Aims/hypothesis
Low-grade inflammation and endothelial dysfunction may play a role in the pathogenesis of type 2 diabetes and cardiovascular disease. We evaluated whether a diet high in fatty fish, ...bilberries and wholegrain products (Healthy Diet) improves biomarkers reflecting inflammation and endothelial dysfunction in individuals with impaired glucose metabolism.
Methods
We recruited individuals with impaired glucose metabolism and features of the metabolic syndrome into a 12 week, parallel design, dietary intervention trial conducted at the Department of Clinical Nutrition, University of Eastern Finland (Kuopio, Finland). Randomisation was performed by matching according to sex and medians of age, BMI and fasting plasma glucose of the study population at screening. The primary endpoint in the present study was the change in plasma inflammatory markers and the measurements were performed blinded to group assignment. High-sensitivity (hs) C-reactive protein (CRP) and E-selectin responses were also analysed separately in participants not using statins (
n
= 76).
Results
Altogether, 131 individuals were assigned to either the Healthy Diet (
n
= 44), a whole-grain-enriched diet (WGED) (
n
= 42) or a control (
n
= 45) diet, and 104 participants (mean ± SD: age 59 ± 7 years; BMI 31.1 ± 3.5 kg/m
2
) who had completed the study, were analysed (Healthy Diet
n
= 36, WGED
n
= 34 and control diet
n
= 34). Plasma E-selectin decreased only in the Healthy Diet group. This occurred in all group participants (
p
< 0.05) and also after excluding participants using statins (
p
< 0.05). Plasma hsCRP levels decreased in the Healthy Diet (median −17%,
p
< 0.05) and WGED (median −27%,
p
< 0.01) groups in participants not using statins. Controlling for confounding factors, including BMI or insulin sensitivity, did not alter the results. A greater increase in plasma concentration of very-long-chain
n
-3 fatty acids and in the intake of fibre during the study was associated with a greater decrease in plasma E-selectin (
p
< 0.05). The intake of test breads consumed during the Healthy Diet and WGED interventions was inversely associated with the change in hsCRP levels (
p
< 0.001).
Conclusions/interpretation
Our results suggest that the combined effect of fatty fish, bilberries and wholegrain products may improve endothelial dysfunction and inflammation in overweight and obese individuals at high risk of developing diabetes.
Trial registration:
ClinicalTrials.gov NCT00573781
Funding:
The study was funded by the Academy of Finland (117844 and 118590 to M. Uusitupa; 131460 to K. Poutanen; 130469 to H. Mykkänen and 131593 to V. D. F. de Mello); the Kuopio University Hospital (5106, 5168, 5254 to M. Uusitupa); the Finnish Diabetes Research Foundation; the Sigrid Juselius Foundation; the Nordic Centre of Excellence on ‘Systems biology in controlled dietary interventions and cohort studies’ (SYSDIET; 070014); and the European Commission in the Communities 6th Framework Programme, Project HEALTHGRAIN (FOOD-CT-2005-514008).
The amounts of quercetin, myricetin, and kaempferol aglycons in 25 edible berries were analyzed by an optimized RP-HPLC method with UV detection and identified with diode array and electrospray ...ionization mass spectrometry detection. Sixteen species of cultivated berries and nine species of wild berries were collected in Finland in 1997. Quercetin was found in all berries, the contents being highest in bog whortleberry (158 mg/kg, fresh weight), lingonberry (74 and 146 mg/kg), cranberry (83 and 121 mg/kg), chokeberry (89 mg/kg), sweet rowan (85 mg/kg), rowanberry (63 mg/kg), sea buckthorn berry (62 mg/kg), and crowberry (53 and 56 mg/kg). Amounts between 14 and 142 mg/kg of myricetin were detected in cranberry, black currant, crowberry, bog whortleberry, blueberries, and bilberry. Kaempferol was detected only in gooseberries (16 and 19 mg/kg) and strawberries (5 and 8 mg/kg). Total contents of these flavonols (100−263 mg/kg) in cranberry, bog whortleberry, lingonberry, black currant, and crowberry were higher than those in the commonly consumed fruits or vegetables, except for onion, kale, and broccoli. Keywords: Flavonoid; flavonol; quercetin; myricetin; kaempferol; berry; fruit; HPLC
The probiotic Lactobacillus rhamnosus GG is able to bind the potent hepatocarcinogen aflatoxin B₁ (AFB₁) and thus potentially restrict its rapid absorption from the intestine. In this study we ...investigated the potential of GG to reduce AFB₁ availability in vitro in Caco-2 cells adapted to express cytochrome P-450 (CYP) 3A4, such that both transport and toxicity could be assessed. Caco-2 cells were grown as confluent monolayers on transmembrane filters for 21 days prior to all studies. AFB₁ levels in culture medium were measured by high-performance liquid chromatography. In CYP 3A4-induced monolayers, AFB₁ transport from the apical to the basolateral chamber was reduced from 11.1% ± 1.9% to 6.4% ± 2.5% (P = 0.019) and to 3.3% ± 1.8% (P = 0.002) within the first hour in monolayers coincubated with GG (1 x 10¹⁰ and 5 x 10¹⁰ CFU/ml, respectively). GG (1 x 10¹⁰ and 5 x 10¹⁰ CFU/ml) bound 40.1% ± 8.3% and 61.0% ± 6.0% of added AFB₁ after 1 h, respectively. AFB₁ caused significant reductions of 30.1% (P = 0.01), 49.4% (P = 0.004), and 64.4% (P < 0.001) in transepithelial resistance after 24, 48, and 72 h, respectively. Coincubation with 1 x 10¹⁰ CFU/ml GG after 24 h protected against AFB₁-induced reductions in transepithelial resistance at both 24 h (P = 0.002) and 48 h (P = 0.04). DNA fragmentation was apparent in cells treated only with AFB₁ cells but not in cells coincubated with either 1 x 10¹⁰ or 5 x 10¹⁰ CFU/ml GG. GG reduced AFB₁ uptake and protected against both membrane and DNA damage in the Caco-2 model. These data are suggestive of a beneficial role of GG against dietary exposure to aflatoxin.
Alkylresorcinols (ARs) have been suggested as biomarkers of whole-grain wheat and rye intake. Plasma AR concentrations have a short half-life; hence, long-term biomarkers are needed. This study ...evaluated the responsiveness of ARs in adipose tissue biopsies as biomarkers after a whole-grain intake intervention.
Samples and data of 27 participants from a 12-week randomized parallel-group dietary intervention were available. The participants were replacing their habitual diet with a whole-grain-enriched diet (WGDG) or a refined grain diet (RDG) during the intervention. Blood samples and adipose tissue biopsies were collected at baseline and after 12 weeks, and AR concentrations in the plasma and adipose tissues from the participants were compared against estimated whole-grain intake.
AR concentrations in the adipose tissue and plasma did not change after 12 weeks in the WGDG group, as no significant increase in whole-grain intake was observed, but was significantly lower than baseline in the RDG group (P<0.05), owing to decreased whole-grain intake in this group. Plasma and adipose tissue AR concentrations were significantly higher in the WGDG group than in the RDG group (P<0.05), and were highly correlated with average whole-grain intake estimated by food records (Spearman's r=0.60-0.72 (P<0.05, n=16) for total and individual AR homolog concentrations in the plasma; r=0.60--0.84, (P<0.05, n=16) for total and individual AR homolog concentrations in the adipose tissue).
In this small pilot study, AR concentrations in adipose tissue responded to reduced intake of whole grain over 12 weeks. Although not significantly different from plasma AR, adipose tissue AR concentrations were highly correlated with whole-grain intake after a 12-week intervention. These results show that adipose tissue AR concentrations have promise as biomarkers of whole-grain wheat and rye intake. Larger studies are needed to evaluate whether they are better long-term biomarkers than AR in the plasma.
Aflatoxin B1 (AFB1) is a well-known carcinogen and reducing its bioavailability is of great interest for human and animal health. Several probiotic bacteria are able to bind AFB1 in vitro, including ...Lactobacillus rhamnosus LC-705 and Propionibacterium freudenreichii subsp. shermanii JS. A mixture of these two probiotics is used by the food and feed industry as biopreservative (Bioprofit), making it a promising candidate for future applications. Consequently, this study aims to investigate the in vitro and ex vivo ability of this probiotic mixture to bind AFB1. For in vitro experiments, probiotic mixture was suspended in an AFB1 solution (5 micromolar), incubated for 1 to 30 min, centrifuged, and AFB1 residues were quantitated in supernatant and pellet. For ex vivo experiments, duodenal loops of chicks were ligated and injected with either AFB1 solution alone or probiotic mixture suspension and AFB1 solution. Lumen content was centrifuged and AFB1 was quantitated in supernatant and pellet. Additionally, AFB1 was extracted from duodenal tissue to calculate tissue uptake. In vitro, 57 to 66% of AFB1 was removed from the solution by the probiotic mixture, but only 38 to 47% could be extracted from the bacterial surface. In ex vivo experiments, only up to 25% of AFB1 was bound by bacteria, and tissue uptake of AFB1 was significantly reduced when probiotic bacteria were present in the duodenal loop. Furthermore, the effect of intestinal mucus on the bacterial binding ability was investigated in vitro and was found to significantly reduce AFB1 binding by the probiotic mixture. However, probiotic mixture could only retard but not prevent AFB1 absorption in duodenal loops. Further work needs to assess the potential of probiotics in different experimental setups.
Selected flavonoids (kaempferol, quercetin, myricetin) and phenolic acids (
p-coumaric, caffeic, ferulic,
p-hydroxybenzoic, gallic and ellagic acids) were simultaneously detected from 19 berries ...using a simple High Performance Liquid Chromatographic (HPLC) method. These phenolics have been proposed to have beneficial effects on health as antioxidants and anticarcinogens. Marked differences were observed in the phenolic profiles among the berries, with certain similarities within families and genera. The major phenolic compound analyzed in the genus
Vaccinium was quercetin in lingonberry and cranberry, and its level was high also in blueberries and bilberry. In the genus
Ribes, quercetin was the main compound in gooseberry, red currant and black currant. Ellagic acid was the main phenolic compound in the berries of the genus
Rubus (red raspberry, Arctic bramble and cloudberry) and genus
Fragaria (strawberry). Our data suggest that berries have potential as good dietary sources of quercetin or ellagic acid.
Antimicrobial treatment may disturb the colonization resistance of gastrointestinal microflora, which may induce clinical symptoms, most commonly diarrhea. The severity of antibiotic-associated ...diarrhea may range from a brief, self-limiting disease to devastating diarrhea with electrolyte disturbances, dehydration, crampy abdominal pain, pseudomembranous colitis, toxic megacolon, or even death. The incidence of diarrhea in children receiving a single antimicrobial treatment is unclear. In addition to more critical use of antimicrobials, adjunctive preventive measures to antibiotic-associated diarrhea are needed. The objective of this study was to evaluate the incidence of diarrhea after antimicrobial treatment in children with no history of antimicrobial use during the previous 3 months. Another aim of this study was to assess the preventive potential of Lactobacillus rhamnosus GG (Lactobacillus GG; American Type Culture Collection 53103), a probiotic strain with a documented safety record and a therapeutic effect in viral gastroenteritis on antibiotic-associated diarrhea.
Oral antimicrobial agents were prescribed for the treatment of acute respiratory infections at the clinics of the Health Care Center of the City of Tampere or Tampere University Hospital, Finland, to 167 patients who were invited to participate in the study. Of the patients, 48 were lost to follow-up; therefore, the final study population consisted of 119 children from 2 weeks to 12. 8 years of age (mean: 4.5 years). All study subjects met the inclusion criteria: they had not received any antimicrobial medication during the previous 3 months, they did not suffer from gastrointestinal disorders, and they did not need intravenous antimicrobial treatment. The patients were randomized to receive placebo or 2 x 10(10) colony-forming units of Lactobacillus GG in capsules given twice daily during the antimicrobial treatment. Lactobacillus GG and placebo capsules were indistinguishable in appearance and taste. The parents kept a daily symptom diary and recorded stool frequency and consistency at home for 3 months. Diarrhea was defined as at least three watery or loose stools per day for a minimum of 2 consecutive days. In the case of diarrhea, viral (adenovirus, rotavirus, calicivirus and astrovirus) and bacterial (Salmonella, Shigella, Yersinia, Campylobacter, Clostridium difficile, Staphylococcus aureus, and yeasts) analyses were studied in fecal samples. The metabolic activity of the gut microflora was assessed by analysis of fecal urease, beta-glucosidase, and beta-glucuronidase activities. The primary outcome measure was diarrhea during the first 2 weeks after the beginning of the antimicrobial treatment, because this period most likely reflects the effects of antimicrobial use. Secondary outcome measures were the activities of fecal urease, beta-glucuronidase, and beta-glucosidase.
On the entire follow-up, 80% of any gastrointestinal symptoms were reported during the first 2 weeks after the beginning of the antimicrobial treatment. The incidence of diarrhea was 5% in the Lactobacillus GG group and 16% in the placebo group within 2 weeks of antimicrobial therapy (chi(2) = 3.82). The treatment effect (95% confidence interval) of Lactobacillus GG was -11% (-21%-0%). In diarrheal episodes, the viral and bacterial analyses were positive for Clostridium difficile in 2 cases and for Norwalk-like calicivirus in 3 cases. The age of the patients with diarrhea was between 3 months and 5 years in 75% of cases in both groups. The severity of diarrhea was comparable in the study groups, as evidenced by similar stool frequency (mean: 5 per day; range: 3-6) and the duration of diarrhea (mean: 4 days; range: 2-8). The activities of fecal urease and beta-glucuronidase, but not beta-glucosidase, changed significantly after the beginning of the antimicrobial treatment in the Lactobacillus GG group and in the placebo group alike. (ABSTRACT TRUNCATED)
ABSTRACT
The probiotic
Lactobacillus rhamnosus
GG is able to bind the potent hepatocarcinogen aflatoxin B
1
(AFB
1
) and thus potentially restrict its rapid absorption from the intestine. In this ...study we investigated the potential of GG to reduce AFB
1
availability in vitro in Caco-2 cells adapted to express cytochrome P-450 (CYP) 3A4, such that both transport and toxicity could be assessed. Caco-2 cells were grown as confluent monolayers on transmembrane filters for 21 days prior to all studies. AFB
1
levels in culture medium were measured by high-performance liquid chromatography. In CYP 3A4-induced monolayers, AFB
1
transport from the apical to the basolateral chamber was reduced from 11.1% ± 1.9% to 6.4% ± 2.5% (
P
= 0.019) and to 3.3% ± 1.8% (
P
= 0.002) within the first hour in monolayers coincubated with GG (1 × 10
10
and 5 × 10
10
CFU/ml, respectively). GG (1 × 10
10
and 5 × 10
10
CFU/ml) bound 40.1% ± 8.3% and 61.0% ± 6.0% of added AFB
1
after 1 h, respectively. AFB
1
caused significant reductions of 30.1% (
P
= 0.01), 49.4% (
P
= 0.004), and 64.4% (
P
< 0.001) in transepithelial resistance after 24, 48, and 72 h, respectively. Coincubation with 1 × 10
10
CFU/ml GG after 24 h protected against AFB
1
-induced reductions in transepithelial resistance at both 24 h (
P
= 0.002) and 48 h (
P
= 0.04). DNA fragmentation was apparent in cells treated only with AFB
1
cells but not in cells coincubated with either 1 × 10
10
or 5 × 10
10
CFU/ml GG. GG reduced AFB
1
uptake and protected against both membrane and DNA damage in the Caco-2 model. These data are suggestive of a beneficial role of GG against dietary exposure to aflatoxin.
Aflatoxins are a major risk factor for hepatocellular carcinoma (HCC), and thus understanding the pattern of aflatoxin exposure in different regions is important in order to develop targeted ...intervention strategies. Given the early onset of HCC in many countries early life exposures may be important. This study investigated aflatoxin exposure in Egyptian children (
n
=
50, aged 1–2.5 years) by assessing urinary aflatoxin metabolite (AFM
1, AFB
1, AFB
2, AFG
1, AFG
2) levels. Samples from Guinean children (
n
=
50, aged 2–4 years) were analyzed in parallel providing a comparison to a region of established frequent aflatoxin exposure. Aflatoxins were isolated from urine using C18-cartridges followed by immunoaffinity clean-up, and quantified by HPLC with fluorescence detection. Overall aflatoxins were less frequently present in Egyptian (38%) than Guinean urine samples (86%) (
p
<
0.001), which was particularly related to differences in detection rates of AFM
1 (8% compared to 64%, respectively, (
p
<
0.001)). For AFM
1 the geometric mean level in Guinea (16.3
pg/ml; 95% CI: 10.1, 26.6
pg/ml) was 6-fold higher (
p
<
0.001) than in Egypt (2.7
pg/ml; 95% CI: 2.5, 2.8
pg/ml). Urinary aflatoxins from healthy children in these two regions have not previously been reported, and exposure appears modest in Egypt compared to Guinea. These data suggest that measures to reduce aflatoxin exposure in both regions are important, though particularly in Guinea.
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