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Inulin-type fructans and 2'fucosyllactose alter both microbial composition and appear to alleviate stress-induced mood state in a working population compared to placebo (maltodextrin): the EFFICAD Trial, a randomized, controlled trial.
Jackson, PP, Wijeyesekera, A, Williams, CM, Theis, S, van Harsselaar, J, Rastall, RA
The American journal of clinical nutrition. 2023;118(5):938-955
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Anxiety and depression are the most common mental health disorders and a bidirectional relationship exists between the gut and the brain, the gut-brain axis, which may be mediated by metabolites of the gut microbiome, which include various neurotransmitters. Prebiotics, such as 2'fucosyllactose (2FS, a human milk oligosaccharide) and oligofructose (OF, an inulin-type fructan) can modulate the microbiome and may as such affect mood. The aim of this double-blind, randomised-controlled trial, including 96 healthy adults with mild/moderate levels of stress/anxiety, was to evaluate the effect of a 4-week course of 2FS and OF individually and combined versus maltodextrin (as a placebo) on the microbiome and mood. Significant positive changes in the microbiome were seen in the OF and the OF+2FS groups, compared to control. Improvements in mood (anxiety, depression, positive and negative affect and cortisol awakening response) were seen in all 3 intervention groups compared to control but generally stronger in the OF and the OF+2FS groups. The authors concluded that OF alone and in combination with 2FS has beneficial effects for mood and microbiome composition, whilst the effects on the microbiome of 2FS alone require further study.
Abstract
BACKGROUND There is increasing interest in the bidirectional relationship existing between the gut and brain and the effects of both oligofructose and 2'fucosyllactose to alter microbial composition and mood state. Yet, much remains unknown about the ability of oligofructose and 2'fucosyllactose to improve mood state via targeted manipulation of the gut microbiota. OBJECTIVES We aimed to compare the effects of oligofructose and 2'fucosyllactose alone and in combination against maltodextrin (comparator) on microbial composition and mood state in a working population. METHODS We conducted a 5-wk, 4-arm, parallel, double-blind, randomized, placebo-controlled trial in 92 healthy adults with mild-to-moderate levels of anxiety and depression. Subjects were randomized to oligofructose 8 g/d (plus 2 g/d maltodextrin); maltodextrin 10 g/d; oligofructose 8 g/d plus 2'fucosyllactose (2 g/d) or 2'fucosyllactose 2 g/d (plus 8 g/d maltodextrin). Changes in microbial load (fluorescence in situ hybridization-flow cytometry) and composition (16S ribosomal RNA sequencing) were the primary outcomes. Secondary outcomes included gastrointestinal sensations, bowel habits, and mood state parameters. RESULTS There were significant increases in several bacterial taxa including Bifidobacterium, Bacteroides, Roseburia, and Faecalibacterium prausnitzii in both the oligofructose and oligofructose/2'fucosyllactose interventions (all P ≤ 0.05). Changes in bacterial taxa were highly heterogenous upon 2'fuscoyllactose supplementation. Significant improvements in Beck Depression Inventory, State Trait Anxiety Inventory Y1 and Y2, and Positive and Negative Affect Schedule scores and cortisol awakening response were detected across oligofructose, 2'fucosyllactose, and oligofructose/2'fucosyllactose combination interventions (all P ≤ 0.05). Both sole oligofructose and oligofructose/2'fuscosyllactose combination interventions outperformed both sole 2'fucosyllactose and maltodextrin in improvements in several mood state parameters (all P ≤ 0.05). CONCLUSION The results of this study indicate that oligofructose and combination of oligofructose/2'fucosyllactose can beneficially alter microbial composition along with improving mood state parameters. Future work is needed to understand key microbial differences separating individual responses to 2'fucosyllactose supplementation. This trial was registered at clinicaltrials.gov as NCT05212545.
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Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses to an Arithmetic Stress Task in Healthy Subjects: A Randomised Clinical Trial and Proof-of-Concept Study.
Edebol Carlman, HMT, Rode, J, König, J, Repsilber, D, Hutchinson, AN, Thunberg, P, Persson, J, Kiselev, A, Pruessner, JC, Brummer, RJ
Nutrients. 2022;14(7)
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Physiological and psychological stress can affect gut function and its interaction with the brain (gut-brain axis). Different types of stress and different phases of stress regulation can affect the brain in different ways. Manipulation of the gut microbiota using probiotic bacteria has been shown to improve cognition and stress response. However, probiotic interventions are likely to have different effects depending on the strains used. The aim of this study was to assess the effects of a probiotic intervention on brain activity and stress response. This study is a randomised double-blinded placebo-controlled crossover study with 22 healthy subjects. Subjects were randomised to two study groups receiving the intervention in different orders (probiotics or placebo first). Results demonstrate that the probiotic intervention: - altered activity in specific brain regions known to regulate emotion and stress response. - significantly altered functional connectivity between the upper limbic and medioventral regions. - did not affect the activation of other limbic or subcortical areas. Authors conclude that their findings could further lead to possible clinical implications for improving stress resilience and potential roles in the treatment of affective and gut-brain axis disorders.
Abstract
Probiotics are suggested to impact physiological and psychological stress responses by acting on the gut-brain axis. We investigated if a probiotic product containing Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 affected stress processing in a double-blinded, randomised, placebo-controlled, crossover proof-of-concept study (NCT03615651). Twenty-two healthy subjects (24.2 ± 3.4 years, 6 men/16 women) underwent a probiotic and placebo intervention for 4 weeks each, separated by a 4-week washout period. Subjects were examined by functional magnetic resonance imaging while performing the Montreal Imaging Stress Task (MIST) as well as an autonomic nervous system function assessment during the Stroop task. Reduced activation in regions of the lateral orbital and ventral cingulate gyri was observed after probiotic intervention compared to placebo. Significantly increased functional connectivity was found between the upper limbic region and medioventral area. Interestingly, probiotic intervention seemed to predominantly affect the initial stress response. Salivary cortisol secretion during the task was not altered. Probiotic intervention did not affect cognitive performance and autonomic nervous system function during Stroop. The probiotic intervention was able to subtly alter brain activity and functional connectivity in regions known to regulate emotion and stress responses. These findings support the potential of probiotics as a non-pharmaceutical treatment modality for stress-related disorders.
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Effect of Combined Ingestion of L-Theanine and L-Arginine for Short-Term Psychological Stress in Young Adults: A Randomized Placebo-Controlled Study.
Furushima, D, Sugiyama, I, Nomura, Y, Unno, K, Yamada, H
Journal of nutritional science and vitaminology. 2022;68(6):540-546
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The beneficial effects of green tea and its components are well known. The ingredient L-Theanine is the most abundant water soluble non-proteinous amino acid component in green tea. The second most abundant ingredient is L-Arginine. It also exhibits a high stress-reducing effect. The hypothesis of this study was that the combined ingestion of L-arginine and L-theanine could have beneficial clinical effects for psychological stress compared with ingestion of theanine alone. This study was a randomised placebo-controlled, single-blinded study in healthy young adults. Participants (n=120) were randomly assigned to one of the three groups (1:1:1); L-theanine alone, L-theanine and L-arginine or placebo. Results show that combined ingestion of L-theanine and L-arginine tended to have greater stress reducing effects than ingestion of L-theanine alone. However, the difference was not statistically significant. Authors conclude that their findings are suggestive of synergistic effects of L-theanine and L-arginine against stress in young adults.
Abstract
l-Theanine, the most abundant amino acid component in green tea, has anti-stress effects and refreshes the mental state. A recent study demonstrated that l-arginine, the second most abundant amino acid in green tea, might enhance the anti-stress effects of l-theanine. The aim of this study was to evaluated the effects of combined ingestion of l-theanine and l-arginine on psychological stress in humans. A randomized placebo-controlled trial was conducted including 120 healthy young adults (mean age 22.4 y, 63.3% female). Subjects were randomly assigned to theanine (200 mg l-theanine), combined theanine/arginine (200 mg l-theanine, 50 mg l-arginine), or placebo groups. After consuming a test beverage, we administered a stress-loading test (Uchida-Kraepelin performance test) and performed salivary alpha-amylase activity (sAA) measurements to assess the physiological stress response at 0 min (immediately after), 5 min, and 15 min. The changes in sAA at 15 min after the stress-loading test were -2.75 (11.2) kIU/L in the theanine/arginine group, -0.40 (11.5) kIU/L in the theanine group, and 6.95 (18.6) kIU/L in the placebo group. The values in the theanine/arginine (p=0.007) and theanine (p=0.02) groups differed significantly from those in the placebo group. However, the difference between theanine/arginine and theanine groups, was not statistically significant (p=0.74). From this study, no clear conclusion could be drawn regarding the potentiating effect of theanine and arginine combined ingestion on anti-stress effects in human.
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A combination of green tea, rhodiola, magnesium and B vitamins modulates brain activity and protects against the effects of induced social stress in healthy volunteers.
Boyle, NB, Billington, J, Lawton, C, Quadt, F, Dye, L
Nutritional neuroscience. 2022;25(9):1845-1859
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Stress is a leading cause of work-related time off. Low magnesium intake has been shown to be associated with anxiety and supplementation has been shown to relieve anxiety-related-symptoms, especially when combined with B vitamins. Green tea and rhodiola have also been used to alleviate stress, anxiety, and fatigue, the latter after just 3 days of intake. This randomised control trial of 100 moderately stressed adults aimed to determine the effects of combining magnesium, B vitamins, green tea, and rhodiola after induced social stress. The results showed that supplementation with a combination of magnesium, B vitamins, green tea, and rhodiola induced a relaxed, alert state and lowered stress, anxiety, and mood disturbances. However, it did not affect stress hormones, heart rate or blood pressure in response to stress. It was concluded that combination treatment is a promising therapy for stress. This study could be used by healthcare professionals to recommend the combination of magnesium, B vitamins, green tea, and rhodiola to individuals with social anxiety before they enter a socially stressful situation.
Abstract
BACKGROUND Magnesium (Mg), green tea and rhodiola extracts have, in isolation, been shown to possess stress and anxiety relieving effects. Green tea and rhodiola have been shown to modulate EEG oscillatory brain activity associated with relaxation and stress perception. The combined capacity of these ingredients to confer protective effects under conditions of acute stress has yet to be examined. We tested the hypothesis that a combination of Mg (with B vitamins) + green tea + rhodiola would acutely moderate the effects of stress exposure. METHODS A double blind, randomised, placebo controlled, parallel group design was employed (Clinicaltrials.gov:NCT03262376; 25/0817). One hundred moderately stressed adults received oral supplementation of either (i) Mg + B vitamins + green tea + rhodiola; (ii) Mg + B vitamins + rhodiola; (iii) Mg + B vitamins + green tea; or (iv) placebo. After supplementation participants were exposed to the Trier Social Stress Test. The effects of the study treatments on electroencephalogram (EEG) resting state alpha and theta, subjective state/mood, blood pressure, heart rate variability and salivary cortisol responses after acute stress exposure were assessed. RESULTS The combined treatment significantly increased EEG resting state theta (p < .02) - considered indicative of a relaxed, alert state, attenuated subjective stress, anxiety and mood disturbance, and heightened subjective and autonomic arousal (p < .05). CONCLUSIONS Mg, B vitamins, rhodiola and green tea extracts are a promising combination of ingredients that may enhance coping capacity and offer protection from the negative effects of stress exposure.Trial registration: ClinicalTrials.gov identifier: NCT03262376.
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Exploring Associations between Interindividual Differences in Taste Perception, Oral Microbiota Composition, and Reported Food Intake.
Cattaneo, C, Riso, P, Laureati, M, Gargari, G, Pagliarini, E
Nutrients. 2019;11(5)
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There are many known drivers of food choice and habits, however, taste is considered one of the main predictors. Each taste quality is associated with different nutritional or physiological requirements or indicates a potential dietary risk. The main aim of this study was to explore whether variation in gustatory functions among individuals could be related to different dietary patterns and intake. A secondary aim was to examine the relationship between gustatory functions and dietary patterns in relation to oral microbiota composition. The study recruited 59 (27 male and 32 female) healthy, normal-weight volunteers aged between 18 and 30 years of age. Seven concentrations for each taste stimulus were prepared to determine the recognition thresholds. Results indicate that: (i) recognition thresholds for the basic tastes were associated with each other, even though in different ways, (ii) interindividual differences in taste perception may influence habitual food consumption and intake, and (iii) there are gender-related differences in food consumption frequency and intake. Authors conclude that nongenetic factors, such as the oral bacteria lining the tongue, should be adequately considered in order to gain new insights into taste-related eating habits that may influence long-term health outcomes.
Abstract
The role of taste perception, its relationship with oral microbiota composition, and their putative link with eating habits and food intake were the focus of the present study. A sample of 59 reportedly healthy adults (27 male, 32 female; age: 23.3 ± 2.6 years) were recruited for the study and taste thresholds for basic tastes, food intake, and oral microbiota composition were evaluated. Differences in taste perception were associated with different habitual food consumption (i.e., frequency) and actual intake. Subjects who were orally hyposensitive to salty taste reported consuming more bakery and salty baked products, saturated-fat-rich products, and soft drinks than hypersensitive subjects. Subjects hyposensitive to sweet taste reported consuming more frequently sweets and desserts than the hypersensitive group. Moreover, subjects hypersensitive to bitter taste showed higher total energy and carbohydrate intakes compared to those who perceived the solution as less bitter. Some bacterial taxa on tongue dorsum were associated with gustatory functions and with vegetable-rich (e.g., Prevotella) or protein/fat-rich diets (e.g., Clostridia). Future studies will be pivotal to confirm the hypothesis and the potential exploitation of oral microbiome as biomarker of long-term consumption of healthy or unhealthy diets.
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Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial.
Hidese, S, Ogawa, S, Ota, M, Ishida, I, Yasukawa, Z, Ozeki, M, Kunugi, H
Nutrients. 2019;11(10)
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L-theanine (γ-glutamylethylamide) is a unique non-protein amino acid found in green tea (Camellia sinensis), a widely consumed beverage associated with human health. The aim of this study was to examine the effects of four weeks L-theanine administration (200 mg/day, four weeks) in a healthy population, i.e., individuals without any major psychiatric disorder. This study is a randomized, placebo-controlled, crossover, and double-blind trial. The study enrolled thirty individuals (n = 9 men and n = 21 women). Participants received either an enzymatic synthetic product L-theanine or placebo tablets who had to orally self-administer before sleep each night for four weeks. Results show that four weeks L-theanine administration has positive effects on stress-related symptoms and cognitive function in a healthy population. Furthermore, the reduction in sleep quality problems (disturbances in sleep latency, sleep disturbance and use of sleep medication) was greater in the L-theanine administration compared to the placebo administration, while verbal fluency, especially letter fluency, was improved in the L-theanine administration among individuals who showed relatively low performance at pre-treatment. Authors conclude that L-theanine may be a suitable nutraceutical ingredient for improving mental conditions in a healthy population.
Abstract
This randomized, placebo-controlled, crossover, and double-blind trial aimed to examine the possible effects of four weeks L-theanine administration on stress-related symptoms and cognitive functions in healthy adults. Participants were 30 individuals (nine men and 21 women; age: 48.3 ± 11.9 years) who had no major psychiatric illness. L-theanine (200 mg/day) or placebo tablets were randomly and blindly assigned for four-week administration. For stress-related symptoms, Self-rating Depression Scale, State-Trait Anxiety Inventory-trait, and Pittsburgh Sleep Quality Index (PSQI) scores decreased after L-theanine administration (p = 0.019, 0.006, and 0.013, respectively). The PSQI subscale scores for sleep latency, sleep disturbance, and use of sleep medication reduced after L-theanine administration, compared to the placebo administration (all p < 0.05). For cognitive functions, verbal fluency and executive function scores improved after L-theanine administration (p = 0.001 and 0.031, respectively). Stratified analyses revealed that scores for verbal fluency (p = 0.002), especially letter fluency (p = 0.002), increased after L-theanine administration, compared to the placebo administration, in individuals who were sub-grouped into the lower half by the median split based on the mean pretreatment scores. Our findings suggest that L-theanine has the potential to promote mental health in the general population with stress-related ailments and cognitive impairments.
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A lecithin phosphatidylserine and phosphatidic acid complex (PAS) reduces symptoms of the premenstrual syndrome (PMS): Results of a randomized, placebo-controlled, double-blind clinical trial.
Schmidt, K, Weber, N, Steiner, M, Meyer, N, Dubberke, A, Rutenberg, D, Hellhammer, J
Clinical nutrition ESPEN. 2018;24:22-30
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PMS is characterized by a cluster of somatic and psychological symptoms of varying severity. These symptoms occur only during the luteal phase of the menstrual cycle and resolve during the first days of menses. Recent observational data suggest that supplementation with Lipogen's phosphatidylserine and phosphatidic acid complex (PAS) alleviates these PMS symptoms. The aim of this study was to observe the effects of PAS on PMS symptom severity. This study is a prospective, randomised, placebo-controlled, double-blind single centre study with two arms (PAS or placebo). Participants were randomly assigned to one of the two groups. Results show beneficial effects of a daily intake of PAS over 3 cycles on symptom levels as assessed by several well-recognized instruments for PMS evaluation. The PAS complex alleviated the PMS symptoms, providing a safe alternative to standard pharmacological treatment. Authors conclude that their findings merit consideration of developing the PAS complex as a botanical drug for treatment of PMS symptoms.
Abstract
BACKGROUND & AIMS Many women experience emotional and physical symptoms around the time of ovulation and more so before menstruation interfering with their daily normal life also known as premenstrual syndrome (PMS). Recent observational data suggest that supplementation with Lipogen's phosphatidylserine (PS) and phosphatidic acid (PA) complex (PAS) alleviates these PMS symptoms. The aim of this study was to confirm these observations on the effects of PAS on PMS symptom severity within a controlled clinical trial setting. METHODS Forty women aged 18-45 years with a diagnosis of PMS were assigned to either take PAS (containing 400 mg PS & 400 mg PA per day) or a matching placebo. The study comprised 5 on-site visits including 1 baseline menstrual cycle followed by 3 treatment cycles. Treatment intake was controlled for by using an electronic device, the Medication Event Monitoring System (MEMS®). Primary outcome of the study was the PMS symptoms severity as assessed by using the Daily Record of Severity of Problems (DRSP). Further, SIPS questionnaire (a German version of the Premenstrual Symptoms Screening Tool (PSST)), salivary hormone levels (cortisol awakening response (CAR) and evening cortisol levels) as well as serum levels (cortisol, estradiol, progesterone and corticosteroid binding globulin (CBG)) were assessed. RESULTS PMS symptoms as assessed by the DRSP Total score showed a significantly better improvement (p = 0.001) over a 3 cycles PAS intake as compared to placebo. In addition, PAS treated women reported a greater improvement in physical (p = 0.002) and depressive symptoms (p = 0.068). They also reported a lower reduction of productivity (p = 0.052) and a stronger decrease in interference with relationships with others (p = 0.099) compared to the placebo group. No other DRSP scale or item showed significant results. Likewise, the reduction in the number of subjects fulfilling PMS or premenstrual dysphoric disorder (PMDD) criteria as classified by the SIPS did not differ between the PAS and the placebo group. For the biomarkers, the salivary cortisol percentage increase of the CAR was significantly less pronounced in the follicular phase of cycle 4 than in the follicular phase of cycle 1 for subjects taking PAS when compared to subjects taking placebo (p = 0.018). Furthermore, the change of serum cortisol levels between visit 1 and visit 5 differed significantly between groups (p = 0.043). While serum cortisol levels of PAS treated females slightly decreased between visit 1 and visit 5, cortisol levels of females treated with placebo increased. For all other biomarkers, no treatment effects were observed over the 4 cycles study period. Overall, this study confirms that a daily intake of PAS, containing 400 mg PS and 400 mg PA, can be considered as safe. CONCLUSIONS Results substantiate the efficacy of PAS in reducing symptoms of PMS. In view of the recent inclusion of severe PMS symptoms (PMDD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the positive results of this clinical study merits consideration of developing the PAS complex as a botanical drug for treatment of PMDD. CLINICAL TRIAL REGISTRATION The study is registered at Deutsches Register Klinischer Studien with the registration number DRKS00009005.
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Placebo-controlled dietary intervention of stress-induced neurovegetative disorders with a specific amino acid composition: a pilot-study.
Chaborski, K, Bitterlich, N, Alteheld, B, Parsi, E, Metzner, C
Nutrition journal. 2015;14:43
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Psychosocial stress leads to altered neuroendocrine functions resulting in imbalances between various neurotransmitters and hormones. Supplementation of amino acids as precursors of neurotransmitters is an important therapeutic approach that may reduce sensitivity to stress. The aim of this study was to investigate whether daily administration of an amino acid and micronutrient mixture could reduce neurovegetative disorders in 32 psychologically stressed patients. Psychological status, serotonin level, cortisol level and dietary intake were recorded at baseline and 12 weeks after amino acid supplementation. This study showed that both treatment and placebo group resulted in a significant decrease of neurovegetative symptoms, indicating that daily supplementation of the amino acid composition used in this study resulted in no improvement of neurovegetative disorders compared with placebo.
Abstract
BACKGROUND Psychosocial stress leads to altered neuroendocrine functions, such as serotonergic dysfunction, as well as alterations of the autonomic nervous system and the hypothalamic-pituitary-adrenal (HPA)-axis activity resulting in an imbalance between inhibitory and excitatory neurotransmitters. Poor dietary intake of L-tryptophan as a precursor of serotonin increases sensitivity to stress. METHODS This randomized, double-blind, placebo-controlled study investigated the effect of a specific amino acid composition with micronutrients on neurovegetative disorders and the cardiometabolic risk profile in psychosocially stressed patients. 32 patients (18-65 years) were eligible for protocol analysis. Points in the Psychological Neurological Questionnaire (PNF), clinical and blood parameter, in particular the serotonin level, salivary cortisol levels, and dietary intake were evaluated at baseline and 12 weeks after supplementation. RESULTS The intervention in the form of either verum or placebo resulted in both groups in a significant decrease of neurovegetative symptoms. However, patients of the placebo group achieved significantly less points in the PNF compared to the verum group. But the rate of responders (≥10 points loss in PNF) was not significantly different between the groups. The macronutrient intake did not differ between verum and placebo group. On average, the HPA-axis was not disturbed in both groups. Blood serotonin indicated in both groups no significant correlation with dietary tryptophan intake or PNF. CONCLUSIONS Daily supplementation of a specific amino acid composition with micronutrients in psychologically stressed patients resulted in no improvement of neurovegetative disorders as measured by the PNF when compared to the placebo group. TRIAL REGISTRATION Clinical Trials.gov ( NCT01425983 ).
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Excessive Sugar Consumption May Be a Difficult Habit to Break: A View From the Brain and Body.
Tryon, MS, Stanhope, KL, Epel, ES, Mason, AE, Brown, R, Medici, V, Havel, PJ, Laugero, KD
The Journal of clinical endocrinology and metabolism. 2015;100(6):2239-47
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It is widely known that people eat to relieve stress. Rodent studies have shown that sugar consumption switches off activity in the networks that mediate the stress induced hypothalamic-pituitary-adrenal (HPA) autonomic nervous system. This study aimed to compare the effects of consuming drinks, sweetened with either sucrose or aspartame, on cortisol responses induced by stress. The researchers found that sucrose consumption was associated reduced stress induced cortisol, and a trend towards lower cortisol. Aspartame did not have the same effect. The Montreal Imaging Stress Task (MIST) was used to map areas of the brain associated with stress. It was found that sugar consumption caused a diminished response to MIST after two weeks of sucrose consumption, and cortisol was elevated after two weeks of aspartame. The study concluded that brain negative feedback pathways are affected by sugar, and consequently may make stressed individuals more reliant or addicted to sugar. In turn, this increases the likelihood of obesity and its associated chronic diseases.
Abstract
CONTEXT Sugar overconsumption and chronic stress are growing health concerns because they both may increase the risk for obesity and its related diseases. Rodent studies suggest that sugar consumption may activate a glucocorticoid-metabolic-brain-negative feedback pathway, which may turn off the stress response and thereby reinforce habitual sugar overconsumption. OBJECTIVE The objective of the study was to test our hypothesized glucocorticoid-metabolic-brain model in women consuming beverages sweetened with either aspartame of sucrose. DESIGN This was a parallel-arm, double-masked diet intervention study. SETTING The study was conducted at the University of California, Davis, Clinical and Translational Science Center's Clinical Research Center and the University of California, Davis, Medical Center Imaging Research Center. PARTICIPANTS Nineteen women (age range 18-40 y) with a body mass index (range 20-34 kg/m(2)) who were a subgroup from a National Institutes of Health-funded investigation of 188 participants assigned to eight experimental groups. INTERVENTION The intervention consisted of sucrose- or aspartame-sweetened beverage consumption three times per day for 2 weeks. MAIN OUTCOME MEASURES Salivary cortisol and regional brain responses to the Montreal Imaging Stress Task were measured. RESULTS Compared with aspartame, sucrose consumption was associated with significantly higher activity in the left hippocampus (P = .001). Sucrose, but not aspartame, consumption associated with reduced (P = .024) stress-induced cortisol. The sucrose group also had a lower reactivity to naltrexone, significantly (P = .041) lower nausea, and a trend (P = .080) toward lower cortisol. CONCLUSION These experimental findings support a metabolic-brain-negative feedback pathway that is affected by sugar and may make some people under stress more hooked on sugar and possibly more vulnerable to obesity and its related conditions.