition and thus lead to a higher total energy intake and possibly obesity, a view supported by the bread study of Grimes and Gordon.2 However, Elaine Bryson and her colleagues (Aug. 4, p. 260) found no difference in total energy intakes of healthy volunteers offered either unlimited white bread or unlimited wholemeal bread (in addition to unSIR,-Dr Heaton (Sept. 15, p. 593)
restates
his
on the influence of diet on obesity in phase (this requiring a longitudinal study) there evidence linking DCF consumption with obesity.
information
Department of Clinical Epidemiology, London Hospital Medical College, London E1 2AD
its dynamic is no direct
ALAN
J. SILMAN
OPIOID PEPTIDES AND OBESITY
SIR,-Dr McCloy and Mr McCloy (July 21, p. 156) relate obesity to autoaddiction to endogenous opioid peptides. Not only endogenous opioids but also exogenous peptides with opioid activity might contribute to the development of obesity. Zioudrou et al. have reported that pepsin hydrolysates of wheat gluten and oc-casein contain peptide fragments with opioid activity, which they call "exorphins". These exorphins are likely to be normally produced within the stomach. They are resistant to intestinal proteases and are probably absorbed without further degradation; they would, therefore, be capable of reaching the brain. Anxiety and stress can increase food intake.2 Opioid peptides have euphoric properties, and all of them can produce addiction. There is no reason to suppose that exorphins are an exception in this respect. It seems probable, therefore, that anxiety-induced overeating reflects an attempt to overcome psychic discomfort by increasing the concentrations of euphoric brain opioids via increased production and absorption of exorphins. Permanent psychic discomfort or stress, therefore, may lead ultimately to a true addiction to food. Klinisches Institut fur Herzinfarktforschung, Medizinischen Universitätsklinik, D-69 Heidelberg, West Germany
HORST KATHER BERND SIMON
DCF INTAKE AND BODY-WEIGHT
ACUTE GRAFT-VERSUS-HOST DISEASE IN RECIPIENTS OF BONE-MARROW TRANSPLANTS FROM IDENTICAL TWIN DONORS paper by Dr Rappeport and his colleagues (Oct. 717) caused us no surprise. Work in this laboratory on mice long ago3.4 revealed a syndrome of "secondary disease" in radiation chimeeras where no graft-versus-host reaction would then in theory have been anticipated. The studies, first reported in some detail at the Fifth Tissue Transplantation Conference,5 have seldom been cited. We quote:
SIR,-The
6,
limited quantities of butter and jam in both groups). Their results, though, do not necessarily contradict those of Grimes and Gordon, because Bryson compared energy intakes whilst Grimes and Gordon compared intakes of different breads. Bryshow whether the wholemeal bread group did less bread or rather compensated for this by their increasing energy intake from butter or jam. Indeed most foods containing a high proportion of dietary fibre from cereal sources (DCF) are unpalatable without the addition of other high-energy foods such as fats and refined sugar. I have studied the relationship between DCF and total energy intake in a group of middle-aged men. The results from 77 man-days of observation showed there was no significant correlation between the two variables (r=—0- 3). Whether DCF intake is a factor in obesity was determined in a dietary study of 112 men. I was unable to demonstrate any relationship between DCF intake and either body-weight (see table) or body-weight/height. Though these data provide no son et
in fact
al. do
not
consume
6. Amsterdam JD, Winokur A, Mendels J, et al. Multiple hormonal response to TRH in depressed patients and normal controls. Presented at Conference of International Society of Psychoneuroendocrinology, Park City, Utah. Aug. 8-11, 1979. 1. Heaton KW. Food fibre as an obstacle to energy intake. Lancet 1973; ii: 1418-21. 2. Grimes DS, Gordon C. Satiety values of wholemeal and white bread. Lancet 1978; ii: 106.
p.
"These experiments have involved the restoration of lethally X-irradiated CBA male mice with syngeneic or closely related allogeneic (C3H) cells. A syndrome with characteristics of secondary disease has been seen in the following four situations: 1. Treatment with syngeneic fetal liver. 2. Treatment with syngeneic bone marrow after serial passage through successive syngeneic hosts. 3. Treatment with small numbers (< 106 cells per mouse) of normal syngeneic bone marrow cells. 4. Treatment with normal adult C3H bone marrow." "In every case additional treatment with 2 million to 10 million lymph node cells reduced the incidence of the disease and lowered mor-
tality". We concluded that the syndrome was due to aplasia of lymtissues and did "not necessarily depend on a graft-versus-host immune reaction". Consequently "compatible lymphoid cells are at least as important in reducing secondary disease as incompatible lymphoid cells are in causing it". Rappeport et al. do not provide quantitative data on the marrow cells given or on the lymphocytes of the three syn-
phoid
1. Zioudrou C, Streaty RA, Klee WA. J Biol Chem 1979; 243: 2446. 2. Kaplan HI, Kaplan HS. J Nerv Ment Dis 1957; 125: 181. 3. Loutit JF. Lancet 1962; ii: 1106-08. 4. 5. Barnes DWH, Loutit JF, Micklem HS. Ann NY Acad. Sci 1962; 99: 374-85.
Sljivić VS. Int J Radiat Biol 1966;11:273-86
supported by grants
was
MH 14654, and RSDA-MH
00044, and V. A. Research Funds. University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; and Depression Research Unit, V. A. Hospital, Philadelphia, Pennsylvania 19104, U.S.A.
CEREAL
J. D. AMSTERDAM A. WINOKUR J. MENDELS P. SNYDER
FIBRE, TOTAL ENERGY INTAKE, AND OBESITY
hypothesis’I that diets depleted in unrefined carbohydrates are more likely to encourage overnutrition and thus lead to a higher total energy intake and possibly obesity, a view supported by the bread study of Grimes and Gordon.2 However, Elaine Bryson and her colleagues (Aug. 4, p. 260) found no difference in total energy intakes of healthy volunteers offered either unlimited white bread or unlimited wholemeal bread (in addition to unSIR,-Dr Heaton (Sept. 15, p. 593)
restates
his
on the influence of diet on obesity in phase (this requiring a longitudinal study) there evidence linking DCF consumption with obesity.
information
Department of Clinical Epidemiology, London Hospital Medical College, London E1 2AD
its dynamic is no direct
ALAN
J. SILMAN
OPIOID PEPTIDES AND OBESITY
SIR,-Dr McCloy and Mr McCloy (July 21, p. 156) relate obesity to autoaddiction to endogenous opioid peptides. Not only endogenous opioids but also exogenous peptides with opioid activity might contribute to the development of obesity. Zioudrou et al. have reported that pepsin hydrolysates of wheat gluten and oc-casein contain peptide fragments with opioid activity, which they call "exorphins". These exorphins are likely to be normally produced within the stomach. They are resistant to intestinal proteases and are probably absorbed without further degradation; they would, therefore, be capable of reaching the brain. Anxiety and stress can increase food intake.2 Opioid peptides have euphoric properties, and all of them can produce addiction. There is no reason to suppose that exorphins are an exception in this respect. It seems probable, therefore, that anxiety-induced overeating reflects an attempt to overcome psychic discomfort by increasing the concentrations of euphoric brain opioids via increased production and absorption of exorphins. Permanent psychic discomfort or stress, therefore, may lead ultimately to a true addiction to food. Klinisches Institut fur Herzinfarktforschung, Medizinischen Universitätsklinik, D-69 Heidelberg, West Germany
HORST KATHER BERND SIMON
DCF INTAKE AND BODY-WEIGHT
ACUTE GRAFT-VERSUS-HOST DISEASE IN RECIPIENTS OF BONE-MARROW TRANSPLANTS FROM IDENTICAL TWIN DONORS paper by Dr Rappeport and his colleagues (Oct. 717) caused us no surprise. Work in this laboratory on mice long ago3.4 revealed a syndrome of "secondary disease" in radiation chimeeras where no graft-versus-host reaction would then in theory have been anticipated. The studies, first reported in some detail at the Fifth Tissue Transplantation Conference,5 have seldom been cited. We quote:
SIR,-The
6,
limited quantities of butter and jam in both groups). Their results, though, do not necessarily contradict those of Grimes and Gordon, because Bryson compared energy intakes whilst Grimes and Gordon compared intakes of different breads. Bryshow whether the wholemeal bread group did less bread or rather compensated for this by their increasing energy intake from butter or jam. Indeed most foods containing a high proportion of dietary fibre from cereal sources (DCF) are unpalatable without the addition of other high-energy foods such as fats and refined sugar. I have studied the relationship between DCF and total energy intake in a group of middle-aged men. The results from 77 man-days of observation showed there was no significant correlation between the two variables (r=—0- 3). Whether DCF intake is a factor in obesity was determined in a dietary study of 112 men. I was unable to demonstrate any relationship between DCF intake and either body-weight (see table) or body-weight/height. Though these data provide no son et
in fact
al. do
not
consume
6. Amsterdam JD, Winokur A, Mendels J, et al. Multiple hormonal response to TRH in depressed patients and normal controls. Presented at Conference of International Society of Psychoneuroendocrinology, Park City, Utah. Aug. 8-11, 1979. 1. Heaton KW. Food fibre as an obstacle to energy intake. Lancet 1973; ii: 1418-21. 2. Grimes DS, Gordon C. Satiety values of wholemeal and white bread. Lancet 1978; ii: 106.
p.
"These experiments have involved the restoration of lethally X-irradiated CBA male mice with syngeneic or closely related allogeneic (C3H) cells. A syndrome with characteristics of secondary disease has been seen in the following four situations: 1. Treatment with syngeneic fetal liver. 2. Treatment with syngeneic bone marrow after serial passage through successive syngeneic hosts. 3. Treatment with small numbers (< 106 cells per mouse) of normal syngeneic bone marrow cells. 4. Treatment with normal adult C3H bone marrow." "In every case additional treatment with 2 million to 10 million lymph node cells reduced the incidence of the disease and lowered mor-
tality". We concluded that the syndrome was due to aplasia of lymtissues and did "not necessarily depend on a graft-versus-host immune reaction". Consequently "compatible lymphoid cells are at least as important in reducing secondary disease as incompatible lymphoid cells are in causing it". Rappeport et al. do not provide quantitative data on the marrow cells given or on the lymphocytes of the three syn-
phoid
1. Zioudrou C, Streaty RA, Klee WA. J Biol Chem 1979; 243: 2446. 2. Kaplan HI, Kaplan HS. J Nerv Ment Dis 1957; 125: 181. 3. Loutit JF. Lancet 1962; ii: 1106-08. 4. 5. Barnes DWH, Loutit JF, Micklem HS. Ann NY Acad. Sci 1962; 99: 374-85.
Sljivić VS. Int J Radiat Biol 1966;11:273-86