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Background Colorectal cancer is the third most common malignancy worldwide and is strongly linked to lifestyle and environmental risk factors. Although several drinking-water disinfection by-products are confirmed rodent carcinogens, the evidence in humans for carcinogenicity associated with these by-products, including colorectal cancer, is still inconclusive. Methods We assessed the association of long-term exposure to trihalomethanes (THMs), the most prevalent disinfection by-products in chlorinated drinking water, with incidence of colorectal cancer in 58 672 men and women in 2 population-based cohorts. Exposure was assessed by combining long-term information of residential history with drinking water–monitoring data. Participants were categorized according to no exposure, low exposure (<15 µg/L), and high exposure (≥15 µg/L). Incident cases of colorectal cancer were ascertained by use of the Swedish National Cancer Register. Results During an average follow-up of 16.8 years (988 144 person-years), 1913 cases of colorectal cancer were ascertained (1176 cases in men and 746 in women, respectively). High THM concentrations in drinking water (≥15 µg/L) were associated with increased risk of colorectal cancer in men (hazard ratio = 1.26, 95% confidence interval = 1.05-1.51) compared with no exposure. When subsites were assessed, the association was statistically significant for proximal colon cancer (hazard ratio = 1.59, 95% confidence interval = 1.11 to 2.27) but not for distal colon cancer or rectal cancer. In women, we observed overall no association of THMs with colorectal cancer. Conclusion These results add further evidence that disinfection by-products in drinking water may be a possible risk factor for proximal colon cancer in men. This observation was made at THM concentrations lower than those in most previous studies. [ABSTRACT FROM AUTHOR]

Objectives: The aim was to systematically review the associations among white meat consumption, cardiovascular diseases (CVD), and type 2 diabetes (T2D). Methods: Databases MEDLINE, Embase, and Cochrane Central Register of Controlled Trials and Scopus were searched (15th October 2021) for randomized intervention trials (RCTs, ≥ 4 weeks of duration) and prospective cohort studies (≥12 month of follow-up) assessing the consumption of white meat as the intervention/exposure. Eligible outcomes for RCTs were cardiometabolic risk factors and for cohorts, fatal and non-fatal CVD and incident T2D. Risk of bias was estimated using the Cochrane's RoB2 and Risk of Bias for Nutrition Observational Studies. Meta-analysis was conducted in case of ≥3 relevant intervention studies or ≥5 cohort studies using random-effects models. The strength of evidence was evaluated using the World Cancer Research Fund's criteria. Results: The literature search yielded 5,795 scientific articles, and after screening 43 full-text articles, 23 cohort studies and three intervention studies were included. All included intervention studies matched fat content of intervention and control diets, and none of them showed any significant effects on the selected outcomes of white meat when compared to red meat. Findings from the cohort studies generally did not support any associations between white meat intake and outcomes. Meta-analyses were conducted for CVD mortality (RR: 0.95, 95% CI: 0.87-1.02, P = 0.23, I² = 25%) and T2D incidence (RR: 0.98, 95% CI: 0.87-1.11, P = 0.81, I² = 82%). Conclusion: The currently available evidence does not indicate a role, beneficial or detrimental, of white meat consumption for CVD and T2D. Future studies investigating potentially different health effects of processed versus unprocessed white meat and substitution of red meat with white meat are warranted. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to systematically review the evidence for associations between consumption of legumes and cardiovascular disease (CVD), type 2 diabetes (T2D) and their risk factors among healthy adults. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus up to 16 May 2022 for ≥4 weeks long randomized (RCT) and non-randomized controlled trials and prospective cohort studies with follow-up ≥12 months, assessing legume intake (beans/lentils/peas/soybeans, excluding peanuts and legume-products/protein/powder/flour) as the intervention or exposure. Outcomes were CVD, coronary heart disease (CHD), stroke, T2D and in intervention trials only: changes in blood lipids, glycemic markers, and blood pressure. Risk of bias (RoB) was evaluated with Cochrane's RoB2, ROBINS-I, and US Department of Agriculture (USDA)'s RoB-NObS. Effect sizes were pooled using random-effects meta-analyses and expressed as relative risk or weighed mean differences with 95% confidence intervals, heterogeneity quantified as I². The evidence was appraised according to World Cancer Research Fund's criteria. Results: Of the 181 full-text articles assessed for eligibility, 47 were included: 31 cohort studies (2,081,432 participants with generally low legume consumption), 14 crossover RCTs (448 participants), one parallel RCT and one non-randomized trial. Meta-analyses of cohort studies were suggestive of null associations for CVD, CHD, stroke and T2D. Meta-analyses of RCTs suggested a protective effect on total cholesterol (mean difference -0.22 mmol/L), low density lipoprotein (LDL)-cholesterol (-0.19 mmol/L), fasting glucose (-0.19 mmol/L), and HOMA-IR (-0.30). Heterogeneity was high (I² = 52% for LDL-cholesterol, >75% for others). The overall evidence for associations between consumption of legumes and risk of CVD and T2D was considered limited -- no conclusion. Conclusion: Legume consumption was not found to influence risk of CVD and T2D in healthy adult populations with generally low legume consumption. However, protective effects on risk factors, seen in RCTs, lend some support for recommending legume consumption as part of diverse and healthy dietary patterns for prevention of CVD and T2D. [ABSTRACT FROM AUTHOR]

Objectives: To systematically review the evidence on the effect of replacing the intake of animal protein with plant protein on cardiovascular disease (CVD) and type 2 diabetes (T2D) and their intermediate risk factors. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus up to 12th May 2022 for randomized controlled trials (RCTs) or prospective cohort studies that investigated replacement of animal protein with plant protein from foods. Outcomes were CVDs, T2D, and in RCTs also the effects on blood lipids, glycemic markers, and blood pressure. Risk of bias was evaluated with the Cochrane's RoB2, ROBINS-I, and USDA's RoB-NObS tools. Random-effects meta-analyses assessed the effects of plant vs. animal proteins on blood lipids in RCTs. The evidence was appraised according to the World Cancer Research Fund's criteria. Results: After screening 15,090 titles/abstracts, full text of 124 papers was scrutinized in detail, from which 13 RCTs and seven cohort studies were included. Eight of the RCTs had either some concern or high risk of bias, while the corresponding evaluation of cohort studies resulted in moderate risk of bias for all seven. Meta-analyses of RCTs suggested a protective effect on total cholesterol (mean difference -0.11 mmol/L; 95% CI -0.22, -0.01) and low-density lipoprotein cholesterol (-0.14 mmol/L; 95% CI -0.25, -0.02) by replacing animal protein with plant protein. The substitution of animal protein with plant protein (percentage of energy intake) in cohort studies was associated with lower CVD mortality (n = 4) and lower T2D incidence (n = 2). The evidence was considered limited-suggestive for both outcomes. Conclusion: Evidence that the substitution of animal protein with plant protein reduces risk of both CVD mortality and T2D incidence is limited-suggestive. Replacing animal protein with plant protein for aspects of sustainability may also be a public health strategy to lower the risk of CVD mortality and T2D. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to systematically review studies and evaluate the strength of the evidence on nuts/seeds consumption and cardiometabolic diseases and their risk factors among adults. Methods: A protocol was pre-registered in PROSPERO (CRD42021270554). We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to September 20, 2021 for prospective cohort studies and ≥12-week randomized controlled trials (RCTs). Main outcomes were cardiovascular disease (CVD), coronary heart disease (CHD), stroke and type 2 diabetes (T2D), secondary total-/low density lipoprotein (LDL)-cholesterol, blood pressure and glycaemic markers. Data extraction and risk of bias (RoB) assessments (using RoB 2.0 and RoB-NObS) were performed in duplicate. Effect sizes were pooled using random-effects meta-analyses and expressed as relative risk (RR) or weighted mean differences with 95% confidence intervals (CI); heterogeneity quantified as I². One-stage dose-response analyses assessed the linear and non-linear associations with CVD, CHD, stroke and T2D. The strength of evidence was classified per the World Cancer Research Fund criteria. Results: After screening 23,244 references, we included 42 papers from cohort studies (28 unique cohorts, 1,890,573 participants) and 18 RCTs (2,266 participants). In the cohorts, mainly populations with low consumption, high versus low total nuts/seeds consumption was inversely associated with total CVD (RR 0.81; 95% CI 0.75, 0.86; I² = 67%), CVD mortality (0.77; 0.72, 0.82; I² = 59.3%), CHD (0.82; 0.76, 0.89; I² = 64%), CHD mortality (0.75; 0.65, 0.87; I² = 66.9%) and non-fatal CHD (0.85; 0.75, 0.96; I² = 62.2%). According to the non-linear dose-response analyses, consumption of 30 g/day of total nuts/seeds was associated with RRs of similar magnitude. For stroke and T2D the summary RR for high versus low intake was 0.91 (95% CI 0.85, 0.97; I² = 24.8%) and 0.95 (0.75, 1.21; I² = 82.2%). Intake of nuts (median ~50 g/day) lowered total (-0.15 mmol/L; -0.22, -0.08; I² = 31.2%) and LDL-cholesterol (-0.13 mmol/L; -0.21, -0.05; II² = 68.6%), but not blood pressure. Findings on fasting glucose, HbA1c and insulin resistance were conflicting. The results were robust to sensitivity and subgroup analyses. We rated the associations between nuts/seeds and both CVD and CHD as probable. There was limited but suggestive evidence for no association with stroke. No conclusion could be made for T2D. Conclusion: There is a probable relationship between consumption of nuts/seeds and lower risk of CVD, mostly driven by CHD, possibly in part through effects on blood lipids. More research on stroke and T2D may affect the conclusions. The evidence of specific nuts should be further investigated. [ABSTRACT FROM AUTHOR]

BACKGROUND: Drinking water chlorination by-products have been associated with adverse reproductive outcomes, although the findings for congenital malformations are still inconclusive. OBJECTIVE: We conducted a nationwide register-based prospective study to assess whether first trimester maternal exposure to the four most common trihalomethanes [total trihalomethanes (TTHM)] via municipal drinking water was associated with risk of congenital malformation among newborns. METHODS: We included all births during 2005–2015 (live and stillbirths) of mothers residing in Swedish localities having >10,000 inhabitants, two or fewer operating water works, and sufficient municipal TTHM monitoring data. Individual maternal first trimester exposure was obtained by linking TTHM measurements to residential information, categorized into no chlorination and <5, 5–15, and >15 μg TTHM/L. We also made chlorination treatment-specific analyses (exclusive use of chloramine or hypochlorite). Outcomes and covariates were obtained via linkage to health care and administrative registers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. RESULTS: Based on 623,468 births and a prevalence of congenital malformation of ~2 cases/100 births, we observed associations between TTHM exposure in areas using chloramine and malformations of the nervous system (OR = 1:82; 95% CI: 1.07, 3.12), urinary system (OR = 2:06; 95% CI: 1.53, 2.78), genitals (OR = 1:77; 95% CI: 1.38, 2.26), and limbs (OR = 1:34; 95% CI: 1.10, 1.64), comparing the highest exposed category with the unexposed. No associations were observed in areas using exclusively hypochlorite as the primary water treatment method. By contrast, for malformations of the heart, a significant inverse association was observed only in areas using hypochlorite. DISCUSSION: TTHM exposure was associated with the increased risk of malformations of the nervous system, urinary system, genitals, and limbs in areas exclusively using chloramine. An association between chloramine-related chlorination by-products and congenital malformations has not previously been highlighted and needs further attention. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although randomized controlled trials (RCTs) have demonstrated that high fluoride increases bone mineral density (BMD) and skeletal fragility, observational studies of low-dose chronic exposure through drinking water (<1.5 mg/L, the maximum recommended by the World Health Organization) have been inconclusive. OBJECTIVE: We assessed associations of fluoride in urine, and intake via diet and drinking water, with BMD and fracture incidence in postmenopausal women exposed to drinking water fluoride ≤ mg/L. METHODS: Data were from participants in the Swedish Mammography Cohort-Clinical, a population-based prospective cohort study. At baseline (2004-2009), fluoride exposure was assessed based on urine concentrations (푛=4,306) and estimated dietary intake (including drinking water) (푛=4,072), and BMD was measured using dual energy X-ray absorptiometry. Incident fractures were ascertained via register-linkage through 2017. Residential history was collected to identify women with long-term consistent drinking water exposures prior to baseline. RESULTS: At baseline, mean urine fluoride was 1.2 mg/g creatinine (±1.9) and mean dietary intake was 2.2 mg/d (±0:9), respectively. During follow up, 850, 529, and 187 cases of any fractures, osteoporotic fractures, and hip fractures, respectively, were ascertained. Baseline BMD was slightly higher among women in the highest vs. lowest tertiles of exposure. Fluoride exposures were positively associated with incident hip fractures, with multivariable-adjusted hazard ratios of 1.50 (95% CI: 1.04, 2.17) and 1.59 (95% CI: 1.10, 2.30), for the highest vs. lowest tertiles of urine fluoride and dietary fluoride, respectively. Associations with other fractures were less pronounced for urine fluoride, and null for dietary fluoride. Restricting the analyses to women with consistent long-term drinking water exposures prior to baseline strengthened associations between fractures and urinary fluoride. DISCUSSION: In this cohort of postmenopausal women, the risk of fractures was increased in association with two separate indicators of fluoride exposure. Our findings are consistent with RCTs and suggest that high consumption of drinking water with a fluoride concentration of ~1 mg/L may increase both BMD and skeletal fragility in older women [ABSTRACT FROM AUTHOR]

Background: Conflicting evidence associates diet acidity with the incidence of chronic diseases such as hypertension, diabetes, kidney disease, and bone-mineral disorders. It is currently unknown whether dietary acidity is associated with death.Objective: We investigated the association of dietary acid load with the risk of all-cause and cardiovascular disease (CVD) mortality.Methods: We used data from 2 prospective cohorts, the Swedish Mammography Cohort and the Cohort of Swedish Men, which included 36,740 women and 44,957 men aged 45-84 y at the start of a 15-y follow-up period (1998-2012). Acid load was estimated from food-frequency questionnaires by use of the validated potential renal acid load (PRAL) algorithm. Deaths were ascertained via record linkage. Associations of PRAL with mortality were modeled by use of restricted cubic splines.Results: The median PRAL was 0.65 mEq/d (range: -109 to 81.5 mEq/d) in women and 12.3 mEq/d (-111 to 121 mEq/d) in men. During a mean of 13.5 ± 3.3 y of follow-up, there were 8576 and 13,332 deaths, of which 3203 and 5427 were attributed to cardiovascular causes in woman and men, respectively. In both sexes, a nonlinear U-shaped relation was observed, with higher mortality rates for both dietary acid and alkali excess. Compared with neutral PRAL (0 mEq/d), the HRs for all-cause mortality for the 10th and 90th percentiles of PRAL were 1.05 (95% CI: 1.01, 1.10) and 1.03 (95% CI: 0.98, 1.08), respectively, in women. The corresponding results for men were HRs 1.01 (95% CI: 1.00, 1.02) and 1.04 (95% CI: 1.00, 1.08) respectively. This relation was slightly stronger for CVD mortality.Conclusions: Excess diet alkalinity and acidity both showed weak associations with higher mortality in Swedish adults. An acid-base balanced diet was associated with the lowest mortality, but the magnitude of mortality reduction was modest. The Swedish Mammography Cohort was registered at clinicaltrials.gov as NCT01127698 The Cohort of Swedish Men was registered at clinicaltrials.gov as NCT01127711. [ABSTRACT FROM AUTHOR]

Background: Exposure to cadmium (Cd) has long been recognized as a health hazard, both in industry and in general populations with high exposure. Under the currently prevailing health risk assessment, the relationship between urinary Cd (U-Cd) concentrations and tubular proteinuria is used. However, doubts have recently been raised regarding the justification of basing the risk assessment on this relationship at very low exposure. Objectives: Our objective was to review available information on health effects of Cd exposure with respect to human health risk assessment. Discussion: The associations between U-Cd and urinary proteins at very low exposure may not be due to Cd toxicity, and the clinical significance of slight proteinuria may also be limited. More importantly, other effects have been reported at very low Cd exposure. There is reason to challenge the basis of the existing health risk assessment for Cd. Our review of the literature found that exposure to low concentrations of Cd is associated with effects on bone, including increased risk of osteoporosis and fractures, and that this observation has implications for the health risk assessment of Cd. Other effects associated with Cd should also be considered, in particular cancer, although the information is still too limited for appropriate use in quantitative risk assessment. Conclusion: Non-renal effects should be considered critical effects in the health risk assessment of Cd. [ABSTRACT FROM AUTHOR]

The prevalence of obesity is increasing in most parts of the world. The objective of this study was to examine whether changes in food patterns were associated with changes in BMI among women over 9 y. Data were from 33,840 women participating in the Swedish Mammography Cohort in 1987 and 1997. Diet was assessed with a FFQ at both time points and 4 food patterns were derived using confirmatory factor analysis (Healthy, Western/Swedish, Alcohol, and Sweets). Our exposure variables were defined as change in factor score for each food pattern from 1987 to 1997. Our outcome variable was defined as change in BMI during the same period, and we also examined change in weight. Normal weight and overweight women had positive changes in weight and BMI during follow-up, whereas obese women had negative changes in BMI and weight; we observed a significant interaction between change in food patterns and baseline BMI. Obese subjects who increased their factor score for the Healthy pattern had larger decreases in BMI (beta = -0.18 kg/m(2) for a 1 unit increase in SD score, CI: -0.26 to -0.10; P < 0.0001), whereas normal weight and overweight women who increased their Healthy pattern score had smaller increases in BMI (-0.05 kg/m(2) and -0.11 kg/m(2), respectively; P < 0.05 for both). Obese women who increased their Healthy pattern score >3 SD had almost a 4 kg decrease in weight and a 1 unit decrease in BMI at follow-up. In conclusion, changes in eating patterns were significantly related to changes in BMI over 9 y and the effect was modified by baseline BMI. Pattern analysis is helpful in generating hypotheses regarding the role of diet in obesity, and additional research is needed to understand which elements of our patterns are protective or risk factors for weight gain. [ABSTRACT FROM AUTHOR]

• Several CBP substances have been suggested to possess carcinogenic properties. • 3 Out of the 4 most common THMs are genotoxic and 2 are rodent carcinogens. • Human data on the cancer link is limited as confirmation from cohorts is lacking. • We evaluated the association of THM with bladder cancer in two large cohort studies. • No association of THM exposure up to 20 µg/L and risk of bladder cancer was found. Chlorination by-products have been consistently associated with risk of bladder cancer in case-control studies, but confirmation from large-scale cohort studies is lacking. We assessed the association of drinking water trihalomethanes (THM), a proxy for chlorination by-products, with risk of bladder cancer in 58,672 men and women. Data came from two population-based cohorts, parts of the Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research (SIMPLER). Individual exposure to THM was assessed by combining residential information with tap water monitoring data. Participants were categorized into non-exposed, low (<15 µg/L) or high (≥15 µg/L) THM exposure. Incident cases were ascertained from 1998 through 2019 via register linkage. During 16 years of follow-up (965,590 person-years), 831 bladder cancer cases were ascertained. We observed no overall association of THM with risk of bladder cancer, hazard ratio for the highest exposed compared to the non-exposed 0.90 (95% confidence interval: 0.73 – 1.11). The null association remained after restricting the analysis to long-term residents and across strata of smoking status and cancer stage. Our results indicate that chlorination by-product exposure at THM concentrations representative of chlorinated drinking waters in most European countries, is not associated with an increased risk of bladder cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Osteoporosis and its main health outcome, fragility fractures, are large and escalating public health problems. Cadmium, a widespread food contaminant, is a proposed risk factor; still the association between estimated dietary cadmium exposure and bone mineral density (BMD) has never been assessed. Within a sub-cohort of the Swedish Mammography Cohort, we assessed dietary cadmium exposure based on a food frequency questionnaire (1997) and urinary cadmium (2004–2008) in relation to total-body BMD and risk of osteoporosis and fractures (1997–2009) among 2676 women (aged 56–69years). In multivariable-adjusted linear regression, dietary cadmium was inversely associated with BMD at the total body and lumbar spine. After further adjustment for dietary factors important for bone health and cadmium bioavailability—calcium, magnesium, iron and fiber, the associations became more pronounced. A 32% increased risk of osteoporosis (95% CI: 2–71%) and 31% increased risk for any first incident fracture (95% CI: 2–69%) were observed comparing high dietary cadmium exposure (≥13μg/day, median) with lower exposures (<13μg/day). By combining high dietary with high urinary cadmium (≥0.50μg/g creatinine), odds ratios among never-smokers were 2.65 (95% CI: 1.43–4.91) for osteoporosis and 3.05 (95% CI: 1.66–5.59) for fractures. In conclusion, even low-level cadmium exposure from food is associated with low BMD and an increased risk of osteoporosis and fractures. The partial masking of the associations by essential nutrients indicates important interplay between dietary factors and contaminants present in food. In separate analyses, dietary and urinary cadmium underestimated the association with bone effects. [Copyright &y& Elsevier]