Sugar (Sucrose) Restrains the Stress Response

Also see:
PUFA Promote Stress Response; Saturated Fats Suppress Stress Response
Ray Peat, PhD on Low Blood Sugar & Stress Reaction
Thumbs Up: Fructose
Theurapeutic Honey – Cancer and Wound Healing
Carbohydrates and Bone Health
Carbohydrate Lowers Exercise Induced Stress
Carbohydrate Lowers Serotonin from Exercise
HFCS – More to it than we thought
Protection from Endotoxin

J Neuroendocrinol. 2001 Sep;13(9):827-35.
A new perspective on glucocorticoid feedback: relation to stress, carbohydrate feeding and feeling better.
Laugero KD.
Input to and regulation of activity in the hypothalamic-pituitary-adrenal (HPA) axis is diverse and complex. Glucocorticoid feedback is a major component that determines activity in this classic neuroendocrine axis and, while feedback occurs through the brain, the pathways that mediate glucocorticoid feedback remain unknown. In this review, I discuss findings that have led us to view glucocorticoid feedback in the HPA axis in a new light. Much of what has precipitated this view comes from a very surprising finding in our laboratory; sucrose ingestion normalizes feeding, energy balance and central corticotropin releasing factor expression in adrenalectomized (ADX) rats. Since this discovery, a diverse set of literature that supports this view of glucocorticoid feedback has been found. Taken together, recent findings of the well-known importance of glucocorticoids to feeding and energy balance, and the modulatory actions of carbohydrate ingestion on both basal and stress-induced activity in the HPA axis, strongly suggest that many metabolic (e.g. obesity) and psychological (e.g. depression) pathologies, which often present together and have been associated with stress and HPA dysregulation, might, in part, be understood in light of our new view of glucocorticoid feedback.

“In monkeys living in the wild, when their diet is mainly fruit, their cortisol is low, and it rises when they eat a diet with less sugar (Behie, et al., 2010). Sucrose consumption lowers ACTH, the main pituitary stress hormone (Klement, et al., 2009; Ulrich-Lai, et al., 2007), and stress promotes increased sugar and fat consumption (Pecoraro, et al., 2004). If animals’ adrenal glands are removed, so that they lack the adrenal steroids, they choose to consume more sucrose (Laugero, et al., 2001). Stress seems to be perceived as a need for sugar. In the absence of sucrose, satisfying this need with starch and fat is more likely to lead to obesity.” -Ray Peat, PhD

Am J Primatol. 2010 Jun;72(7):600-6.
Sources of variation in fecal cortisol levels in howler monkeys in Belize.
Behie AM, Pavelka MS, Chapman CA.
High cortisol levels are known to cause low fecundity and increased mortality; thus, the prospect of using cortisol as a measure of population health is an exciting one. However, because so many factors can interact to influence cortisol release, it can be difficult to interpret what exactly is creating changes to cortisol levels. This study investigates variation in fecal cortisol levels in a population of black howlers (Alouatta pigra) from 350 fecal samples collected from 33 individuals in more than 4 years. A general linear mixed model revealed that cortisol varied significantly with fruit availability and contact with tourists. When fruit availability was low, cortisol increased, likely because when fruit availability is low monkeys eat less fruit, thus obtaining less sugar. This result may simply reflect cortisol’s metabolic function of mobilizing glucose. It also indicates that these monkeys may be experiencing periods of food stress throughout the year, which was earlier thought to be minimal for a primarily folivorous species. Presence of tourists was the only other factor found to lead to high cortisol; with exposure to tourists increasing stress levels. These results highlight the importance of understanding how physiological factors can influence cortisol, making it easier to interpret results and determine the external social or ecological stressors that may increase cortisol.

Metabolism. 2009 Dec;58(12):1825-31. Epub 2009 Aug 25.
Effects of glucose infusion on neuroendocrine and cognitive parameters in Addison disease.
Klement J, Hubold C, Hallschmid M, Loeck C, Oltmanns KM, Lehnert H, Born J, Peters A.
Sucrose intake has been shown to suppress increased adrenocorticotropic hormone (ACTH) levels in adrenalectomized rats, suggesting that increased cerebral energy supply can compensate for the loss of glucocorticoid feedback inhibition of the hypothalamo-pituitary-adrenal axis. We hypothesized that glucose infusion might acutely down-regulate increased ACTH secretion in patients with Addison disease. We studied 8 patients with primary adrenal insufficiency (Addison group) with short-term discontinuation of hydrocortisone substitution and 8 matched healthy controls in 2 randomized conditions. Subjects received either intravenous glucose infusion (0.75 g glucose per kilogram body weight for 2.5 hours) or placebo. Concentrations of ACTH, cortisol, catecholamines, growth hormone, glucagon, and insulin were measured; and cognitive functions as well as neuroglycopenic and autonomic symptoms were assessed. The ACTH concentrations were not affected by glucose infusion either in the Addison or in the control group. Likewise, concentrations of cortisol, epinephrine, norepinephrine, growth hormone, and glucagon remained unchanged in both groups. Neurocognitive performance and symptom scores were likewise not affected. Independent of glucose infusion, attention of the Addison patients was impaired in comparison with the control group. Our study in patients with Addison disease was not able to support the assumption of a compensatory effect of intravenous glucose infusion on hormonal parameters and neurocognitive symptoms in states of chronic cortisol deficiency. Further studies should examine whether different regimens of glucose administration are more effective.

Physiol Behav. 2011 Apr 18;103(1):104-10. Epub 2010 Dec 17.
HPA axis dampening by limited sucrose intake: reward frequency vs. caloric consumption.
Ulrich-Lai YM, Ostrander MM, Herman JP.
Individuals often cope with stress by consuming calorically-dense, highly-palatable ‘comfort’ foods. The present work explores the stress-relieving properties of palatable foods in a rat model of limited sucrose intake. In this model, adult male rats with free access to chow and water are given additional access to a small amount of sucrose drink (or water as a control). A history of such limited sucrose intake reduces the collective (HPA axis, sympathetic, and behavioral-anxiety) stress response. Moreover, the stress-dampening by sucrose appears to be mediated primarily by its rewarding properties, since beneficial effects are reproduced by the noncaloric sweetener saccharin but not oral intragastric gavage of sucrose. The present work uses an alternate strategy to address the hypothesis that the rewarding properties of sucrose mediate its stress-dampening. This work varies the duration, frequency, and/or volume of sucrose and assesses the ability to attenuate HPA axis stress responses. The data indicate that HPA-dampening is optimal with a greater duration and/or frequency of sucrose, whereas increasing the volume of sucrose consumed is without effect. This finding suggests that the primary factor mediating stress-dampening is the number/rate of reward (i.e., sucrose) exposures, rather than the total sucrose calories consumed. Collectively, these data support the hypothesis that stress relief by limited palatable food intake is mediated primarily by its hedonic/rewarding properties. Moreover, the results support the contention that naturally rewarding behaviors are a physiological means to produce stress relief.

Endocrinology. 2004 Aug;145(8):3754-62. Epub 2004 May 13.
Chronic stress promotes palatable feeding, which reduces signs of stress: feedforward and feedback effects of chronic stress.
Pecoraro N, Reyes F, Gomez F, Bhargava A, Dallman MF.
We suggested a new model of the effects of glucocorticoids (GCs) exerted during chronic stress, in which GCs directly stimulate activities in the brain while indirectly inhibiting activity in the hypothalamo-pituitary-adrenal (HPA) axis through their metabolic shifts in energy stores in the periphery. This study is an initial test of our model. In a 2 x 2 design, we provided ad lib access to calorically dense lard and sucrose (comfort food) + chow or chow alone, and repeatedly restrained half of the rats in each group for 5 d (3 h/d). We measured caloric intake, body weight, caloric efficiency, ACTH, corticosterone (B), and testosterone during the period of restraint and leptin, insulin, and fat depot weights, as well as hypothalamic corticotropin-releasing factor mRNA at the end of the period. We hypothesized that chronically restrained rats would exhibit a relative increase in comfort food ingestion and that these rats would have reduced HPA responses to repeated restraint. Although total caloric intake was reduced in both groups of restrained rats, compared with controls, the proportion of comfort food ingested increased in the restrained rats compared with their nonrestrained controls. Moreover, caloric efficiency was rescued in the stressed, comfort food group. Furthermore, ACTH and B responses to the repeated restraint bouts were reduced in the rats with access to comfort food. Corticotropin-releasing factor mRNA was reduced in control rats eating comfort food compared with those eating chow, but there were no differences between the stressed groups. The results of this experiment tend to support our model of chronic effects of stress and GCs, showing a stressor-induced preference for comfort food, and a comfort-food reduction in activity of the HPA axis.

Endocrinology. 2001 Jul;142(7):2796-804.
Sucrose ingestion normalizes central expression of corticotropin-releasing-factor messenger ribonucleic acid and energy balance in adrenalectomized rats: a glucocorticoid-metabolic-brain axis?
Laugero KD, Bell ME, Bhatnagar S, Soriano L, Dallman MF.
Both CRF and norepinephrine (NE) inhibit food intake and stimulate ACTH secretion and sympathetic outflow. CRF also increases anxiety; NE increases attention and cortical arousal. Adrenalectomy (ADX) changes CRF and NE activity in brain, increases ACTH secretion and sympathetic outflow and reduces food intake and weight gain; all of these effects are corrected by administration of adrenal steroids. Unexpectedly, we recently found that ADX rats drinking sucrose, but not saccharin, also have normal caloric intake, metabolism, and ACTH. Here, we show that ADX (but not sham-ADX) rats prefer to consume significantly more sucrose than saccharin. Voluntary ingestion of sucrose restores CRF and dopamine-beta-hydroxylase messenger RNA expression in brain, food intake, and caloric efficiency and fat deposition, circulating triglyceride, leptin, and insulin to normal. Our results suggest that the brains of ADX rats, cued by sucrose energy (but not by nonnutritive saccharin) maintain normal activity in systems that regulate neuroendocrine (hypothalamic-pituitary-adrenal), behavioral (feeding), and metabolic functions (fat deposition). We conclude that because sucrose ingestion, like glucocorticoid replacement, normalizes energetic and neuromodulatory effects of ADX, many of the actions of the steroids on the central nervous system under basal conditions may be indirect and mediated by signals that result from the metabolic effects of adrenal steroids.

Nutr Rev. 2003 May;61(5 Pt 2):S27-33.
Effects of a high-sucrose diet on body weight, plasma triglycerides, and stress tolerance.
Kanazawa M, Xue CY, Kageyama H, Suzuki E, Ito R, Namba Y, Osaka T, Kimura S, Inoue S.
We examine the effects of feeding a high-sucrose diet on body weight gain, plasma triglycerides, and stress tolerance in rats. Feeding a high-sucrose (60%) diet for 2 weeks did not induce a greater body weight gain compared with that of standard diet when caloric intake was similar in ventromedial hypothalamic-lesioned obese and sham-operated lean animals. The high-sucrose diet elevated plasma triglycerides by increasing the triglyceride secretion rate and decreasing the fractional catabolic rate in both groups. In response to stress, feeding a high-sucrose diet for one week induced enhanced gene expressions of heat shock proteins (HSP 70 and 27) and suppressed NOx production in the brain, whereas the standard diet did not. Results suggest that feeding a high-sucrose diet does not induce obesity in lean rats or enhance weight gain in obese rats, if caloric intake is appropriate. The diet does elevate plasma triglyerides in lean and obese rats, but it may have the potential to improve stress tolerance.

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Sucrose and Metabolism:

Am J Med. 1986 Aug;81(2):280-4.
Sucrose substitution in prevention and reversal of the fall in metabolic rate accompanying hypocaloric diets.
Hendler RG, Walesky M, Sherwin RS.
Hypocaloric diets cause a fall in resting metabolic rate that interferes with weight loss. To evaluate the mechanisms underlying this phenomenon, resting metabolic rate was measured sequentially in six healthy obese women on a weight maintenance diet (more than 2,300 kilocalories), after 15 days of an 800 kilocalories carbohydrate-free diet, and after isocaloric sucrose replacement for an additional 15 days. The carbohydrate-free diet produced a 21 percent decline in resting metabolic rate (p less than 0.005) as well as a decrease in circulating triiodothyronine (41 percent, p less than 0.02) and insulin (38 percent, p less than 0.005) concentrations. Plasma norepinephrine levels also tended to decline (10 percent, 0.05 greater than p less than 0.1). However, when sucrose was substituted, resting metabolic rate rose toward baseline values even though total caloric intake was unchanged and weight loss continued. The sucrose-induced rise in resting metabolic rate was accompanied by a rise in serum triiodothyronine values, but not plasma insulin or norepinephrine concentrations. Throughout, changes in resting metabolic rate correlated with changes in serum triiodothyronine levels (r = 0.701, p less than 0.01). In four obese women, a hypocaloric sucrose diet was given at the outset for 15 days. The fall in both resting metabolic rate and triiodothyronine concentration was markedly reduced as compared with values during the carbohydrate-free diet. It is concluded that carbohydrate restriction plays an important role in mediating the fall in resting metabolic rate during hypocaloric feeding. This effect may, at least in part, be related to changes in circulating triiodothyronine levels. Incorporation of carbohydrate in diet regimens may, therefore, minimize the thermic adaptation to weight loss.