The DIANA-5 randomized controlled trial assessed the effectiveness of a diet based on Mediterranean and macrobiotic traditions (macro-Mediterranean diet) in reducing breast cancer recurrence.
The ...DIANA-5 study involved 1,542 patients with breast cancer at high risk of recurrence because of estrogen receptor-negative cancer, or metabolic syndrome, or high plasma levels of insulin or testosterone. Women were randomly assigned to an active dietary intervention (IG) or a control group (CG). Both groups received the 2007 American Institute for Cancer Research/World Cancer Research Fund recommendations for cancer prevention. The intervention consisted of meetings with kitchen classes, community meals, and dietary recommendations. Recommended foods included whole grain cereals, legumes, soy products, vegetables, fruit, nuts, olive oil, and fish. Foods to be avoided were refined products, potatoes, sugar and desserts, red and processed meat, dairy products, and alcoholic drinks. A compliance Dietary Index was defined by the difference between recommended and discouraged foods.
Over the 5 years of follow-up, 95 patients of the IG and 98 of the CG developed breast cancer recurrence HR = 0.99; 95% confidence interval (CI): 0.69-1.40. The analysis by compliance to the dietary recommendations (IG and CG together) showed that the women in the upper tertile of Dietary Index change had an HR of recurrence of 0.59 (95% CI: 0.36-0.92) compared with women in the lower tertile.
The DIANA-5 dietary intervention trial failed to show a reduction in breast cancer recurrence, although self-reported diet at year 1 in IG and CG combined showed a protective association with the higher Dietary Index change. See related commentary by McTiernan, p. 931.
The Diet and Androgen-5 (DIANA-5) trial aimed at testing whether a dietary change based on the Mediterranean diet and on macrobiotic principles can reduce the incidence of breast cancer (BC)-related ...events. We analyzed the adherence to the DIANA-5 dietary recommendations by randomization group after 1 year of intervention. We evaluated the association between dietary adherence and changes in body weight and metabolic syndrome (MS) parameters. BC women aged 35–70 years were eligible. After the baseline examinations, women were randomized into an intervention group (IG) or a control group (CG). A total of 1344 BC women (689 IG and 655 CG) concluded the first year of dietary intervention. IG showed greater anthropometric and metabolic improvements compared to CG. These changes were significantly associated with increased adherence to the dietary recommendations. Women who increased recommended foods consumption or reduced discouraged foods consumption showed an Odds Ratio (OR) of 1.37 (0.70–2.67) and 2.02 (1.03–3.98) to improve three or more MS parameters. Moreover, women in the higher category of dietary change showed a four times higher OR of reducing body weight compared to the lower category (p < 0.001). The DIANA-5 dietary intervention is effective in reducing body weight and MS parameters.
Processed meat intake is associated with a higher risk of colorectal and stomach cancers, coronary artery disease, and type 2 diabetes and with higher mortality, but the estimation of intake of ...different processed meat products in this heterogeneous food group in epidemiological studies remains challenging.
This work aimed at identifying novel biomarkers for processed meat intake using metabolomics.
An untargeted, multi-tiered metabolomics approach based on LC-MS was applied to 33 meat products digested in vitro and secondly to urine and plasma samples from a randomized crossover dietary intervention in which 12 volunteers consumed successively 3 processed meat products (bacon, salami, and hot dog) and 2 other foods used as controls, over 3 consecutive days. The putative biomarkers were then measured in urine from 474 subjects from the European Prospective Investigation into Cancer and Nutrition (EPIC) cross-sectional study for which detailed 24-h dietary recalls and FFQs were available.
Syringol and 4 derivatives of syringol were found to be characteristic of in vitro digests of smoked meat products. The same compounds present as sulfate esters in urine increased at 2 and 12 h after consumption of smoked meat products (hot dog, bacon) in the intervention study. The same syringol sulfates were also positively associated with recent or habitual consumption of smoked meat products in urine samples from participants of the EPIC cross-sectional study. These compounds showed good discriminative ability for smoked meat intake with receiver operator characteristic areas under the curve ranging from 0.78 to 0.86 and 0.74 to 0.79 for short-term and habitual intake, respectively.
Four novel syringol sulfates were identified as potential biomarkers of smoked meat intake and may be used to improve assessment of smoked meat intake in epidemiological studies. This trial was registered at clinicaltrials.gov as NCT03354130.
Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated ...with increased mortality after CRC diagnosis. We examined pre‐diagnostic serum resistin concentrations in relation to CRC‐specific and all‐cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC‐specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause‐specific Cox proportional hazards models and further in sensitivity analyses using Fine–Gray proportional subdistribution hazards models. For all‐cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow‐up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC‐specific mortality (HRQ4vsQ1 = 0.95, 95% CI: 0.73–1.23; Ptrend = .97; and HRper doubling of resistin concentration = 1.00; 95% CI: 0.84–1.19; P = .98) or all‐cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre‐diagnostic circulating resistin concentrations and CRC‐specific or all‐cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.
What's new?
Previous studies suggested that obesity and inflammation are related to cancer progression, and resistin was proposed as an obesity biomarker involved in inflammatory processes in humans. However, it remained unclear whether resistin is associated with increased mortality after colorectal cancer diagnosis. In this study the authors examined the novel association between pre‐diagnostic level of resistin and mortality in 1343 incident colorectal cancer patients. Resistin concentrations measured 4.8 years before diagnosis were not associated with mortality in individuals with CRC. These findings do not support the hypothesis that resistin may contribute to cancer progression.
Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative ...stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: N
-carboxy-methyllysine (CML), N
-carboxyethyllysine (CEL), and N
-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HR
.
= 0.92, 95% CI = 0.85-1.00) and MG-H1 (HR
.
= 0.92, 95% CI = 0.85-1.00), but not for CEL (HR
.
= 0.97, 95% CI = 0.89-1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development.
Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5′-phosphate (PLP) is a commonly used measure of vitamin B6 ...status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health.
We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics.
Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP.
In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 95% credible interval (CrI): 1.50, 1.71; Hcy:Cys 0.87 95% CrI: 0.84, 0.90; Cysta:Cys 0.89 95% CrI: 0.84, 0.94; HKr 0.88 95% CrI: 0.85, 0.91; PAr 1.00 95% CrI: 0.95, 1.05). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers.
We found that 5 different markers, capturing different aspects of vitamin B6–related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors.
Purpose
In this study, we aimed to study the correlation between acute and habitual intakes of flavonols, their main food sources and their 24-h urinary concentrations in an European population.
...Methods
A 24-h dietary recall (24-HDR) and 24-h urine samples were collected on the same day from a convenience subsample of 475 men and women from four countries (France, Italy, Greece and Germany) of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A standardized 24-HDR software and a country/centre-specific validated dietary questionnaire (DQ) were used to collect acute and habitual dietary data, respectively. The intake of dietary flavonols was estimated using the Phenol-Explorer database. Urinary flavonols (quercetin, isorhamnetin, and kaempferol) were analysed using tandem mass spectrometry with a previous enzymatic hydrolysis.
Results
Weak partial Spearman correlations between both dietary acute and habitual intake and urinary concentrations of quercetin (both
R
partial
~ 0.3) and total flavonols (both
R
partial
~ 0.2) were observed. No significant correlations were found for kaempferol and isorhamentin. Regarding flavonol-rich foods, weak correlations were found between urinary concentrations of quercetin and total flavonols and the acute intake of onions and garlics, fruits, tea, and herbal tea (all
R
partial
~ 0.2). For habitual intake, statistically significant correlations were only found between urinary quercetin concentration and herbal tea (
R
partial
= 0.345) and between urinary total flavonol concentration and tea, and herbal tea consumption (
R
partial
~ 0.2).
Conclusions
Our results suggest that urinary quercetin level can be used as potential concentration biomarkers of both acute and habitual quercetin intake, while urinary concentrations of flavonols are unlikely to be useful biomarkers of individual flavonol-rich foods.
Purpose
Excess iron is involved in the development of non-communicable diseases such as cancer, type 2 diabetes and cardiovascular conditions. We aimed to describe the prevalence of excess iron and ...its determinants in healthy European adults.
Methods
Sociodemographic, lifestyle, iron status, dietary information, and
HFE
genotyping were obtained from controls from the nested case–control study EPIC-EurGast study. High sensitivity C-reactive protein (hsCRP) was measured to address possible systemic inflammation. Descriptive and multivariate analyses were used to assess iron status and its determinants.
Results
Out of the 828 participants (median age: 58.7 years), 43% were females. Median serum ferritin and prevalence of excess iron were 143.7 µg/L and 35.2% in males, respectively, and 77 µg/L and 20% in females, both increasing with latitude across Europe. Prevalence of
HFE
C282Y mutation was significantly higher in Northern and Central Europe (~ 11%) than in the South (5%). Overweight/obesity, age, and daily alcohol and heme iron intake were independent determinants for iron status, with sex differences even after excluding participants with hsCRP > 5 mg/L. Obese males showed a greater consumption of alcohol, total and red meat, and heme iron, compared with those normal weight.
Conclusion
Obesity, higher alcohol and heme iron consumption were the main risk factors for excess iron in males while only age was associated with iron overload in females. Weight control and promoting healthy lifestyle may help prevent iron overload, especially in obese people. Further research is needed to clarify determinants of excess iron in the healthy adult population, helping to reduce the associated comorbidities.
This study examines the correlation of acute and habitual dietary intake of flavan-3-ol monomers, proanthocyanidins, theaflavins, and their main food sources with the urinary concentrations of ...(+)-catechin and (-)-epicatechin in the European Prospective Investigation into Cancer and Nutrition study (EPIC). Participants (N = 419, men and women) provided 24-h urine samples and completed a 24-h dietary recall (24-HDR) on the same day. Acute and habitual dietary data were collected using a standardized 24-HDR software and a validated dietary questionnaire, respectively. Intake of flavan-3-ols was estimated using the Phenol-Explorer database. Concentrations of (+)-catechin and (-)-epicatechin in 24-h urine were analyzed using tandem mass spectrometry after enzymatic deconjugation. Simple and partial Spearman's correlations showed that urinary concentrations of (+)-catechin, (-)-epicatechin and their sum were more strongly correlated with acute than with habitual intake of individual and total monomers (acute
= 0.13-0.54,
< 0.05; and habitual
= 0.14-0.28,
< 0.01), proanthocyanidins (acute
= 0.24-0.49,
< 0.001; and habitual
= 0.10-0.15,
< 0.05), theaflavins (acute
= 0.22-0.31,
< 0.001; and habitual
= 0.20-0.26,
< 0.01), and total flavan-3-ols (acute
= 0.40-0.48,
< 0.001; and habitual
= 0.23-0.33,
< 0.001). Similarly, urinary concentrations of flavan-3-ols were weakly correlated with both acute (
= 0.12-0.30,
< 0.05) and habitual intake (
= 0.10-0.27,
< 0.05) of apple and pear, stone fruits, berries, chocolate and chocolate products, cakes and pastries, tea, herbal tea, wine, red wine, and beer and cider. Moreover, all comparable correlations were stronger for urinary (-)-epicatechin than for (+)-catechin. In conclusion, our data support the use of urinary concentrations of (+)-catechin and (-)-epicatechin, especially as short-term nutritional biomarkers of dietary catechin, epicatechin and total flavan-3-ol monomers.
Accurate assessment of polyphenol intakes is needed in epidemiologic research in order to study their health effects, and this can be particularly challenging in international study settings.
The ...purpose of this work is to describe the procedures to prepare a comprehensive polyphenol food-composition database that was used to calculate standardized polyphenol intakes from 24-h diet recalls (24HDRs) and dietary questionnaires (DQs) in the European Prospective Investigation into Cancer and Nutrition (EPIC).
With the use of the comparable food classification and facet-descriptor system of the computerized 24HDR program EPIC-Soft (renamed GloboDiet), foods reported in the 24HDR (n = 74,626) were first aggregated following a stepwise process. Multi-ingredient and generic foods were broken down into ingredients or more-specific foods with consideration of regional consumption habits before matching to foods in the Phenol-Explorer database. Food-composition data were adjusted by using selected retention factors curated in Phenol-Explorer. DQ foods (n = 13,946) were matched to a generated EPIC 24HDR polyphenol-composition database before calculation of daily intakes from the 24HDR and DQ.
Food matching yielded 2.0% and 2.7% of foods with missing polyphenol content in the 24HDR and DQ food data sets, respectively. Process-specific retention factors for 42 different polyphenol compounds were applied to adjust the polyphenol content in 35 prioritized Phenol-Explorer foods, thereby adjusting the polyphenol content in 70% of all of the prepared 24 food occurrences. A detailed food-composition database was finally generated for 437 polyphenols in 19,899 aggregated raw and prepared foods reported by 10 EPIC countries in the 24HDR.
An efficient procedure was developed to build the most-comprehensive food-composition database for polyphenols, thereby standardizing the calculations of dietary polyphenol intakes obtained from different dietary assessment methods and European populations. The whole database is accessible online. This procedure could equally be used for other food constituents and in other cohorts.
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