Perceptions of flatulence from bean consumption among adults in 3 feeding studies Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.


Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. Objective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. Design: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. Results: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer–specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). Conclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer–specific mortality and a statistically significant reduced risk of recurrence. One of the studies included in the After Breast Cancer Pooling Project, the Women's Healthy Eating & Living Study, was registered at clinicaltrials.gov as NCT00003787.


Legumes: the most important dietary predictor of survival in older people of different ethnicities. To identify protective dietary predictors amongst long-lived elderly people (N= 785), the "Food Habits in Later Life "(FHILL) study was undertaken among five cohorts in Japan, Sweden, Greece and Australia. Between 1988 and 1991, baseline data on food intakes were collected. There were 785 participants aged 70 and over that were followed up to seven years. Based on an alternative Cox Proportional Hazard model adjusted to age at enrollment (in 5-year intervals), gender and smoking, the legume food group showed 7-8% reduction in mortality hazard ratio for every 20g increase in daily intake with or without controlling for ethnicity (RR 0.92; 95% CI 0.85-0.99 and RR 0.93; 95% CI 0.87-0.99, respectively). Other food groups were not found to be consistently significant in predicting survival amongst the FHILL cohorts.


A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome. OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.


Positive effects of soy isoflavone food on survival of breast cancer patients in China. AIM: Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis. METHODS: A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event). RESULTS: After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93). CONCLUSION: Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed.


Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial. BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.


Optimized LC/MS/MS analysis of morphine and codeine in poppy seed and evaluation of their fate during food processing as a basis for risk analysis. The opiate alkaloids present in poppy seed intended for use in food recently have raised major concerns. An efficient method for routine analysis of morphine and codeine using liquid chromatography in combination with tandem mass spectrometry on a triple quadrupole instrument (LC/MS/MS) was therefore developed. The optimal sample preparation was found to be cold extraction of 10 g of unground poppy seed with 30 mL of methanol containing 0.1% acetic acid for 60 min shaken at 250 rpm. The fate of morphine during food processing was also studied. All experiments led to a significant reduction of morphine and codeine. For poppy cake only 16-50% of the morphine was recovered, and in poppy buns at the highest temperature (220 degrees C) only 3% of the original morphine content was found. Ground poppy seed showed significantly lower recoveries than untreated seed. Morphine elimination during food processing has to be taken into account in the current discussion about its maximum limits in poppy seed.


Morphine levels in urine subsequent to poppy seed consumption. Urine morphine levels after the consumption of poppy seeds were measured in two separate trials. Maximum levels of approximately 18 micrograms/ml were found using RIA, EMIT-ST and GC methodologies. Positive immunoassay results were seen up to 60 h post-ingestion. Several different lots of seeds from various sources were assayed for morphine and found to range from 4-200 mg/kg. Differentiation of poppy seed eaters from opiate users was not possible via the identification of minor alkaloid constituents of poppy seeds. It is, however, possible to analyse opiate urines with respect to 6-O-acetylmorphine. Below the level of approximately 5 micrograms/ml total opiates, GC/MS is the method of choice for this analysis.


Poppy seed foods and opiate drug testing--where are we today? Seeds of the opium poppy plant are legally sold and widely consumed as food. Due to contamination during harvesting, the seeds can contain morphine and other opiate alkaloids. The objective of this study is to review the toxicology of poppy seed foods regarding influence on opiate drug tests. Computer-assisted literature review resulted in 95 identified references. Normal poppy seed consumption is generally regarded as safe. During food processing, the morphine content is considerably reduced (up to 90%). The possibility of false-positive opiate drug tests after poppy food ingestion exists. There are no unambiguous markers available to differentiate poppy food ingestion from heroin or pharmaceutical morphine use. This is also a problem in heroin-assisted maintenance programs. A basic requirement in such substitution programs is the patients' abstinence from any other drugs, including additional illicit heroin. Also a lack of forensic ingestion trials was detected that consider all factors influencing the morphine content in biologic matrices after consumption. Most studies did not control for the losses during food processing, so that the initial morphine dosage was overestimated. The large reduction of the morphine content during past years raises questions about the validity of the "poppy seed defence." However, a threshold of food use that would not lead to positive drug tests with certainty is currently unavailable. Research is needed to prove if the morphine contents in today's foods still pose the possibility of influencing drug tests. Future trials should consider processing-related morphine losses.


Sympathetic nervous system activity and resting metabolic rate in vegetarians. We examined the resting metabolic rate (RMR) and sympathetic nervous system activity of young male vegetarians (n = 17) and nonvegetarians (n = 40). Subjects were characterized for RMR by indirect calorimetry, norepinephrine kinetics from infusions of tritiated norepinephrine, energy and macronutrient intake from a 3-day food diary, and body composition by underwater weighing. Vegetarians reported a greater relative intake of carbohydrates (62% +/- 5% v 51% +/- 6%, P < .01) and a lower relative intake of fat (25% +/- 5% v 33% +/- 6%, P < .01) than nonvegetarians, whereas no differences were observed in daily energy intake, body composition, or maximal aerobic capacity (VO2max) between groups. Vegetarians exhibited an 11% higher absolute RMR (1.29 +/- 0.15 v 1.16 +/- 0.13 kcal/min, P < .01), a higher plasma concentration of norepinephrine (216 +/- 33 v 165 +/- 18 pg/mL, P < .01), and a greater norepinephrine appearance rate (0.50 +/- 0.08 v 0.36 +/- 0.09 micrograms/min, P < .01) than nonvegetarians. After statistically controlling for differences in relative amounts of carbohydrate and fat in the diet and for norepinephrine concentrations, no significant differences in adjusted RMR between vegetarians and nonvegetarians were noted. These results suggest that the higher RMR observed in young male vegetarians is partially mediated by differences in dietary macronutrient composition and increased sympathetic nervous system activity.


Four therapeutic diets: adherence and acceptability. Many health conditions are treated, at least in part, by therapeutic diets. Although the success of any intervention depends on its acceptability to the patient, the acceptability of therapeutic diets and factors that influence it have been largely neglected in nutrition research. A working definition of acceptability is proposed and an examination and summary are provided of available data on the acceptability of common diet regimens used for medical conditions. The goal is to suggest ways to improve the success of therapeutic diets. The proposed working definition of "acceptability" refers to the user's judgment of the advantages and disadvantages of a therapeutic diet-in relation to palatability, costs, and effects on eating behaviour and health-that influence the likelihood of adherence. Very low-calorie, reduced-fat omnivorous, vegetarian and vegan, and low-carbohydrate diets all achieve acceptability among the majority of users in studies of up to one year, in terms of attrition and adherence rates and results of questionnaires assessing eating behaviours. Longer studies are fewer, but they suggest that vegetarian, vegan, and reduced-fat diets are acceptable, as indicated by sustained changes in nutrient intake. Few studies of this length have been published for very low-calorie or low-carbohydrate diets. Long-term studies of adherence and acceptability of these and other therapeutic diets are warranted.


Do circulating leucocytes and lymphocyte subtypes increase in response to brief exercise in children with and without asthma? Background Exercise can alter health in children in both beneficial (eg reduced long‐term risk of atherosclerosis) and adverse (eg exercise‐induced asthma) ways. The mechanisms linking exercise and health are not known, but may rest, partly, on the ability of exercise to increase circulating immune cells. Little is known about the effect of brief exercise, more reflective of naturally occurring patterns of physical activity in children, on immune cell responses. Objectives To determine whether (1) a 6‐min bout of exercise can increase circulating inflammatory cells in healthy children and (2) the effect of brief exercise is greater in children with a history of asthma. Methods Children with mild–moderate persistent asthma and age‐matched controls (n = 14 in each group, mean age 13.6 years) performed a 6‐min bout of cycle‐ergometer exercise. Spirometry was performed at baseline and after exercise. Blood was drawn before and after exercise, leucocytes were quantified and key lymphocyte cell surface markers were assessed by flow cytometry. Results Exercise decreased spirometry only in children with asthma, but increased (p<0.001) most types of leucocytes (eg lymphocytes (controls, mean (SD) 1210 (208) cells/μl; children with asthma, 1119 (147) cells/μl) and eosinophils (controls, 104 (22) cells/μl; children with asthma, 88 (20) cells/μl)) to the same degree in both groups. Similarly, exercise increased T helper cells (controls, 248 (60) cells/μl; children with asthma, 232 (53) cells/μl) and most other lymphocyte subtypes tested. By contrast, although basophils (16 (5) cells/μl) and CD4+ CD45RO+ RA+ lymphocytes (19 (4) cells/μl) increased in controls, no increase in these cell types was found in children with asthma. Conclusions Exercise increased many circulating inflammatory cells in both children with asthma and controls. Circulating inflammatory cells did increase in children with asthma, but not to a greater degree than in controls. In fact, basophils and T helper lymphocyte memory transition cells did not increase in children with asthma, whereas they did increase in controls. Even brief exercise in children and adolescents robustly mobilises circulating immune cells.


Baker's yeast β-glucan supplementation increases monocytes and cytokines post-exercise: implications for infection risk? Strenuous aerobic exercise is known to weaken the immune system, and while many nutritional supplements have been proposed to boost post-exercise immunity, few are known to be effective. The purpose of the present study was to evaluate whether 10 d of supplementation with a defined source of baker's yeast β-glucan (BG, Wellmune WGP®) could minimise post-exercise immunosuppression. Recreationally active men and women (n 60) completed two 10 d trial conditions using a cross-over design with a 7 d washout period: placebo (rice flour) and baker's yeast BG (250 mg/d of β-1,3/1,6-glucans derived from Saccharomyces cerevisiae) before a bout of cycling (49 ± 6 min) in a hot (38 ± 2°C), humid (45 ± 2 % relative humidity) environment. Blood was collected at baseline (before supplement), pre- (PRE), post- (POST) and 2 h (2H) post-exercise. Total and subset monocyte concentration was measured by four-colour flow cytometry. Plasma cytokine levels and lipopolysaccharide (LPS)-stimulated cytokine production were measured using separate multiplex assays. Total (CD14⁺) and pro-inflammatory monocyte concentrations (CD14⁺/CD16⁺) were significantly greater at POST and 2H (P<0·05) with BG supplementation. BG supplementation boosted LPS-stimulated production of IL-2, IL-4, IL-5 and interferon-γ (IFN-γ) at PRE and POST (P<0·05). Plasma IL-4, IL-5 and IFN-γ concentrations were greater at 2H following BG supplementation. It appears that 10 d of supplementation with BG increased the potential of blood leucocytes for the production of IL-2, IL-4, IL-5 and IFN-γ. The key findings of the present study demonstrate that BG may have potential to alter immunity following a strenuous exercise session.


Effect of BETA 1, 3/1, 6 GLUCAN on Upper Respiratory Tract Infection Symptoms and Mood State in Marathon Athletes This was a placebo-controlled, double-blind study designed to evaluate the effect of a commercially available dietary supplement on upper-respiratory tract symptoms (URTI) and mood state. Seventy-five marathon runners (35 men, 40 women) ranging in age from 18-53 years, mean age: 36 ± 9, self-administered placebo, 250 mg or 500 mg of BETA 1,3/1,6 GLUCAN (commercial name Wellmune WGP®) daily during the 4 week post-marathon trial period following the 2007 Carlsbad Marathon. Subjects filled out the profile of mood state (POMS) assessment and a questionnaire style health log measuring health status and URTI symptoms after 2- and 4-week treatment administrations. During the course of the 4-week study, subjects in the treatment groups (250 mg and 500 mg BETA-GLUCAN per day) reported significantly fewer URTI symptoms, better overall health and decreased confusion, fatigue, tension, and anger, and increased vigor based on the POMS survey compared to placebo. BETA-GLUCAN may prevent URTI symptoms, and improve overall health and mood following a competitive marathon. Key points


Is infection risk linked to exercise workload? Anecdotal, survey, and epidemiological data suggest that endurance athletes are at an increased risk for upper respiratory tract infection (URTI) during periods of heavy training and the 1 - to 2-wk period after race events. The majority of athletes, however, who participate in endurance race events do not experience illness. Of greater public health importance is the consistent finding of a reduction in URTI risk reported by fitness enthusiasts and athletes who engage in regular exercise training while avoiding overreaching/overtraining. Although it naturally follows that infection risk should in some way be linked to acute and chronic exercise-induced alterations in immunity, attempts thus far to measure this association have been unsuccessful. There is growing evidence that for several hours subsequent to heavy exertion, several components of both the innate and adaptive immune system exhibit suppressed function. The immune response to heavy exertion is transient, however, and further research on the mechanisms underlying the immune response to prolonged and intensive endurance exercise is necessary before meaningful clinical applications can be drawn. Some attempts have been made through chemical or nutritional means (e.g., indomethacin, glutamine, vitamin C, and carbohydrate supplementation) to attenuate immune changes after intensive exercise to lower the risk of infection. No consistent relationship between nutritional interventions, exercise immunology, and alteration in URTI risk has yet been established.


Aerobic fitness is associated with lower proportions of senescent blood T-cells in man. Senescent T-cells accumulate with age, lowering the naïve T-cell repertoire and increasing host infection risk. As this response is likely to be influenced by certain lifestyle factors, we examined the association between aerobic fitness (VO(2max)) and the age-related accumulation of senescent T-cells. Blood lymphocytes from 102 healthy males (18-61 yr) were analyzed for KLRG1, CD57, CD28, CD45RA, CD45RO surface expression on CD4+ and CD8+ T-cells by 4-color flow cytometry. Advancing age (yr) was positively associated with the proportion (%) of senescent (KLRG1+/CD57+; KLRG1+/CD28-) CD4+ (B=1.00; 1.02) and CD8+ (B=0.429; 1.02) T-cells and inversely associated with naïve (KLRG1-/CD28+) CD4+ (B=-1.000) and CD8+ (B=-0.993) T-cells. VO(2max) was inversely associated with senescent CD4+ (B=-0.97) and CD8+ (B=-0.240). Strikingly, age was no longer associated with the proportions of senescent or naïve T-cells after adjusting for VO(2max), while the association between VO(2max) and these T-cell subsets withstood adjustment for age, BMI and percentage body fat. Ranking participants by age-adjusted VO(2max) revealed that the highest tertile had 17% more naïve CD8+ T-cells and 57% and 37% less senescent CD4+ and CD8+ T-cells, respectively, compared to the lowest tertile. VO(2max) was not associated with latent cytomegalovirus (CMV), Epstein-Barr virus (EBV) or herpes simplex virus-1 (HSV-1) infection, indicating that the moderating associations of VO(2max) were not confounded by persistent viral infections. This is the first study to show that aerobic fitness is associated with a lower age-related accumulation of senescent T-cells, highlighting the beneficial effects of maintaining a physically active lifestyle on the aging immune system. Copyright © 2011 Elsevier Inc. All rights reserved.


Short-term blackcurrant extract consumption modulates exercise-induced oxidative stress and lipopolysaccharide-stimulated inflammatory responses. Exercise-induced oxidative stress is instrumental in achieving the health benefits from regular exercise. Therefore, inappropriate use of fruit-derived products (commonly applied as prophalytic antioxidants) may counteract the positive effects of exercise. Using human exercise and cellular models we found that 1) blackcurrant supplementation suppressed exercise-induced oxidative stress, e.g., plasma carbonyls (0.9 +/- 0.1 vs. 0.6 +/- 0.1 nmol/mg protein, placebo vs. blackcurrant), and 2) preincubation of THP-1 cells with an anthocyanin-rich blackcurrant extract inhibited LPS-stimulated cytokine secretion [TNF-alpha (16,453 +/- 322 vs. 10,941 +/- 82 pg/ml, control vs. extract, P < 0.05) and IL-6 (476 +/- 14 vs. 326 +/- 32 pg/ml, control vs. extract, P < 0.05)] and NF-kappaB activation. In addition to its antioxidant and anti-inflammatory properties, we found that postexercise plasma collected after blackcurrant supplementation enhanced the differential temporal LPS-stimulated inflammatory response in THP-1 cells, resulting in an early suppression of TNF-alpha (1,741 +/- 32 vs. 1,312 +/- 42 pg/ml, placebo vs. blackcurrant, P < 0.05) and IL-6 (44 +/- 5 vs. 36 +/- 3 pg/ml, placebo vs. blackcurrant, P < 0.05) secretion after 24 h. Furthermore, by using an oxidative stress cell model, we found that preincubation of THP-1 cells with hydrogen peroxide (H(2)O(2)) prior to extract exposure caused a greater suppression of LPS-stimulated cytokine secretion after 24 h, which was not evident when cells were simultaneously incubated with H(2)O(2) and the extract. In summary, our findings support the concept that consumption of blackcurrant anthocyanins alleviate oxidative stress, and may, if given at the appropriate amount and time, complement the ability of exercise to enhance immune responsiveness to potential pathogens.


Effect of vitamin C supplements on physical performance. Vitamin C is an essential component of the diet and may reduce the adverse effects of exercise-induced reactive oxygen species, including muscle damage, immune dysfunction, and fatigue. However, reactive oxygen species may mediate beneficial training adaptations that vitamin C attenuates; indeed, from a total of 12 studies, vitamin C in doses >1 g·d(-1) impaired sport performance substantially in four of four studies, possibly by reducing mitochondrial biogenesis, while a further four studies demonstrated impairments that were not statistically significant. Doses of ∼0.2 g·d(-1) of vitamin C consumed through five or more servings of fruit and vegetables may be sufficient to reduce oxidative stress and provide other health benefits without impairing training adaptations.


Inhibition of xanthine oxidase by flavonoids. Various dietary flavonoids were evaluated in vitro for their inhibitory effect on xanthine oxidase, which has been implicated in oxidative injury to tissue by ischemia-reperfusion. Xanthine oxidase activity was determined by directly measuring uric acid formation by HPLC. The structure-activity relationship revealed that the planar flavones and flavonols with a 7-hydroxyl group such as chrysin, luteolin, kaempferol, quercetin, myricetin, and isorhamnetin inhibited xanthine oxidase activity at low concentrations (IC50 values from 0.40 to 5.02 microM) in a mixed-type mode, while the nonplanar flavonoids, isoflavones and anthocyanidins were less inhibitory. These results suggest that certain flavonoids might suppress in vivo the formation of active oxygen species and urate by xanthine oxidase.


Effect of lemon verbena supplementation on muscular damage markers, proinflammatory cytokines release and neutrophils' oxidative stress in chronic ... Intense exercise is directly related to muscular damage and oxidative stress due to excessive reactive oxygen species (ROS) in both, plasma and white blood cells. Nevertheless, exercise-derived ROS are essential to regulate cellular adaptation to exercise. Studies on antioxidant supplements have provided controversial results. The purpose of this study was to determine the effect of moderate antioxidant supplementation (lemon verbena extract) in healthy male volunteers that followed a 90-min running eccentric exercise protocol for 21 days. Antioxidant enzymes activities and oxidative stress markers were measured in neutrophils. Besides, inflammatory cytokines and muscular damage were determined in whole blood and serum samples, respectively. Intense running exercise for 21 days induced antioxidant response in neutrophils of trained male through the increase of the antioxidant enzymes catalase, glutathione peroxidase and glutathione reductase. Supplementation with moderate levels of an antioxidant lemon verbena extract did not block this cellular adaptive response and also reduced exercise-induced oxidative damage of proteins and lipids in neutrophils and decreased myeloperoxidase activity. Moreover, lemon verbena supplementation maintained or decreased the level of serum transaminases activity indicating a protection of muscular tissue. Exercise induced a decrease of interleukin-6 and interleukin-1β levels after 21 days measured in basal conditions, which was not inhibited by antioxidant supplementation. Therefore, moderate antioxidant supplementation with lemon verbena extract protects neutrophils against oxidative damage, decreases the signs of muscular damage in chronic running exercise without blocking the cellular adaptation to exercise.


Antioxidants prevent health-promoting effects of physical exercise in humans Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases mitochondrial formation of presumably harmful reactive oxygen species (ROS). Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unknown. We evaluated the effects of a combination of vitamin C (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as measured by glucose infusion rates (GIR) during a hyperinsulinemic, euglycemic clamp in previously untrained (n = 19) and pretrained (n = 20) healthy young men. Before and after a 4 week intervention of physical exercise, GIR was determined, and muscle biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential influences of vitamins on exercise effects. Exercise increased parameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisome-proliferator-activated receptor gamma (PPARγ), and PPARγ coactivators PGC1α and PGC1β only in the absence of antioxidants (P < 0.001 for all). Molecular mediators of endogenous ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase) were also induced by exercise, and this effect too was blocked by antioxidant supplementation. Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.


Can nutrition limit exercise-induced immunodepression? Prolonged exercise and heavy training are associated with depressed immune cell function. To maintain immune function, athletes should eat a well-balanced diet sufficient to meet their energy, carbohydrate, protein, and micronutrient requirements. Consuming carbohydrate during prolonged strenuous exercise attenuates rises in stress hormones and appears to limit the degree of exercise-induced immune depression. Recent evidence suggests that antioxidant vitamin supplementation may also reduce exercise stress and impairment of leukocyte functions. Further research is needed to evaluate the effects of other antioxidants and dietary immunostimulants such as probiotics and echinacea on exercise-induced immune impairment.


Free radicals in skin and muscle: damaging agents or signals for adaptation? Much of the current literature regarding the biological effects of antioxidant nutrients has concentrated on their potential role in inhibiting or preventing tissue damage induced by free radical species produced during metabolism. Recent findings indicate that antioxidants may also have more subtle roles, regulating changes in gene expression induced by oxidizing free radical species. There is increasing evidence that free radicals act as signals for cell adaptation in a variety of cell types and the nature of the mechanisms by which free radical species influence gene expression is the subject of much current research. Processes such as these may be particularly important in tissues regularly exposed to varying amounts of oxidative stress as part of their normal physiological functions. Examples of such tissues include skin exposed to u.v. light and skeletal muscle subjected to repeated bouts of exercise.


The effect of acute pre-exercise dark chocolate consumption on plasma antioxidant status, oxidative stress and immunoendocrine responses to prolong... PURPOSE: Acute antioxidant supplementation may modulate oxidative stress and some immune perturbations that typically occur following prolonged exercise. The aims of the present study were to examine the effects of acutely consuming dark chocolate (high polyphenol content) on plasma antioxidant capacity, markers of oxidative stress and immunoendocrine responses to prolonged exercise. METHODS: Fourteen healthy men cycled for 2.5 h at ~60% maximal oxygen uptake 2 h after consuming 100 g dark chocolate (DC), an isomacronutrient control bar (CC) or neither (BL) in a randomised-counterbalanced design. RESULTS: DC enhanced pre-exercise antioxidant status (P = 0.003) and reduced by trend (P = 0.088) 1 h post-exercise plasma free [F₂-isoprostane] compared with CC (also, [F₂-isoprostane] increased post-exercise in CC and BL but not DC trials). Plasma insulin concentration was significantly higher pre-exercise (P = 0.012) and 1 h post-exercise (P = 0.026) in the DC compared with the CC trial. There was a better maintenance of plasma glucose concentration on the DC trial (2-way ANOVA trial × time interaction P = 0.001), which decreased post-exercise in all trials but was significantly higher 1 h post-exercise (P = 0.039) in the DC trial. There were no between trial differences in the temporal responses (trial × time interactions all P > 0.05) of hypothalamic-pituitary-adrenal axis stress hormones, plasma interleukin-6, the magnitude of leukocytosis and neutrophilia and changes in neutrophil function. CONCLUSION: Acute DC consumption may affect insulin, glucose, antioxidant status and oxidative stress responses, but has minimal effects on immunoendocrine responses, to prolonged exercise.


Flavonoid Glycosides Isolated from Unique Legume Plant Extracts as Novel Inhibitors of Xanthine Oxidase Legumes and the polyphenolic compounds present in them have gained a lot of interest due to their beneficial health implications. Dietary polyphenolic compounds, especially flavonoids, exert antioxidant properties and are potent inhibitors of xanthine oxidase (XO) activity. XO is the main contributor of free radicals during exercise but it is also involved in pathogenesis of several diseases such as vascular disorders, cancer and gout. In order to discover new natural, dietary XO inhibitors, some polyphenolic fractions and pure compounds isolated from two legume plant extracts were tested for their effects on XO activity. The fractions isolated from both Vicia faba and Lotus edulis plant extracts were potent inhibitors of XO with IC50 values range from 40–135 µg/mL and 55–260 µg/mL, respectively. All the pure polyphenolic compounds inhibited XO and their Ki values ranged from 13–767 µM. Ten of the compounds followed the non competitive inhibitory model whereas one of them was a competitive inhibitor. These findings indicate that flavonoid isolates from legume plant extracts are novel, natural XO inhibitors. Their mode of action is under investigation in order to examine their potential in drug design for diseases related to overwhelming XO action.


Calcified neurocysticercosis among patients with primary headache. BACKGROUND: Anecdotal reports and a single case-control epidemiological survey have suggested an association between the helminthic disease neurocysticercosis and primary headache. The present study was undertaken to determine whether neurocysticercosis is more common among patients with primary headaches than in other neurological disorders. METHODS: We determined the prevalence of neurocysticercosis in a cohort of patients with primary headache who were seen at our institution over a 20-year period. We used as controls all people from the same cohort with four major different categories of neurological disorders, including cerebrovascular disease, degenerative disorders of the CNS, head trauma, and primary brain tumors. We evaluated differences in the prevalence of neurocysticercosis between patients and controls. RESULTS: Forty-eight of 1017 patients with primary headache and 31 of 1687 controls had neurocysticercosis (4.7% vs 1.8%, p < 0.0001). Calcified parenchymal brain cysticerci were more frequent among patients with primary headache than in those with cerebrovascular disease (4.7% vs 1%, p < 0.001), degenerative disorders of the CNS (4.7% vs 2.4%, p < 0.05), and head trauma (4.7% vs 2.3%, p < 0.05). There were no significant differences, however, for the subset of controls with primary brain tumors (4.7% vs 3.5%), a condition that has also been associated with neurocysticercosis. CONCLUSIONS: There is a relationship between calcified neurocysticercosis and primary headache disorders. It is possible that periodic remodeling of cysticercotic calcifications, with liberation of antigens to the brain parenchyma, contributes to the occurrence of headache in these patients.


Cognitive Changes and Quality of Life in Neurocysticercosis: A Longitudinal Study Background Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. Methodology/Principal Findings The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC. Conclusions/Significance Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. Author Summary Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. Cognitive changes have been frequently reported with this disease but have not been well studied. Our study team recruited a group of new onset NCC cases and a matched set of healthy neighborhood controls and new onset epilepsy controls in Lima, Peru for this study. A neuropsychological battery was administered at baseline and at 6 months to all groups. Brain MRI studies were also obtained on NCC cases at baseline and at 6 months. Newly diagnosed patients with NCC had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. This study is the first to assess cognitive status and quality of life longitudinally in patients with NCC and provides new data on an important clinical morbidity outcome.


Freezing of infested pork muscle kills cysticerci. A method for culturing cysticerci that allows successful evagination and growth of scolexes from metacestodes of Taenia solium was used to study the survival of cysticerci subjected to low temperatures. Refrigeration of pork muscle infested with cysticerci at temperatures above 0 degrees C did not affect the parasites' survival in culture. Conversely, freezing of meat prevented survival of cysts. A practical procedure to kill cysticerci is the storage of pork muscle for four days at -5 degrees C, three days at -15 degrees C, or one day at -24 degrees C. These simple measures would help prevent the most frequent parasitosis of man's central nervous system.


Neurocysticercosis and oncogenesis. Recent studies suggest that neurocysticercosis may be a risk factor for human cancer. Pathogenetic mechanisms explaining possible oncogenic effects of cysticerci include the following: (a) parasite-induced modulation of the host immune response that may be associated with loss of regulatory mechanisms implicated in the immunological surveillance against cancer; (b) transfer of genetic material from the parasite to the host, causing DNA damage and malignant transformation of host cells, and (c) chronic inflammation with liberation of nitric oxide and inhibition of tumor suppressor genes. Further research is needed to confirm the potential role of cysticercosis in the development of cancer. These studies should determine the presence of cysticercotic factors responsible for the transfer of genetic material and potential mutations in the tumor suppressor genes in proliferating astrocytes surrounding cysticercotic lesions. Additionally, the complex interaction between the immune state of the host with variable cytokine release and the presence of inflammatory cells releasing nitric oxide that cause DNA damage and impair tumor suppressive mechanisms needs to be investigated.


Natural mood foods: The actions of polyphenols against psychiatric and cognitive disorders Objectives Polyphenols, natural compounds found in plant-based foods, possess special properties that can battle oxidative stress and stimulate the activation of molecules that aid in synaptic plasticity, a process that underlies cognitive function. Unlike many traditional treatments, polyphenols affect a broad range of mechanisms in the brain that can assist in the maintenance of cognitive and mental health, as well as the recovery from neurodegenerative diseases. Examining the molecular basis underlying the link between food intake and brain function has presented the exciting possibility of using diet as a viable method to battle cognitive and psychiatric disorders. Methods We will discuss the molecular systems that link polyphenols, the gut, and the brain, as well as introduce published human and animal studies demonstrating the effects of polyphenol consumption on brain plasticity and cognition. Results By influencing cellular energy metabolism and modulating the signaling pathways of molecules involved with brain plasticity, dietary factors – formerly recognized for just their effects on bodily systems – have emerged as affecters of the brain. Conclusion Thus, the consumption of diets enriched with polyphenols may present the potential of dietary manipulation as a non-invasive, natural, and inexpensive therapeutic means to support a healthy brain.


The Impact of Neurocysticercosis in California: A Review of Hospitalized Cases To assess the burden of neurocysticercosis (NCC) in California we examined statewide hospital discharge data for 2009. There were 304 cases hospitalized with NCC identified (incidence = 0.8 per 100,000). Cases were mostly Latino (84.9%), slightly more likely to be male than female (men 57.6%, women 42.4%) with an average age of 43.5 years. A majority of cases were hospitalized in Southern California (72.1%) and many were hospitalized in Los Angeles County (44.7%). Men were more likely than women to have severe disease including hydrocephalus (29.7% vs. 18.6%, p = 0.027), resulting in longer hospitalizations (>4 days, 48.0% vs. 32.6%, p = 0.007) that were more costly (charge>$40 thousand men = 46.9% vs. woman = 4.1%, p = 0.026). Six deaths were recorded (2.0%). The total of NCC-related hospital charges exceeded $17 million; estimated hospital costs exceeded $5 million. Neurocysticercosis causes appreciable disease and exacts a considerable economic burden in California. Author Summary Neurocysticercosis (NCC) is considered one of the major neglected infections of poverty in the United States, with mortality studies indicating that California bears the highest burden of this disease. Although NCC is a reportable disease in California, studies indicate that this disease goes largely under-reported, contributing to the lack of information about the disease distribution and burden. In this manuscript, we reviewed the distribution of NCC hospitalizations in California, demographics of those hospitalized and total hospital-related charges for 2009. This study revealed that a majority of persons hospitalized with NCC in California receive their medical service in Southern California hospitals, primarily in the County of Los Angeles. As compared to women hospitalized for this disease, men had a longer and more costly hospitalization with more severe symptoms such as hydrocephalus, a diagnosis suggestive of extraparenchymal infection. The reasons for this difference in NCC severity by gender are not clear, but do not appear to be due to delay in seeking medical care or a language barrier. The intensity of hospital care needed to manage these cases and the sizable NCC hospitalization charge underscores the considerable economic burden this disease presents in California.


Neurocysticercosis in pregnancy: not just another headache. Infection with pork tapeworm, or Taenia solium, affects approximately 50 million people worldwide. The most important and potentially devastating form of the infestation, neurocysticercosis, occurs when the parasite invades the central nervous system. There has been a significant increase in the number of cases in the United States due to immigration from endemic areas. This case study of a pregnant woman in the 35th week of gestation exemplifies the serious consequences of this infection in pregnancy, and discusses an evidence-based approach to the diagnosis, treatment and eradication of this preventable disease. © 2012 AWHONN.


Is dementia reversible in patients with neurocysticercosis? Methods: Ninety consecutive patients with untreated NCC underwent a cognitive assessment (Mini-mental State Examination, Neurobehavioral Cognitive Status Examination, and IQCODE) and were classified as having or not having dementia according to DSM-IV criteria. Imaging and cerebrospinal fluid examination data were recorded. The cognitive measures were repeated six months after treatment with albendazole and steroids. Results: At the initial evaluation 15.5% (n = 14) of the patients were classified as having dementia. Dementia was associated with older age, lower education level, increased number of parasitic lesions in the brain (mostly in the frontal, temporal, and parietal lobes). After six months, 21.5% of the patients from the dementia group continued to have a full dementia disorder and 78.5% no longer fulfilled the DSM-IV criteria for dementia, although some of these patients still showed mild cognitive decline. Conclusions: The results of this study suggest that dementia occurs frequently in patients with untreated NCC, and it is reversible in most cases.


Neurocysticercosis: the enigmatic disease. Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) caused by the metacestode larval form of the parasite Taenia sp. Many factors can contribute to the endemic nature of cysticercosis. The inflammatory process that occurs in the tissue surrounding the parasite and/or distal from it can result from several associated mechanisms and may be disproportionate with the number of cysts. This discrepancy may lead to difficulty with the proper diagnosis in people from low endemic regions or regions that lack laboratory resources. In the CNS, the cysticerci have two basic forms, isolated cysts (Cysticercus cellulosae=CC) and racemose cysts (Cysticercus racemosus=CR), and may be meningeal, parenchymal, or ventricular or have a mixed location. The clinical manifestations are based on two fundamental syndromes that may occur in isolation or be associated: epilepsy and intracranial hypertension. They may be asymptomatic, symptomatic or fatal; have an acute, sub-acute or chronic picture; or may be in remission or exacerbated. The cerebrospinal fluid (CSF) may be normal, even in patients with viable cysticerci, until the patients begin to exhibit the classical syndrome of NCC in the CSF, or show changes in one or more routine analysed parameters. Computed tomography (CT) and magnetic resonance imaging (MRI) have allowed non-invasive diagnoses, but can lead to false negatives. Treatment is a highly controversial issue and is characterised by individualised therapy sessions. Two drugs are commonly used, praziquantel (PZQ) and albendazole (ABZ). The choice of anti-inflammatory drugs includes steroids and dextrochlorpheniramine (DCP). Hydrocephalus is a common secondary effect of NCC. Surgical cases of hydrocephalus must be submitted to ventricle-peritoneal shunt (VPS) immediately before cysticidal treatment, and surgical extirpation of the cyst may lead to an absence of the surrounding inflammatory process. The progression of NCC may be simple or complicated, have remission with or without treatment and may exhibit symptoms that can disappear for long periods of time or persist until death. Unknown, neglected and controversial aspects of NCC, such as the impaired fourth ventricle syndrome, the presence of chronic brain oedema and psychic complaints, in addition to the lack of detectable glucose in the CSF and re-infection are discussed.


Clinical manifestations, diagnosis, and treatment of neurocysticercosis. Neurocysticercosis (NCC) is the most frequent parasitic disease of the human brain. Modern imaging studies, CT and MRI, have defined the diagnosis and characterization of the disease. Through these studies the therapeutic approach for each case may be individualized with the aid of antihelmintics, steroids, symptomatic medicines, or surgery. The use of one or various therapeutic measures largely depends on the peculiar combination of number, location, and biological stage of lesions as well as the degree of inflammatory response to the parasites. Although there is not a typical clinical picture of NCC, epilepsy is the most frequent manifestation of parenchymal NCC, whereas hydrocephalus is the most frequent manifestation of meningeal NCC. Eradication of cysticercosis is an attainable goal by public education and sanitary improvement in endemic areas.


Cognitive impairment and dementia in neurocysticercosis: a cross-sectional controlled study. OBJECTIVES: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, affecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of patients with NCYST in comparison with cognitively healthy controls (HC) and patients with cryptogenic epilepsy (CE). METHODS: Forty treatment-naive patients with NCYST, aged 39.25 +/- 10.50 years and fulfilling absolute criteria for definitive active NCYST on MRI, were submitted to a comprehensive cognitive and functional evaluation and were compared with 49 HC and 28 patients with CE of similar age, educational level, and seizure frequency. RESULTS: Patients with NCYST displayed significant impairment in executive functions, verbal and nonverbal memory, constructive praxis, and verbal fluency when compared with HC (p < 0.05). Dementia was diagnosed in 12.5% patients with NCYST according to DSM-IV criteria. When compared with patients with CE, patients with NCYST presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatial orientation. No correlation emerged between cognitive scores and number, localization, or type of NCYST lesions on MRI. CONCLUSIONS: Cognitive impairment was ubiquitous in this sample of patients with active neurocysticercosis (NCYST). Antiepileptic drug use and seizure frequency could not account for these features. Dementia was present in a significant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in world public health.


Aneurysm and Neurocysticercosis: Casual or Causal Relationship? Case Report and Review of the Literature Four cases of suggestive inflammatory aneurysms in patients with neurocysticercosis have been described. We report a case of a 49-year-old woman who presented with subarachnoid haemorrhage from a right middle cerebral artery bifurcation aneurysm and had a casual relationship with neurocysticercosis. At surgery, a viable cysticercus without signs of inflammation or thickened leptomeninges was found in the distal position of the aneurysm. Postoperatively, the patient received albendazole and dextrochlorpheniramine. In the subsequent three years, the patient was asymptomatic and took drugs to prevent convulsion and arterial hypertension. The relationship between NCC and the presence of cerebral aneurysm is discussed.


Psychiatric manifestations of neurocysticercosis: a study of 38 patients from a neurology clinic in Brazil. OBJECTIVE: To determine the frequency and features of psychiatric morbidity in a cross section of 38 outpatients with neurocysticercosis. METHODS: Diagnosis of neurocysticercosis was established by CT, MRI, and CSF analysis. Psychiatric diagnoses were made by using the present state examination and the schedule for affective disorders and schizophrenia-lifetime version; cognitive state was assessed by mini mental state examination and Strub and Black's mental status examination. RESULTS: Signs of psychiatric disease and cognitive decline were found in 65.8 and 87.5% of the cases respectively. Depression was the most frequent psychiatric diagnosis (52.6%) and 14.2% of the patients were psychotic. Active disease and intracranial hypertension were associated with higher psychiatric morbidity, and previous history of mood disorders was strongly related to current depression. Other variables, such as number and type of brain lesions, severity of neuropsychological deficits, epilepsy, and use of steroids did not correlate with mental disturbances in this sample. CONCLUSIONS: Psychiatric abnormalities, particularly depression syndromes, are frequent in patients with neurocysticercosis. Although regarded as a rare cause of dementia, mild cognitive impairment may be a much more prevalent neuropsychological feature of patients with neurocysticercosis. The extent to which organic mechanisms related to brain lesions may underlie the mental changes is yet unclear, although the similar sex distribution of patients with and without depression, as well as the above mentioned correlations, provide further evidence of the part played by organic factors in the cause of these syndromes.


A review of cases of human cysticercosis in Canada. OBJECTIVE: Review of human cysticercosis in Canada, to estimate the magnitude of the disease and to describe the pattern of disease expression in this country. METHODS: MEDLINE and manual search of case reports and case series of patients with cysticercosis diagnosed in Canada. ed data included year of diagnosis, citizenship status, clinical manifestations, and form of cysticercosis. FINDINGS: A total of 21 articles reporting 60 patients were found. Forty (67%) of these patients were diagnosed in the past two decades. Most cases came from Ontario (n=43) and Quebec (n=14). Immigrants accounted for 96% of the 28 cases in whom citizenship information was available. Neurocysticercosis was observed in 55 patients, and isolated compromise of striated muscles in the remaining five. Seizures was the primary or sole manifestation of the disease in 72% of patients, and most of them had parenchymal brain cysticerci (either viable cysts or calcifications). Two of seven patients were positive for Taenia eggs. In no case were household contacts of the patients investigated for taeniasis. CONCLUSIONS: An increasing number of patients with cysticercosis have been reported from Canada in the past two decades, suggesting that the prevalence of this parasitic disease may be on the rise. While most cases occur in immigrants, it is possible that at least some of these patients had acquired the disease in Canada.


11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.


Beef in an Optimal Lean Diet study: effects on lipids, lipoproteins, and apolipoproteins Background: A Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol. To our knowledge, no studies have evaluated a low–saturated fatty acid (SFA) (<7% calories) diet that contains lean beef. Objective: We studied the effect on LDL cholesterol of cholesterol-lowering diets with varying amounts of lean beef [ie, Dietary Approaches to Stop Hypertension (DASH): 28 g beef/d; Beef in an Optimal Lean Diet (BOLD): 113 g beef/d; and Beef in an Optimal Lean Diet plus additional protein (BOLD+): 153 g beef/d] compared with that of a healthy American diet (HAD). Design: Thirty-six hypercholesterolemic participants (with LDL-cholesterol concentrations >2.8 mmol/L) were randomly assigned to consume each of the 4 diets (HAD: 33% total fat, 12% SFA, 17% protein, and 20 g beef/d), DASH (27% total fat, 6% SFA, 18% protein, and 28 g beef/d), BOLD (28% total fat, 6% SFA, 19% protein, and 113 g beef/d), and BOLD+ (28% total fat, 6% SFA, 27% protein, and 153 g beef/d) for 5 wk. Results: There was a decrease in total cholesterol (TC) and LDL-cholesterol concentrations (P < 0.05) after consumption of the DASH (−0.49 ± 0.11 and −0.37 ± 0.09 mmol/L, respectively), BOLD (−0.48 ± 0.10 and −0.35 ± 0.9 mmol/L, respectively), and BOLD+ (−0.50 ± 0.10 and −0.345 ± 0.09 mmol/L, respectively) diets compared with after consumption of the HAD (−0.22 ± 0.10 and −0.14 ± 0.10 mmol/L, respectively). Apolipoprotein A-I, C-III, and C-III bound to apolipoprotein A1 particles decreased after BOLD and BOLD+ diets compared with after the HAD, and there was a greater decrease in apolipoprotein B after consumption of the BOLD+ diet than after consumption of the HAD (P < 0.05 for both). LDL cholesterol and TC decreased after consumption of the DASH, BOLD, and BOLD+ diets when the baseline C-reactive protein (CRP) concentration was <1 mg/L; LDL cholesterol and TC decreased when baseline CRP concentration was >1 mg/L with the BOLD and BOLD+ diets. Conclusions: Low-SFA, heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease (CVD) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern. These results, in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets, which were greater with the BOLD+ diet, provide support for including lean beef in a heart-healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT00937898.


Cheese intake in large amounts lowers LDL-cholesterol concentrations compared with butter intake of equal fat content. BACKGROUND: Despite its high content of saturated fatty acids, cheese does not seem to increase plasma total and LDL-cholesterol concentrations when compared with an equivalent intake of fat from butter. This effect may be due to the high calcium content of cheese, which results in a higher excretion of fecal fat. OBJECTIVES: The objective was to compare the effects of diets of equal fat content rich in either hard cheese or butter or a habitual diet on blood pressure and fasting serum blood lipids, C-reactive protein, glucose, and insulin. We also examined whether fecal fat excretion differs with the consumption of cheese or butter. DESIGN: The study was a randomized dietary intervention consisting of two 6-wk crossover periods and a 14-d run-in period during which the subjects consumed their habitual diet. The study included 49 men and women who replaced part of their habitual dietary fat intake with 13% of energy from cheese or butter. RESULTS: After 6 wk, the cheese intervention resulted in lower serum total, LDL-, and HDL-cholesterol concentrations and higher glucose concentrations than did the butter intervention. Cheese intake did not increase serum total or LDL-cholesterol concentrations compared with the run-in period, during which total fat and saturated fat intakes were lower. Fecal fat excretion did not differ between the cheese and butter periods. CONCLUSION: Cheese lowers LDL cholesterol when compared with butter intake of equal fat content and does not increase LDL cholesterol compared with a habitual diet. This trial is registered at clinicaltrials.gov as NCT01140165.


Potential risks resulting from fruit/vegetable-drug interactions: effects on drug-metabolizing enzymes and drug transporters. It has been well established that complex mixtures of phytochemicals in fruits and vegetables can be beneficial for human health. Moreover, it is becoming increasingly apparent that phytochemicals can influence the pharmacological activity of drugs by modifying their absorption characteristics through interactions with drug transporters as well as drug-metabolizing enzyme systems. Such effects are more likely to occur in the intestine and liver, where high concentrations of phytochemicals may occur. Alterations in cytochrome P450 and other enzyme activities may influence the fate of drugs subject to extensive first-pass metabolism. Although numerous studies of nutrient-drug interactions have been published and systematic reviews and meta-analyses of these studies are available, no generalizations on the effect of nutrient-drug interactions on drug bioavailability are currently available. Several publications have highlighted the unintended consequences of the combined use of nutrients and drugs. Many phytochemicals have been shown to have pharmacokinetic interactions with drugs. The present review is limited to commonly consumed fruits and vegetables with significant beneficial effects as nutrients and components in folk medicine. Here, we discuss the phytochemistry and pharmacokinetic interactions of the following fruit and vegetables: grapefruit, orange, tangerine, grapes, cranberry, pomegranate, mango, guava, black raspberry, black mulberry, apple, broccoli, cauliflower, watercress, spinach, tomato, carrot, and avocado. We conclude that our knowledge of the potential risk of nutrient-drug interactions is still limited. Therefore, efforts to elucidate potential risks resulting from food-drug interactions should be intensified in order to prevent undesired and harmful clinical consequences. © 2011 Institute of Food Technologists®


Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study In vitro and in vivo studies have shown that cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of oestrogens. There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma oestrogen concentrations. Since it is well established that oestrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer. We investigated the association of grapefruit intake with breast cancer risk in the Hawaii–Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50 000 postmenopausal women from five racial/ethnic groups. A total of 1657 incident breast cancer cases were available for analysis. Grapefruit intake was significantly associated with an increased risk of breast cancer (relative risk=1.30, 95% confidence interval 1.06–1.58) for subjects in the highest category of intake, that is, one-quarter grapefruit or more per day, compared to non-consumers (Ptrend=0.015). An increased risk of similar magnitude was seen in users of oestrogen therapy, users of oestrogen+progestin therapy, and among never users of hormone therapy. Grapefruit intake may increase the risk of breast cancer among postmenopausal women.


Effects of grapefruit, grapefruit juice and water preloads on energy balance, weight loss, body composition, and cardiometabolic risk in free-living obese adults Background Reducing dietary energy density has proven to be an effective strategy to reduce energy intakes and promote weight control. This effect appears most robust when a low energy dense preload is consumed before meals. Yet, much discussion continues regarding the optimal form of a preload. The purpose of the present study was to compare effects of a solid (grapefruit), liquid (grapefruit juice) and water preload consumed prior to breakfast, lunch and dinner in the context of caloric restriction. Methods Eighty-five obese adults (BMI 30-39.9) were randomly assigned to (127 g) grapefruit (GF), grapefruit juice (GFJ) or water preload for 12 weeks after completing a 2-week caloric restriction phase. Preloads were matched for weight, calories, water content, and energy density. Weekly measures included blood pressure, weight, anthropometry and 24-hour dietary intakes. Resting energy expenditure, body composition, physical performance and cardiometabolic risk biomarkers were assessed. Results The total amount (grams) of food consumed did not change over time. Yet, after preloads were combined with caloric restriction, average dietary energy density and total energy intakes decreased by 20-29% from baseline values. Subjects experienced 7.1% weight loss overall, with significant decreases in percentage body, trunk, android and gynoid fat, as well as waist circumferences (-4.5 cm). However, differences were not statistically significant among groups. Nevertheless, the amount and direction of change in serum HDL-cholesterol levels in GF (+6.2%) and GFJ (+8.2%) preload groups was significantly greater than water preload group (-3.7%). Conclusions These data indicate that incorporating consumption of a low energy dense dietary preload in a caloric restricted diet is a highly effective weight loss strategy. But, the form of the preload did not have differential effects on energy balance, weight loss or body composition. It is notable that subjects in GF and GFJ preload groups experienced significantly greater benefits in lipid profiles. Trial registration ClinicalTrials.gov NCT00581074


Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. 1. The effects of grapefruit juice and naringenin on the activity of the human cytochrome P450 isoform CYP1A2 were evaluated using caffeine as a probe substrate. 2. In vitro naringin was a potent competitive inhibitor of caffeine 3-demethylation by human liver microsomes (Ki = 7-29 microM). 3. In vivo grapefruit juice (1.2 l day-1 containing 0.5 g l-1 naringin, the glycone form of naringenin) decreased the oral clearance of caffeine by 23% (95% CI: 7%-30%) and prolonged its half-life by 31% (95% CI: 20%-44%) (n = 12). 4. We conclude that grapefruit juice and naringenin inhibit CYP1A2 activity in man. However, the small effect on caffeine clearance in vivo suggests that in general the ingestion of grapefruit juice should not cause clinically significant inhibition of the metabolism of other drugs that are substrates of CYPIA2.


Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans. The contents of the bioactive compounds in red and blond grapefruits and their influence on humans suffering from hypertriglyceridemia were studied. It was found that red grapefruit has a higher content of bioactive compounds and a higher antioxidant potential than blond grapefruit, determined by oxygen radical scavenging capacity, 1,1-diphenyl-2-picrylhydrazyl, carotenoid bleaching, and Folin-Ciocalteu assays. Fifty-seven hyperlipidemic patients, ages 39-72 years, after coronary bypass surgery, recruited from the Institute's pool of volunteers, were randomly divided into three equal in number (19) groups: two experimental (red and blond groups) and one control group (CG). During 30 consecutive days of the investigation the diets of the patients of the red and blond dietary groups were daily supplemented with one equal in weight fresh red or blond grapefruit, respectively. Before and after this trial, serum lipid levels of all fractions and serum antioxidant activity were determined. It was found that serum lipid levels in patients of the red and blond groups versus the CG after treatment were decreased: (a) total cholesterol, 6.69 versus 7.92 mmol/L, 15.5%, and 7.32 versus 7.92 mmol/L, 7.6%, respectively; (b) low-density lipoprotein cholesterol, 5.01 versus 6.29 mmol/L, 20.3%, and 5.62 versus 6.29 mmol/L, 10.7%, respectively; (c) triglycerides, 1.69 versus 2.32 mmol/L, 17.2%, and 2.19 versus 2.32 mmol/L, 5.6%, respectively. No changes in the serum lipid levels in patients of the CG were found. In conclusion, fresh red grapefruit contains higher quantities of bioactive compounds and has significantly higher antioxidant potential than blond grapefruit. Diet supplemented with fresh red grapefruit positively influences serum lipid levels of all fractions, especially serum triglycerides and also serum antioxidant activity. The addition of fresh red grapefruit to generally accepted diets could be beneficial for hyperlipidemic, especially hypertriglyceridemic, patients suffering from coronary atherosclerosis.


Management of grapefruit-drug interactions. Grapefruit is a healthy addition to a well-balanced diet. However, the fruit has been shown to affect the metabolism of many medications, increasing the risk of toxicity and adverse effects. Characteristics of oral medications that may interact with grapefruit include extensive metabolism through the intestinal cytochrome P450 3A4 system, low bioavailability, and a narrow therapeutic index. Prominent medications known to interact with grapefruit include statins, antiarrhythmic agents, immunosuppressive agents, and calcium channel blockers. There are equally effective alternatives to these drug classes that do not have the potential to interact with grapefruit. These alternative drugs may be substituted if a patient experiences or is at risk of a grapefruit-drug interaction. Patients also may choose to exclude grapefruit from their diets and consume other fruits, including other types of citrus, to avoid an interaction.


Prospective study of the association between grapefruit intake and risk of breast cancer in the European Prospective Investigation into Cancer and ... Grapefruit inhibits cytochrome P450 3A4 and may affect estrogen metabolism. In the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the relationships of grapefruit intake with risk of breast cancer and with serum sex hormone levels. 114,504 women with information on dietary intake of grapefruit and on reproductive and lifestyle risk factors were followed for a median 9.5 years and 3,747 incident breast cancers were identified. Fifty-nine percent of women reported eating grapefruit, 4% ate > or = 60 g/day. Cox proportional hazard models were used to estimate the hazard ratio (HR) for breast cancer according to grapefruit intake, adjusting for study centre, reproductive factors, body mass index, energy intake, and alcohol intake. Grapefruit intake was not related to the risk of breast cancer: compared with women who ate no grapefruit, women with the highest intake of > or =60 g/day had a HR of 0.93 (95% CI 0.77-1.13), p for linear trend = 0.5. There was no relationship between grapefruit intake and breast cancer risk among premenopausal women, all postmenopausal women, or postmenopausal women categorized by hormone replacement therapy use (all p>0.05). There was no association between grapefruit intake and estradiol or estrone among postmenopausal women. In this study, we found no evidence of an association between grapefruit intake and risk of breast cancer.


The effects of grapefruit on weight and insulin resistance: relationship to the metabolic syndrome. To study the effects of grapefruit and grapefruit products on body weight and metabolic syndrome, 91 obese patients were randomized to either placebo capsules and 7 ounces (207 mL) of apple juice, grapefruit capsules with 7 ounces (207 mL) of apple juice, 8 ounces (237 mL) of grapefruit juice with placebo capsule, or half of a fresh grapefruit with a placebo capsule three times a day before each meal. Metabolic syndrome parameters were measured at the beginning and end of 12 weeks. After 12 weeks, the fresh grapefruit group had lost 1.6 kg, the grapefruit juice group had lost 1.5 kg, the grapefruit capsule group had lost 1.1 kg, and the placebo group had lost 0.3 kg. The fresh grapefruit group lost significantly more weight than the placebo group (P < .05). A secondary analysis of those with the metabolic syndrome in the four treatment groups demonstrated a significantly greater weight loss in the grapefruit, grapefruit capsule, and grapefruit juice groups compared with placebo (P < .02). There was also a significant reduction in 2-hour post-glucose insulin level in the grapefruit group compared with placebo. Half of a fresh grapefruit eaten before meals was associated with significant weight loss. In metabolic syndrome patients the effect was also seen with grapefruit products. Insulin resistance was improved with fresh grapefruit. Although the mechanism of this weight loss is unknown it would appear reasonable to include grapefruit in a weight reduction diet.


The grapefruit: an old wine in a new glass? Metabolic and cardiovascular perspectives Summary Grapefruit is a popular, tasty and nutritive fruit enjoyed globally. Biomedical evidence in the last 10 years has, however, shown that consumption of grapefruit or its juice is associated with drug interactions, which, in some cases, have been fatal. Grapefruit-induced drug interactions are unique in that the cytochrome P450 enzyme CYP3A4, which metabolises over 60% of commonly prescribed drugs as well as other drug transporter proteins such as P-glycoprotein and organic cation transporter proteins, which are all expressed in the intestines, are involved. However, the extent to which grapefruit–drug interactions impact on clinical settings has not been fully determined, probably because many cases are not reported. It has recently emerged that grapefruit, by virtue of its rich flavonoid content, is beneficial in the management of degenerative diseases such as diabetes and cardiovascular disorders. This potentially explosive subject is reviewed here.


A low-energy-dense diet adding fruit reduces weight and energy intake in women. This study evaluated the effect of adding fruit or oats to the diet of free-living women on energy consumption and body weight. Fruit and oat cookies had the same amount of fiber and total calories ( approximately 200 kcal), but differed in energy density. We analyzed data from a clinical trial conducted in a primary care unit in Rio de Janeiro, Brazil. Forty-nine women, ages ranging from 30 to 50 years, with body mass index (BMI)>25 kg/m2, were randomly chosen to add three apples (0.63 kcal/g energy density) or three pears (0.64 kcal/g energy density) or three oat cookies (3.7 kcal/g energy density) to their usual diet for 10 weeks. Fiber composition was similar ( approximately 6g). Statistical analysis of the repeated measures of dietary composition and body weight were analyzed using mixed model procedures. Results showed a significant decrease in the energy density during the follow-up (-1.23 kcal/g, p<0.04, and -1.29 kcal/g, p<0.05) for apples and pears, respectively, compared to the oat group. The energy intake also decreased significantly (-25.05 and -19.66 kcal/day) for the apple and pear group, respectively, but showed a small increase (+0.93) for the oat group. Apples and pears were also associated (p<0.001) with weight reduction (-0.93 kg for the apple and -0.84 for the pear group), whereas weight was unchanged (+0.21; p=0.35) in the oat group. Results suggest that energy densities of fruits, independent of their fiber amount can reduce energy consumption and body weight over time.


Can grapefruit juice influence ethinylestradiol bioavailability? The effects of grapefruit juice on the bioavailability of 17 alpha-ethinylestradiol (EE2) after a single oral administration of 50 micrograms EE2 have been investigated. The pharmacokinetics of EE2 were studied in an open, randomized, cross-over study in which 13 healthy volunteers were administered the drug with herbal tea or grapefruit juice (naringin, 887 mg/ml). In contrast to herbal tea, grapefruit juice increased the peak plasma concentration (Cmax) significantly to 137% (mean; range 64% to 214%, p = 0.0088) and increased the area under plasma concentration-time curve from 0 to 8 hours (AUC0-8) to 128% (mean; range 81% to 180%, p = 0.0186). This study shows that grapefruit juice increases the bioavailable amount of EE2. A possible explanation may be that grapefruit juice inhibits the metabolic degradation of EE2. Whether the increased bioavailability of EE2 following grapefruit juice administration is of clinical importance should be investigated in long-term studies.


The effects of daily consumption of grapefruit on body weight, lipids, and blood pressure in healthy, overweight adults. Folklore has suggested that consuming grapefruit may promote weight control. Sparse data exist to support this hypothesis, although there is some evidence of health promotion effects with regard to blood pressure control and modulation of circulating lipids. The aim of this randomized controlled trial was to prospectively evaluate the role of grapefruit in reducing body weight and blood pressure and in promoting improvements in the lipid profile in overweight adults (N = 74). Following a 3-week washout diet low in bioactive-rich fruits and vegetables, participants were randomized to either the control diet (n = 32) or daily grapefruit (n = 42) in the amount of one half of a fresh Rio-Red grapefruit with each meal (3× daily) for 6 weeks. No differences between group in weight, blood pressure, or lipids were demonstrated. Grapefruit consumption was associated with modest weight loss (-0.61 ± 2.23 kg, P = .097), a significant reduction in waist circumference (-2.45 ± 0.60 cm, P = .0002), and a significant reduction in systolic blood pressure (-3.21 ± 10.13 mm Hg, P = .03) compared with baseline values. Improvements were observed in circulating lipids of those consuming grapefruit, with total cholesterol and low-density lipoprotein significantly decreasing by -11.7 mg/dL (P = .002) and -18.7 mg/dL (P < .001), respectively, compared with baseline values. This study suggests that consumption of grapefruit daily for 6 weeks does not significantly decrease body weight, lipids, or blood pressure as compared with the control condition. However, the improvements in blood pressure and lipids demonstrated in the intervention group suggest that grapefruit should be further evaluated in the context of obesity and cardiovascular disease prevention. Copyright © 2012 Elsevier Inc. All rights reserved.


Excess dietary protein can adversely affect bone. The average American diet, which is high in protein and low in fruits and vegetables, generates a large amount of acid, mainly as sulfates and phosphates. The kidneys respond to this dietary acid challenge with net acid excretion, as well as ammonium and titratable acid excretion. Concurrently, the skeleton supplies buffer by active resorption of bone. Indeed, calciuria is directly related to net acid excretion. Different food proteins differ greatly in their potential acid load, and therefore in their acidogenic effect. A diet high in acid-ash proteins causes excessive calcium loss because of its acidogenic content. The addition of exogenous buffers, as chemical salts or as fruits and vegetables, to a high protein diet results in a less acid urine, a reduction in net acid excretion, reduced ammonium and titratable acid excretion, and decreased calciuria. Bone resorption may be halted, and bone accretion may actually occur. Alkali buffers, whether chemical salts or dietary fruits and vegetables high in potassium, reverse acid-induced obligatory urinary calcium loss. We conclude that excessive dietary protein from foods with high potential renal acid load adversely affects bone, unless buffered by the consumption of alkali-rich foods or supplements.


Low protein intake: the impact on calcium and bone homeostasis in humans. Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both.


Age and systemic acid-base equilibrium: analysis of published data. To investigate whether systemic acid-base equilibrium changes with aging in normal adult humans, we reviewed published articles reporting the acid-base composition of arterial, arterialized venous, or capillary blood in age-identified healthy subjects. We extracted or calculated blood hydrogen ion concentration ([H+]), plasma bicarbonate concentration ([HCO3(-)]), blood PCO2, and age, and computed a total of 61 age-group means, distributed among eight 10-year intervals from age 20 to 100 years. Using linear regression analysis, we found that with increasing age, there is a significant increase in the steady-state blood [H+] (p < .001), and reduction in steady-state plasma [HCO3(-)] (p < .001), indicative of a progressively worsening low-level metabolic acidosis. Blood PCO2 decreased with age (p < .05), in keeping with the expected respiratory adaptation to metabolic acidosis. Such age-related increasing metabolic acidosis may reflect in part the normal decline of renal function with increasing age. The role of age-related metabolic acidosis in the pathogenesis of the degenerative diseases of aging warrants consideration.


Alkaline diets favor lean tissue mass in older adults Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.


Effect of urine pH changed by dietary intervention on uric acid clearance mechanism of pH-dependent excretion of urinary uric acid Background The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. Methods Within the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl−,SO42−,PO4−) necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. Results and discussion Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body.


Hypercalciuria Associated with High Dietary Protein Intake Is Not Due to Acid Load Context and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Participants and Interventions: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). Results: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. Conclusions: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.


The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women. Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.


Dietary protein and bone health: harmonizing conflicting theories. A precise understanding of the role of dietary protein in bone health has been evasive despite decades of research. It is known that a dietary acid load is harmful to bone, and sulfur-containing amino acids are metabolized to provide such an acid load. It is also known that protein elevates urine calcium loss. However, recent clinical studies and a meta-analysis have indicated either no effect or a modest benefit associated with higher protein intakes. These contradictory considerations may be explained by the existence of a two-faced relationship between protein and bone, with simultaneous positive and negative pathways. In opposition to the negative effects of dietary acid load, protein may exert positive effects related to improving calcium absorption, increasing insulin-like growth factor 1, or improving lean body mass, which, in turn, improves bone strength. Putative mechanisms behind these pathways are reviewed here, and some limitations in the historical literature as well as suggested measures to counter these in the future are identified. When positive and negative pathways are considered in tandem, protein may offer modest benefits to bone in the presence of adequate dietary calcium and acid-neutralizing fruits and vegetables. © 2011 International Life Sciences Institute.


Protein intake, calcium balance and health consequences. High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.