Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations.

Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.

Diet and risk of inflammatory bowel disease.

BACKGROUND: A better understanding of the environmental factors leading to inflammatory bowel disease should help to prevent occurrence of the disease and its relapses. AIM: To review current knowledge on dietary risk factors for inflammatory bowel disease. METHODS: The PubMed, Medline and Cochrane Library were searched for studies on diet and risk of inflammatory bowel disease. RESULTS: Established non-diet risk factors include family predisposition, smoking, appendectomy, and antibiotics. Retrospective case-control studies are encumbered with methodological problems. Prospective studies on European cohorts, mainly including middle-aged adults, suggest that a diet high in protein from meat and fish is associated with a higher risk of inflammatory bowel disease. Intake of the n-6 polyunsaturated fatty acid linoleic acid may confer risk of ulcerative colitis, whereas n-3 polyunsaturated fatty acids may be protective. No effect was found of intake of dietary fibres, sugar, macronutrients, total energy, vitamin C, D, E, Carotene, or Retinol (vitamin A) on risk of ulcerative colitis. No prospective data was found on risk related to intake of fruits, vegetables or food microparticles (titanium dioxide and aluminium silicate). CONCLUSIONS: A diet high in protein, particular animal protein, may be associated with increased risk of inflammatory bowel disease and relapses. N-6 polyunsaturated fatty acids may predispose to ulcerative colitis whilst n-3 polyunsaturated fatty acid may protect. These results should be confirmed in other countries and in younger subjects before dietary counselling is recommended in high risk subjects. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Turmeric (curcumin) remedies gastroprotective action

The purpose of this review is to summarize the pertinent literature published in the present era regarding the antiulcerogenic property of curcumin against the pathological changes in response to ulcer effectors (Helicobacter pylori infection, chronic ingestion of non-steroidal anti-inflammatory drugs, and exogenous substances). The gastrointestinal problems caused by different etiologies was observed to be associated with the alterations of various physiologic parameters such as reactive oxygen species, nitric oxide synthase, lipid peroxidation, and secretion of excessive gastric acid. Gastrointestinal ulcer results probably due to imbalance between the aggressive and the defensive factors. In 80% of the cases, gastric ulcer is caused primarily due to the use of non-steroidal anti-inflammatory category of drug, 10% by H. pylori, and about 8-10% by the intake of very spicy and fast food. Although a number of antiulcer drugs and cytoprotectants are available, all these drugs have side effects and limitations. In the recent years a widespread search has been launched to identify new antiulcer drugs from synthetic and natural resources. An Indian dietary derivative (curcumin), a yellow pigment found in the rhizome of Curcuma longa, has been widely used for the treatment of several diseases. Epidemiologically, it was suggested that curcumin might reduce the risk of inflammatory disorders, such as cancer and ulcer. These biological effects are attributed to its anti-inflammatory and antioxidant activities. It can, therefore, be reported from the literature that curcumin PRevents gastrointestinal-induced ulcer and can be recommended as a novel drug for ulcer treatment.

Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study

Background and aims: The causes of relapses of ulcerative colitis (UC) are unknown. Dietary factors have been implicated in the pathogenesis of UC. The aim of this study was to determine which dietary factors are associated with an increased risk of relapse of UC. Methods: A prospective cohort study was performed with UC patients in remission, recruited from two district general hospitals, who were followed for one year to determine the effect of habitual diet on relapse. Relapse was defined using a validated disease activity index. Nutrient intake was assessed using a food frequency questionnaire and categorised into tertiles. Adjusted odds ratios for relapse were determined using multivariate logistic regression, controlling for non-dietary factors. Results: A total of 191 patients were recruited and 96% completed the study. Fifty two per cent of patients relapsed. Consumption of meat (odds ratio (OR) 3.2 (95% confidence intervals (CI) 1.3–7.8)), particularly red and processed meat (OR 5.19 (95% CI 2.1–12.9)), protein (OR 3.00 (95% CI 1.25–7.19)), and alcohol (OR 2.71 (95% CI 1.1–6.67)) in the top tertile of intake increased the likelihood of relapse compared with the bottom tertile of intake. High sulphur (OR 2.76 (95% CI 1.19–6.4)) or sulphate (OR 2.6 (95% CI 1.08–6.3)) intakes were also associated with relapse and may offer an explanation for the observed increased likelihood of relapse. Conclusions: Potentially modifiable dietary factors, such as a high meat or alcoholic beverage intake, have been identified that are associated with an increased likelihood of relapse for UC patients. Further studies are needed to determine if it is the sulphur compounds within these foods that mediates the likelihood of relapse and if reducing their intake would reduce relapse frequency.

Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature.

OBJECTIVES: The incidence of inflammatory bowel disease (IBD) is increasing. Dietary factors such as the spread of the "Western" diet, high in fat and protein but low in fruits and vegetables, may be associated with the increase. Although many studies have evaluated the association between diet and IBD risk, there has been no systematic review. METHODS: We performed a systematic review using guideline-recommended methodology to evaluate the association between pre-illness intake of nutrients (fats, carbohydrates, protein) and food groups (fruits, vegetables, meats) and the risk of subsequent IBD diagnosis. Eligible studies were identified via structured keyword searches in PubMed and Google Scholar and manual searches. RESULTS: Nineteen studies were included, encompassing 2,609 IBD patients (1,269 Crohn's disease (CD) and 1,340 ulcerative colitis (UC) patients) and over 4,000 controls. Studies reported a positive association between high intake of saturated fats, monounsaturated fatty acids, total polyunsaturated fatty acids (PUFAs), total omega-3 fatty acids, omega-6 fatty acids, mono- and disaccharides, and meat and increased subsequent CD risk. Studies reported a negative association between dietary fiber and fruits and subsequent CD risk. High intakes of total fats, total PUFAs, omega-6 fatty acids, and meat were associated with an increased risk of UC. High vegetable intake was associated with a decreased risk of UC. CONCLUSIONS: High dietary intakes of total fats, PUFAs, omega-6 fatty acids, and meat were associated with an increased risk of CD and UC. High fiber and fruit intakes were associated with decreased CD risk, and high vegetable intake was associated with decreased UC risk.

Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.

Bismuth therapy in gastrointestinal diseases.

Bismuth therapy has shown efficacy against two major gastrointestinal disorders: peptic ulcer disease and diarrhea. In peptic ulcer disease it is as effective as the H2-receptor antagonists, costs considerably less, and offers a lower rate of relapse. When Helicobacter pylori is implicated, bismuth acts as an antimicrobial agent, suppressing the organism but not eliminating it. In recent studies, bismuth compounds have been used with conventional antibiotics, producing elimination of the organism, histological improvement, and amelioration of symptoms for periods longer than one year. Bismuth subsalicylate has shown modest efficacy in treating traveler's diarrhea and acute and chronic diarrhea in children, and it is effective prophylactically for traveler's diarrhea. An epidemic of neurological toxicity was reported in France in the 1970's with prolonged bismuth treatment, usually bismuth subgallate and subnitrate. Such toxicity has been rare with bismuth subsalicylate and colloidal bismuth subcitrate. However, recent studies have demonstrated intestinal absorption of bismuth (about 0.2% of the ingested dose) and sequestration of this heavy metal in multiple tissue sites, even occurring with conventional dosing over a 6-week period. These findings have inspired recommendations that treatment periods with any bismuth-containing compound should last no longer than 6-8 weeks, followed by 8-week bismuth-free intervals.

Probiotics for preventing acute upper respiratory tract infections.

BACKGROUND: Probiotics may improve a person's health by regulating their immune function. Some studies show that probiotic strains can prevent respiratory infections. However, no evidence of the benefits of probiotics for acute upper respiratory tract infections (URTIs) and related potential adverse effects has been published. OBJECTIVES: To assess the effectiveness and safety of probiotics for preventing acute URTIs. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (Ovid) (1950 to May week 1, 2011), EMBASE (1974 to May 2011), Web of Science which includes Science Citation Index (from 1900 to May 2011) and Conference Proceedings Citation Index (from 1991 to May 2011), the Chinese Biomedical Literature Database, which includes the China Biological Medicine Database (from 1978 to May 2011), the Chinese Medicine Popular Science Literature Database (from 2000 to May 2011) and the Masters Degree Dissertation of Beijing Union Medical College Database (from 1981 to May 2011). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing probiotics with placebo to prevent acute URTIs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility, quality of trials and extracted data. MAIN RESULTS: We included 14 RCTs, although we could only extract available data to meta-analyse in 10 trials which involved 3451 participants. We found that probiotics were better than placebo when measuring the number of participants experiencing episodes of acute URTI: at least one episode: odds ratio (OR) 0.58; 95% confidence interval (CI) 0.36 to 0.92; at least three episodes: OR 0.53; 95% CI 0.36 to 0.80; rate ratio of episodes of acute URTI: rate ratio 0.88; 95% CI 0.81 to 0.96; and reduced antibiotic prescription rates for acute URTIs: OR 0.67; 95% CI 0.45 to 0.98. Probiotics and placebo were similar when measuring the mean duration (MD) of an episode of acute URTI: MD -0.29; 95% CI -3.71 to 3.13 and adverse events: OR 0.92; 95% CI 0.37 to 2.28. Side effects of probiotics were minor and gastrointestinal symptoms were the most common. We found that some subgroups had a high level of heterogeneity when conducting pooled analyses. AUTHORS' CONCLUSIONS: Probiotics were better than placebo in reducing the number of participants experiencing episodes of acute URTIs, the rate ratio of episodes of acute URTI and reducing antibiotic use. This indicates that probiotics may be more beneficial than placebo for preventing acute URTIs. However, the results have some limitations and there were no data for older people.

Ability of a high-total antioxidant capacity diet to increase stool weight and bowel antioxidant status in human subjects.

There is limited knowledge about the possible effect of unabsorbed dietary antioxidants that reach the large intestine on bowel habits. The aim of the present study was to investigate whether a dietary recommendation directed to increase diet total antioxidant capacity (TAC) is able to affect gut function in human subjects. In this cross-over intervention, nineteen subjects followed a high-TAC (HT) and a low-TAC (LT) diet for 2 weeks, which were comparable for energy, macronutrient, total dietary fibre and alcohol contents. At the end of each intervention period, the 48 h stool output was recorded. In the faecal samples obtained from a subset of nine subjects, moisture, pH, ammonia content, Lactobacillus and Bifidobacterium counts, faecal water antioxidants and genotoxicity were measured. A 3 d weighed food record was used to assess the diet composition during HT and LT diet intake. Significant increases in the intake of TAC, vitamins E and C and phenolic compounds were observed during the HT diet intake. The higher intake of antioxidants led to increased 48 h stool output (324 (SD 38) g in HT v. 218 (SD 22) g in LT), and to higher TAC and total phenolic concentrations in faecal water. No significant variation in the other measured parameters was observed between the diets. In conclusion, a diet selected to raise the intake of dietary antioxidants is able to increase stool bulk and antioxidant content of faeces.

An association between dietary arachidonic acid, measured in adipose tissue, and ulcerative colitis.

BACKGROUND & AIMS: Dietary arachidonic acid, an n-6 polyunsaturated fatty acid (n-6 PUFA), might be involved in the etiology of ulcerative colitis (UC). We performed a prospective cohort study to determine whether high levels of arachidonic acid in adipose tissue samples (which reflects dietary intake) are associated with UC. METHODS: We analyzed data collected from 57,053 men and women in the EPIC-Denmark Prospective Cohort Study from 1993 to 1997. Adipose tissue biopsy samples were collected from gluteal regions at the beginning of the study, the cohort was monitored over subsequent years, and participants who developed UC were identified. A subcohort of 2510 randomly selected participants were used as controls. Concentrations of arachidonic acid were measured in adipose tissue samples. In the analysis, arachidonic acid levels were divided into quartiles; relative risks (RR) were calculated and adjusted for smoking, use of aspirin and nonsteroidal anti-inflammatory drugs, and levels of n-3 PUFAs. RESULTS: A total of 34 subjects (56% men) developed incident UC at a median age of 58.8 years (range, 50.0-69.0 years). Those in the highest quartile for arachidonic acid concentrations in adipose tissue had an RR for UC of 4.16 (95% confidence interval [CI]: 1.56-11.04); a trend per 0.1% increase in arachidonic acid of 1.77 in RR was observed (95% CI: 1.38-2.27). The fraction attributed the highest levels of arachidonic acid was 40.3%. CONCLUSIONS: Individuals with the highest relative concentrations of arachidonic acid in adipose tissue have a significantly greater risk of developing UC. Dietary modifications might therefore prevent UC or reduce disease symptoms. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Relevance of protein fermentation to gut health.

It is generally accepted that carbohydrate fermentation results in beneficial effects for the host because of the generation of short chain fatty acids, whereas protein fermentation is considered detrimental for the host's health. Protein fermentation mainly occurs in the distal colon, when carbohydrates get depleted and results in the production of potentially toxic metabolites such as ammonia, amines, phenols and sulfides. However, the effectivity of these metabolites has been established mainly in in vitro studies. In addition, some important bowel diseases such as colorectal cancer (CRC) and ulcerative colitis appear most often in the distal colon, which is the primary site of protein fermentation. Finally, epidemiological studies revealed that diets rich in meat are associated with the prevalence of CRC, as is the case in Western society. Importantly, meat intake not only increases fermentation of proteins but also induces increased intake of fat, heme and heterocyclic amines, which may also play a role in the development of CRC. Despite these indications, the relationship between gut health and protein fermentation has not been thoroughly investigated. In this review, the existing evidence about the potential toxicity of protein fermentation from in vitro animal and human studies will be summarized. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bowel obsession syndrome in a patient with ulcerative colitis.

Gastroenterologists are often faced with the diagnostic problem of differentiating acute symptoms of ulcerative colitis from functional intestinal disorders. Bowel obsession syndrome (BOS) is an OCD-like, functional syndrome characterized by fear of fecal incontinence and compulsive behaviors of evacuation-checking. Only sparse case studies on treatment of BOS with antidepressants have been published. This is the first study on successful psychotherapy of a male patient with ulcerative colitis overlapping functional bowel symptoms and marked symptoms of BOS. Clinical recognition of BOS may help clinicians in differential diagnosis, prevent unnecessary investigations, and give patients the most appropriate treatment.

Gerson regimen.

The Gerson regimen, developed by Max Gerson in the 1930s, is promoted as an alternative cancer treatment. It involves consuming fresh, raw fruit and vegetable juices, eliminating salt from the diet, taking supplements such as potassium, vitamin B12, thyroid hormone, pancreatic enzymes, and detoxifying liver with coffee enemas to stimulate metabolism. Gerson therapy is based on the theory that cancer is caused by alteration of cell metabolism by toxic environmental substances and processed food, which changes its sodium and potassium content. It emphasizes increasing potassium intake and minimizing sodium consumption in an effort to correct the electrolyte imbalance, repair tissue, and detoxify the liver. The coffee enemas are believed to cause dilation of bile ducts and excretion of toxic breakdown products by the liver and through the colon wall. None of these theories has been substantiated by scientific research. Despite proponents' claims of recovery rates as high as 70% to 90%, case reviews by the National Cancer Institute (NCI) and the New York County Medical Society found no evidence of usefulness for the Gerson diet. An NCI-sponsored study of Gonzalez therapy, which is similar to the Gerson diet, showed that patients with inoperable pancreatic adenocarcinoma who underwent standard chemotherapy with gemcitabine (Gemzar) survived three times longer and had better quality of life than those who chose enzyme treatment, which included pancreatic enzymes, nutritional supplements, detoxification, and an organic diet.

Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials

Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.

Plant-derived health: the effects of turmeric and curcuminoids.

Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.

A Prospective Study of Long-term Intake of Dietary Fiber and Risk of Crohn’s Disease and Ulcerative Colitis

Background & Aims Increased intake of dietary fiber has been proposed to reduce risk of inflammatory bowel diseases (Crohn’s disease [CD], ulcerative colitis [UC]). However, few prospective studies have examined associations between long-term intake of dietary fiber and risk of incident CD or UC. Methods We collected and analyzed data from 170,776 women, followed over 26 y, who participated in the Nurses’ Health Study, followed for 3,317,425 person-y. Dietary information was prospectively ascertained via administration of a validated semi-quantitative food frequency questionnaire every 4 y. Self-reported CD and UC were confirmed through review of medical records. Cox proportional hazards models, adjusting for potential confounders, were used to calculate hazard ratios (HRs). Results We confirmed 269 incident cases of CD (incidence 8/100,000 person-y) and 338 cases of UC (incidence 10/100,000 person-y). Compared to the lowest quintile of energy-adjusted cumulative average intake of dietary fiber, intake of the highest quintile (median of 24.3 g/day) was associated with a 40% reduction in risk of CD (multivariate HR for CD, 0.59; 95% confidence interval [CI], 0.39–0.90). This apparent reduction appeared to be greatest for fiber derived from fruits; fiber from cereals, whole grains, or legumes did not modify risk. In contrast, neither total intake of dietary fiber (multivariate HR, 0.82; 95% CI 0.58–1.17) nor intake of fiber from specific sources appeared to be significantly associated with risk of UC. Conclusion Based on data from the Nurses’ Health Study, long-term intake of dietary fiber, particularly from fruit, is associated with lower risk of CD but not UC. Further studies are needed to determine the mechanisms that mediate this association.

Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa: a potential role for these agents in the pathogenesis of ulcerativ...

It has been shown that feces of patients with ulcerative colitis uniformly contain sulfate reducing bacteria. Sulfide produced by these bacteria interferes with butyrate-dependent energy metabolism of cultured colonocytes and may be involved in the pathogenesis of ulcerative colitis. Mucosal biopsies from the sigmoid rectum of 10 patients (no caner, polyps, inflammatory bowel disease) were incubated with either NaCl, sodium hydrogen sulfide (1 mmol/L), a combination of both sodium hydrogen sulfide and butyrate (10 mmol/L), or butyrate. Mucosal proliferation was assessed by bromodeoxyuridine labeling of cells in S-phase. Compared to NaCl, sulfide increased the labeling of the entire crypt significantly, by 19% (p < 0.05). This effect was due to an expansion of the proliferative zone to the upper crypt (compartments 3-5), where the increase in proliferation was 54%. Sulfide-induced hyperproliferation was reversed when samples were coincubated with sulfide and butyrate. The study shows that sodium hydrogen sulfide induces mucosal hyperproliferation. Our data support a possible role of sulfide in the pathogenesis of UC and confirm the role of butyrate in the regulation of colonic proliferation and in the treatment of UC.

Immune potentiation of ultrafine dietary particles in normal subjects and patients with inflammatory bowel disease.

Various specific and non-specific environmental factors have been associated with the induction and/or exacerbation of disease activity in patients with Crohn's disease and ulcerative colitis. One such factor is the potential role of ingested ultrafine particles. In fact, based on a Western diet, recent data suggest that more than 10(12)ultrafine particles are ingested per person every day. These microparticles have been considered inert although they adsorb endogenous constituents of the intestinal lumen and are taken up by human intestinal lymphoid aggregates. Based on these observations, we determined whether one such dietary microparticle, titanium dioxide (TiO(2)), alters intestinal cell responsiveness to lipopolysaccharide (LPS) using colonic biopsy specimens from 28 patients with ulcerative colitis, 21 with Crohn's disease, and 36 healthy controls. These samples, as well as peripheral blood mononuclear cells when available, were incubated alone (control), or with either (a) LPS (1-2,000 ng/ml), (b) TiO(2)(5 microg/ml) or (c) LPS (1 ng/ml) adsorbed to TiO(2)(5 microg/ml). In each case, the levels of interleukin 1 (IL-1) produced in these assays were quantitated by bioassay and by ELISA. Interestingly, there was dramatic stimulation of peripheral blood mononuclear cells using the TiO(2)-LPS conjugate, with values 30-60-fold above controls and only minor stimulation with LPS or TiO(2)alone. In intestinal organ cultures there was no increase in IL-1 secretion when challenged with TiO(2)alone or with up to 2,000 ng/ml LPS. However, the TiO(2)-LPS conjugate produced a two-to-three-fold, significant increase in the intestinal secretion of IL-1. Our data demonstrate that ultrafine dietary particles are not immunologically inert and may be important adjuncts in overcoming normal gut cell hyporesponsiveness to endogenous luminal molecules. This may be particularly relevant to patients with inflammatory bowel disease where there is abnormal intestinal permeability. Copyright 2000 Academic Press.

Treatment of abdominal pain in irritable bowel syndrome.

Functional abdominal pain in the context of irritable bowel syndrome (IBS) is a challenging problem for primary care physicians, gastroenterologists and pain specialists. We review the evidence for the current and future non-pharmacological and pharmacological treatment options targeting the central nervous system and the gastrointestinal tract. Cognitive interventions such as cognitive behavioral therapy and hypnotherapy have demonstrated excellent results in IBS patients, but the limited availability and labor-intensive nature limit their routine use in daily practice. In patients who are refractory to first-line therapy, tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors are both effective to obtain symptomatic relief, but only TCAs have been shown to improve abdominal pain in meta-analyses. A diet low in fermentable carbohydrates and polyols (FODMAP) seems effective in subgroups of patients to reduce abdominal pain, bloating, and to improve the stool pattern. The evidence for fiber is limited and only isphagula may be somewhat beneficial. The efficacy of probiotics is difficult to interpret since several strains in different quantities have been used across studies. Antispasmodics, including peppermint oil, are still considered the first-line treatment for abdominal pain in IBS. Second-line therapies for diarrhea-predominant IBS include the non-absorbable antibiotic rifaximin and the 5HT3 antagonists alosetron and ramosetron, although the use of the former is restricted because of the rare risk of ischemic colitis. In laxative-resistant, constipation-predominant IBS, the chloride-secretion stimulating drugs lubiprostone and linaclotide, a guanylate cyclase C agonist that also has direct analgesic effects, reduce abdominal pain and improve the stool pattern.

Nutrition and colonic health: the critical role of the microbiota.

PURPOSE OF REVIEW: To highlight mechanisms whereby diet affects colonic function and disease patterns. RECENT FINDINGS: Topical nutrients are preferentially used by the gut mucosa to maintain structure and function. With the colon, topical nutrients are generated by the colonic microbiota to maintain mucosal health. Most importantly, short chain fatty acids control proliferation and differentiation, thereby reducing colon cancer risk. In patients with massive loss of small intestine, short chain fatty acid production supports survival by releasing up to 1000 kcal energy/day. Human studies show that the microbiota synthesizes a large pool of utilizable folate which may support survival in impoverished populations. Unfortunately, the microbiota may also elaborate toxic products from food residues such as genotoxic hydrogen sulfide by sulfur-reducing bacteria in response to a high-meat diet. The employment of culture-free techniques based on 16S regions of DNA has revealed that our colons harbor over 800 bacterial species and 7000 different strains. Evidence suggests that the diet directly influences the diversity of the microbiota, providing the link between diet, colonic disease, and colon cancer. The microbiota, however, can determine the efficiency of food absorption and risk of obesity. SUMMARY: Our investigations have focused on a small number of bacterial species: characterization of microbiota and its metabolism can be expected to provide the key to colonic health and disease.

Effect of a very-high-fiber vegetable, fruit, and nut diet on serum lipids and colonic function.

We tested the effects of feeding a diet very high in fiber from fruit and vegetables. The levels fed were those, which had originally inspired the dietary fiber hypothesis related to colon cancer and heart disease prevention and also may have been eaten early in human evolution. Ten healthy volunteers each took 3 metabolic diets of 2 weeks duration. The diets were: high-vegetable, fruit, and nut (very-high-fiber, 55 g/1,000 kcal); starch-based containing cereals and legumes (early agricultural diet); or low-fat (contemporary therapeutic diet). All diets were intended to be weight-maintaining (mean intake, 2,577 kcal/d). Compared with the starch-based and low-fat diets, the high-fiber vegetable diet resulted in the largest reduction in low-density lipoprotein (LDL) cholesterol (33% +/- 4%, P <.001) and the greatest fecal bile acid output (1.13 +/- 0.30 g/d, P =.002), fecal bulk (906 +/- 130 g/d, P <.001), and fecal short-chain fatty acid outputs (78 +/- 13 mmol/d, P <.001). Nevertheless, due to the increase in fecal bulk, the actual concentrations of fecal bile acids were lowest on the vegetable diet (1.2 mg/g wet weight, P =.002). Maximum lipid reductions occurred within 1 week. Urinary mevalonic acid excretion increased (P =.036) on the high-vegetable diet reflecting large fecal steroid losses. We conclude that very high-vegetable fiber intakes reduce risk factors for cardiovascular disease and possibly colon cancer. Vegetable and fruit fibers therefore warrant further detailed investigation. Copyright 2001 by W.B. Saunders Company

Oligo-antigenic diet in the treatment of chronic anal fissures. Evidence for a relationship between food hypersensitivity and anal fissures.

OBJECTIVES: Patients with chronic constipation due to food hypersensitivity (FH) had an elevated anal sphincter resting pressure. No studies have investigated a possible role of FH in anal fissures (AFs). We aimed to evaluate (1) the effectiveness of diet in curing AFs and to evaluate (2) the clinical effects of a double-blind placebo-controlled (DBPC) challenge, using cow's milk protein or wheat. METHODS: One hundred and sixty-one patients with AFs were randomized to receive a "true-elimination diet" or a "sham-elimination diet" for 8 weeks; both groups also received topical nifedipine and lidocaine. Sixty patients who were cured with the "true-elimination diet" underwent DBPC challenge in which cow's milk and wheat were used. RESULTS: At the end of the study, 69% of the "true-diet group" and 45% of the "sham-diet group" showed complete healing of AFs (P<0.0002). Thirteen of the 60 patients had AF recurrence during the 2-week cow's milk DBPC challenge and 7 patients had AF recurrence on wheat challenge. At the end of the challenge, anal sphincter resting pressure significantly increased in the patients who showed AF reappearance (P<0.0001), compared with the baseline values. The patients who reacted to the challenges had a significantly higher number of eosinophils in the lamina propria and intraepithelial lymphocytes than those who did not react to the challenges. CONCLUSIONS: An oligo-antigenic diet combined with medical treatment improved the rate of chronic AF healing. In more than 20% of the patients receiving medical and dietary treatment, AFs recurred on DBPC food challenge.

Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre.

Dietary fibres are indigestible food ingredients that reach the colon and are then fermented by colonic bacteria, resulting mainly in the formation of short-chain fatty acids (SCFA) such as acetate, propionate, and butyrate. Those SCFA, especially butyrate, are recognised for their potential to act on secondary chemoprevention by slowing growth and activating apoptosis in colon cancer cells. Additionally, SCFA can also act on primary prevention by activation of different drug metabolising enzymes. This can reduce the burden of carcinogens and, therefore, decrease the number of mutations, reducing cancer risk. Activation of GSTs by butyrate has been studied on mRNA, protein, and enzyme activity level by real-time RT-PCR, cDNA microarrays, Western blotting, or photometrical approaches, respectively. Butyrate had differential effects in colon cells of different stages of cancer development. In HT29 tumour cells, e.g., mRNA GSTA4, GSTP1, GSTM2, and GSTT2 were induced. In LT97 adenoma cells, GSTM3, GSTT2, and MGST3 were induced, whereas GSTA2, GSTT2, and catalase (CAT) were elevated in primary colon cells. Colon cells of different stages of carcinogenesis differed in post-transcriptional regulatory mechanisms because butyrate increased protein levels of different GST isoforms and total GST enzyme activity in HT29 cells, whereas in LT97 cells, GST protein levels and activity were slightly reduced. Because butyrate increased histone acetylation and phosphorylation of ERK in HT29 cells, inhibition of histone deacetylases and the influence on MAPK signalling are possible mechanisms of GST activation by butyrate. Functional consequences of this activation include a reduction of DNA damage caused by carcinogens like hydrogen peroxide or 4-hydroxynonenal (HNE) in butyrate-treated colon cells. Treatment of colon cells with the supernatant from an in vitro fermentation of inulin increased GST activity and decreased HNE-induced DNA damage in HT29 cells. Additional animal and human studies are needed to define the exact role of dietary fibre and butyrate in inducing GST activity and reducing the risk of colon cancer.

Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis.

BACKGROUND & AIMS: Familialadenomatous polyposis (FAP) is an autosomal-dominant disorder characterized by the development of hundreds of colorectal adenomas and eventual colorectal cancer. Regression of adenomas in this syndrome occurs with the administration of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors, but these compounds can have considerable side effects. We evaluated the efficacy of the combination of diet-derived nonprescription supplements curcumin and quercetin to regress adenomas in patients with FAP. METHODS: Five FAP patients with prior colectomy (4 with retained rectum and 1 with an ileal anal pouch) received curcumin 480 mg and quercetin 20 mg orally 3 times a day. The number and size of polyps were assessed at baseline and after therapy. The Wilcoxon signed-rank test was used to determine differences in the number and size of polyps. Treatment side effects and medication compliance also were evaluated. RESULTS: All 5 patients had a decreased polyp number and size from baseline after a mean of 6 months of treatment with curcumin and quercetin. The mean percent decrease in the number and size of polyps from baseline was 60.4% (P < .05) and 50.9% (P < .05), respectively. Minimal adverse side effects and no laboratory abnormalities were noted. CONCLUSIONS: The combination of curcumin and quercetin appears to reduce the number and size of ileal and rectal adenomas in patients with FAP without appreciable toxicity. Randomized controlled trials are needed to validate these findings.

Lignans and human health.

This review focuses on the possible role in human health of the consumption of lignan-rich foods. Most of the plant lignans in human foods are converted by the intestinal microflora in the upper part of the large bowel to enterolactone and enterodiol, called mammalian or enterolignans. The protective role of these compounds, particularly in chronic Western diseases, is discussed. Evidence suggests that fiber- and lignan-rich whole-grain cereals, beans, berries, nuts, and various seeds are the main protective foods. Many factors, in addition to diet, such as intestinal microflora, smoking, antibiotics, and obesity affect circulating lignan levels in the body. Lignan-rich diets may be beneficial, particularly if consumed for life. Experimental evidence in animals has shown clear anticarcinogenic effects of flaxseed or pure lignans in many types of cancer. Many epidemiological results are controversial, partly because the determinants of plasma enterolactone are very different in different countries. The source of the lignans seems to play a role because other factors in the food obviously participate in the protective effects. The results are promising, but much work is still needed in this area of medicine.

Hydrogen sulfide induces direct radical-associated DNA damage.

Hydrogen sulfide (H(2)S) is produced by indigenous sulfate-reducing bacteria in the large intestine and represents an environmental insult to the colonic epithelium. Clinical studies have linked the presence of either sulfate-reducing bacteria or H(2)S in the colon with chronic disorders such as ulcerative colitis and colorectal cancer, although at this point, the evidence is circumstantial and underlying mechanisms remain undefined. We showed previously that sulfide at concentrations similar to those found in the human colon induced genomic DNA damage in mammalian cells. The present study addressed the nature of the DNA damage by determining if sulfide is directly genotoxic or if genotoxicity requires cellular metabolism. We also questioned if sulfide genotoxicity is mediated by free radicals and if DNA base oxidation is involved. Naked nuclei from untreated Chinese hamster ovary cells were treated with sulfide; DNA damage was induced by concentrations as low as 1 micromol/L. This damage was effectively quenched by cotreatment with butylhydroxyanisole. Furthermore, sulfide treatment increased the number of oxidized bases recognized by formamidopyrimidine [fapy]-DNA glycosylase. These results confirm the genotoxicity of sulfide and strongly implicate that this genotoxicity is mediated by free radicals. These observations highlight the possible role of sulfide as an environmental insult that, given a predisposing genetic background, may lead to genomic instability or the cumulative mutations characteristic of colorectal cancer.

Steam cooking significantly improves in vitro bile acid binding of collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage.

Bile acid binding capacity has been related to the cholesterol-lowering potential of foods and food fractions. Lowered recirculation of bile acids results in utilization of cholesterol to synthesize bile acid and reduced fat absorption. Secondary bile acids have been associated with increased risk of cancer. Bile acid binding potential has been related to lowering the risk of heart disease and that of cancer. Previously, we have reported bile acid binding by several uncooked vegetables. However, most vegetables are consumed after cooking. How cooking would influence in vitro bile acid binding of various vegetables was investigated using a mixture of bile acids secreted in human bile under physiological conditions. Eight replicate incubations were conducted for each treatment simulating gastric and intestinal digestion, which included a substrate only, a bile acid mixture only, and 6 with substrate and bile acid mixture. Cholestyramine (a cholesterol-lowering, bile acid binding drug) was the positive control treatment and cellulose was the negative control. Relative to cholestyramine, in vitro bile acid binding on dry matter basis was for the collard greens, kale, and mustard greens, 13%; broccoli, 10%; Brussels sprouts and spinach, 8%; green bell pepper, 7%; and cabbage, 5%. These results point to the significantly different (P < or = .05) health-promoting potential of collard greens = kale = mustard greens > broccoli > Brussels sprouts = spinach = green bell pepper > cabbage as indicated by their bile acid binding on dry matter basis. Steam cooking significantly improved the in vitro bile acid binding of collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage compared with previously observed bile acid binding values for these vegetables raw (uncooked). Inclusion of steam-cooked collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage in our daily diet as health-promoting vegetables should be emphasized. These green/leafy vegetables, when consumed regularly after steam cooking, would lower the risk of cardiovascular disease and cancer, advance human nutrition research, and improve public health.

Diet and cell growth modulation by ammonia.

Fiber is not digested by endogenous enzymes but is fermented by microbes principally in the large intestine. With fermentable energy available, microbes synthesize protein by using ammonia released by their enzymes from urea and other nitrogenous substances in ingesta and intestinal secretions. Fibber fermentation also yields fatty acids that lower the concentration of free ammonia by lowering pH. Fiber increases bulk and water of intestinal contents, shortens transit time, and decreases the concentration of toxic substances in contact with the intestinal mucosa. These processes decrease duration and intensity of exposure of the intestinal mucosa to free ammonia, the form of nitrogen that is most toxic and most readily absorbed by cells. At concentrations found in the lower bowel on usual Western diets, ammonia destroys cells, alters nucleic acid synthesis, increases intestinal mucosal cell mass, increases virus infections, favors growth of cancerous cells over noncancerous cells in tissue culture, and increases virus infections. Ammonia in the bowel increases as protein intake increases. The attributes of ammonia and the epidemiological evidence comparing populations that maintain low intakes of unrefined carbohydrate with those that consume high intakes of protein, fat, and refined carbohydrates implicate ammonia in carcinogenesis and other disease processes.

Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn's disease.

Crohn's disease is a modern Western disease characterised by transmural inflammation of the gastrointestinal tract. It is of unknown aetiology, but evidence suggests that it results from a combination of genetic predisposition and environmental factors. Bacterial-sized microparticles (0.1-1.0 microm) are potent adjuvants in model antigen-mediated immune responses and are increasingly associated with disease. Microparticles of TiO2 and aluminosilicate accumulate in macrophages of human gut-associated lymphoid tissue where the earliest signs of lesions in Crohn's disease are observed. Dietary microparticles are of endogenous or exogenous origin. Endogenous microparticles dominate and are calcium phosphate (most probably hydroxyapatite), which precipitates in the lumen of the mid-distal gastrointestinal tract due to secretion of Ca and phosphate in the succus entericus. Exogenous dietary microparticles are contaminants (soil and/or dust) and food additives. TiO2, for example, is a food colourant, and aluminosilicates are anti-caking agents, although some aluminosilicates occur as natural contaminants. Food additives alone account for ingestion of approximately 10(12) particles/person per d. Possible mechanisms for the role of exogenous and endogenous dietary microparticles in promoting toleragenic or immune responses of gastrointestinal mucosal phagocytosis are discussed. In a double-blind randomised pilot study we have shown that a diet low in Ca and exogenous microparticles appears to alleviate the symptoms of ileal Crohn's disease, with a significant (P= 0.002) improvement in the Crohn's disease activity index. A multi-centre trial and further mechanistic studies at the cellular level are underway.

Chronic constipation as a symptom of cow milk allergy.

Twenty-seven consecutive infants (mean age, 20.6 months) with chronic "idiopathic" constipation were studied to investigate the possible relation between constipation and cow milk protein allergy (CMPA). The infants were initially observed on an unrestricted diet, and the number of stools per day was recorded. Subsequently the infants were put on a diet free of cow milk protein (CMP) for two periods of 1 month each, separated by two challenges with CMP. During the CMP-free diet, there was a resolution of symptoms in 21 patients; during the two consecutive challenges, constipation reappeared within 48 to 72 hours. In another six patients the CMP-free diet did not lead to improvement of constipation. Only four of the patients who improved on the CMP-free diet had concomitant symptoms of suspected CMPA, but a medical history of CMPA was found in 15 of the 21 patients cured and in only one of the six patients whose condition had not improved (p < 0.05); in addition, in 15 of the 21 cured patients, results of one or more laboratory tests (specific IgE, IgG, anti-beta-lactoglobulin, circulating eosinophils) were positive at the time of diagnosis, indicating hypersensitivity, compared with one of the six patients whose condition did not improve (p < 0.05). The endoscopic and histologic findings at the time of diagnosis showed proctitis with monocytic infiltration in two patients cured with the CMP-free diet; after 1 month on this diet, they were completely normal. We conclude that constipation in infants may have an allergic pathogenesis.

Flatulence--causes, relation to diet and remedies.

In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.

The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load.

Residents of Okinawa, the southernmost prefecture of Japan, are known for their long average life expectancy, high numbers of centenarians, and accompanying low risk of age-associated diseases. Much of the longevity advantage in Okinawa is thought to be related to a healthy lifestyle, particularly the traditional diet, which is low in calories yet nutritionally dense, especially with regard to phytonutrients in the form of antioxidants and flavonoids. Research suggests that diets associated with a reduced risk of chronic diseases are similar to the traditional Okinawan diet, that is, vegetable and fruit heavy (therefore phytonutrient and antioxidant rich) but reduced in meat, refined grains, saturated fat, sugar, salt, and full-fat dairy products. Many of the characteristics of the diet in Okinawa are shared with other healthy dietary patterns, such as the traditional Mediterranean diet or the modern DASH (Dietary Approaches to Stop Hypertension) diet. Features such as the low levels of saturated fat, high antioxidant intake, and low glycemic load in these diets are likely contributing to a decreased risk for cardiovascular disease, some cancers, and other chronic diseases through multiple mechanisms, including reduced oxidative stress. A comparison of the nutrient profiles of the three dietary patterns shows that the traditional Okinawan diet is the lowest in fat intake, particularly in terms of saturated fat, and highest in carbohydrate intake, in keeping with the very high intake of antioxidant-rich yet calorie-poor orange-yellow root vegetables, such as sweet potatoes, and green leafy vegetables. Deeper analyses of the individual components of the Okinawan diet reveal that many of the traditional foods, herbs, or spices consumed on a regular basis could be labeled "functional foods" and, indeed, are currently being explored for their potential health-enhancing properties.

Diverticular disease: Epidemiology and management

Diverticular disease of the colon is among the most prevalent conditions in western society and is among the leading reasons for outpatient visits and causes of hospitalization. While previously considered to be a disease primarily affecting the elderly, there is increasing incidence among individuals younger than 40 years of age. Diverticular disease most frequently presents as uncomplicated diverticulitis, and the cornerstone of management is antibiotic therapy and bowel rest. Segmental colitis associated with diverticula shares common histopathological features with inflammatory bowel disease and may benefit from treatment with 5-aminosalicylates. Surgical management may be required for patients with recurrent diverticulitis or one of its complications including peridiverticular abscess, perforation, fistulizing disease, and strictures and/or obstruction. Résumé La maladie diverticulaire du côlon est l’une des pathologies les plus prévalentes de la société occidentale et des principales causes de consultations ambulatoires et d’hospitalisations. On croyait qu’elle touchait surtout les personnes âgées, mais son incidence est en croissance auprès des personnes de moins de 40 ans. La maladie diverticulaire se manifeste surtout sous forme de diverticulite sans complication, et la pierre angulaire du traitement est l’antibiothérapie et le repos intestinal. La colite segmentaire associée aux diverticules partage des caractéristiques histopathologiques avec les maladies inflammatoires de l’intestin et peut profiter d’un traitement aux 5-aminosalicylates. Une prise en charge chirurgicale peut s’imposer en présence de diverticulite récurrente ou de l’une de ses complications, y compris un abcès péridiverticulaire, une perforation, une fistulisation et des sténoses ou des obstructions.

Efficacy and tolerability of a low microparticle diet in a double blind, randomized, pilot study in Crohn's disease.

BACKGROUND: Ultrafine and fine particles are potent adjuvants in antigen-mediated immune responses, and cause inflammation in susceptible individuals. Following recent findings that microparticles accumulate in the phagocytes of intestinal lymphoid aggregates, this study is the first investigation of whether their reduction in the diet improves the symptoms of Crohn's disease. METHODS: In a double blind study, 20 patients with active corticosteroid-treated ileal or ileo-colonic Crohn's disease randomly received either a low microparticle diet (trial group; n = 10) or a control diet (n = 10) for 4 months. Crohn's disease activity index (CDAI) and corticosteroid requirements were compared. RESULTS: One patient in each group was withdrawn. In the trial group there was a progressive decrease in CDAI from entry (392 +/- 25) to month 4 (145 +/- 47) (P = 0.002 vs control group) and seven patients were in remission (CDAI <150). In contrast, the control group had returned to baseline levels (302 +/- 28 on entry and 295 +/- 25 at month 4), with none in remission. Corticosteroid intake was reduced more in the trial group although this did not reach significance. CONCLUSIONS: A low microparticle diet may be effective in the management of ileal Crohn's disease and could explain the efficacy of elemental diets, which similarly are low in microparticles.

Faecal urobilinogen levels and pH of stools in population groups with different incidence of cancer of the colon, and their possible role in its aetiology.

Mean faecal urobilinogen levels and the pH of stools were both found to be higher in subjects from a population group at high risk of developing cancer of the colon than in subjects matched for age, sex and socioeconomic status from a low-risk population group. An alkaline reaction of the colon contents seems to have a tumorigenic effect by a direct action on the mucus of the mucous cells. An acidic reaction, on the other hand, appears to be protective. These differences are dependent on the patterns of diet and manner of eating. Proper mastication of food, roughage, cellulose and vegetable fibre, and short-chain fatty acids of milk and fermented milk products in the diet appear to be protective.

Antioxidants in vegan diet and rheumatic disorders.

Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.

Hazelnut-enriched diet improves cardiovascular risk biomarkers beyond a lipid-lowering effect in hypercholesterolemic subjects.

BACKGROUND: Tree nuts, particularly almonds, walnuts, and pistachios, have been shown to possess cardioprotective effects. However, there is little information on the effects of hazelnut consumption on cardiovascular risk markers. METHODS: The antiatherogenic effect of hazelnut before and after consumption in hypercholesterolemic subjects was investigated. Twenty-one hypercholesterolemic volunteers (18 men and 3 women) were recruited in a double control sandwich model intervention study with a single group and three isoenergetic diet periods. These were control diet I (4 weeks), hazelnut-enriched diet (4 weeks; hazelnut contributing 18%-20% of the total daily energy intake), and control diet period II (4 weeks). The cardiovascular risk biomarkers such as endothelial function, using flow-mediated dilation (FMD) technique, low-density lipoprotein (LDL) oxidation products and inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as lipids and lipoprotein levels were monitored. RESULTS: Consumption of a hazelnut-enriched diet significantly improved FMD (56.6%), total cholesterol (-7.8%), triacylglycerol (-7.3%), LDL-cholesterol (-6.17%), and high-density lipoprotein cholesterol (6.07%) compared with the control diet I. Oxidized-LDL, hs-CRP, and sVCAM-1 levels were significantly lower in the group ingesting a hazelnut-enriched diet compared with the control diets I and II. Modest correlations between sVCAM-1 and FMD and between sVCAM-1 and hs-CRP were observed (r = -0.49, P < .025; r = 0.66, P < .001, respectively). CONCLUSION: Hazelnut-enriched diets may exert antiatherogenic effect by improving endothelial function, preventing LDL oxidation, and inflammatory markers, in addition to their lipid and lipoprotein-lowering effects. These beneficial effects appeared to be reversible after 4 weeks on a hazelnut-free diet. Therefore, hazelnut may be incorporated into daily diet without change in total caloric intake for sustained health benefit. Copyright © 2013 National Lipid Association. All rights reserved.

Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheumatoid arthritis patients treated with fasting and a one year vegetarian diet.

OBJECTIVE: To measure Proteus mirabilis and Escherichia coli antibody levels in patients with rheumatoid arthritis (RA) during treatment by vegetarian diet. METHODS: Sera were collected from 53 RA patients who took part in a controlled clinical trial of fasting and a one year vegetarian diet. P mirabilis and E coli antibody levels were measured by an indirect immunofluorescence technique and an enzyme immunoassay, respectively. RESULTS: The patients on the vegetarian diet had a significant reduction in the mean anti-proteus titres at all time points during the study, compared with baseline values (all p < 0.05). No significant change in titre was observed in patients who followed an omnivorous diet. The decrease in anti-proteus titre was greater in the patients who responded well to the vegetarian diet compared with diet non-responders and omnivores. The total IgG concentration and levels of antibody against E coli, however, were almost unchanged in all patient groups during the trial. The decrease from baseline in proteus antibody levels correlated significantly (p < 0.001) with the decrease in a modified Stoke disease activity index. CONCLUSION: The decrease in P mirabilis antibody levels in the diet responders and the correlation between the decrease in proteus antibody level and decrease in disease activity supports the suggestion of an aetiopathogenetic role for P mirabilis in RA.

Curcumin as "Curecumin": from kitchen to clinic.

Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin".

Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition.

The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.

Suppression of colonic cancer by dietary phytic acid.

Large differences exist between human populations in the frequency of colonic cancer. Epidemiological evidence indicates that these differences are strongly influenced by country of residence, and a negative correlation has been found between the fiber content of the diet and frequency of colonic cancer. This has prompted the hypothesis that high-fiber diets are in some way protective. However, reanalysis of the dietary data provides equally strong support for the hypothesis that the protective element may be phytic acid (inositol hexaphosphate). This heat- and acid-stable substance is present in high concentration in many food items, including cereal grains, nuts, and seeds. Phytic acid forms chelates with various metals and suppresses damaging iron-catalyzed redox reactions. Inasmuch as colonic bacteria have been shown to produce oxygen radicals in appreciable amounts, dietary phytic acid might suppress oxidant damage to intestinal epithelium and neighboring cells. Indeed, rapidly accumulating data from animal models indicate that dietary supplementation with phytic acid may provide substantial protection against experimentally induced colonic cancer. Should further investigations yield additional support for this hypothesis, purposeful amplification of dietary phytic acid content would represent a simple method for reducing the risk of colonic carcinogenesis.

Cow's milk protein intolerance and chronic constipation in children.

Cow's milk protein (CMP) allergy was investigated in 25 children (age-range 3 months to 11 years) with chronic constipation. A diagnosis of constipation was made on the basis of a history of painful elimination of hard stools for at least 1 month, whether or not associated with a reduced frequency of stools or soiling. The children were evaluated using clinical parameters and the following laboratory tests: total serum immunoglobulin E (IgE); specific IgE (radioallergosorbent test [RAST]) for whole cow's milk, alpha-lactoalbumin, beta-lactoglobulin, and a food group; and skin-prick tests with whole milk, alpha-lactoalbumin, beta-lactoglobulin, and casein. Following the evaluation, the children were submitted to a CMP-free diet for a period of 4 weeks. In seven patients (28%), constipation disappeared during the CMP-free diet and reappeared within 48-72 h following challenge with cow's milk. In two infants a rectal biopsy revealed allergic colitis and they therefore did not undergo the challenge. High serum levels of total IgE were observed in five of the children who showed a clinical improvement (71%), a positive skin-test in two (29%), and detectable specific IgE in two (29%). These results suggest that CMP allergy or intolerance should be considered as a cause of chronic refractory constipation in children, although the underlying mechanism still require further investigation.

Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer

Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.

Vegetarian diet ameliorates symptoms of atopic dermatitis through reduction of the number of peripheral eosinophils and of PGE2 synthesis by monocy...

Many patients with atopic dermatitis are dissatisfied with conventional treatments based on topical steroids and have experienced some traditional remedies and alternative therapies. However, most of such therapies have not been evaluated scientifically and clinically by specialists. This study was designed to assess whether a certain vegetarian diet might be effective for atopic dermatitis and if so, to identify the mechanisms of this remedy through analyses of immunological parameters. An open-trial study was carried out in twenty patients with atopic dermatitis. An improvement of dermatitis was evaluated by SCORAD index and serological and immunological parameters were monitored. After a two-month treatment, the severity of dermatitis was strikingly inhibited, as assessed by SCORAD index and serological parameters including LDH5 activity and a number of peripheral eosinophils. A sharp reduction in eosinophils and neutrophils was observed prior to improvement in the skin inflammation. In addition, PGE2 production by peripheral blood mononuclear cells was reduced by this treatment. In contrast, serum IgE levels did not change during the same period. Although this study is an open-trial one, it suggests that this treatment may be useful for the treatment of adult patients with severe atopic dermatitis.

Lack of efficacy of a reduced microparticle diet in a multi-centred trial of patients with active Crohn's disease.

BACKGROUND AND AIMS: Dietary microparticles, which are bacteria-sized and non-biological, found in the modern Western diet, have been implicated in both the aetiology and pathogenesis of Crohn's disease. Following on from the findings of a previous pilot study, we aimed to confirm whether a reduction in the amount of dietary microparticles facilitates induction of remission in patients with active Crohn's disease, in a single-blind, randomized, multi-centre, placebo controlled trial. METHODS: Eighty-three patients with active Crohn's disease were randomly allocated in a 2 x 2 factorial design to a diet low or normal in microparticles and/or calcium for 16 weeks. All patients received a reducing dose of prednisolone for 6 weeks. Outcome measures were Crohn's disease activity index, Van Hees index, quality of life and a series of objective measures of inflammation including erythrocyte sedimentation rate, C-reactive protein, intestinal permeability and faecal calprotectin. After 16 weeks patients returned to their normal diet and were followed up for a further 36 weeks. RESULTS: Dietary manipulation provided no added effect to corticosteroid treatment on any of the outcome measures during the dietary trial (16 weeks) or follow-up (to 1 year); e.g., for logistic regression of Crohn's disease activity index based rates of remission (P=0.1) and clinical response (P=0.8), in normal versus low microparticle groups. CONCLUSIONS: Our adequately powered and carefully controlled dietary trial found no evidence that reducing microparticle intake aids remission in active Crohn's disease.

Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes

Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [–6.2 kg (95% CI –6.6 to –5.3) vs. –3.2 kg (95% CI –3.7 to –2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5–39) vs. 20% (95% CI 14–25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.

Dietary clues to the pathogenesis of Crohn's disease.

Crohn's disease is a complex inherited disorder of unknown pathogenesis with environmental, genetic and microbial factors involved in the development of the disease. A remarkable feature of this disease in childhood is the effective response to exclusive enteral nutrition (EEN) therapy and the need for complete exclusion of normal diet required for success (principle of exclusivity). EEN or dietary interventions might act through removal of dietary components, which affect microbial composition, decrease a proinflammatory response and promote restitution of the epithelial barrier, likewise allowing termination of this vicious disease-forming cycle before a critical threshold is reached. Multiple traditional and nontraditional dietary components may affect the microbiome, mucous layer, intestinal permeability, or adherence and translocation of pathobionts. We review the epidemiological data, as well as data from animal models and cell lines, and propose a model for pathogenesis we have termed the 'bacterial penetration cycle', whereby dietary components such as animal fat, high sugar intake and gliadin, and consumption of emulsifiers, maltodextrin as well as low-fiber diets may be able to cause a localized acquired bacterial clearance defect, leading to bacterial adhesion and penetration, and subsequently inflammation in the gut. © 2014 S. Karger AG, Basel.

Diet and cancer of the colon and rectum: a case-control study in China.

A case-control study was carried out in Harbin city to assess the role of diet in the aetiology of colorectal cancer. A total of 336 incident cases of histologically confirmed colorectal cancer (111 colon cancer and 225 rectal cancer) and an equal number of controls with other non-neoplastic diseases were interviewed in hospital wards. Data concerning the average frequency of consumption and amount consumed of single food items were obtained by a dietary history questionnaire. Odds ratios and their confidence limits were computed. Multiple regression for risk status was also used. Vegetables, particularly green vegetables, chives and celery, have a strong protective effect against colorectal cancer. Reduced consumption of meat, eggs, bean products and grain was associated with increasing risk for cancer of the rectum. Alcohol intake was found to be an important risk factor for developing colon cancer and male rectal cancer.

Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity.

Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.

Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial...

Traditional cardiovascular risk factors are associated with endothelial dysfunction. The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat. We propose to determine the chronic effect of three diets with different fat compositions on postprandial endothelial function and inflammatory biomarkers. Twenty healthy men followed three 4-week diets in a randomised cross-over design: a Western diet, rich in saturated fat (22% SFA, 12% MUFA and 0.4% alpha-linolenic acid (ALA), all fractions are % of energy); a Mediterranean diet, rich in MUFA ( < 10 % SFA, 24 % MUFA and 0.4% ALA); a low-fat diet enriched in ALA ( < 10% SFA, 12% MUFA and 2% ALA). At the end of each dietary period all subjects underwent a postprandial study. Plasma concentrations of lipid parameters, soluble intercellular cell-adhesion molecule-1, soluble vascular cell-adhesion molecule-1 (sVCAM-1), nitrates and nitrites (NOx) and endothelial function studied by laser Doppler were examined at 0, 2, 4, 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets (P = 0.031). The 4 h postprandial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet (P = 0.043). The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets (P = 0.027). We found no differences in the other parameters measured. Chronic ingestion of a Mediterranean diet avoids the postprandial deterioration of endothelial function associated with Westernised diets in healthy individuals.

Prevalence and incidence of gastroduodenal ulcers during treatment with vascular protective doses of aspirin.

BACKGROUND: Aspirin is valuable for preventing vascular events, but information about ulcer frequency is necessary to inform risk-benefit decisions in individual patients. AIM: To determine ulcer prevalence and incidence in a population representative of those given aspirin therapy and evaluate risk predictors. METHODS: Patients taking aspirin 75-325 mg daily were recruited from four countries. Exclusions included use of gastroprotectant drugs or other non-steroidal anti-inflammatory drugs. We measured point prevalence of endoscopic ulcers, after quantitating dyspeptic symptoms. Incidence was assessed 3 months later in those eligible to continue (no baseline ulcer or reason for gastroprotectants). RESULTS: In 187 patients, ulcer prevalence was 11% [95% confidence interval (CI) 6.3-15.1%]. Only 20% had dyspeptic symptoms, not significantly different from patients without ulcer. Ulcer incidence in 113 patients followed for 3 months was 7% (95% CI 2.4-11.8%). Helicobacter pylori infection increased the risk of a duodenal ulcer [odds ratio (OR) 18.5, 95% CI 2.3-149.4], as did age >70 for ulcers in stomach and duodenum combined (OR 3.3, 95% CI 1.3-8.7). CONCLUSIONS: Gastroduodenal ulcers are found in one in 10 patients taking low-dose aspirin, and most are asymptomatic; this needs considering when discussing risks/benefits with patients. Risk factors include older age and H. pylori (for duodenal ulcer).

Olive oil and walnut breakfasts reduce the postprandial inflammatory response in mononuclear cells compared with a butter breakfast in healthy men.

BACKGROUND: Inflammation is crucial in all stages of atherosclerosis, and few studies have investigated the effect of dietary fat on markers of inflammation related to this disease during the postprandial period. OBJECTIVE: To evaluate the chronic effects of dietary fat on the postprandial expression of proinflammatory genes in peripheral blood mononuclear cells (PBMCs) in healthy subjects. DESIGN: 20 healthy men followed three different diets for 4 weeks each, according to a randomized crossover design: Western diet: 15% protein, 47% carbohydrates (CHO), 38% fat (22% saturated fatty acid (SFA)); Mediterranean diet: 15% protein, 47% CHO, 38% fat (24% monounsaturated fatty acid (MUFA)); CHO-rich and n-3 diet: 15% protein, 55% CHO, <30% fat (8% polyunsaturated fatty acid (PUFA)). After 12-h fast, volunteers were given a breakfast with a fat composition similar to that consumed in each of the diets-butter breakfast: 35% SFA; olive oil breakfast: 36% MUFA; walnut breakfast: 16% PUFA, 4% alpha-linolenic acid (LNA). RESULTS: The butter breakfast induced a higher increase in tumor necrosis factor (TNF)-alpha messenger RNA (mRNA) expression than the olive oil or walnut breakfasts (P=0.014) in PBMCs. Moreover, we found a higher postprandial response in the mRNA of interleukin (IL)-6 with the intake of butter and olive oil breakfasts than with the walnut breakfast (P=0.025) in these cells. However, the effects of the three fatty breakfasts on the plasma concentrations of these proinflammatory parameters showed no significant differences (P=N.S.). CONCLUSION: Consumption of a butter-enriched meal elicits greater postprandial expression of proinflammatory cytokine mRNA in PBMCs, compared to the olive oil and walnut breakfasts.

Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an...

Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.

Colon cancer and diet, with special reference to intakes of fat and fiber.

Colon cancer, rare in the past, and in developing populations, currently accounts for 2 to 4% of all deaths in Western populations. Evidence suggests the primary cause to be changes in diet, which affect the bowel milieu intérieur. It is possible that in sophisticated populations, the higher concentrations of fecal bile acids and sterols, and longer transit time, favor the production of potentially carcinogenic metabolites. Of secular changes in diet, evidence suggests that the following may have etiological importance: 1) the fall in intake of fiber-containing foods with its effects on bowel physiology, and 2) the decreased fiber but increased fat intakes, in their respective capacities to raise concentrations of fecal bile acids, sterols, and other noxious substances. For possible prophylaxis against colon cancer, recommendations for a lower fat intake, or a higher intake of fiber-containing foods (apart from fiber ingestion from bran) are extremely unlikely to be adopted. For future research, western populations with considerably lower than average mortality rates, e.g., Seventh Day Adventists, Mormons, the rural Finnish population, as well as developing populations, demand intensive study. Also requiring elucidation are the respective roles of diet and of genetic constitution on concentrations of fecal bile acids, etc., and on transit time, in prone and nonprone populations.

High alpha-linolenic acid flaxseed (Linum usitatissimum): some nutritional properties in humans.

Although high alpha-linolenic acid flaxseed (Linum usitatissimum) is one of the richest dietary sources of alpha-linolenic acid and is also a good source of soluble fibre mucilage, it is relatively unstudied in human nutrition. Healthy female volunteers consumed 50 g ground, raw flaxseed/d for 4 weeks which provided 12-13% of energy intake (24-25 g/100 g total fat). Flaxseed raised alpha-linolenic acid and long-chain n-3 fatty acids in both plasma and erythrocyte lipids, as well as raising urinary thiocyanate excretion 2.2-fold. Flaxseed also lowered serum total cholesterol by 9% and low-density-lipoprotein-cholesterol by 18%. Changes in plasma alpha-linolenic acid were equivalent when 12 g alpha-linolenic acid/d was provided as raw flaxseed flour (50 g/d) or flaxseed oil (20 g/d) suggesting high bioavailability of alpha-linolenic acid from ground flaxseed. Test meals containing 50 g carbohydrate from flaxseed or 25 g flaxseed mucilage each significantly decreased postprandial blood glucose responses by 27%. Malondialdehyde levels in muffins containing 15 g flaxseed oil or flour/kg were similar to those in wheat-flour muffins. Cyanogenic glycosides (linamarin, linustatin, neolinustatin) were highest in extracted flaxseed mucilage but were not detected in baked muffins containing 150 g flaxseed/kg. We conclude that up to 50 g high-alpha-linolenic acid flaxseed/d is palatable, safe and may be nutritionally beneficial in humans by raising n-3 fatty acids in plasma and erythrocytes and by decreasing postprandial glucose responses.

Phase II trial of curcumin in patients with advanced pancreatic cancer.

PURPOSE: Pancreatic cancer is almost always lethal, and the only U.S. Food and Drug Administration-approved therapies for it, gemcitabine and erlotinib, produce objective responses in <10% of patients. We evaluated the clinical biological effects of curcumin (diferuloylmethane), a plant-derived dietary ingredient with potent nuclear factor-kappaB (NF-kappaB) and tumor inhibitory properties, against advanced pancreatic cancer. EXPERIMENTAL DESIGN: Patients received 8 g curcumin by mouth daily until disease progression, with restaging every 2 months. Serum cytokine levels for interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonists and peripheral blood mononuclear cell expression of NF-kappaB and cyclooxygenase-2 were monitored. RESULTS: Twenty-five patients were enrolled, with 21 evaluable for response. Circulating curcumin was detectable as drug in glucuronide and sulfate conjugate forms, albeit at low steady-state levels, suggesting poor oral bioavailability. Two patients showed clinical biological activity. One had ongoing stable disease for >18 months; interestingly, one additional patient had a brief, but marked, tumor regression (73%) accompanied by significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL-10, and IL-1 receptor antagonists). No toxicities were observed. Curcumin down-regulated expression of NF-kappaB, cyclooxygenase-2, and phosphorylated signal transducer and activator of transcription 3 in peripheral blood mononuclear cells from patients (most of whom had baseline levels considerably higher than those found in healthy volunteers). Whereas there was considerable interpatient variation in plasma curcumin levels, drug levels peaked at 22 to 41 ng/mL and remained relatively constant over the first 4 weeks. CONCLUSIONS: Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer.

A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer.

A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.

Celiac disease: Management of persistent symptoms in patients on a gluten-free diet

AIM: To investigate all patients referred to our center with non-responsive celiac disease (NRCD), to establish a cause for their continued symptoms. METHODS: We assessed all patients referred to our center with non-responsive celiac disease over an 18-mo period. These individuals were investigated to establish the eitiology of their continued symptoms. The patients were first seen in clinic where a thorough history and examination were performed with routine blood work including tissue transglutaminase antibody measurement. They were also referred to a specialist gastroenterology dietician to try to identift any lapses in the diet and sources of hidden gluten ingestion. A repeat small intestinal biopsy was also performed and compared to biopsies from the referring hospital where possible. Colonoscopy, lactulose hydrogen breath testing, pancreolauryl testing and computed tomography scan of the abdomen were undertaken if the symptoms persisted. Their clinical progress was followed over a minimum of 2 years. RESULTS: One hundred and twelve consecutive patients were referred with NRCD. Twelve were found not to have celiac disease (CD). Of the remaining 100 patients, 45% were not adequately adhering to a strict gluten-free diet, with 24 (53%) found to be inadvertently ingesting gluten, and 21 (47%) admitting non-compliance. Microscopic colitis was diagnosed in 12% and small bowel bacterial overgrowth in 9%. Refractory CD was diagnosed in 9%. Three of these were diagnosed with intestinal lymphoma. After 2 years, 78 patients remained well, eight had continuing symptoms, and four had died. CONCLUSION: In individuals with NRCD, a remediable cause can be found in 90%: with continued gluten ingestion as the leading cause. We propose an algorithm for investigation.

Probiotics, prebiotics infant formula use in preterm or low birth weight infants: a systematic review

Background Previous reviews (2005 to 2009) on preterm infants given probiotics or prebiotics with breast milk or mixed feeds focused on prevention of Necrotizing Enterocolitis, sepsis and diarrhea. This review assessed if probiotics, prebiotics led to improved growth and clinical outcomes in formula fed preterm infants. Methods Cochrane methodology was followed using randomized controlled trials (RCTs) which compared preterm formula containing probiotic(s) or prebiotic(s) to conventional preterm formula in preterm infants. The mean difference (MD) and corresponding 95% confidence intervals (CI) were reported for continuous outcomes, risk ratio (RR) and corresponding 95% CI for dichotomous outcomes. Heterogeneity was assessed by visual inspection of forest plots and a chi2 test. An I2 test assessed inconsistencies across studies. I2> 50% represented substantial heterogeneity. Results Four probiotics studies (N=212), 4 prebiotics studies (N=126) were included. Probiotics: There were no significant differences in weight gain (MD 1.96, 95% CI: -2.64 to 6.56, 2 studies, n=34) or in maximal enteral feed (MD 35.20, 95% CI: -7.61 to 78.02, 2 studies, n=34), number of stools per day increased significantly in probiotic group (MD 1.60, 95% CI: 1.20 to 2.00, 1 study, n=20). Prebiotics: Galacto-oligosaccharide / Fructo-oligosaccharide (GOS/FOS) yielded no significant difference in weight gain (MD 0.04, 95% CI: -2.65 to 2.73, 2 studies, n=50), GOS/FOS yielded no significant differences in length gain (MD 0.01, 95% CI: -0.03 to 0.04, 2 studies, n=50). There were no significant differences in head growth (MD −0.01, 95% CI: -0.02 to 0.00, 2 studies, n=76) or age at full enteral feed (MD −0.79, 95% CI: -2.20 to 0.61, 2 studies, n=86). Stool frequency increased significantly in prebiotic group (MD 0.80, 95% CI: 0.48 to 1.1, 2 studies, n=86). GOS/FOS and FOS yielded higher bifidobacteria counts in prebiotics group (MD 2.10, 95% CI: 0.96 to 3.24, n=27) and (MD 0.48, 95% CI: 0.28 to 0.68, n=56). Conclusions There is not enough evidence to state that supplementation with probiotics or prebiotics results in improved growth and clinical outcomes in exclusively formula fed preterm infants.

Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis.

Fasting is an effective treatment for rheumatoid arthritis, but most patients relapse on reintroduction of food. The effect of fasting followed by one year of a vegetarian diet was assessed in a randomised, single-blind controlled trial. 27 patients were allocated to a four-week stay at a health farm. After an initial 7-10 day subtotal fast, they were put on an individually adjusted gluten-free vegan diet for 3.5 months. The food was then gradually changed to a lactovegetarian diet for the remainder of the study. A control group of 26 patients stayed for four weeks at a convalescent home, but ate an ordinary diet throughout the whole study period. After four weeks at the health farm the diet group showed a significant improvement in number of tender joints, Ritchie's articular index, number of swollen joints, pain score, duration of morning stiffness, grip strength, erythrocyte sedimentation rate, C-reactive protein, white blood cell count, and a health assessment questionnaire score. In the control group, only pain score improved score. In the control group, only pain score improved significantly. The benefits in the diet group were still present after one year, and evaluation of the whole course showed significant advantages for the diet group in all measured indices. This dietary regimen seems to be a useful supplement to conventional medical treatment of rheumatoid arthritis.

Diets high in palmitic acid (16:0), lauric and myristic acids (12:0 + 14:0), or oleic acid (18:1) do not alter postprandial or fasting plasma homoc...

BACKGROUND: Dietary fat type is known to modulate the plasma lipid profile, but its effects on plasma homocysteine and inflammatory markers are unclear. OBJECTIVE: We investigated the effects of high-protein Malaysian diets prepared with palm olein, coconut oil (CO), or virgin olive oil on plasma homocysteine and selected markers of inflammation and cardiovascular disease (CVD) in healthy adults. DESIGN: A randomized-crossover intervention with 3 dietary sequences of 5 wk each was conducted in 45 healthy subjects. The 3 test fats, namely palmitic acid (16:0)-rich palm olein (PO), lauric and myristic acid (12:0 + 14:0)-rich CO, and oleic acid (18:1)-rich virgin olive oil (OO), were incorporated at two-thirds of 30% fat calories into high-protein Malaysian diets. RESULTS: No significant differences were observed in the effects of the 3 diets on plasma total homocysteine (tHcy) and the inflammatory markers TNF-α, IL-1β, IL-6, and IL-8, high-sensitivity C-reactive protein, and interferon-γ. Diets prepared with PO and OO had comparable nonhypercholesterolemic effects; the postprandial total cholesterol for both diets and all fasting lipid indexes for the OO diet were significantly lower (P < 0.05) than for the CO diet. Unlike the PO and OO diets, the CO diet was shown to decrease postprandial lipoprotein(a). CONCLUSION: Diets that were rich in saturated fatty acids prepared with either PO or CO, and an OO diet that was high in oleic acid, did not alter postprandial or fasting plasma concentrations of tHcy and selected inflammatory markers. This trial was registered at clinicaltrials.gov as NCT00941837.

Food selection based on high total antioxidant capacity improves endothelial function in a low cardiovascular risk population.

BACKGROUND AND AIMS: Oxidative stress has been advocated as a major cause for cardiovascular disease (CVD), and low plasma antioxidant concentrations are associated with endothelial dysfunction, the first step towards atherosclerosis. However, although the antioxidant content in fruits and vegetables may explain at least in part their protective effect against CVD, supplementation with antioxidant vitamins fails to improve endothelial function and reduce CVD risk. The aim of this study was to investigate the impact of a diet rich in antioxidants on endothelial function measured by flow-mediated dilatation (FMD) in volunteers at low cardiovascular risk. METHODS AND RESULTS: In a crossover trial, 24 subjects (13 women, mean age 61 ± 3 years), received, in a randomised order, a 14-day high (HT) and a 14-day low (LT) antioxidant diets, with a 2-week wash-out (WO) in between. Both diets were comparable in daily portions of fruits and vegetables, and in alcohol, fibre and macronutrient intake, but differed in their total antioxidant capacity. Before and after each diet, anthropometrics, blood pressure, fasting plasma glucose, lipid profile, hepatic enzymes, circulating antioxidant concentrations, high sensitivity C-reactive protein (hs-CRP) and FMD were assessed. FMD increased significantly during the HT diet compared to the LT (p < 0.000). FMD values were 2.3% higher after HT compared with LT (p < 0.001) after adjustment for age, gender and diet order. α-tocopherol increased significantly (p < 0.05) and hs-CRP and of γ-glutamyltranspeptidase decreased significantly (p < 0.05 and p < 0.01, respectively) during the HT diet, compared with the LT diet. CONCLUSIONS: A short-term HT diet improves endothelial function in volunteers at low cardiovascular risk, which may further reduce their risk of CVD. Copyright © 2010 Elsevier B.V. All rights reserved.

The effect of dietary factors on nitrosoproline levels in human urine.

The effect of dietary components on the levels of nitrosoproline ( NPRO ) excreted over a 24 h period in the urine was examined in volunteers ingesting known amounts of various food products. The ingestion of nitrite-preserved meats (85-170 g per meal), including canned, rolled or Yunnan ham, cured pork, luncheon meat, and various Chinese and European-style sausages, led to urinary NPRO excretion levels ranging from 2.5 to 78.5 micrograms/24 h, whereas the consumption of non-preserved meat and fish products, including chicken, herring, salmon, shrimp, ground beef (hamburger), pork chops and beef liver, led to relatively low NPRO excretion levels, ranging from 0.0 to 0.8 micrograms/24 h. The urinary NPRO levels of 22 vegetarians and 14 lacto-vegetarians averaged 0.8 and 1.4 micrograms/24 h, respectively. A change from a nitrite-preserved meat diet to a vegetarian diet was accompanied by an approximately six-fold reduction in urinary NPRO levels; however, these remained above control levels for at least 3 days following the dietary change. The relatively high NPRO levels following the ingestion of nitrite-preserved meats could not be reduced by nitrite-trapping chemicals, including ascorbic acid, ferulic acid, caffeic acid, or phenolic-containing mixtures such as coffee and tea, which were effective in suppressing endogenous NPRO formation following the intake of nitrate and proline. The high urinary NPRO levels after ingestion of preserved meat products appear to be due to the consumption of preformed NPRO . An understanding of the relative contribution of preformed and endogenously formed nitrosamines appears to be essential when designing dietary intervention programmes.

High polyphenol, low probiotic diet for weight loss because of intestinal microbiota interaction.

The relative proportion of Bacteroidetes to Firmicutes is decreased in obese people. This imbalance in gut microbiota generates signals controlling the expression of genes by the epithelial intestinal cells. Both dairy and non-dairy probiotics increase body weight, reportedly through Lactobacillus species growth in the gut. On the other hand, daily intake of some fruits and drinks such as three apples or three pears or grapefruit, or green tea, which all are rich in polyphenols, can significantly reduce body weight in obese people. Metabolism of polyphenols by microbiota involves the cleavage of glycosidic linkages. Glycans, which are the product of glycosidic cleavage, are necessary for survival of the intestinal microbiota as a nutrient foundation. There are two pivotal points: (i) Firmicutes possess a disproportionately smaller number of glycan-degrading enzymes than Bacteroidetes, (ii) Firmicutes are more repressed than the Bacteroidetes by phenolic compounds' antimicrobial properties. The Bacteroidetes community prevails following dietary polyphenol intake and its fermentation to phenolic compounds, due to having more glycan-degrading enzymes, so this may thus be a mechanism by which dietary polyphenols exert their weight lowering effect. I suggest that future studies utilize clone libraries and fingerprinting techniques enabling identification of the composition and community structure of the microbiota, and dot blot hybridization or fluorescent in situ hybridization to analyze abundance of particular taxa in obese and individuals. A supplementation with polyphenols with high bioavailability in obese individuals with higher Firmicutes/Bacteroides community ratio phenotype, when associated to a probiotic restricted diet, is proposed for weight loss; this hypothesis could have relevant implication in planning a successful dietary regimen and/or neutraceutical/pharmaceutical preparations for achieving and maintaining a normal body weight in obese individuals, especially including much more use of polyphenol-rich foodstuffs and/or polyphenol-rich syrups, and including low amounts of probiotic-rich foodstuffs like yogurt, soy yogurt, or as probiotic supplements. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial.

CONTEXT: The metabolic syndrome has been identified as a target for dietary therapies to reduce risk of cardiovascular disease; however, the role of diet in the etiology of the metabolic syndrome is poorly understood. OBJECTIVE: To assess the effect of a Mediterranean-style diet on endothelial function and vascular inflammatory markers in patients with the metabolic syndrome. DESIGN, SETTING, AND PATIENTS: Randomized, single-blind trial conducted from June 2001 to January 2004 at a university hospital in Italy among 180 patients (99 men and 81 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III. INTERVENTIONS: Patients in the intervention group (n = 90) were instructed to follow a Mediterranean-style diet and received detailed advice about how to increase daily consumption of whole grains, fruits, vegetables, nuts, and olive oil; patients in the control group (n = 90) followed a prudent diet (carbohydrates, 50%-60%; proteins, 15%-20%; total fat, <30%). MAIN OUTCOME MEASURES: Nutrient intake; endothelial function score as a measure of blood pressure and platelet aggregation response to l-arginine; lipid and glucose parameters; insulin sensitivity; and circulating levels of high-sensitivity C-reactive protein (hs-CRP) and interleukins 6 (IL-6), 7 (IL-7), and 18 (IL-18). RESULTS: After 2 years, patients following the Mediterranean-style diet consumed more foods rich in monounsaturated fat, polyunsaturated fat, and fiber and had a lower ratio of omega-6 to omega-3 fatty acids. Total fruit, vegetable, and nuts intake (274 g/d), whole grain intake (103 g/d), and olive oil consumption (8 g/d) were also significantly higher in the intervention group (P<.001). The level of physical activity increased in both groups by approximately 60%, without difference between groups (P =.22). Mean (SD) body weight decreased more in patients in the intervention group (-4.0 [1.1] kg) than in those in the control group (-1.2 [0.6] kg) (P<.001). Compared with patients consuming the control diet, patients consuming the intervention diet had significantly reduced serum concentrations of hs-CRP (P =.01), IL-6 (P =.04), IL-7 (P = 0.4), and IL-18 (P = 0.3), as well as decreased insulin resistance (P<.001). Endothelial function score improved in the intervention group (mean [SD] change, +1.9 [0.6]; P<.001) but remained stable in the control group (+0.2 [0.2]; P =.33). At 2 years of follow-up, 40 patients in the intervention group still had features of the metabolic syndrome, compared with 78 patients in the control group (P<.001). CONCLUSION: A Mediterranean-style diet might be effective in reducing the prevalence of the metabolic syndrome and its associated cardiovascular risk.

The effect of oral alpha-galactosidase on intestinal gas production and gas-related symptoms.

Bloating, abdominal distention, and flatulence represent very frequent complaints in functional disorders but their pathophysiology and treatment are largely unknown. Patients frequently associate these symptoms with excessive intestinal gas and the reduction of gas production may represent an effective strategy. The aim was to evaluate the effect of alpha-galactosidase administration, in a randomized double-blind placebo-controlled protocol, on intestinal gas production and gas-related symptoms after a challenge test meal in healthy volunteers. Eight healthy volunteers ingested 300 or 1200 GalU of alpha-galactosidase or placebo during a test meal containing 420 g of cooked beans. Breath hydrogen excretion and occurrence of bloating, abdominal pain, discomfort, flatulence, and diarrhea were measured for 8 hr. The administration of 1200 GalU of alpha-galactosidase induced a significant reduction of both breath hydrogen excretion and severity of flatulence. A reduction in severity was apparent for all considered symptoms, but both 300 and 1200 GalU induced a significant reduction in the total symptom score. Alpha-galactosidase reduced gas production following a meal rich in fermentable carbohydrates and may be helpful in patients with gas-related symptoms.

Diverticular disease: eat your fiber!

In industrialized nations, diverticular disease affects up to 70% of individuals by 60 years of age, with symptoms that can range from mild gastrointestinal disturbance to incapacitating pain. Diverticular disease appears to be related to increasing affluence and changed diet: Current theory holds that diverticular disease's origin is low-fiber diet. This explains why its incidence is highest and accelerating in the more prosperous countries where intake of fiber has decreased and intake of milled grains and refined sugars has increased over time. Not all patients develop symptoms, but if they do, the most frequent complaints associated with diverticulosis are cramping in the left-lower quadrant, bloating, constipation, and soiling. If diverticula perforate the gut's wall into the pericolic tissue, small and large abscesses, accompanied by bleeding, can form. Fistulization, when it occurs, most often penetrates to the bladder. Treatment addresses symptoms and may require hospitalization. During symptomatic periods, patients do best on low-fiber, bland diets. Once the acute episode or highly symptomatic period resolves or chronic disease is managed, patients should gradually increase dietary fiber to 20 to 30 grams daily or take dietary fiber in the form of bulk stimulants like psyllium.

Fecal bacterial beta-glucuronidase: control by diet.

The effect of a mixed Western, high meat diet or a nonmeat diet on the intestinal bacterial beta-glucuronidase activity was studied in human volunteers. This enzyme was significantly higher in stools of subjects on a high meat diet as compared to the nonmeat regimen. Thus, intestinal flora of subjects on a high meat diet was more able to hydrolyze glucuronide conjugates than that of individuals on a nonmeat diet. This, in turn, may raise the amount of substances, such as carcinogens, within the colonic lumen.

Products of the colonic microbiota mediate the effects of diet on colon cancer risk.

It is estimated that most colon cancers can be attributed to dietary causes. We have hypothesized that diet influences the health of the colonic mucosa through interaction with the microbiota and that it is the milieu interior that regulates mucosal proliferation and therefore cancer risk. To validate this further, we compared colonic contents from healthy 50- to 65-y-old people from populations with high and low risk, specifically low risk Native Africans (cancer incidence <1:100,000; n = 17), high risk African Americans (risk 65:100,000; n = 17), and Caucasian Americans (risk 50:100,000; n = 18). Americans typically consume a high-animal protein and -fat diet, whereas Africans consume a staple diet of maize meal, rich in resistant starch and low in animal products. Following overnight fasting, rapid colonic evacuation was performed with 2 L polyethylene glycol. Total colonic evacuants were analyzed for SCFA, vitamins, nitrogen, and minerals. Total SCFA and butyrate were significantly higher in Native Africans than in both American groups. Colonic folate and biotin content, measured by Lactobacillus rhamnoses and Lactobacillus plantarum ATCC 8014 bioassay, respectively, exceeded normal daily dietary intakes. Compared with Africans, calcium and iron contents were significantly higher in Caucasian Americans and zinc content was significantly higher in African Americans, but nitrogen content did not differ among the 3 groups. In conclusion, the results support our hypothesis that the microbiota mediates the effect diet has on colon cancer risk by their generation of butyrate, folate, and biotin, molecules known to play a key role in the regulation of epithelial proliferation.

Diet and gallbladder cancer: a case-control study.

Cancer of the gallbladder is rare but fatal, and has an unusual geographic and demographic distribution. Gallstones and obesity have been suggested as possible risk factors. As diet is known to influence both these factors, we carried out the present study to evaluate the possible role of diet in gallbladder carcinogenesis. A case-control study involving 64 newly diagnosed cases of gallbladder cancer and 101 cases of gallstones was carried out. The dietary evaluation was carried out by the dietary recall method based on a preset questionnaire developed specifically for the present study, keeping in mind the common dietary habits prevailing in this part of the world. Odds ratios (OR) and 95% confidence interval (CI) were calculated for various dietary items. A significant reduction in odds ratio was seen with the consumption of radish (OR 0.4; 95% CI 0.17-0.94), green chilli (OR 0.45; 95% CI 0.21-0.94) and sweet potato (OR 0.33; 95% CI 0.13-0.83) among vegetables, and mango (OR 0.4; 95% CI 0.16-0.99), orange (OR; 0.45; 95% CI 0.22-0.93), melon (OR 0.3; 95% CI 0.14-0.64) and papaya (OR 0.44; 95% 0.2-0.64) among fruits. A reduction in odds was also seen with the consumption of cruciferous vegetables, beans, onion and turnip, however the difference was not statistically significant. On the other hand, an increase in the odds was observed with consumption of capsicum (OR 2.2), beef (OR 2.58), tea (OR 1.98), red chilli (OR 1.29) and mutton (OR 1.2), however the difference was statistically not significant. In conclusion, the results of the present study show a protective effect of vegetables and fruits on gallbladder carcinogenesis, but red meat (beef and mutton) was found to be associated with increased risk of gallbladder cancer.

Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and...

In a previous clinical study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P < 0·05) and alleviated psychological distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0·05; somatisation, P < 0·05; depression, P < 0·05; and anger-hostility, P < 0·05), the HADS (HADS global score, P < 0·05; and HADS-anxiety, P < 0·06), and by the CCL (problem solving, P < 0·05) and the UFC level (P < 0·05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers.

Suppressive Effects of Selected Food Phytochemicals on CD74 Expression in NCI-N87 Gastric Carcinoma Cells

Helicobacter pylori (H. pylori) is one of the most widespread human pathogens, and plays major roles in chronic gastritis and gastric cancer. CD74 of gastric epithelial cells has recently been identified as an adhesion molecule to urease in H. pylori. In this study, we found that CD74 is highly expressed in a constitutive manner in NCI-N87 human gastric carcinoma cells at both the protein and mRNA levels as compared with Hs738St./Int fetal gastric cells. Subsequently, a novel cell-based ELISA able to rapidly screen the suppressive agents of CD74 expression was established. NCI-N87 cells were treated separately with 25 different food phytochemicals (4–100 µM) for 48 h and subjected to our novel assay. From those results, a citrus coumarin, bergamottin, was indicated to be the most promising compound with an LC50/IC50 value greater than 7.1, followed by luteolin (>5.4), nobiletin (>5.3), and quercetin (>5.1). Our findings suggest that these CD74 suppressants are unique candidates for preventing H. pylori adhesion and subsequent infection with reasonable action mechanisms.

Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies.

The aim of these studies was to evaluate the potential of some nutritional approaches to prevent or reduce the body load of organochlorines (OC) in humans. Study 1 compared plasma OC concentrations between vegans and omnivores while study 2 verified if the dietary fat substitute olestra could prevent the increase in OC concentrations that is generally observed in response to a weight-reducing programme. In study 1, nine vegans and fifteen omnivores were recruited and the concentrations of twenty-six OC (beta-hexachlorocyclohexane (beta-HCH), p, p'-dichlorodiphenyldichloroethane (p, p'-DDE), p, p'-dichlorodiphenyltrichloroethane (p, p'-DDT), hexachlorobenzene, mirex, aldrin, alpha-chlordane, gamma-chlordane, oxychlordane, cis-nonachlor, trans-nonachlor, polychlorinated biphenyl (PCB) nos. 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, and aroclor 1260) were determined. In study 2, the concentrations of these twenty-six OC were measured before and after weight loss over 3 months in thirty-seven obese men assigned to one of the following treatments: standard group (33 % fat diet; n 13), fat-reduced group (25 % fat diet; n 14) or fat-substituted group (1/3 of dietary lipids substituted by olestra; n 10). In study 1, plasma concentrations of five OC compounds (aroclor 1260 and PCB 99, PCB 138, PCB 153 and PCB 180) were significantly lower in vegans compared with omnivores. In study 2, beta-HCH was the only OC which decreased in the fat-substituted group while increasing in the other two groups (P = 0.045). In conclusion, there was a trend toward lesser contamination in vegans than in omnivores, and olestra had a favourable influence on beta-HCH but did not prevent plasma hyperconcentration of the other OC during ongoing weight loss.

A diet high in fat and meat but low in dietary fibre increases the genotoxic potential of 'faecal water'.

To determine the effects of different diets on the genotoxicity of human faecal water, a diet rich in fat, meat and sugar but poor in vegetables and free of wholemeal products (diet 1) was consumed by seven healthy volunteers over a period of 12 days. One week after the end of this period, the volunteers started to consume a diet enriched with vegetables and wholemeal products but poor in fat and meat (diet 2) over a second period of 12 days. The genotoxic effect of faecal waters obtained after both diets was assessed with the single cell gel electrophoresis (Comet assay) using the human colon adenocarcinoma cell line HT29 clone 19a as a target. The fluorescence and length of the tails of the comet images reflects the degree of DNA damage in single cells. The mean DNA damage, expressed as the ratio of tail intensity (fluorescence in the tail) to total intensity of the comet after incubation with faecal water from volunteers consuming diet 1 was about twice as high as for diet 2. The susceptibility of the cells incubated with faecal water to DNA damage caused by additional hydrogen peroxide treatment showed no significant differences between the two diets. Generation of oxidized pyrimidine and purine bases revealed no differences after pretreatment with both types of faecal water. The results indicate that diets high in fat and meat but low in dietary fibre increase the genotoxicity of faecal water to colonic cells and may contribute to an enhanced risk of colorectal cancer.

Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function.

OBJECTIVES: We sought to investigate whether the addition of walnuts or olive oil to a fatty meal have differential effects on postprandial vasoactivity, lipoproteins, markers of oxidation and endothelial activation, and plasma asymmetric dimethylarginine (ADMA). BACKGROUND: Compared with a Mediterranean diet, a walnut diet has been shown to improve endothelial function in hypercholesterolemic patients. We hypothesized that walnuts would reverse postprandial endothelial dysfunction associated with consumption of a fatty meal. METHODS: We randomized in a crossover design 12 healthy subjects and 12 patients with hypercholesterolemia to 2 high-fat meal sequences to which 25 g olive oil or 40 g walnuts had been added. Both test meals contained 80 g fat and 35% saturated fatty acids, and consumption of each meal was separated by 1 week. Venipunctures and ultrasound measurements of brachial artery endothelial function were performed after fasting and 4 h after test meals. RESULTS: In both study groups, flow-mediated dilation (FMD) was worse after the olive oil meal than after the walnut meal (p = 0.006, time-period interaction). Fasting, but not postprandial, triglyceride concentrations correlated inversely with FMD (r = -0.324; p = 0.024). Flow-independent dilation and plasma ADMA concentrations were unchanged, and the concentration of oxidized low-density lipoproteins decreased (p = 0.051) after either meal. The plasma concentrations of soluble inflammatory cytokines and adhesion molecules decreased (p < 0.01) independently of meal type, except for E-selectin, which decreased more (p = 0.033) after the walnut meal. CONCLUSIONS: Adding walnuts to a high-fat meal acutely improves FMD independently of changes in oxidation, inflammation, or ADMA. Both walnuts and olive oil preserve the protective phenotype of endothelial cells.

The aryl hydrocarbon receptor in inflammatory bowel disease: linking the environment to disease pathogenesis.

PURPOSE OF REVIEW: The aryl hydrocarbon receptor (AhR), a transcription factor activated by a large number of environmental agents, modulates the activity of immune and nonimmune cells in the gut, and may represent an important link between the environment and the immune perturbations which underlie the pathogenesis of inflammatory bowel disease. This review will summarize the current knowledge of the role of AhR in regulation of intestinal immune homeostasis and inflammation. RECENT FINDINGS: Activation of AhR by dietary ligands is necessary for the maintenance or expansion of innate immune cells in the gut, such as intraepithelial lymphocytes (IELs) and interleukin (IL)-22-producing lymphoid cells (ILC22). AhR-deficient mice lack IELs, have reduced number of ILC22 cells, and are more susceptible to bacterial infections and experimental colitis. In animal models, AhR activators inhibit proinflammatory cytokine synthesis and attenuate colitis by a pathway that involves IL-22. Analysis of AhR in the human gut reveals that intestinal T cells and natural killer cells isolated from Crohn's disease patients express low levels of AhR and respond to AhR ligands by downregulating inflammatory cytokines and upregulating IL-22. SUMMARY: These novel findings may help explain how environmental factors may regulate mucosal immune responses.

Antioxidant activity in human faeces.

Scarcely-absorbed antioxidants might reach the large bowel and exhibit antioxidant activity, opposing the action of reactive O species by bacterial and cellular metabolism and thus contributing to protection from oxidative damage-induced gastrointestinal diseases. This study was carried out to evaluate the antioxidant activity in the faeces of a group of healthy subjects on a freely-selected diet, and to look for possible associations with the intake of some macro- and micronutrients and food groups. Fourteen subjects recorded their food intake three times for a period of 2 d, each time collecting all the faeces passed during the next 24 h. Total antioxidant activity (TAA; mmol 6-hydroxy-2,5,7,8 tetramethylchroman-2-carboxylic acid (Trolox)/kg) of faecal suspensions was measured using the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid radical cation (ABTS(.+)) decolorisation assay. The average TAA value of faeces was 26.6 (sd 10.2) mmol Trolox/kg wet faeces (range 7.5-50.5). The total amount of antioxidant equivalents excreted over 24 h, derived by multiplying the TAA by the amount of faeces passed over 24 h, was 3.24 (sd 1.51) mmol Trolox (range 0.92-5.82) and this was significantly correlated with the average 24 h intake of coffee red wine and particularly to the sum of coffee and red wine In conclusion, the faeces of healthy subjects show detectable capacity to scavenge radical cations, suggesting that antioxidant activity occurs in the colonic lumen. Moreover, such activity seems at least in part to be related to dietary habits.

Berry fruits for cancer prevention: current status and future prospects.

Overwhelming evidence suggests that edible small and soft-fleshed berry fruits may have beneficial effects against several types of human cancers. The anticancer potential of berries has been related, at least in part, to a multitude of bioactive phytochemicals that these colorful fruits contain, including polyphenols (flavonoids, proanthocyanidins, ellagitannins, gallotannins, phenolic acids), stilbenoids, lignans, and triterpenoids. Studies show that the anticancer effects of berry bioactives are partially mediated through their abilities to counteract, reduce, and also repair damage resulting from oxidative stress and inflammation. In addition, berry bioactives also regulate carcinogen and xenobiotic metabolizing enzymes, various transcription and growth factors, inflammatory cytokines, and subcellular signaling pathways of cancer cell proliferation, apoptosis, and tumor angiogenesis. Berry phytochemicals may also potentially sensitize tumor cells to chemotherapeutic agents by inhibiting pathways that lead to treatment resistance, and berry fruit consumption may provide protection from therapy-associated toxicities. Although a wide variety of berry fruits are consumed worldwide, this paper focuses on those commonly consumed in North America, namely, blackberries, black raspberries, blueberries, cranberries, red raspberries, and strawberries. In addition, a large body of studies on singly purified berry bioactives is available, but this paper focuses on studies of "whole berries" per se, that is, as berry extracts and purified fractions, juices, and freeze-dried powders. Potential mechanisms of anticancer action and bioavailability of berry phenolics, as well as gaps in knowledge and recommendations for future berry research, are also briefly discussed.

Prevention of upper respiratory tract infections by gargling: a randomized trial.

BACKGROUND: Gargling to wash the throat is commonly performed in Japan, and people believe that such hygienic routine, especially with gargle medicine, prevents upper respiratory tract infections (URTIs). Its effectiveness, however, has not been established by clinical trials. DESIGN: Randomized controlled trial carried out in 2002-2003 winter season and analyzed in 2003 and 2004. PARTICIPANTS: Healthy volunteers (387) aged 18 to 65 years. INTERVENTION: Participants were randomly assigned to water gargling, povidone-iodine gargling, and usual care (control). Subjects in the two gargling groups were requested to gargle with water or diluted povidone-iodine at least three times a day. Participants were followed for 60 days. MAIN OUTCOME MEASURES: The primary outcome measure was first URTI incidence. Severity of URTI symptoms among incident cases was also evaluated. Both outcomes were assessed with a self-administered symptom record. Analyses were performed on an intention-to-treat basis. RESULTS: A total of 130 participants contracted URTIs. The incidence rate of first URTI was 0.26 episodes/30 person-days among control subjects. The rate decreased to 0.17 episodes/30 person-days in the water gargling group, and 0.24 episodes/30 person-days in the povidone-iodine gargling group. Respective incidence rate ratios against controls were 0.64 (95% confidence interval [CI]=0.41-0.99) and 0.89 (95% CI=0.60-1.33). A Cox regression (proportional hazard model) revealed the efficacy of water gargling (hazard ratio=0.60, 95% CI=0.39-0.95). Even when a URTI occurred, water gargling tended to attenuate bronchial symptoms (p=0.055). CONCLUSIONS: Simple water gargling was effective to prevent URTIs among healthy people. This virtually cost-free modality would appreciably benefit the general population.

The postprandial effect of components of the Mediterranean diet on endothelial function.

OBJECTIVES: This study investigated the postprandial effect of components of the Mediterranean diet on endothelial function, which may be an atherogenic factor. BACKGROUND: The Mediterranean diet, containing olive oil, pasta, fruits, vegetables, fish, and wine, is associated with an unexpectedly low rate of cardiovascular events. The Lyon Diet Heart Study found that a Mediterranean diet, which substituted omega-3-fatty-acid-enriched canola oil for the traditionally consumed omega-9 fatty-acid-rich olive oil, reduced cardiovascular events. METHODS: We fed 10 healthy, normolipidemic subjects five meals containing 900 kcal and 50 g fat. Three meals contained different fat sources: olive oil, canola oil, and salmon. Two olive oil meals also contained antioxidant vitamins (C and E) or foods (balsamic vinegar and salad). We measured serum lipoproteins and glucose and brachial artery flow-mediated vasodilation (FMD), an index of endothelial function, before and 3 h after each meal. RESULTS: All five meals significantly raised serum triglycerides, but did not change other lipoproteins or glucose 3 h postprandially. The olive oil meal reduced FMD 31% (14.3 +/- 4.2% to 9.9 +/- 4.5%, p = 0.008). An inverse correlation was observed between postprandial changes in serum triglycerides and FMD (r = -0.47, p < 0.05). The remaining four meals did not significantly reduce FMD. CONCLUSIONS: In terms of their postprandial effect on endothelial function, the beneficial components of the Mediterranean and Lyon Diet Heart Study diets appear to be antioxidant-rich foods, including vegetables, fruits, and their derivatives such as vinegar, and omega-3-rich fish and canola oils.

Purine-rich foods intake and recurrent gout attacks

Objective To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients. Methods The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods. Results This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine. Conclusions The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.

Primary constipation: an underlying mechanism.

Primary (simple) constipation is a consequence of habitual bowel elimination on common toilet seats. A considerable proportion of the population with normal bowel movement frequency has difficulty emptying their bowels, the principal cause of which is the obstructive nature of the recto-anal angle and its association with the sitting posture normally used in defecation. The only natural defecation posture for a human being is squatting. The alignment of the recto-anal angle associated with squatting permits smooth bowel elimination. This prevents excessive straining with the potential for resultant damage to the recto-anal region and, possibly, to the colon and other organs. There is no evidence that habitual bowel elimination at a given time each day contributes considerably to the final act of rectal emptying. The natural behavior to empty the bowels in response to a strong defecation reflex alleviates bowel emptying by means of the recto anal inhibitory reflex.

Diet and inflammation.

The emerging role of chronic inflammation in the major degenerative diseases of modern society has stimulated research into the influence of nutrition and dietary patterns on inflammatory indices. Most human studies have correlated analyses of habitual dietary intake as determined by a food frequency questionnaire or 24-hour recall with systemic markers of inflammation like high-sensitivity C-reactive protein (HS-CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). An occasional study also includes nutrition analysis of blood components. There have been several controlled interventions which evaluated the effect of a change in dietary pattern or of single foods on inflammatory markers in defined populations. Most studies reveal a modest effect of dietary composition on some inflammatory markers in free-living adults, although different markers do not vary in unison. Significant dietary influences have been established for glycemic index (GI) and load (GL), fiber, fatty acid composition, magnesium, carotenoids, and flavonoids. A traditional Mediterranean dietary pattern, which typically has a high ratio of monounsaturated (MUFA) to saturated (SFA) fats and ω-3 to ω-6 polyunsaturated fatty acid (PUFAs) and supplies an abundance of fruits, vegetables, legumes, and grains, has shown anti-inflammatory effects when compared with typical North American and Northern European dietary patterns in most observational and interventional studies and may become the diet of choice for diminishing chronic inflammation in clinical practice.

Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans

Background: Epidemiologic studies have suggested that most cases of sporadic colon cancer can be attributed to diet. The recognition that colonic microbiota have a major influence on colonic health suggests that they might mediate colonic carcinogenesis. Objective: To examine the hypothesis that the influence of diet on colon cancer risk is mediated by the microbiota through their metabolites, we measured differences in colonic microbes and their metabolites in African Americans with a high risk and in rural native Africans with a low risk of colon cancer. Design: Fresh fecal samples were collected from 12 healthy African Americans aged 50–65 y and from 12 age- and sex-matched native Africans. Microbiomes were analyzed with 16S ribosomal RNA gene pyrosequencing together with quantitative polymerase chain reaction of the major fermentative, butyrate-producing, and bile acid–deconjugating bacteria. Fecal short-chain fatty acids were measured by gas chromatography and bile acids by liquid chromatography–mass spectrometry. Results: Microbial composition was fundamentally different, with a predominance of Prevotella in native Africans (enterotype 2) and of Bacteroides in African Americans (enterotype 1). Total bacteria and major butyrate-producing groups were significantly more abundant in fecal samples from native Africans. Microbial genes encoding for secondary bile acid production were more abundant in African Americans, whereas those encoding for methanogenesis and hydrogen sulfide production were higher in native Africans. Fecal secondary bile acid concentrations were higher in African Americans, whereas short-chain fatty acids were higher in native Africans. Conclusion: Our results support the hypothesis that colon cancer risk is influenced by the balance between microbial production of health-promoting metabolites such as butyrate and potentially carcinogenic metabolites such as secondary bile acids.

Nutritional intervention in patients with periodontal disease: clinical, immunological and microbiological variables during 12 months.

The role of nutrition in onset, progression and treatment of periodontitis has not been thoroughly evaluated. In the present prospective clinical study, we investigated the influence of a nutritional intervention on changes in clinical, microbiological and immunological periodontal variables during a period of 12 months in patients with the metabolic syndrome and chronic periodontitis. Twenty female subjects with the metabolic syndrome and mild to moderate chronic periodontitis participated in a guided nutritional intervention programme. Examinations were assessed before, and at 2 weeks, 3, 6 and 12 months after intervention. Clinical measurements included probing depth, Löe and Silness gingival index and Quigley-Hein plaque index. In gingival crevicular fluid, periodontopathogens, levels of IL-1beta and IL-6 as well as the activity of granulocyte elastase were determined. In stimulated saliva, antioxidative and oxidative variables were measured. After 12 months the following significant changes could be observed: reduction of clinical probing depth (2.40 v. 2.20 mm; P < 0.001), reduction of gingival inflammation (gingival index 1.13 v. 0.9; P < 0.001), reduced concentrations of IL-1beta (4.63 v. 1.10 pg/ml per site; P < 0.001) as well as IL-6 (1.85 v. 0.34 pg/ml per site; P = 0.022) in gingival crevicular fluid. Bacterial counts in gingival crevicular fluid as well as oxidative and antioxidative variables in saliva showed no significant changes. Only salivary catalase showed a tendency to lower values. These findings indicate that in patients with the metabolic syndrome wholesome nutrition might reduce inflammatory variables of periodontal disease and promote periodontal health.

Avenanthramides inhibit proliferation of human colon cancer cell lines in vitro.

A high intake of whole grain foods is associated with reduced risk of colon cancer, but the mechanism underlying this protection has yet to be elucidated. Chronic inflammation and associated cyclooxygenase-2 (COX-2) expression in the colon epithelium are causally related to epithelial carcinogenesis, proliferation, and tumor growth. We examined the effect of avenanthramides (Avns), unique polyphenols from oats with anti-inflammatory properties, on COX-2 expression in macrophages, colon cancer cell lines, and on proliferation of human colon cancer cell lines. We found that Avns-enriched extract of oats (AvExO) had no effect on COX-2 expression, but it did inhibit COX enzyme activity and prostaglandin E(2) (PGE(2)) production in lipopolysaccharide-stimulated mouse peritoneal macrophages. Avns (AvExO, Avn-C, and the methylated form of Avn-C (CH3-Avn-C)) significantly inhibited cell proliferation of both COX-2-positive HT29, Caco-2, and LS174T, and COX-2-negative HCT116 human colon cancer cell lines, CH3-Avn-C being the most potent. However, Avns had no effect on COX-2 expression and PGE(2) production in Caco-2 and HT29 colon cancer cells. These results indicate that the inhibitory effect of Avns on colon cancer cell proliferation may be independent of COX-2 expression and PGE(2) production. Thus, Avns might reduce colon cancer risk through inhibition of macrophage PGE(2) production and non-COX-related antiproliferative effects in colon cancer cells. Interestingly, Avns had no effect on cell viability of confluence-induced differentiated Caco-2 cells, which display the characteristics of normal colonic epithelial cells. Our results suggest that the consumption of oats and oat bran may reduce the risk of colon cancer not only because of their high fiber content but also due to Avns, which attenuate proliferation of colonic cancer cells.

Effects of Diets High in Walnuts and Flax Oil on Hemodynamic Responses to Stress and Vascular Endothelial Function

Background Polyunsaturated fatty acids (PUFA) have beneficial effects on cardiovascular risk, although the mechanisms are incompletely understood. In a previous article, we showed significant reductions in low-density lipoprotein cholesterol and several markers of inflammation with increasing intake of alpha-linolenic acid (ALA) from walnuts and flax. Objective To examine effects of ALA on cardiovascular responses to acute stress, flow-mediated dilation (FMD) of the brachial artery, and blood concentrations of endothelin-1 and arginine-vasopressin (AVP). Design Using a randomized, crossover study design, cardiovascular responses to acute stress were assessed in 20 hypercholesterolemic subjects, a subset of whom also underwent FMD testing (n = 12). Participants were fed an average American diet (AAD) and 2 experimental diets that varied in the amount of ALA and linoleic acid (LA) that they contained. The AAD provided 8.7% energy from PUFA (7.7% LA, 0.8% ALA). On the LA diet, saturated fat was reduced, and PUFA from walnuts and walnut oil provided 16.4% of energy (12.6% LA, 3.6% ALA). On the ALA diet, walnuts, walnut oil, and flax oil provided 17% energy from PUFA (10.5% LA, 6.5% ALA). Results The ALA and LA diets significantly reduced diastolic blood pressure (−2 to −3 mm Hg) and total peripheral resistance (−4%), and this effect was evident at rest and during stress (main effect of diet, p < 0.02). FMD increased (+34%) on the diet containing additional ALA. AVP also increased by 20%, and endothelin-1 was unchanged. Conclusions These results suggest novel mechanisms for the cardioprotective effects of walnuts and flax, and further work is needed to identify the bioactives responsible for these effects.

Probiotics as prevention and treatment for diarrhea.

PURPOSE OF REVIEW: To critically appraise evidence on probiotic use for prevention and treatment of diarrhea in children and adults. RECENT FINDINGS: Several randomized controlled trials and meta-analyses suggested that probiotics are effective in primary and secondary prevention of gastroenteritis and its treatment. Selected Lactobacillus strains had a modest, although significant effect in primary prevention. Saccharomyces boulardii was effective in antibiotic-associated and in Clostridium difficile diarrhea. There is evidence that it might prevent diarrhea in day-care centers. Lactobacillus rhamnosus GG was associated with reduced diarrheal duration and severity, more evident in case of childhood Rotavirus diarrhea. Similar, although weaker, evidence was obtained with S. boulardii. Both strains are included in evidence-based recommendations for gastroenteritis management in children. Data on other Lactobacillus strains are preliminary. Probiotic efficacy was related to cause, early administration and bacterial load, and their mechanisms were associated with antiinfectious action in the intestine or, indirectly, to modulation of innate and adaptive immunity. SUMMARY: Probiotics have gained a role as adjunctive treatment of infantile gastroenteritis together with rehydration. Their efficacy is less convincing in adults, but promising in antibiotic-associated diarrhea. However, evidence of efficacy is limited to a few strains.

Colonic fermentation of indigestible carbohydrates contributes to the second-meal effect.

BACKGROUND: Low postprandial blood glucose is associated with low risk of metabolic diseases. A meal's ability to diminish the glucose response to carbohydrates eaten during the following meal is known as the "second-meal effect" (SME). The reduced glycemia elicited by low-glycemic-index (LGI) foods consumed during the first meal has been suggested as the main mechanism for SME. However, LGI foods often increase colonic fermentation because of the presence of fiber and resistant starch. OBJECTIVE: The objective was to study the SME of greater fermentation of high-glycemic-index (HGI) and LGI carbohydrates eaten during a previous meal. DESIGN: Ten healthy volunteers ate 3 breakfast test meals consisting of sponge cakes made with rapidly digestible, nonfermentable amylopectin starch plus cellulose (HGI meal), amylopectin starch plus the fermentable disaccharide lactulose (HGI-Lac meal), or slowly digestible, partly fermentable amylose starch plus cellulose (LGI meal). Five hours later, subjects were fed the same standard lunch containing 93 g available carbohydrates. Blood was collected for measurement of glucose, insulin, and nonesterified fatty acids (NEFAs). Breath hydrogen was measured as a marker of colonic fermentation. Postlunch gastric emptying was measured by using ultrasonography. RESULTS: Both the HGI-Lac and LGI meals improved glucose tolerance at lunch. In the case of the HGI-Lac meal, this effect was concomitant with low NEFA concentrations and delayed gastric emptying. CONCLUSION: Fermentable carbohydrates, independent of their effect on a food's glycemic index, have the potential to regulate postprandial responses to a second meal by reducing NEFA competition for glucose disposal and, to a minor extent, by affecting intestinal motility.

Dietary suppression of colonic cancer. Fiber or phytate?

The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.

Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a r...

CONTEXT: Combining foods with recognized cholesterol-lowering properties (dietary portfolio) has proven highly effective in lowering serum cholesterol under metabolically controlled conditions. OBJECTIVE: To assess the effect of a dietary portfolio administered at 2 levels of intensity on percentage change in low-density lipoprotein cholesterol (LDL-C) among participants following self-selected diets. DESIGN, SETTING, AND PARTICIPANTS: A parallel-design study of 351 participants with hyperlipidemia from 4 participating academic centers across Canada (Quebec City, Toronto, Winnipeg, and Vancouver) randomized between June 25, 2007, and February 19, 2009, to 1 of 3 treatments lasting 6 months. INTERVENTION: Participants received dietary advice for 6 months on either a low-saturated fat therapeutic diet (control) or a dietary portfolio, for which counseling was delivered at different frequencies, that emphasized dietary incorporation of plant sterols, soy protein, viscous fibers, and nuts. Routine dietary portfolio involved 2 clinic visits over 6 months and intensive dietary portfolio involved 7 clinic visits over 6 months. MAIN OUTCOME MEASURES: Percentage change in serum LDL-C. RESULTS: In the modified intention-to-treat analysis of 345 participants, the overall attrition rate was not significantly different between treatments (18% for intensive dietary portfolio, 23% for routine dietary portfolio, and 26% for control; Fisher exact test, P = .33). The LDL-C reductions from an overall mean of 171 mg/dL (95% confidence interval [CI], 168-174 mg/dL) were -13.8% (95% CI, -17.2% to -10.3%; P < .001) or -26 mg/dL (95% CI, -31 to -21 mg/dL; P < .001) for the intensive dietary portfolio; -13.1% (95% CI, -16.7% to -9.5%; P < .001) or -24 mg/dL (95% CI, -30 to -19 mg/dL; P < .001) for the routine dietary portfolio; and -3.0% (95% CI, -6.1% to 0.1%; P = .06) or -8 mg/dL (95% CI, -13 to -3 mg/dL; P = .002) for the control diet. Percentage LDL-C reductions for each dietary portfolio were significantly more than the control diet (P < .001, respectively). The 2 dietary portfolio interventions did not differ significantly (P = .66). Among participants randomized to one of the dietary portfolio interventions, percentage reduction in LDL-C on the dietary portfolio was associated with dietary adherence (r = -0.34, n = 157, P < .001). CONCLUSION: Use of a dietary portfolio compared with the low-saturated fat dietary advice resulted in greater LDL-C lowering during 6 months of follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00438425.

Diet and prevention of oral cancer: strategies for clinical practice.

BACKGROUND: Oral health care professionals can play an important role in preventing oral cancer by performing oral mucosal examinations to detect pre-cancerous changes and by educating patients about oral cancer prevention strategies, including dietary approaches. CONCLUSIONS: Current evidence supports a diet high in fruits, vegetables and plant-based foods for prevention of oral cancer. Dietary supplements-including vitamins and minerals-have not been shown to be effective as substitutes for a diet high in fruits and vegetables. CLINICAL IMPLICATIONS: In addition to discussing tobacco and alcohol use with patients (and, if relevant, betel nut and gutka consumption), as well as the risk of sexual transmission of human papillo-mavirus, clinicians should provide dietary advice for the prevention of oral cancer as part of routine patient education practices.

The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash.

Recent studies surprisingly show that dietary inorganic nitrate, abundant in vegetables, can be metabolized in vivo to form nitrite and then bioactive nitric oxide. A reduction in blood pressure was recently noted in healthy volunteers after dietary supplementation with nitrate; an effect consistent with formation of vasodilatory nitric oxide. Oral bacteria have been suggested to play a role in bioactivation of nitrate by first reducing it to the more reactive anion nitrite. In a cross-over designed study in seven healthy volunteers we examined the effects of a commercially available chlorhexidine-containing antibacterial mouthwash on salivary and plasma levels of nitrite measured after an oral intake of sodium nitrate (10mg/kg dissolved in water). In the control situation the salivary and plasma levels of nitrate and nitrite increased greatly after the nitrate load. Rinsing the mouth with the antibacterial mouthwash prior to the nitrate load had no effect on nitrate accumulation in saliva or plasma but abolished its conversion to nitrite in saliva and markedly attenuated the rise in plasma nitrite. We conclude that the acute increase in plasma nitrite seen after a nitrate load is critically dependent on nitrate reduction in the oral cavity by commensal bacteria. The removal of these bacteria with an antibacterial mouthwash will very likely attenuate the NO-dependent biological effects of dietary nitrate.

Diet and risk of ischemic heart disease in India.

BACKGROUND: Ischemic heart disease (IHD) is a leading cause of death in India. Dietary changes could reduce risk, but few studies have addressed the association between diet and IHD risk in India. OBJECTIVE: The goal was to address the association between diet and IHD risk among Indians in New Delhi (northern India) and Bangalore (southern India). DESIGN: We collected data from 350 cases of acute myocardial infarction and 700 controls matched on the basis of age, sex, and hospital as part of a hospital-based case-control study in 8 hospitals. Long-term dietary intake was assessed by using food-frequency questionnaires developed for New Delhi and Bangalore. We used conditional logistic regression to control for the matching factors and other predictors of risk. RESULTS: We observed a significant and dose-dependent inverse association between vegetable intake and IHD risk. The inverse association was stronger for green leafy vegetables; in multivariate analysis, persons consuming a median of 3.5 servings/wk had a 67% lower relative risk (RR: 0.33; 95% CI: 0.17, 0.64; P for trend = 0.0001) than did those consuming 0.5 servings/wk. Controlling for other dietary covariates did not alter the association. Cereal intake was also associated with a lower risk. Use of mustard oil, which is rich in alpha-linolenic acid, was associated with a lower risk than was use of sunflower oil [for use in cooking: RR: 0.49 (95% CI: 0.24, 0.99); for use in frying, RR: 0.29 (95% CI: 0.13, 0.64)]. CONCLUSION: Diets rich in vegetables and use of mustard oil could contribute to the lower risk of IHD among Indians.

Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease.

In a prospective, randomised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infarct prudent diet. After a first myocardial infarction, patients were randomly assigned to the experimental (n = 302) or control group (n = 303). Patients were seen again 8 weeks after randomisation, and each year for 5 years. The experimental group consumed significantly less lipids, saturated fat, cholesterol, and linoleic acid but more oleic and alpha-linolenic acids confirmed by measurements in plasma. Serum lipids, blood pressure, and body mass index remained similar in the 2 groups. In the experimental group, plasma levels of albumin, vitamin E, and vitamin C were increased, and granulocyte count decreased. After a mean follow up of 27 months, there were 16 cardiac deaths in the control and 3 in the experimental group; 17 non-fatal myocardial infarction in the control and 5 in the experimental groups: a risk ratio for these two main endpoints combined of 0.27 (95% CI 0.12-0.59, p = 0.001) after adjustment for prognostic variables. Overall mortality was 20 in the control, 8 in the experimental group, an adjusted risk ratio of 0.30 (95% CI 0.11-0.82, p = 0.02). An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death.

Red meat and colon cancer: should we become vegetarians, or can we make meat safer?

The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.

A legume-based hypocaloric diet reduces proinflammatory status and improves metabolic features in overweight/obese subjects.

BACKGROUND: The nutritional composition of the dietary intake could produce specific effects on metabolic variables and inflammatory marker concentrations. This study assessed the effects of two hypocaloric diets (legume-restricted- vs. legume-based diet) on metabolic and inflammatory changes, accompanying weight loss. METHODS: Thirty obese subjects (17 M/13F; BMI: 32.5 ± 4.5 kg/m(2); 36 ± 8 years) were randomly assigned to one of the following hypocaloric treatments (8 weeks): Calorie-restricted legume-free diet (Control: C-diet) or calorie-restricted legume-based diet (L-diet), prescribing 4 weekly different cooked-servings (160-235 g) of lentils, chickpeas, peas or beans. Body composition, blood pressure (BP), blood biochemical and inflammatory marker concentrations as well as dietary intake were measured at baseline and after the nutritional intervention. RESULTS: The L-diet achieved a greater body weight loss, when compared to the C-diet (-7.8 ± 2.9% vs. -5.3 ± 2.7%; p = 0.024). Total and LDL cholesterol levels and systolic BP were improved only when consuming the L-diet (p < 0.05). L-diet also resulted in a significant higher reduction in C-reactive protein (CRP) and complement C3 (C3) concentrations (p < 0.05), compared to baseline and C-diet values. Interestingly, the reduction in the concentrations of CRP and C3 remained significantly higher to L-diet group, after adjusting by weight loss (p < 0.05). In addition, the reduction (%) in CRP concentrations was positively associated with decreases (%) in systolic BP and total cholesterol concentration specifically in the L-diet group, independent from weight loss (p < 0.05). CONCLUSION: The consumption of legumes (4 servings/week) within a hypocaloric diet resulted in a specific reduction in proinflammatory markers, such as CRP and C3 and a clinically significant improvement of some metabolic features (lipid profile and BP) in overweight/ obese subjects, which were in some cases independent from weight loss.