OBJECTIVE: To determine whether chicken-based formula can replace soy-based formula in infants with cow milk allergy.

SUBJECTS AND METHODS: Thirty-eight infants with cow's milk allergy, aged between 2-24 months of age were randomized to receive either chicken-based formula or soy-based formula for 14 days.

RESULTS: In the group of soy-based formula, 12 out of 18 infants had evidence of intolerance and could not continue with the formula. However, only 4 out of 20 infants in the chicken-based formula group had evidence of clinical intolerance. All other 16 infants were fed the chicken-based formula with success. The number of infants who were intolerant to chicken formula was significantly lower than the number of those fed soy-based formula (p = 0.009).

CONCLUSION: Chicken-based formula can be used more effectively than soy-based formula in infants with cow milk allergy.

Adherence to traditional Mediterranean diet (MD) has been reported to be inversely associated with total, as well as cardiovascular, mortality. We have examined the relation between degree of such adherence and incidence of cancer overall in a general population sample of 25 623 participants (10 582 men, 15 041 women) of the Greek segment of the European Prospective Investigation into Cancer and nutrition (EPIC). All subjects completed a validated, interviewer-administered, semi-quantitative food-frequency questionnaire at enrolment. Degree of adherence to the traditional MD was assessed through a 10-point scale (0 minimal; 9 maximal) that incorporated key dietary characteristics. During a median follow-up of 7.9 years and 188 042 total person-years, 851 medically confirmed incident cancer cases (421 men, 430 women) were recorded. Using proportional hazards regression with adjustment for potential confounders, we found that a higher degree of MD adherence was associated with lower overall cancer incidence. A two-point increase in the score corresponded to a 12% reduction in cancer incidence (adjusted hazard ratio, 0.88 (95% confidence interval 0.80, 0.95)). The association was exposure-dependent and stronger among women. This inverse association with MD adherence was considerably stronger than that predicted on the basis of the associations of the individual components of this diet and points to the value of analysing dietary patterns in cancer studies.

Recent identification of a mammary gland-specific microbiome led to studies investigating bacteria populations in breast cancer. Malignant breast tumors have lower Lactobacillus abundance compared with benign lesions, implicating Lactobacillus as a negative regulator of breast cancer. Diet is a main determinant of gut microbial diversity. Whether diet affects breast microbiome populations is unknown. In a non-human primate model, we found that consumption of a Western or Mediterranean diet modulated mammary gland microbiota and metabolite profiles. Mediterranean diet consumption led to increased mammary gland Lactobacillus abundance compared with Western diet-fed monkeys. Moreover, mammary glands from Mediterranean diet-fed monkeys had higher levels of bile acid metabolites and increased bacterial-processed bioactive compounds. These data suggest that diet directly influences microbiome populations outside the intestinal tract in distal sites such as the mammary gland. Our study demonstrates that diet affects the mammary gland microbiome, establishing an alternative mechanistic pathway for breast cancer prevention.

Cruciferous vegetables contain isothiocyanates, which show potent chemopreventive activity against bladder cancer in both in vitro and in vivo studies. However, previous epidemiologic studies investigating cruciferous vegetable intake and bladder cancer risk have been inconsistent. Cooking can substantially reduce or destroy isothiocyanates, and could account for study inconsistencies. In this hospital-based case-control study involving 275 individuals with incident, primary bladder cancer and 825 individuals without cancer, we examined the usual prediagnostic intake of raw and cooked cruciferous vegetables in relation to bladder cancer risk. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with unconditional logistic regression, adjusting for smoking and other bladder cancer risk factors. We observed a strong and statistically significant inverse association between bladder cancer risk and raw cruciferous vegetable intake (adjusted OR for highest versus lowest category = 0.64; 95% CI, 0.42-0.97), with a significant trend (P = 0.003); there were no significant associations for fruit, total vegetables, or total cruciferous vegetables. The associations observed for total raw crucifers were also observed for individual raw crucifers. The inverse association remained significant among current and heavy smokers with three or more servings per month of raw cruciferous vegetables (adjusted ORs, 0.46 and 0.60; 95% CI, 0.23-0.93 and 0.38-0.93, respectively). These data suggest that cruciferous vegetables, when consumed raw, may reduce the risk of bladder cancer, an effect consistent with the role of dietary isothiocyanates as chemopreventive agents against bladder cancer.

Epilepsy is too complex to be considered as a disease; it is more of a syndrome, characterized by seizures, which can be caused by a diverse array of afflictions. As such, drug interventions that target a single biological pathway will only help the specific individuals where that drug's mechanism of action is relevant to their disorder. Most likely, this will not alleviate all forms of epilepsy nor the potential biological pathways causing the seizures, such as glucose/amino acid transport, mitochondrial dysfunction, or neuronal myelination. Considering our current inability to test every individual effectively for the true causes of their epilepsy and the alarming number of misdiagnoses observed, we propose the use of the ketogenic diet (KD) as an effective and efficient preliminary/long-term treatment. The KD mimics fasting by altering substrate metabolism from carbohydrates to fatty acids and ketone bodies (KBs). Here, we underscore the need to understand the underlying cellular mechanisms governing the KD's modulation of various forms of epilepsy and how a diverse array of metabolites including soluble fibers, specific fatty acids, and functional amino acids (e.g., leucine, D-serine, glycine, arginine metabolites, and N-acetyl-cysteine) may potentially enhance the KD's ability to treat and reverse, not mask, these neurological disorders that lead to epilepsy.

To determine whether an elemental diet or prednisolone would be more effective for treating acute Crohn's disease, a controlled trial was conducted on 20 patients with acute Crohn's disease who had never received specific treatment. The first ten patients were put on an elemental diet and the remaining ten were prescribed prednisolone for six weeks at an initial dose of 0.7 mg/kg/day. Patients were assessed using the simple activity index, body weight, erythrocyte sedimentation rate, C-reactive protein and alpha 2 globulin, serum albumin, and radiographic findings of bowel lesions. At six weeks, the patients on the elemental diet showed a significantly greater improvement in the activity index, inflammatory signs such as C-reactive protein and alpha 2 globulin, and radiographic findings of bowel lesions than did those on the steroid. Patients who were given steroids for six weeks and then treated with the elemental diet for four weeks showed improvement in the radiographic findings of bowel lesions and inflammation. The present study strongly suggests that elemental diet is superior to steroids for treating active Crohn's disease.

BACKGROUND:Here, we aim to identify cortical electrofunctional correlates of responsiveness to short-lasting preventiveintervention with ketogenic diet (KD) in migraine.

METHODS:Eighteen interictal migraineurs underwent visual (VEPs) and median nerve somatosensory (SSEPs) evokedpotentials before and after 1 month of KD during ketogenesis. We measured VEPs N1-P1 and SSEPs N20-P25 amplitudes respectively in six and in two sequential blocks of 100 sweeps as well as habituation as theslope of the linear regression between block 1 to 6 for VEPs or between 1 to 2 for SSEPs.

RESULTS:After 1-month of KD, a significant reduction in the mean attack frequency and duration was observed (all P< 0.001). The KD did not change the 1st SSEP and VEP block of responses, but significantly inducednormalization of the interictally reduced VEPs and SSEPs (all p< 0.01) habituation during the subsequentblocks.

CONCLUSIONS:KD could restore normal EPs habituation curves during stimulus repetition without significantly changing theearly amplitude responses. Thus, we hypothesize that KD acts on habituation regulating the balancebetween excitation and inhibition at the cortical level.

BACKGROUND: Chronic stress is associated with a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis consisting on disturbances on the cortisol response and lipid metabolism.

OBJECTIVE: To evaluate the HPA axis activity in women from a Mediterranean area, comparing three different measurements: daily cortisol secretory variability, postprandial cortisol secretion and glucocorticoid feedback sensitivity. In addition, HPA axis disturbance is correlated with dietary habits and plasma fatty acid profiles.

DESIGN: The participants were 41 women born during the first 6 months of 1960 and living in a Mediterranean area (Murcia, Spain). They were of normal weight, with a waist circumference of 80.5 +/- 9.3 cm. Their salivary cortisol levels, 7-day dietary record and plasma fatty acid profile were evaluated. Daily cortisol variability and postlunch cortisol secretion were recorded and a dexamethasone suppression test is performed in order to detect possible HPA disturbance.

RESULTS: Both the methods used for HPA axis evaluation were positively correlated (r = 0.448, P = 0.004). Subjects with normal diurnal curves (high cortisol variability) showed significantly higher cortisol values in the morning and postprandial cortisol secretion than women with pathological curves (medium and low variability). Cortisol variability was inversely correlated with waist circumference (r = -0.312, P = 0.047), suggesting that a disturbed HPA axis response may lead to an android pattern of body fat distribution. Dietary fat and saturated fatty acid intake were lower in the high cortisol variability group, while monounsaturated fatty acid intake was higher (P<0.05). No major differences were reported in plasma fatty acid profile.

CONCLUSIONS: A disturbed HPA axis is associated with abdominal fat distribution and a higher content of fat and saturated fatty acids in the diet. Women who chose a dietary pattern closer to the Mediterranean diet, with high monounsaturated fatty acid intake, showed lower levels on HPA axis disturbance.

Dietary curcumin was studied for its potential to decrease adiposity and reverse obesity- associated cognitive impairment in a mouse model of midlife sedentary obesity. We hypothesized that curcumin intake, by decreasing adiposity, would improve cognitive function in a manner comparable to caloric restriction (CR), a weight loss regimen. 15-month-old male C57BL/6 mice were assigned in groups to receive the following dietary regimens for 12 weeks: (i) a base diet (Ain93M) fed ad libitum (AL), (ii) the base diet restricted to 70% of ad libitum (CR) or (iii) the base diet containing curcumin fed AL (1000 mg/kg diet, CURAL). Blood markers of inflammation, interleukin 6 (IL-6) and C-reactive protein (CRP), as well as an indicator of redox stress (GSH: GSSG ratio), were determined at different time points during the treatments, and visceral and subcutaneous adipose tissue were measured upon completion of the experiment. After 8 weeks of dietary treatment, the mice were tested for spatial cognition (Morris water maze) and cognitive flexibility (discriminated active avoidance). The CR group showed significant weight loss and reduced adiposity, whereas CURAL mice had stable weight throughout the experiment, consumed more food than the AL group, with no reduction of adiposity. However, both CR and CURAL groups took fewer trials than AL to reach criterion during the reversal sessions of the active avoidance task, suggesting an improvement in cognitive flexibility. The AL mice had higher levels of CRP compared to CURAL and CR, and GSH as well as the GSH: GSSG ratio were increased during curcumin intake, suggesting a reducing shift in the redox state. The results suggest that, independent of their effects on adiposity; dietary curcumin and caloric restriction have positive effects on frontal cortical functions that could be linked to anti-inflammatory or antioxidant actions.

In head and neck squamous cell carcinoma (HNSCC) aerobic glycolysis is the key feature for energy supply of the tumor. Quantitative microdialysis (μD) offers an online method to measure parameters of the carbohydrate metabolism in vivo. The aim was to standardize a quantitative μD-study in patients with HNSCC and to prove if a ketogenic diet would differently influence the carbohydrate metabolism of the tumor tissue. Commercially available 100 kDa-CMA71-μD- catheters were implanted in tumor-free and in tumor tissue in patients with HNSCC for simultaneous measurements up to 5 days. The metabolic pattern and circadian rhythm of urea, glucose, lactate, and pyruvate was monitored during 24 h of western diet and subsequent up to 4 days ofketogenic diet. After 3 days of ketogenic diet the mean lactate concentration declines to a greater extent in the tumor tissue than in the tumor-free mucosa, whereas the mean glucose and pyruvate concentrations rise. The in vivo glucose metabolism of the tumor tissue is clearly influenced by nutrition. The decline of mean lactate concentration in the tumor tissue after ketogenic diet supports the hypothesis that HNSCC tumor cells might use lactate as fuel for oxidative glucose metabolism.

With insulin at 0.1 ng/ml, the binding of (125I)insulin in vitro to circulating lymphocytes from 11 obese patients was less than that observed with cells from 10 thin volunteers. Furthermore, with obese cells, unlabeled insulin was less effective in competing with labeled hormone for binding, both at low and high concentrations of unlabeled insulin. These differences were not accounted for by the high concentrations of insulin in the circulation of the obese patients at the time fthe blood was drawn, or by differences in degradation of hormone, or in the characteristics of the cell population. The decrease in binding appears to be due to a lowering of the receptor concentration, but some loss of affinity has not been excluded. Institution of a calorie restricted diet (nine patients) which ameliorated the hyperinsulinemia, produced an improvement in hormone binding. Since the insulin receptors of lymphocytes in metabolic disorders seem to reflect the state of insulin receptors or target cells such as liver and fat, the lymphocytes or other leukocytes appear to be ideal for studies of impaired cell responsiveness to hormones in man.

OBJECTIVE: There is evidence of gut barrier and immune system dysfunction in some patients with type 1 diabetes, possibly linked with exposure to dietary wheat polypeptides (WP). However, questions arise regarding the frequency of abnormal immune responses to wheat and their nature, and it remains unclear whether such responses are diabetes specific.

RESEARCH DESIGN AND METHODS: In type 1 diabetic patients and healthy control subjects, the immune response of peripheral CD3(+) T-cells to WPs, ovalbumin, gliadin, alpha-gliadin 33-mer peptide, tetanus toxoid, and phytohemagglutinin was measured using a carboxyfluorescein diacetate succinimidyl ester (CFSE) proliferation assay. T-helper cell type 1 (Th1), Th2, and Th17 cytokines were analyzed in WP-stimulated peripheral blood mononuclear cell (PBMNC) supernatants, and HLA was analyzed by PCR.

RESULTS: Of 42 patients, 20 displayed increased CD3(+) T-cell proliferation to WPs and were classified as responders; proliferative responses to other dietary antigens were less pronounced. WP-stimulated PBMNCs from patients showed a mixed proinflammatory cytokine response with large amounts of IFN-gamma, IL-17A, and increased TNF. HLA-DQ2, the major celiac disease risk gene, was not significantly different. Nearly all responders carried the diabetes risk gene HLA-DR4. Anti-DR antibodies blocked the WP response and inhibited secretion of Th1 and Th17 cytokines. High amounts of WP-stimulated IL-6 were not blocked.

CONCLUSIONS: T-cell reactivity to WPs was frequently present in type 1 diabetic patients and associated with HLA-DR4 but not HLA-DQ2. The presence of an HLA-DR-restricted Th1 and Th17 response to WPs in a subset of patients indicates a diabetes-related inflammatory state in the gut immune tissues associated with defective oral tolerance and possibly gut barrier dysfunction.

BACKGROUND:Although it is recognized that diarrhoea commonly complicates enteral nutrition, the causes remain unknown.

AIM:To identify factors associated with diarrhoea in patients receiving enteral nutrition with specific attention to formula composition.

METHODS:Medical histories of in-patients receiving enteral nutrition were identified by ICD-10-AM coding and randomly selected from the year 2003 to 2008. Clinical and demographic data were extracted. Formulas were classified according to osmolality, fibre and FODMAP (fermentable oligo-, di- and mono-saccharides and polyols) content.

RESULTS:Formula FODMAP levels ranged from 10.6 to 36.5 g/day. Of 160 patients receiving enteral nutrition, 61% had diarrhoea. Univariate analysis showed diarrhoea was associated with length of stay>21 days (OR 4.2), enteral nutrition duration>11 days (OR 4.0) and antibiotic use (OR 2.1). After adjusting for influencing variables through a logistic regression model, a greater than five-fold reduction in risk of developing diarrhoea was seen in patients initiated on Isosource 1.5 (P = 0.029; estimated OR 0.18). The only characteristic unique to this formula was its FODMAP content, being 47-71% lower than any other formula.

CONCLUSIONS:Length of stay and enteral nutrition duration independently predicted diarrhoea development, while being initiated on a lower FODMAP formula reduced the likelihood of diarrhoea. As retrospective evaluation does not support a cause-effect relationship, an interventional study investigating FODMAPs in enteral formula is indicated.

Preventing or postponing the onset of Alzheimer's disease (AD) and delaying or slowing its progression would lead to a consequent improvement of health status and quality of life in older age. Elevated saturated fatty acids could have negative effects on age-related cognitive decline and mild cognitive impairment (MCI). Furthermore, at present, epidemiological evidence suggests a possible association between fish consumption, monounsaturated fatty acids and polyunsaturated fatty acids (PUFA; in particular, n-3 PUFA) and a reduced risk of cognitive decline and dementia. Poorer cognitive function and an increased risk of vascular dementia (VaD) were found to be associated with a lower consumption of milk or dairy products. However, the consumption of whole-fat dairy products may be associated with cognitive decline in the elderly. Light-to-moderate alcohol use may be associated with a reduced risk of incident dementia and AD, while for VaD, cognitive decline and predementia syndromes, the current evidence is only suggestive of a protective effect. The limited epidemiological evidence available on fruit and vegetable consumption and cognition generally supports a protective role of these macronutrients against cognitive decline, dementia and AD. Only recently, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline, although the Mediterranean diet (MeDi) combines several foods, micro- and macro-nutrients already separately proposed as potential protective factors against dementia and predementia syndromes. In fact, recent prospective studies provided evidence that higher adherence to a Mediterranean-type diet could be associated with slower cognitive decline, reduced risk of progression from MCI to AD, reduced risk of AD and a decreased all-cause mortality in AD patients. These findings suggested that adherence to the MeDi may affect not only the risk of AD, but also of predementia syndromes and their progression to overt dementia. Based on the current evidence concerning these factors, no definitive dietary recommendations are possible. However, following dietary advice for lowering the risk of cardiovascular and metabolic disorders, high levels of consumption of fats from fish, vegetable oils, nonstarchy vegetables, low glycemic index fruits and a diet low in foods with added sugars and with moderate wine intake should be encouraged. Hopefully this will open new opportunities for the prevention and management of dementia and AD.

OBJECTIVE: This article discusses the role of diet in the management of asthma. Readers will gain an understanding of how evolution of the western diet has contributed to increased asthma prevalence and how dietary modification that includes management of dietary lipids may reduce symptoms of asthma.

DATA SOURCES: Relevant studies published in English were reviewed.

STUDY SELECTION: Medline search to identify peer-reviewed abstracts and journal articles.

RESULTS: Asthma and obesity, which often occur together, have increased in prevalence in recent years. Studies suggest adaption of a western diet has not only contributed to obesity, but that increased intake of specific nutrients can cause changes in the frequency and severity of asthma. Increased asthma prevalence has also been proposed to arise from increased exposure to diesel particles or lack of exposure to infectious agents or endotoxins during childhood, generating a biased Th2 immune response, and increased cytokine and leukotriene production. Antagonists directed against these pro-inflammatory mediators include anticytokines and antileukotrienes. A reduction in the levels of inflammatory mediators associated with asthma has also been seen with dietary interventions, such as the administration of oils containing gamma-linolenic acid and eicosapentaenoic acid.

CONCLUSIONS: Evidence suggests elevated body mass index and dietary patterns, especially intake of dietary lipids, contribute to symptoms of asthma. Dietary modification may help patients manage their asthma as well as contribute to their overall health.

BACKGROUND:Endometrial cancer is the fourth most common cancer in European women. The major risk factors for endometrial cancer are related to the exposure of endometrium to estrogens not opposed to progestogens, that can lead to a chronic endometrial inflammation. Diet may play a role in cancer risk by modulating chronic inflammation.

METHODS:In the framework of a case-control study, we recruited 297 women with newly diagnosed endometrial cancer and 307 controls from Northern Italy. Using logistic regression, we investigated the role of fruit and vegetable intake, adherence to the Mediterranean diet (MD), and the dietary inflammatory index (DII) in endometrial cancer risk.

RESULTS:Women in the highest quintile of vegetable intake had a statistically significantly lower endometrial cancer risk (adjusted OR 5th quintile vs 1st quintile: 0.34, 95% CI 0.17-0.68). Women with high adherence to the MD had a risk of endometrial cancer that was about half that of women with low adherence to the MD (adjusted OR: 0.51, 95% CI 0.39-0.86). A protective effect was detected for all the lower quintiles of DII, with the highest protective effect seen for the lowest quintile (adjusted OR 5th quintile vs 1st quintile: 3.28, 95% CI 1.30-8.26).

CONCLUSIONS:These results suggest that high vegetable intake, adherence to the MD, and a low DII are related to a lower endometrial cancer risk, with several putative connected biological mechanisms that strengthen the biological plausibility of this association.

Recent evidence underlines the role of Western diet in the pathogenesis of acne. Acne is absent in populations consuming Palaeolithic diets with low glycaemic load and no consumption of milk or dairy products. Two randomized controlled studies, one of which is presented in this issue of Acta Dermato-Venereologica, have provided evidence for the beneficial therapeutic effects of low glycaemic load diets in acne. Epidemiological evidence confirms that milk consumption has an acne-promoting or acne-aggravating effect. Recent progress in understanding the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1) allows a new view of nutrient signalling in acne by both high glycaemic load and increased insulin-, IGF-1-, and leucine signalling due to milk protein consumption. Acne should be regarded as an mTORC1-driven disease of civilization, like obesity, type 2 diabetes and cancer induced by Western diet. Early dietary counselling of teenage acne patients is thus a great opportunity for dermatology, which will not only help to improve acne but may reduce the long-term adverse effects of Western diet on more serious mTORC1-driven diseases of civilization.

Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.

The effects of a low-carbohydrate, ketogenic diet (LCKD) on sleepiness and other narcolepsy symptoms were studied. Nine patients with narcolepsy were asked to adhere to the Atkins' diet plan, and their symptoms were assessed using the Narcolepsy Symptom Status Questionnaire (NSSQ). The NSSQ-Total score decreased by 18% from 161.9 to 133.5 (p = 0.0019) over 8 weeks. Patients with narcolepsy experienced modest improvements in daytime sleepiness on an LCKD.