Glucosamine and chondroitin are popular non-vitamin dietary supplements used for osteoarthritis. Long-term use is associated with lower incidence of colorectal and lung cancers and with lower ...mortality; however, the mechanism underlying these observations is unknown. In vitro and animal studies show that glucosamine and chondroitin inhibit NF-kB, a central mediator of inflammation, but no definitive trials have been done in healthy humans.
We conducted a randomized, double-blind, placebo-controlled, cross-over study to assess the effects of glucosamine hydrochloride (1500 mg/d) plus chondroitin sulfate (1200 mg/d) for 28 days compared to placebo in 18 (9 men, 9 women) healthy, overweight (body mass index 25.0-32.5 kg/m2) adults, aged 20-55 y. We examined 4 serum inflammatory biomarkers: C-reactive protein (CRP), interleukin 6, and soluble tumor necrosis factor receptors I and II; a urinary inflammation biomarker: prostaglandin E2-metabolite; and a urinary oxidative stress biomarker: F2-isoprostane. Plasma proteomics on an antibody array was performed to explore other pathways modulated by glucosamine and chondroitin.
Serum CRP concentrations were 23% lower after glucosamine and chondroitin compared to placebo (P = 0.048). There were no significant differences in other biomarkers. In the proteomics analyses, several pathways were significantly different between the interventions after Bonferroni correction, the most significant being a reduction in the "cytokine activity" pathway (P = 2.6 x 10-16), after glucosamine and chondroitin compared to placebo.
Glucosamine and chondroitin supplementation may lower systemic inflammation and alter other pathways in healthy, overweight individuals. This study adds evidence for potential mechanisms supporting epidemiologic findings that glucosamine and chondroitin are associated with reduced risk of lung and colorectal cancer.
ClinicalTrials.gov NCT01682694.
The gut microbiome may play a role in inflammation associated with type 2 diabetes (T2D) development. This cross-sectional study examined its relation with glycemic status within a subset of the ...Multiethnic Cohort (MEC) and estimated the association of circulating bacterial endotoxin (measured as plasma lipopolysaccharide-binding protein (LBP)) with T2D, which may be mediated by C-reactive protein (CRP).
In 2013-16, cohort members from five ethnic groups completed clinic visits, questionnaires, and stool and blood collections. Participants with self-reported T2D and/or taking medication were considered T2D cases. Those with fasting glucose >125 and 100-125 mg/dL were classified as undiagnosed (UT2D) and pre-diabetes (PT2D) cases, respectively. We characterized the gut microbiome through 16S rRNA gene sequencing and measured plasma LBP and CRP by standard assays. Linear regression was applied to estimate associations of the gut microbiome community structure and LBP with T2D status adjusting for relevant confounders.
Among 1,702 participants (59.9-77.4 years), 735 (43%) were normoglycemic (NG), 506 (30%) PT2D, 154 (9%) UT2D, and 307 (18%) T2D. The Shannon diversity index decreased (ptrend = 0.05), while endotoxin, measured as LBP, increased (ptrend = 0.0003) from NG to T2D. Of 10 phyla, Actinobacteria (ptrend = 0.007), Firmicutes (ptrend = 0.003), and Synergistetes (ptrend = 0.02) were inversely associated and Lentisphaerae (ptrend = 0.01) was positively associated with T2D status. Clostridium sensu stricto 1, Lachnospira, and Peptostreptococcaceae were less, while Escherichia-Shigella and Lachnospiraceae were more abundant among T2D patients, but the associations with Actinobacteria, Clostridium sensu stricto 1, and Escherichia-Shigella may be due metformin use. PT2D/UT2D values were closer to NG than T2D. No indication was detected that CRP mediated the association of LBP with T2D.
T2D but not PT2D/UT2D status was associated with lower abundance of SCFA-producing genera and a higher abundance of gram-negative endotoxin-producing bacteria suggesting that the gut microbiome may contribute to chronic systemic inflammation and T2D through bacterial translocation.
Gut bacterial modification of soy isoflavones produces metabolites that differ in biological activity from the parent compounds. Hydrolysis of glycosides results in more active compounds. In ...contrast, further degradation and transformation of aglycones produce more or less active compounds, depending on the substrate metabolized and the product formed. Bacterial metabolism of soy isoflavones varies among individuals. The predominant daidzein metabolites produced by human intestinal bacteria are equol and O-desmethylangolensin. Among humans, 30-50% have the bacteria capable of producing equol and 80-90% harbor O-desmethylangolensin-producing bacteria. Factors that influence the capacity to produce equol and O-desmethylangolensin are not clearly established; however, gut physiology, host genetics, and diet are reported to contribute to interindividual differences in conversion of daidzein to equol. Effects of these phenotypes on human health are poorly characterized. Some studies in high soy-consuming populations reported an inverse association between urinary and serum equol concentrations and breast and prostate cancer risk. Furthermore, several studies of soy supplementation and bone density suggest that soy products may be more effective in maintaining bone density in equol-producing individuals. Factors that contribute to the phenotypes and the relation of these specific phenotypes to human health need to be further elucidated. The extent to which isoflavone metabolism is key to the efficacy of soy foods remains to be established.
Chronic inflammation, which is associated with obesity, may play a role in the etiology of several diseases. Thus, reducing inflammation may offer a disease-prevention strategy, particularly among ...the obese. Several modifiable factors have been associated with inflammation, including: dietary fiber intake, saturated fat intake, physical activity, smoking, alcohol, and use of certain supplements and medications (glucosamine, chondroitin, fish oil, vitamin E, statins and aspirin). To study whether these associations differ by body mass index (BMI), we used data on 9,895 adults included in the 1999-2004 cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted linear regression was used to evaluate the associations between modifiable factors and serum high-sensitivity C-reactive protein (hsCRP) concentrations across the following groups: underweight/normal weight (BMI<25 kg/m(2)), overweight (25-<30 kg/m(2)) and obese (30+ kg/m(2)). While several factors were significantly associated with decreased hsCRP among the normal weight or overweight groups (increased fiber intake, lower saturated fat intake, physical activity, not smoking, and use of chondroitin, fish oil and statins), only increasing dietary fiber intake and moderate alcohol consumption were associated with reduced hsCRP among the obese. Effect modification by BMI was statistically significant for the saturated fat-hsCRP and smoking-hsCRP associations. These results suggest that posited anti-inflammatory drugs and behaviors may be less strongly associated with inflammation among the obese than among lower weight persons.
Genetic differences in taste preference, food tolerance, and phytochemical absorption and metabolism all potentially influence the effect of plant-based diets on cancer risk. Diet is a mixture of ...carcinogens, mutagens, and protective agents, many of which are metabolized by biotransformation enzymes. Genetic polymorphisms that alter protein expression or enzyme function can modify risk. Genotypes associated with more favorable handling of carcinogens may be associated with less favorable handling of phytochemicals. For example, glutathione S-transferases detoxify polycyclic aromatic hydrocarbons and metabolize isothiocyanates, which are chemopreventive compounds in cruciferous vegetables. A polymorphism in the GSTM1 gene results in lack of GSTM1-1 protein. Pharmacokinetic studies suggest that lack of GSTM1 enzyme is associated with more rapid excretion of the isothiocyanate sulforaphane; therefore, individuals who have this genetic variation may derive less benefit from consuming cruciferous vegetables. Flavonoids are conjugated with glucuronide and sulfate and are excreted in urine and bile. Polymorphisms in UDP-glucuronosyltransferases and sulfotransferases may contribute to variability in phytochemical clearance and efficacy. Genetic polymorphisms in enzymes that metabolize phytochemicals may account in part for variation in disease risk and also have to be considered in the context of other aspects of human genetics, gut bacterial genetics, and environmental exposures.
The impact of soyfood intake on breast cancer risk has been investigated extensively. Much of this focus can be attributed to the soybean being a dietary source that is uniquely rich in isoflavones. ...The chemical structure of isoflavones is similar to that of estrogen, and isoflavones bind to both estrogen receptors (ERα and ERβ) (although they preferentially bind to and activate ERβ) and exert estrogen-like effects under some experimental conditions. Isoflavones also possess nonhormonal properties that are associated with the inhibition of cancer cell growth. Thus, there are several possible mechanisms by which soy may reduce the risk of breast cancer. However, the role of isoflavones in breast cancer has become controversial because, in contrast to the possible beneficial effects, some data from in vitro and animal studies suggest that isoflavones, especially genistein, the aglycone of the main soybean isoflavone genistin, may stimulate the growth of estrogen-sensitive tumors. Limited human data directly address the tumor-promoting effects of isoflavones and soy. Because the use of soyfoods and isoflavone supplements is increasing, it is important from a public health perspective to understand the impact of these products on breast cancer risk in women at high risk of the disease and on the survival of breast cancer patients. To this end, a workshop was held in November 2005 to review the existing literature and to make research recommendations. This paper summarizes the workshop findings and recommendations. The primary research recommendation is that the impact of isoflavones on breast tissue needs to be evaluated at the cellular level in women at high risk for breast cancer.
We compared fat storage in the abdominal region among individuals from 5 different ethnic–racial groups to determine whether fat storage is associated with disparities observed in metabolic syndrome ...and other obesity-associated diseases.
We collected data from 1794 participants in the Multiethnic Cohort Study (60–77 years old; of African, European white, Japanese, Latino, or Native Hawaiian ancestry) with body mass index values of 17.1–46.2 kg/m2. From May 2013 through April 2016, participants visited the study clinic to undergo body measurements, an interview, and a blood collection. Participants were evaluated by dual-energy x-ray absorptiometry and abdominal magnetic resonance imaging. Among ethnic groups, we compared adiposity of the trunk, intra-abdominal visceral cavity, and liver, adjusting for total fat mass; we evaluated the association of adult weight change with abdominal adiposity; and we examined the prevalence of metabolic syndrome mediated by abdominal adiposity.
Relative amounts of trunk, visceral, and liver fat varied significantly with ethnicity—they were highest in Japanese Americans, lowest in African Americans, and intermediate in the other groups. Compared with African Americans, the mean visceral fat area was 45% and 73% greater in Japanese American men and women, respectively, and the mean measurements of liver fat were 61% and 122% greater in Japanese American men and women. The visceral and hepatic adiposity associated with weight gain since participants were 21 years old varied in a similar pattern among ethnic–racial groups. In the mediation analysis, visceral and liver fat jointly accounted for a statistically significant fraction of the difference in metabolic syndrome prevalence, compared with white persons, for African Americans, Japanese Americans, and Native Hawaiian women, independently of total fat mass.
In an analysis of data from the participants in the Multiethnic Cohort Study, we found extensive differences among ethnic–racial groups in the propensity to store fat intra-abdominally. This observation should be considered by clinicians in the prevention and early detection of metabolic disorders.
In the human gut, commensal bacteria metabolize food components that typically serve as energy sources. These components have the potential to influence gut bacterial community composition. ...Cruciferous vegetables, such as broccoli and cabbage, contain distinctive compounds that can be utilized by gut bacteria. For example, glucosinolates can be hydrolyzed by certain bacteria, and dietary fibers can be fermented by a range of species. We hypothesized that cruciferous vegetable consumption would alter growth of certain bacteria, thereby altering bacterial community composition. We tested this hypothesis in a randomized, crossover, controlled feeding study. Fecal samples were collected from 17 participants at the end of 2 14-d intake periods: a low-phytochemical, low-fiber basal diet (i.e. refined grains without fruits or vegetables) and a high ("double") cruciferous vegetable diet basal diet + 14 g cruciferous vegetables/(kg body weight·d). Fecal bacterial composition was analyzed by the terminal restriction fragment length polymorphism (tRFLP) method using the bacterial 16S ribosomal RNA gene and nucleotide sequencing. Using blocked multi-response permutation procedures analysis, we found that overall bacterial community composition differed between the 2 consumption periods (δ = 0.603; P = 0.011). The bacterial community response to cruciferous vegetables was individual-specific, as revealed by nonmetric multidimensional scaling ordination analysis. Specific tRFLP fragments that characterized each of the diets were identified using indicator species analysis. Putative species corresponding to these fragments were identified through gene sequencing as Eubacterium hallii, Phascolarctobacterium faecium, Burkholderiales spp., Alistipes putredinis, and Eggerthella spp. In conclusion, human gut bacterial community composition was altered by cruciferous vegetable consumption, which could ultimately influence gut metabolism of bioactive food components and host exposure to these compounds.
Emerging evidence suggests a positive association of diet and obesity with depression. Researchers have examined several diet-mood hypotheses, including investigating the extent to which ...carbohydrates may impact mood. There is limited research on how glycemic load, a characteristic of carbohydrates, impacts mood in healthy adults. Eighty-two healthy weight and overweight/obese, but otherwise healthy, adults enrolled in a randomized, crossover controlled feeding study testing low-compared to high-glycemic load diets. All participants completed self-report mood and energy level questionnaires during each arm of the intervention. Diets were isocaloric and were matched by macronutrient content as a percent of total energy. Mood was assessed with the Profile of Mood States (POMS) subscales; tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment, total mood disturbance (TMD), and negative affect (NA) in addition to the Center for Epidemiological Studies – Depression (CES-D) scale at baseline and end of both 28-day feeding periods. Linear mixed models tested the intervention effect on mood, controlling for baseline POMS and CES-D scores, diet type, diet sequence, feeding period, sex, and percent body fat classification. The consumption of the high-glycemic load diet resulted in a 38% higher score for depressive symptoms on the CES-D (P = 0.002) compared to the low-glycemic load diet as well as 55% higher score for TMD (P = 0.05), and 26% higher score for fatigue/inertia (P = 0.04). In subgroup analyses, the overweight/obese participants had 40% higher scores on the CES-D scale compared to healthy weight participants (P = 0.05). In conclusion, a high-glycemic load diet was associated with higher depression symptoms, total mood disturbance, and fatigue compared to a low-glycemic load diet especially in overweight/obese, but otherwise healthy, adults.
This trial was registered at clinicaltrials.gov: NCT00622661.
Emerging Research on Equol and Cancer LAMPE, Johanna W
The Journal of nutrition,
07/2010, Letnik:
140, Številka:
7
Conference Proceeding, Journal Article
Recenzirano
Odprti dostop
Mechanisms of action of equol described using in vitro studies suggest possible effects of this compound in relation to cancer risk. However, experimental data are lacking with regard to the effects ...of S-(-)-equol (a gut bacterial product of daidzein), racemic equol, or even daidzein on tumorigenesis in vivo. Rodent studies, using racemic equol or daidzein in equol-producing animals, suggest that equol exposure does not stimulate mammary tumor growth, but there is little evidence that it is protective either. Racemic equol has been shown to inhibit skin carcinogenesis in hairless mice. Epidemiologic studies of associations between urinary or plasma isoflavone concentrations and breast cancer risk in women have reported no association nor increased risk associated with higher equol measures in low-soy-consuming populations but have reported a trend toward decreased cancer risk with increased equol in Asian populations. These population-based differences have been reported for prostate cancer too. Several studies in Asian men report lower equol concentrations or a lower prevalence of equol-producers among men with prostate cancer compared with controls, whereas studies in European populations report no association. Studies using intermediate biomarkers of cancer risk and susceptibility in humans also have examined the effects the equol-producer phenotype in relation to soy intake with varying results. Overall, the role of equol in relation to cancer remains unclear. With the availability of R- and S-equol, animal studies of carcinogenesis and human intervention studies addressing effects of the equol enantiomers on intermediate biomarkers may help to ascertain the role of equol in cancer risk.
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