Effects of Mediterranean Diet or Mindfulness-Based Stress Reduction on Prevention of Small-for-Gestational Age Birth Weights in Newborns Born to At-Risk Pregnant Individuals: The IMPACT BCN Randomized Clinical Trial.

Importance: Being born small for gestational age (SGA) is a leading cause of perinatal morbidity and mortality with no effective prevention or therapy. Maternal suboptimal nutrition and high stress levels have been associated with poor fetal growth and adverse pregnancy outcomes. Objective: To investigate whether structured interventions based on a Mediterranean diet or mindfulness-based stress reduction (stress reduction) in high-risk pregnancies can reduce the percentage of newborns who were born SGA and other adverse pregnancy outcomes. Design, Setting, and Participants: Parallel-group randomized clinical trial conducted at a university hospital in Barcelona, Spain, including 1221 individuals with singleton pregnancies (19-23 weeks' gestation) at high risk for SGA. Enrollment took place from February 1, 2017, to October 10, 2019, with follow-up until delivery (final follow-up on March 1, 2020). Interventions: Participants in the Mediterranean diet group (n = 407) received 2 hours monthly of individual and group educational sessions and free provision of extra-virgin olive oil and walnuts. Individuals in the stress reduction group (n = 407) underwent an 8-week stress reduction program adapted for pregnancy, consisting of weekly 2.5-hour sessions and 1 full-day session. Individuals in the usual care group (n = 407) received pregnancy care per institutional protocols. Main Outcomes and Measures: The primary end point was the percentage of newborns who were SGA at delivery, defined as birth weight below the 10th percentile. The secondary end point was a composite adverse perinatal outcome (at least 1 of the following: preterm birth, preeclampsia, perinatal mortality, severe SGA, neonatal acidosis, low Apgar score, or presence of any major neonatal morbidity). Results: Among the 1221 randomized individuals (median [IQR] age, 37 [34-40] years), 1184 (97%) completed the trial (392 individuals assigned to the Mediterranean diet group, 391 to the stress reduction group, and 401 to the usual care group). SGA occurred in 88 newborns (21.9%) in the control group, 55 (14.0%) in the Mediterranean diet group (odds ratio [OR], 0.58 [95% CI, 0.40-0.84]; risk difference [RD], -7.9 [95% CI, -13.6 to -2.6]; P = .004), and 61 (15.6%) in the stress reduction group (OR, 0.66 [95% CI, 0.46-0.94]; RD, -6.3 [95% CI, -11.8 to -0.9]; P = .02). The composite adverse perinatal outcome occurred in 105 newborns (26.2%) in the control group, 73 (18.6%) in the Mediterranean diet group (OR, 0.64 [95% CI, 0.46-0.90]; RD, -7.6 [95% CI, -13.4 to -1.8]; P = .01), and 76 (19.5%) in the stress reduction group (OR, 0.68 [95% CI, 0.49-0.95]; RD, -6.8 [95% CI, -12.6 to -0.3]; P = .02). Conclusions and Relevance: In this randomized trial conducted at a single institution in Spain, treating pregnant individuals at high risk for SGA with a structured Mediterranean diet or with mindfulness-based stress reduction, compared with usual care, significantly reduced the percentage of newborns with birth weight below the 10th percentile. Due to important study limitations, these findings should be considered preliminary and require replication, as well as assessment in additional patient populations, before concluding that these treatments should be recommended to patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03166332.

Impact of a Nordic diet on psychological function in young students.

BACKGROUND: There has been a rapid increase in the prevalence of psychiatric and psychological disease, and this has attracted interest in identifying modifiable lifestyle factors that may affect an individual's mood. Diet is one potential lifestyle factor that may affect psychological function. AIM: This study aimed to investigate the relationship between adherence to the health-promoting Nordic diet (ND) with neuropsychological function in young women. METHODS: The study comprised 181 female students aged between 18 and 25 years. Psychological function was evaluated using a series of standardized questionnaires, including the Cognitive Ability Questionnaire, Depression Anxiety Stress Scale, Insomnia Severity Index, Epworth Sleep Scale and Quality of Life Questionnaire. A validated food frequency questionnaire, which included 65 types of foods, was used to evaluate the amount of different foods consumed. RESULTS: Evaluation of the dietary composition of the participants showed that the rate of adherence to the ND was positively associated with total energy, carbohydrates, protein, fibre, iron, magnesium, potassium, zinc, folate, phosphorus, vitamin C, thiamine, riboflavin, niacin, vitamins B6 and B12, carotene, whole grain, legumes, cabbage/vegetables, vegetables and fruit (p<0.05). Linear regression showed cabbage/vegetable consumption was inversely related to scores of stress (ß=-0.04; p=0.038) and anxiety (ß=-0.02; p=0.049) and directly associated with the quality-of-life score (0.02; p=0.036). CONCLUSIONS: Adherence to a ND with a high intake of cabbage/vegetables was inversely associated with stress and anxiety scores and directly associated with health-related quality of life.

The Effect of a Single Dose of Dark Chocolate on Cardiovascular Parameters and Their Reactivity to Mental Stress.

Objective: This study investigated the effect of a single administration of dark or milk chocolate on blood pressure (BP), heart rate (HR), and double product (DP) in young healthy women at rest and during acute mental stress.Method: Measurements consisted of anthropometry, BP, and HR. Mean arterial BP (MAP) and DP were computed. The relative reactivity of individual variables was quantified as to their percentage change during the rest or test of mental arithmetic (MA) with respect to the respective baseline value. All subjects underwent two tests of MA-one before chocolate administration and the second one 2 hours after chocolate (1 mg/g of body weight) ingestion.Results: Two hours after ingestion at rest, dark chocolate administration resulted in a significant increase in relative values of systolic BP and DP by 5.1% ± 1.4% and 13.7% ± 3.2%, respectively, compared to the responses in the milk chocolate group (-2.4% ± 1.6% and 0.6% ± 3.4%, respectively, p < 0.04 for both comparisons) without changes in diastolic BP, HR, and MAP. During MA-induced acute stress, the relative magnitude of the reactivity of diastolic BP, HR, MAP, and DP decreased by about 10, 16, 8, and 23 percentage points, respectively, 2 hours after ingestion of dark chocolate compared to the relative reactivity determined before dark chocolate ingestion. Milk chocolate failed to affect any of the above-mentioned parameters at rest or during stress.Conclusions: The single oral intake of 85% dark chocolate increased relative values of systolic BP and DP at rest but buffered the reactivity of diastolic BP, HR, MAP, and DP during mental stress, which was not found after ingestion of milk chocolate. Thus, dark chocolate might have a beneficial effect during acute stress due to its ability to buffer cardiovascular reactivity in young healthy women.

A Randomized Double-Blind, Placebo Controlled, Four-Arm Parallel Study Investigating the Effect of a Broad-Spectrum Wellness Beverage on Mood State in Healthy, Moderately Stressed Adults.

OBJECTIVE: The objective of this study was to investigate the effect of a broad-spectrum wellness beverage (Zeal Wellness [ZW]) on standardized measures of mood states, including overall feelings of vitality, in healthy, moderately stressed adults. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted among 99 eligible participants prescreened for moderate stress. Participants were randomized to one of four groups and received ZW once daily (1-dose-ZW; 14 g), ZW twice daily (2-dose-ZW; 28 g), placebo once daily (1-dose-placebo), or placebo twice daily (2-dose-placebo) for 4 weeks. A stress/vitality questionnaire assessed stress and the Profile of Moods (POMS) Questionnaire assessed vigor via mental/physical energy and global mood state. Safety was assessed by clinical chemistry, liver, kidney function, and anthropometric measures and adverse event reporting. RESULTS: Participants receiving 2-dose-ZW reported a 6.6% decrease in scores on POMS-Total Mood Disturbance (TMD; p < 0.05) and a 6.8% decrease in the anger-hostility mood state (p < 0.022) compared to the combined placebo group at day 29. The 2-dose-ZW provided a 12.8% greater improvement in POMS-TMD scores when compared to participants receiving 1-dose-ZW after 28 days of supplementation (p = 0.014). Within groups, there was a 22.4% and a 9.6% decrease in POMS-TMD scores in participants with 2-dose-ZW and 1-dose-ZW, respectively. In addition, participants receiving 2-dose-ZW showed significant improvements (p = 0.001) in the POMS t-score iceberg profile, which represented a shift to a more healthy profile. CONCLUSION: These data show that daily supplementation with 2-dose-ZW significantly decreased POMS-TMD scores and anger-hostility mood state and shifted the POMS iceberg profile to a healthy profile compared to the combined placebo, reflecting the functional benefit of rice-bran-fruit-vegetable extracts based beverage on health.

Supplementation with macular carotenoids reduces psychological stress, serum cortisol, and sub-optimal symptoms of physical and emotional health in young adults.

PURPOSE: Oxidative stress and systemic inflammation are the root cause of several deleterious effects of chronic psychological stress. We hypothesize that the antioxidant and anti-inflammatory capabilities of the macular carotenoids (MCs) lutein, zeaxanthin, and meso-zeaxanthin could, via daily supplementation, provide a dietary means of benefit. METHODS: A total of 59 young healthy subjects participated in a 12-month, double-blind, placebo-controlled trial to evaluate the effects of MC supplementation on blood cortisol, psychological stress ratings, behavioural measures of mood, and symptoms of sub-optimal health. Subjects were randomly assigned to one of three groups: placebo, 13 mg, or 27 mg / day total MCs. All parameters were assessed at baseline, 6 months, and 12 months. Serum MCs were determined via HPLC, serum cortisol via ELISA, and macular pigment optical density (MPOD) via customized heterochromatic flicker photometry. Behavioural data were obtained via questionnaire. RESULTS: Significant baseline correlations were found between MPOD and Beck anxiety scores (r = -0.28; P = 0.032), MPOD and Brief Symptom Inventory scores (r = 0.27; P = 0.037), and serum cortisol and psychological stress scores (r = 0.46; P < 0.001). Supplementation for 6 months improved psychological stress, serum cortisol, and measures of emotional and physical health (P < 0.05 for all), versus placebo. These outcomes were either maintained or improved further at 12 months. CONCLUSIONS: Supplementation with the MCs significantly reduces stress, cortisol, and symptoms of sub-optimal emotional and physical health. Determining the basis for these effects, whether systemic or a more central (i.e. brain) is a question that warrants further study.

Effects of eicosapentaenoic acid and docosahexaenoic acid on anxiety-like behavior in socially isolated rats.

The effects of fish oil for improving mental health have been reported. The present study was undertaken to compare the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on anxiety-like behavior using a rat model. Experimental diets enriched in EPA or DHA as glycerides were prepared. Rats were exposed to social isolation stress and fed the experimental diet for 14 days. The results of behavioral tests revealed that rats fed the EPA-enriched diet exhibited less anxiety-like behavior than rats fed the control or DHA-enriched diets. Furthermore, EPA suppressed anxiety-like behavior only in socially isolated rats. The increase in EPA contents in the brain phospholipid fraction by feeding EPA-enriched diet was more significant than that of DHA by feeding DHA-enriched diet. These results suggest that dietary EPA is more anxiolytic than DHA in rats exposed to social isolation stress and is effective in increasing EPA content in brain membranes.

Early life diets with prebiotics and bioactive milk fractions attenuate the impact of stress on learned helplessness behaviours and alter gene expression within neural circuits important for stress resistance.

Manipulating gut microbes may improve mental health. Prebiotics are indigestible compounds that increase the growth and activity of health-promoting microorganisms, yet few studies have examined how prebiotics affect CNS function. Using an acute inescapable stressor known to produce learned helplessness behaviours such as failure to escape and exaggerated fear, we tested whether early life supplementation of a blend of two prebiotics, galactooligosaccharide (GOS) and polydextrose (PDX), and the glycoprotein lactoferrin (LAC) would attenuate behavioural and biological responses to stress later in life. Juvenile, male F344 rats were fed diets containing either GOS and PDX alone, LAC alone, or GOS, PDX and LAC. All diets altered gut bacteria, while diets containing GOS and PDX increased Lactobacillus spp. After 4 weeks, rats were exposed to inescapable stress, and either immediately killed for blood and tissues, or assessed for learned helplessness 24 h later. Diets did not attenuate stress effects on spleen weight, corticosterone and blood glucose; however, all diets differentially attenuated stress-induced learned helplessness. Notably, in situ hybridization revealed that all diets reduced stress-evoked cfos mRNA in the dorsal raphe nucleus (DRN), a structure important for learned helplessness behaviours. In addition, GOS, PDX and LAC diet attenuated stress-evoked decreases in mRNA for the 5-HT1A autoreceptor in the DRN and increased basal BDNF mRNA within the prefrontal cortex. These data suggest early life diets containing prebiotics and/or LAC promote behavioural stress resistance and uniquely modulate gene expression in corresponding circuits.

A double-blind, randomized, placebo-controlled trial of Lactobacillus helveticus and Bifidobacterium longum for the symptoms of depression.

OBJECTIVES: This trial investigated whether probiotics improved mood, stress and anxiety in a sample selected for low mood. We also tested whether the presence or severity of irritable bowel syndrome symptoms, and levels of proinflammatory cytokines, brain-derived neurotrophic factor and other blood markers, would predict or impact treatment response. METHOD: Seventy-nine participants (10 dropouts) not currently taking psychotropic medications with at least moderate scores on self-report mood measures were randomly allocated to receive either a probiotic preparation (containing Lactobacillus helveticus and Bifidobacterium longum) or a matched placebo, in a double-blind trial for 8 weeks. Data were analysed as intent-to-treat. RESULTS: No significant difference was found between the probiotic and placebo groups on any psychological outcome measure (Cohen's d range = 0.07-0.16) or any blood-based biomarker. At end-point, 9 (23%) of those in the probiotic group showed a ⩾60% change on the Montgomery-Åsberg Depression Rating Scale (responders), compared to 10 (26%) of those in the placebo group ([Formula: see text], p = ns). Baseline vitamin D level was found to moderate treatment effect on several outcome measures. Dry mouth and sleep disruption were reported more frequently in the placebo group. CONCLUSIONS: This study found no evidence that the probiotic formulation is effective in treating low mood, or in moderating the levels of inflammatory and other biomarkers. The lack of observed effect on mood symptoms may be due to the severity, chronicity or treatment resistance of the sample; recruiting an antidepressant-naive sample experiencing mild, acute symptoms of low mood, may well yield a different result. Future studies taking a preventative approach or using probiotics as an adjuvant treatment may also be more effective. Vitamin D levels should be monitored in future studies in the area. The results of this trial are preliminary; future studies in the area should not be discouraged.

ß-Alanine supplemented diets enhance behavioral resilience to stress exposure in an animal model of PTSD.

This study investigated the effects of ß-alanine (BA) ingestion on the behavioral and neuroendocrine response of post-traumatic stress disorder (PTSD) in a murine model. Animals were fed a normal diet with or without (PL) BA supplementation (100 mg kg(-1)) for 30 days. Animals were then exposed to a predator-scent stress (PSS) or a sham (UNEX). Behaviors were evaluated using an elevated plus maze (EPM) and acoustic startle response (ASR) 7 days following exposure to the PSS. Corticosterone concentrations (CS), expression of brain-derived neurotrophic factor (BDNF), and brain carnosine concentrations were analyzed a day later. Animals in PSS+PL spent significantly less time in the open arms and in the number of entries in the EPM than PSS+BA, UNEX+BA, or UNEX+PL. Animals in PSS+BA had comparable scores to UNEX+BA. Anxiety index was higher (p < 0.05) in PSS+PL compared to PSS+BA or animals that were unexposed. ASR and freezing were greater (p < 0.05) in animals exposed to PSS compared to animals unexposed. CS expression was higher (p < 0.05) in animals exposed to PSS compared to unexposed animals. Brain carnosine concentrations in the hippocampus and other brain sections were significantly greater in animals supplemented with BA compared to PL. BDNF expression in the CA1 and DG subregions of the hippocampus was lower (p < 0.05) in animals exposed and fed a normal diet compared to animals exposed and supplemented with BA, or animals unexposed. In conclusion, BA supplementation in rats increased brain carnosine concentrations and resulted in a reduction in PTSD-like behavior, which may be mediated in part by maintaining BDNF expression in the hippocampus.

Associations between fruit and vegetable consumption and psychological distress: results from a population-based study.

BACKGROUND: Several studies observed associations of various aspects of diet with mental health, but little is known about the relationship between following the 5-a-day recommendation for fruit and vegetables consumption and mental health. Thus, we examined the associations of the Swiss daily recommended fruit and vegetable intake with psychological distress. METHODS: Data from 20,220 individuals aged 15+ years from the 2012 Swiss Health Survey were analyzed. The recommended portions of fruit and vegetables per day were defined as 5-a-day (at least 2 portions of fruit and 3 of vegetables). The outcome was perceived psychological distress over the previous 4 weeks (measured by the 5-item mental health index [MHI-5]). High distress (MHI-5 score ≤ 52), moderate distress (MHI-5 > 52 and ≤ 72) and low distress (MHI-5 > 72 and ≤ 100) were differentiated and multinomial logistic regression analyses adjusted for known confounding factors were performed. RESULTS: The 5-a-day recommendation was met by 11.6 % of the participants with low distress, 9.3 % of those with moderate distress, and 6.2 % of those with high distress. Consumers fulfilling the 5-a-day recommendation had lower odds of being highly or moderately distressed than individuals consuming less fruit and vegetables (moderate vs. low distress: OR = 0.82, 95 % confidence interval [CI] 0.69-0.97; high vs. low distress: OR = 0.55, 95 % CI 0.41-0.75). CONCLUSIONS: Daily intake of 5 servings of fruit and vegetable was associated with lower psychological distress. Longitudinal studies are needed to further determine the causal nature of this relationship.

Placebo-controlled dietary intervention of stress-induced neurovegetative disorders with a specific amino acid composition: a pilot-study.

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 ).

Early prenatal food supplementation ameliorates the negative association of maternal stress with birth size in a randomised trial.

Low birthweight increases the risk of infant mortality, morbidity and poor development. Maternal nutrition and stress influence birth size, but their combined effect is not known. We hypothesised that an early-invitation time to start a prenatal food supplementation programme could reduce the negative influence of prenatal maternal stress on birth size, and that effect would differ by infant sex. A cohort of 1041 pregnant women, who had delivered an infant, June 2003-March 2004, was sampled from among 3267 in the randomised controlled trial, Maternal Infant Nutritional Interventions Matlab, conducted in Matlab, Bangladesh. At 8 weeks gestation, women were randomly assigned an invitation to start food supplements (2.5 MJ d(-1) ; 6 days a week) either early (∼9 weeks gestation; early-invitation group) or at usual start time for the governmental programme (∼20 weeks gestation; usual-invitation group). Morning concentration of cortisol was measured from one saliva sample/woman at 28-32 weeks gestation to assess stress. Birth-size measurements for 90% of infants were collected within 4 days of birth. In a general linear model, there was an interaction between invitation time to start the food supplementation programme and cortisol with birthweight, length and head circumference of male infants, but not female infants. Among the usual-invitation group only, male infants whose mothers had higher prenatal cortisol weighed less than those whose mothers had lower prenatal cortisol. Prenatal food supplementation programmes that begin first trimester may support greater birth size of male infants despite high maternal stress where low birthweight is a public health concern.

Effects of stress and dietary tryptophan enhancement on craving for alcohol in binge and non-binge heavy drinkers.

Stress is known to play an important role in alcohol abuse, whereas binge drinking may increase individuals' susceptibility to the development of alcohol dependence. We set out to investigate whether binge drinkers (BDs) or non-BDs (NBDs) are at a greater risk of an increase in their desire for alcohol following experimental stress induction (modified Trier Social Stress Test; Experiment 1) and to explore the biological mechanisms underlying such an effect (Experiment 2). Preclinical evidence suggests that serotonin may mediate stress-induced reinstatement of alcohol intake. We therefore tested whether dietary tryptophan (TRP) enhancement would modulate stress-induced desire for alcohol and whether it would affect the two populations (BD/NBD) differently. In Experiment 1 (14 NBDs, 10 BDs; mean weekly alcohol intake 50.64 U), stress induction selectively increased strong desire for alcohol compared with the nonstressful condition in BDs. Throughout the experiment, BDs reported greater negative reinforcement type of craving than NBDs, but also a higher expectancy of alcohol-induced negative effects. In Experiment 2, 41 participants (22 NBDs, 19 BDs; mean alcohol intake 38.81 U) were given either the TRP-rich (TRP+; 9 BDs, 11 NBD) or the control (CTR; 10 BD, 11 NBD) diet before undergoing stress induction. In BDs, the TRP+ diet prevented the stress-induced increase in strong desire that was observed in individuals receiving the CTR diet. In NBDs, the TRP+ diet appeared to facilitate an increase in strong desire. These findings suggest that BDs may indeed be at a greater risk than NBDs of an increase in their craving for alcohol when stressed. Furthermore, whereas enhancement of 5-hydroxytryptamine function may moderate the impact of stress on craving in BDs, it seems to facilitate stress-induced craving in NBDs, suggesting that the serotonergic system may be differentially involved depending on individual binge drinking status.

The Potential Effects of the Ketogenic Diet in the Prevention and Co-Treatment of Stress, Anxiety, Depression, Schizophrenia, and Bipolar Disorder: From the Basic Research to the Clinical Practice.

BACKGROUND: The ketogenic diet (KD) has been highly developed in the past for the treatment of epileptic pathological states in children and adults. Recently, the current re-emergence in its popularity mainly focuses on the therapy of cardiometabolic diseases. The KD can also have anti-inflammatory and neuroprotective activities which may be applied to the prevention and/or co-treatment of a diverse range of psychiatric disorders. PURPOSE: This is a comprehensive literature review that intends to critically collect and scrutinize the pre-existing research basis and clinical data of the potential advantageous impacts of a KD on stress, anxiety, depression, schizophrenia and bipolar disorder. METHODS: This literature review was performed to thoroughly represent the existing research in this topic, as well as to find gaps in the international scientific community. In this aspect, we carefully investigated the ultimate scientific web databases, e.g., PubMed, Scopus, and Web of Science, to derive the currently available animal and clinical human surveys by using efficient and representative keywords. RESULTS: Just in recent years, an increasing amount of animal and clinical human surveys have focused on investigating the possible impacts of the KD in the prevention and co-treatment of depression, anxiety, stress, schizophrenia, and bipolar disorder. Pre-existing basic research with animal studies has consistently demonstrated promising results of the KD, showing a propensity to ameliorate symptoms of depression, anxiety, stress, schizophrenia, and bipolar disorder. However, the translation of these findings to clinical settings presents a more complex issue. The majority of the currently available clinical surveys seem to be moderate, usually not controlled, and have mainly assessed the short-term effects of a KD. In addition, some clinical surveys appear to be characterized by enormous dropout rates and significant absence of compliance measurement, as well as an elevated amount of heterogeneity in their methodological design. CONCLUSIONS: Although the currently available evidence seems promising, it is highly recommended to accomplish larger, long-term, randomized, double-blind, controlled clinical trials with a prospective design, in order to derive conclusive results as to whether KD could act as a potential preventative factor or even a co-treatment agent against stress, anxiety, depression, schizophrenia, and bipolar disorder. Basic research with animal studies is also recommended to examine the molecular mechanisms of KD against the above psychiatric diseases.

A cafeteria diet modifies the response to chronic variable stress in rats.

Stress is known to lead to metabolic and behavioral changes. To study the possible relationships between stress and dietary intake, male Sprague-Dawley rats were fed one of three diets for 6 weeks: high carbohydrate (HC), high fat (HF), or "Cafeteria" (CAF) (Standard HC plus a choice of highly palatable cafeteria foods: chocolate, biscuits, and peanut butter). After the first 3 weeks, half of the animals from each group (experimental groups) were stressed daily using a chronic variable stress (CVS) paradigm, while the other half of the animals (control groups) were kept undisturbed. Rats were sacrificed at the end of the 6-week period. The effects of stress and dietary intake on animal adiposity, serum lipids, and corticosterone were analyzed. Results showed that both chronic stress and CAF diet resulted in elevated total cholesterol, increased low-density lipoprotein (LDL), and lower high-density lipoprotein (HDL). In addition, increases in body weight, food intake, and intra-abdominal fat were observed in the CAF group compared with the other dietary groups. In addition, there was a significant interaction between stress and diet on serum corticosterone levels, which manifest as an increase in corticosterone levels in stressed rats relative to non-stressed controls in the HC and HF groups but not in the CAF group. These results show that a highly palatable diet, offering a choice of food items, is associated with a reduction in the response to CVS and could validate a stressor-induced preference for comfort food that in turn could increase body weight.

Isolation stress exposure and consumption of palatable diet during the prepubertal period leads to cellular changes in the hippocampus.

Social isolation is one of the most potent stressors in the prepubertal period and may influence disease susceptibility or resilience in adulthood. The glucocorticoid response and, consequently, the adaptive response to stress involve important changes in mitochondrial functions and apoptotic signaling. Previous studies have shown that consumption of a palatable diet reduces some stress effects. Therefore, the aim of the present study was to investigate whether isolation stress in early life can lead to cellular alterations in the hippocampus. For this, we evaluated oxidative stress parameters, DNA breakage index, mitochondrial mass and potential, respiratory chain enzyme activities, apoptosis, and necrosis in the hippocampus of juvenile male rats submitted or not to isolation stress during the pre-puberty period. We also verified whether consumption of a palatable diet during this period can modify stress effects. Results show that stress led to an oxidative imbalance, DNA breaks, increased the mitochondrial potential and early apoptosis, and decreased the number of live and necrotic cells. In addition, the palatable diet increased glutathione peroxidase activity, high mitochondrial potential and complex I-III activity in the hippocampus of juvenile rats. The administration of a palatable diet during the isolation period prevented the stress effects that caused the reduction in live cells and increased apoptosis. In conclusion, the stress experienced during the pre-pubertal period induced a hippocampal oxidative imbalance, DNA damage, mitochondrial dysfunction, and increased apoptosis, while consumption of a palatable diet attenuated some of these effects of exposure, such as the reduction in live cells and increased apoptosis, besides favoring an increase in antioxidant enzymes activities.

Long-term ω-3 fatty acid supplementation induces anti-stress effects and improves learning in rats.

Chronic stress leads to secretion of the adrenal steroid hormone corticosterone, inducing hippocampal atrophy and dendritic hypertrophy in the rat amygdala. Both alterations have been correlated with memory impairment and increased anxiety. Supplementation with ω-3 fatty acids improves memory and learning in rats. The aim of this study was to evaluate the effects of ω-3 supplementation on learning and major biological and behavioral stress markers. Male Sprague-Dawley rats were randomly assigned to three experimental groups: 1) Control, 2) Vehicle, animals supplemented with water, and 3) ω-3, rats supplemented with ω-3 (100 mg of DHA+25 mg of EPA). Each experimental group was divided into two subgroups: one of which was not subjected to stress while the other was subjected to a restraint stress paradigm. Afterwards, learning was analyzed by avoidance conditioning. As well, plasma corticosterone levels and anxiety were evaluated as stress markers, respectively by ELISA and the plus-maze test. Restraint stress impaired learning and increased both corticosterone levels and the number of entries into the open-arm (elevated plus-maze). These alterations were prevented by ω-3 supplementation. Thus, our results demonstrate that ω-3 supplementation had two beneficial effects on the stressed rats, a strong anti-stress effect and improved learning.

Potential roles of polyunsaturated fatty acid-enriched diets in modulating social stress-like features.

Fish oil or its major constituents, namely omega-3 poly-unsaturated fatty acid (n3-PUFA), are popular supplements to improve neurogenesis, neuroprotection, and overall brain functions. Our objective was to probe the implications of fat enriched diet with variable PUFAs supplements in ameliorating social stress (SS). We fed mice on either of the three diet types, namely the n-3 PUFA-enriched diet (ERD, n3:n6= 7:1), a balanced diet (BLD, n3:n6= 1:1) or a standard lab diet (STD, n3:n6= 1:6). With respect to the gross fat contents, the customized special diets, namely ERD and BLD were extreme diet, not reflecting the typical human dietary composition. Aggressor-exposed SS (Agg-E SS) model triggered behavioral deficiencies that lingered for 6 weeks (6w) post-stress in mice on STD. ERD and BLD elevated bodyweights but potentially helped in building the behavioral resilience to SS. STD adversely affected the gene networks of brain transcriptomics associated with the cell mortality, energy homeostasis and neurodevelopment disorder. Diverging from the ERD's influences on these networks, BLD showed potential long-term benefits in combatting Agg-E SS. The gene networks linked to cell mortality and energy homeostasis, and their subfamilies, such as cerebral disorder and obesity remained at the baseline level of Agg-E SS mice on BLD 6w post-stress. Moreover, neurodevelopment disorder network and its subfamilies like behavioral deficits remained inhibited in the cohort fed on BLD 6w post Agg-E SS.

Protein catabolism and requirements in severe illness.

Reduced total body protein mass is a marker of protein-energy malnutrition and has been associated with numerous complications. Severe illness is characterized by a loss of total body protein mass, mainly from the skeletal muscle. Studies on protein turnover describe an increased protein breakdown and, to a lesser extent, an increased whole-body protein synthesis, as well as an increased flux of amino acids from the periphery to the liver. Appropriate nutrition could limit protein catabolism. Nutritional support limits but does not stop the loss of total body protein mass occurring in acute severe illness. Its impact on protein kinetics is so far controversial, probably due to the various methodologies and characteristics of nutritional support used in the studies. Maintaining calorie balance alone the days after an insult does not clearly lead to an improved clinical outcome. In contrast, protein intakes between 1.2 and 1.5 g/kg body weight/day with neutral energy balance minimize total body protein mass loss. Glutamine and possibly leucine may improve clinical outcome, but it is unclear whether these benefits occur through an impact on total body protein mass and its turnover, or through other mechanisms. Present recommendations suggest providing 20 - 25 kcal/kg/day over the first 72 - 96 hours and increasing energy intake to target thereafter. Simultaneously, protein intake should be between 1.2 and 1.5 g/kg/day. Enteral immunonutrition enriched with arginine, nucleotides, and omega-3 fatty acids is indicated in patients with trauma, acute respiratory distress syndrome (ARDS), and mild sepsis. Glutamine (0.2 - 0.4 g/kg/day of L-glutamine) should be added to enteral nutrition in burn and trauma patients (ESPEN guidelines 2006) and to parenteral nutrition, in the form of dipeptides, in intensive care unit (ICU) patients in general (ESPEN guidelines 2009).