The High-Protein Diet and Cortisol Levels

The research below documents how excessive cortisol is produced by eating high-protein meals, and how that cortisol produces several psychological and physiological effects related to a highly-stressed state, including impaired memory, depression and antisocial behavior. Now of course someone needs to redo some of the following experiments with high-protein diets from other sources (like tofu) and find out how meals high in veg protein compare to those high in animal protein ...


FROM: http://www.ecologos.org/anxiety.htm


In the following abstracts, the sharp increase of cortisol following a high-protein meal is discussed. What is cortisol?

"Cortisol is a steroid hormone that is released from the ... adrenal cortex in response to stress." [1]
"...cortisol [is] secreted independent of circadian rhythm in response to physical and psychological stress. [2]
"The pituitary-adrenal cortical system plays a major role in an organism's adaptation to traumatic conditions." "...activity of the pituitary-adrenal cortical system has been shown to be sensitive to changes in psychological state, especially under conditions eliciting anxiety and negative emotional arousal." "Circumcision (Gomco Clamp method) produced 3- to 4- fold increases in serum cortisol indications at 30 min in 3- to 5- day old human neonates" "Neonatal circumcision is performed without anesthesia and it is clearly stressful for the infant" [3]
"those who reacted most to the stressful event through mood and higher cortisol levels also ate more, and especially more of the sweet snacks" "Cortisol and negative mood may reflect greater vulnerability to stress, it may also be that cortisol is directly affecting appetite. Cortisol can increase insulin, which stimulates appetite" "Stress causes cortisol levels to be elevated all the time, and that tends to facilitate the deposit of fat deep in the belly" "That deep-belly fat is caused by toxic stress" [4] "primary purpose of cortisol (hydrocortisone) and corticosterone in mammals is to mobilize the body's physiological processes against infection and its adverse effects" [5]

"HIV, the AIDS virus, forces the adrenal glands to churn out lots of cortisol, which damages the immune system. "Cortisol is probably one of the most violent immunodepressants there is." "Cortisol is part of the body's fight-or-flight response. Following a stressful event or an injury, the adrenal glands boost the production of cortisol. The hormone increases the amount of blood sugar available for fuel, temporarily slows down some essential bodily functions, and helps boost the heart rate so a person can fight off or run away from a threat. Cortisol also assists the body in routing a viral infection or healing damaged tissue. Such reactions are usually beneficial, but when too much cortisol dampens the immune response, it shuts down the very process that fights a deadly microbe or keeps a malignant cell from exploding into an invasive tumor." "people make cortisol and other hormones in times of stress" [6]

"Cortisol is produced in the body during stress. It belongs to a family of stress hormones called glucocorticoids that, among other actions, can interfere with energy supply to certain brain cells involved in memory" "prolonged exposure to high levels of cortisol--the hormone actually produced in the body in response to high stress--has that same negative effect [on memory]" [7]
"...demonstrated associations between CRH [corticotropin-releasing hormone] and cortisol and depression and antisocial behavior in depressed and antisocial adults..." "CRH is implicated in depression and other mental health disorders" "CRH and cortisol are both linked to antisocial behavior in children, adolescents, and adults" [8]
"Almost immediately after a stressful event, the levels of the regulatory hormones ACTH and CRH increase, causing an immediate rise in cortisol levels." "drinking 2-3 cups of coffee per day can elevate cortisol levels" "persons suffering from depression, anxiety, panic disorder, malnutrition and alcohol abuse also often have elevated cortisol values" "Persons exposed to abnormally high levels of cortisol over time develop a syndrome known as Cushing's Syndrome. This condition generally affects adults, and approximately 10-15 per million persons will develop this condition each year. Signs and symptoms of Cushing's Syndrome include elevated blood pressure, development of diabetes, pink-to-purple stretch marks on the abdominal skin, fatigue, depression, moodiness, and accentuated fatty tissue on the face and upper back. Women with Cushing's Syndrome often have irregular menstrual periods and develop new facial hair growth. Men may show a decrease in sex drive. Treatment options are varied and depend on the cause of the excess cortisol." [9]

Anxiety and Depression in Meat-Eaters
Bol Asoc Med P R 1998 Apr-Jun;90(4-6):58-68
[Indicators of anxiety and depression in subjects with different kinds of diet: vegetarians and omnivores]. [Article in Spanish]
Rodriguez Jimenez J, Rodriguez JR, Gonzalez MJ Centro Caribeno de Estudios Postgraduados (CCEP), UPR.
The following study, one of the first done in Puerto Rico, investigates the different kinds of diet and the level of anxiety and depression that the subjects present. The sample consists of 80 subjects between 25 and 70 years age divided into two main groups (vegetarian versus no vegetarian) depending on their diet consumption.
The basic findings in the three psychological tests given (IDARE-1, IDARE-2 and CES-D) to the subjects demonstrate significant differences in anxiety and depression between groups. More anxiety and depression where reported in the no vegetarian groups in comparison with the vegetarian groups. In addition, diet analysis found more nutritional antioxidant agents levels in the vegetarian group in comparison with the no-vegetarian group.
PMID: 9866269, UI: 99083501

Psychosom Med 1999 Mar;61(2):214-224
Increased salivary cortisol reliably induced by a protein-rich midday meal.
Gibson EL, Checkley S, Papadopoulos A, Poon L, Daley S, Wardle J. Department of Epidemiology and Public Health, University College, London, United Kingdom. l.gibson@ucl.ac.uk
OBJECTIVE: This study was conducted to determine whether an increase in salivary free cortisol would be reliably elicited by a midday meal, thus providing a convenient physiological challenge to the hypothalamic-pituitary-adrenal (HPA) axis, and whether this cortisol release depended on the protein content of the meal. METHOD: In healthy men, free cortisol was measured in saliva samples taken before and after two identical protein-rich midday meals (39% energy as protein) and compared with a day on which no meal was eaten. Next, in healthy women in a nonclinical setting, salivary cortisol was measured before and after a protein-rich meal (32% energy as protein) on one day and a low-protein meal (5% energy as protein) on another day. Measures of mood, appetite, and psychological well-being were also taken. RESULTS: An acute meal-dependent increase in salivary cortisol occurred, which was reliable over 2 test days. This increase in cortisol depended on the proportion of protein in the meal, increasing after the high-protein but not the low-protein meal. The extent of this increase in cortisol correlated significantly with poor psychological well-being in women. Some postmeal improvement of mood (positive affect) was associated with the high- but not the low-protein meal. CONCLUSIONS: The cortisol response to meals may have implications for the effects of meal composition on mood, cognitive function, and food choice. The measurement of free cortisol in saliva provides a psychologically stress-free and reliable technique to assess the cortisol response to a standard protein-rich meal, ie, a physiological challenge to the HPA axis in men and women that could be investigated in naturalistic settings outside the laboratory.
PMID: 10204975

Am J Physiol 1997 Aug;273(2 Pt 2):R548-R553
Systemic immune changes following meal intake in humans.
Hansen K, Sickelmann F, Pietrowsky R, Fehm HL, Born J. Department of Internal Medicine, University of Lubeck, Germany.
Food intake represents a high intestinal antigen exposition requiring host defense. Besides local immune activation, this defense includes a coordinate systemic immune response, which may serve to support local immunity. This study examined influences of a standardized high-protein meal on peripheral blood mononuclear cell counts; on the in vitro mitogen-stimulated production of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interferon-gamma; on the in vivo plasma levels of tumor necrosis factor-alpha and interleukin-6; and on plasma concentrations of cortisol and growth hormone. Ten healthy men (18-35 yr) participated in two experimental sessions in a balanced order. On one occasion, subjects fasted; on the other, they received a high-protein meal at 1230. Blood was sampled every 15 min. Whereas the numbers of neutrophils and platelets were increased for more than 2.5 h after meal intake (P < 0.01) lymphocyte counts decreased (P < 0.01). Meal intake also decreased the production of interferon-gamma but did not affect the production and plasma levels of the other cytokines. Changes in immune cell distribution and function were accompanied by a strong postprandial rise in plasma cortisol concentrations. Some of the systemic immune changes, like the emigration of lymphocytes, probably into extravascular abdominal tissues, may serve to support local immune defense.
PMID: 927753

Physiol Behav 1994 Feb;55(2):375-379
Dietary salbutamol and level of protein: effects on the acute stress response in pigs.
Jensen KH, Oksbjerg N, Jorgensen E. National Institute of Animal Science, Tjele, Denmark.
Effect on the acute stress response of dietary inclusion of 3 ppm salbutamol (beta-2-adrenergic agonist) at two levels of protein were investigated in growing pigs (from 25 kg live weight). The trial comprised six litters (blocks) of four females allocated randomly to four treatment groups in accordance with a 2 x 2 factorial arrangement. The response to an open-field test and to an intruder were measured at 50 kg live weight. Salbutamol increased immobility and looking, reduced total exploration, and increased plasma ACTH after test. At high dietary levels of protein, salbutamol also increased the latency to attack. High dietary levels of protein reduced standing still, latency to contact a novel object and an intruder, and level of plasma cortisol before test. Moreover, high protein without salbutamol seemed to reduce the latency to attack an intruder. In conclusion, chronic treatment with salbutamol shifted the acute stress response in pigs toward a passive response, whereas high dietary level of protein provoked an active response, which may have consequences in pig production.
PMID: 8153181

Life Sci 1987 May 4;40(18):1761-1768
Diet-hormone interactions: protein/carbohydrate ratio alters reciprocally the plasma levels of testosterone and cortisol and their respective binding globulins in man.
Anderson KE, Rosner W, Khan MS, New MI, Pang SY, Wissel PS, Kappas A.
The aim of this study was to determine if a change in protein/carbohydrate ratio influences plasma steroid hormone concentrations. There is little information about the effects of specific dietary components on steroid hormone metabolism in humans. Testosterone concentrations in seven normal men were consistently higher after ten days on a high carbohydrate diet (468 +/- 34 ng/dl, mean +/- S.E.) than during a high protein diet (371 +/- 23 ng/dl, p less than 0.05) and were accompanied by parallel changes in sex hormone binding globulin (32.5 +/- 2.8 nmol/l vs. 23.4 +/- 1.6 nmol/l respectively, p less than 0.01). By contrast, cortisol concentrations were consistently lower during the high carbohydrate diet than during the high protein diet (7.74 +/- 0.71 micrograms/dl vs. 10.6 +/- 0.4 micrograms/dl respectively, p less than 0.05), and there were parallel changes in corticosteroid binding globulin concentrations (635 +/- 60 nmol/l vs. 754 +/- 31 nmol/l respectively, p less than 0.05). The diets were equal in total calories and fat. These consistent and reciprocal changes suggest that the ratio of protein to carbohydrate in the human diet is an important regulatory factor for steroid hormone plasma levels and for liver-derived hormone binding proteins.
PMID: 3573976

J Clin Endocrinol Metab 1983 Dec;57(6):1111-1116
Pituitary hormone release in response to food ingestion: evidence for neuroendocrine signals from gut to brain.
Ishizuka B, Quigley ME, Yen SS.
The synchrony of PRL and cortisol release with feeding is now well established. To delineate further the neuroendocrine mechanisms involved, meal-related pituitary and adrenal cortical activities were investigated in seven normal men in a series of experiments conducted in random sequence at 1-week intervals. Ingestion of a standardized mixed meal elicited a consistent acute release of PRL and cortisol at noon (1200 h), but not at breakfast (0800 h). No measurable changes in other pituitary hormones were observed. The relative magnitudes of PRL and cortisol release in response to lunch were not significantly influenced by a preceding breakfast. These responses appear unrelated to the cephalic or oral phases of food ingestion. However, the composition of the meals was found to be important. Whereas carbohydrate meals had no discernible effects, high protein meals induced a large increase in both PRL and cortisol; high fat meals caused selective release of PRL. Ingestion of L-tyrosine and L-tryptophan induced remarkable increments in serum concentrations of both PRL and cortisol, suggesting that these essential amino acids may be active components of the high protein meal. Choline had no effect. Meal-mediated PRL and cortisol release was unaffected by prior receptor blockade of the opioidergic and cholinergic systems with naloxone and atropine, respectively. These observations indicate that the protein component of the meal was responsible for the midday surges of PRL and cortisol and that the cephalic-vagal pathway was not required in food-entrained pituitary hormone release. Further, our data suggest that the neurotransmitter substrates in the protein meal may serve to link the gut and brain by modifying central catecholamine and serotonin biosynthesis, and thereby influence the hypothalamic factors controlling pituitary PRL and ACTH secretion. The possibility that gastrointestinal hormones may also influence the hypothalamic-pituitary system remains to be explored.
PMID: 6630409

Boll Soc Ital Biol Sper 1982 Feb;58(3-4):121-127
[The influence, in normal subjects, of a high-protein normocaloric diet on the response of cortisol, ACTH, GH, and PRL to insulin hypoglycemia]. [Article in Italian]
Giovannini C, Sellini M, Manzo G, Barletta C, Scavo D.
A protein rich diet causes a remarkable increment of plasma cortisol, corticotropin and somatotropin concentration, but does not modify the plasma prolactin level; this diet, moreover, is followed by a more vivacious response to the Lysin-8-Vasopressin test. In 10 healthy voluntary subjects we have studied the hormonal behaviour during the insulin-induced hypoglycemia test in course of equilibrated diet and after 15 days of protein-rich diet. In these two experimental conditions the insulin-induced hypoglycemia test has promoted a similar increment of the four hormones. The different behaviour between the two tests -Lysin-8-Vasopressin and insulin-induced hypoglycemia- indicates that the increased hormonal levels which follow a protein-rich diet are not provoked by a generic stress effect, but by a direct stimulation of the hypothalamo-hypophyseal structures.
PMID: 6279131

Metabolism 1981 Nov;30(11):1104-1108
Meal stimulation of cortisol secretion: a protein induced effect.
Slag MF, Ahmad M, Gannon MC, Nuttall FQ.
Cortisol and ACTH secretion was studied in 52 healthy subjects who were fasted of fed various diets: standard, high fat, high carbohydrate, high protein. Subjects fed high protein diet (4 gm/kg body weight) showed significant increases in cortisol both at 30 and 60 min after the 1200 hr meal and 30 min after the 1600 hr meal. Increases in cortisol, of a smaller magnitude, were also seen after both the 1200 and 1600 hr meals in each of the diets with 1 gm protein/kg body weight (standard, high fat, high carbohydrate). ACTH was significantly increased following the 1200 hr and 1600 hr meals with the high protein diet. We conclude that dietary protein plays an important role in meal stimulated cortisol release.
PMID: 6270500

Boll Soc Ital Biol Sper 1981 May 15;57(9):963-969
[Behavior of basal values and circadian rhythm of ACTH, cortisol, PRL and GH in a high-protein diet]. [Article in Italian]
Sellini M, Fierro A, Marchesi L, Manzo G, Giovannini C.
Basal values and circadian rhythm of cortisol, ACTH, GH and PRL were studied in 8 normal subjects during a normal balanced caloric diet and during a high protein diet ( + 12% proteins ). GH, ACTH and cortisol levels were considerably higher following the protein rich diet probably on account of the metabolic processes directly related to the higher protein load.
PMID: 6269563