Association Between Improved Serum Fatty Acid Profiles and Cognitive Function During a Dietary Intervention Trial in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Cognitive impairment is a common multiple sclerosis (MS)-related symptom that impacts quality of life (QOL). Diet interventions are shown to be beneficial in managing QOL, and the intake of essential fatty acids is linked with improved cognitive function. However, the effect of diets on serum fatty acid profiles and cognitive function is unknown. METHODS: A previous randomized, parallel-arm trial recruited participants with relapsing-remitting MS (N = 77). Study visits included 4 time points: run-in, baseline, 12 weeks, and 24 weeks. During the run-in phase, participants followed their usual diet and were then randomly assigned to either a modified paleolithic (Wahls) or a low saturated fat (Swank) diet at baseline. Assessments at study visits included cognitive function assessed by Symbol Digit Modalities Test-Oral (SDMT-O) and Perceived Deficits Questionnaire (PDQ), and serum fatty acids, including eicosapentaenoic (EPA), docosahexaenoic (DHA), and arachidonic (ARA) acids. RESULTS: Both groups had significant improvements in all serum fatty acids (P < .01), except for ARA, as well as SDMT-O at 24-weeks (P < .05), total PDQ at 12 and 24 weeks (P < .01) compared with baseline values. The 12-week changes in ω-3 (EPA + DHA) index and EPA serum fatty acids were associated with SDMT-O changes (P ≤ .05); however, the changes in fatty acid levels did not mediate the effect of the diets on SDMT-O or PDQ (P > .05). CONCLUSIONS: Both diets led to improvements in serum fatty acid profiles and cognitive function, with associations between the 12-week ω-3 (EPA + DHA) index and EPA changes with SDMT-O.

The effect of dietary interventions on inflammatory biomarkers among people with multiple sclerosis: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system, characterized by demyelination and neurodegeneration, which has a profound impact on the quality of life. Dysregulated inflammatory processes are a major driver of MS progression, with many areas of research being dedicated to modulating inflammation in people with MS. Several dietary patterns have been associated with improvements in inflammatory biomarkers; although, the findings have been inconsistent. Thus, this study aims to evaluate the effects of dietary interventions on inflammatory markers in adults with MS. METHODS: Electronic databases, including PubMed/MEDLINE, Web of Science, Scopus, and Cochrane/Central, will be searched. Screening, selection, and extraction of data, along with quality assessment of included studies, will be done by two separate reviewers, and any potential conflicts will be settled through discussion. Two reviewers will independently assess the risk of bias in included studies using the Cochrane Risk of Bias Tool. If plausible, the results will be synthesized and pooled for meta-analysis. The overall quality of evidence of each study will be evaluated using the NutriGRADE tool, which is a modification to the Grading Recommendations Assessment, Development, and Evaluation (GRADE) developed specifically for nutrition research. DISCUSSION: Studies have demonstrated conflicting results regarding the effects of dietary interventions on serum levels of inflammatory biomarkers among people with MS. Thus, it is expected that the planned systematic review and meta-analysis will yield robust evidence on the effects of diet on inflammatory profile in the setting of MS.

Traditional Mexican dietary pattern and cancer risk among women of Mexican descent.

PURPOSE: To examine the association of a traditional Mexican diet score with risk of total, breast, and colorectal cancer among women of Mexican ethnic descent in the Women's Health Initiative (WHI). METHODS: Participants were WHI enrollees who self-identified as being of Mexican descent. Data from food frequency questionnaires self-administered at study baseline were used to calculate the MexD score, with higher scores indicating greater adherence to an a priori-defined traditional Mexican diet (high in dietary fiber, vegetables, and legumes). Incident cancers were self-reported by participants from 1993 to 2020 and adjudicated by trained physicians. We used multivariable-adjusted Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among 2,343 Mexican descent women (median baseline age: 59 years), a total of 270 cancers (88 breast, 37 colorectal) occurred during a mean follow-up of 14.4 years. The highest tertile of MexD score was associated with a lower risk of all-cancer incidence (HR: 0.67; 95% CI 0.49-0.91; p-trend: 0.01) and colorectal cancer (HR: 0.38; 95% CI 0.14-0.998; p-trend < 0.05), with each unit increase in the MexD score associated with a 6% lower risk of all-cancer incidence (HR: 0.94; 95% CI 0.88-0.99). There was no statistically significant association with risk of breast cancer. CONCLUSION: Consumption of a traditional Mexican diet was associated with a significantly lower risk of all-cancer incidence and colorectal cancer. Confirmation of these findings in future studies is important, given the prevalence of colorectal cancer and a growing U.S. population of women of Mexican descent.

Dietary Intervention Favorably Influences Physical Functioning: The Women's Health Initiative Randomized Dietary Modification Trial.

BACKGROUND: In the Women's Health Initiative Dietary Modification randomized trial, the dietary intervention reduced breast cancer mortality by 21% (P = .02) and increased physical activity as well. OBJECTIVE: Therefore, the aim was to examine whether or not these lifestyle changes attenuated age-related physical functioning decline. DESIGN: In a randomized trial, the influence of 8 years of a low-fat dietary pattern intervention was examined through 20 years of cumulative follow-up. PARTICIPANTS AND SETTING: From 1993 to 1998, 48,835 postmenopausal women, ages 50 to 79 years with no prior breast cancer and negative baseline mammogram were randomized at 40 US clinical centers to dietary intervention or usual diet comparison groups (40 out of 60). The intervention significantly reduced fat intake and increased vegetable, fruit, and grain intake. MAIN OUTCOME MEASURES: In post hoc analyses, physical functioning, assessed using the RAND 36-Item Short Form Health Survey, evaluated quality or limitations of 10 hierarchical physical activities. Longitudinal physical functioning, reported against a disability threshold (when assistance in daily activities is required) was the primary study outcome. STATISTICAL ANALYSES PERFORMED: Semiparametric linear mixed effect models were used to contrast physical functioning trajectories by randomization groups. RESULTS: Physical functioning score, assessed 495,317 times with 11.0 (median) assessments per participant, was significantly higher in the intervention vs comparison groups through 12 years of cumulative follow-up (P = .001), representing a reduction in age-related functional decline. The intervention effect subsequently attenuated and did not delay time to the disability threshold. Among women in the dietary intervention vs comparison groups, aged 50 to 59 years, who were physically inactive at entry, a persistent, statistically significant, favorable influence on physical functioning with associated delay in crossing the disability threshold by approximately a year was seen (P value for interaction = .007). CONCLUSIONS: In the Women's Health Initiative Dietary Modification randomized trial, a dietary intervention that significantly reduced breast cancer mortality also significantly reduced age-related functional decline through 12 years, which was attenuated with longer follow-up.

Effects of a Remote Multimodal Intervention Involving Diet, Walking Program, and Breathing Exercise on Quality of Life Among Newly Diagnosed People with Multiple Sclerosis: A Quasi-Experimental Non-Inferiority Pilot Study.

Background: Interventions involving diet, physical activity, and breathing exercises are shown to be beneficial in managing both fatigue and quality of life (QoL) related to MS; however, the impact of such interventions among people newly diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS) who decline disease-modifying therapies (DMTs) is unknown. Methods: A 12-month prospective quasi-experimental non-inferiority trial recruited people newly diagnosed with CIS or RRMS who voluntarily declined DMTs (health behavior group; HB, n = 29) or followed standard of care (SOC, n = 15). Participants in the HB group were remotely coached on the study diet, moderate-intensity walking, and breathing exercises. All participants completed questionnaires validated to assess MS symptoms, including perceived mental and physical QoL (MSQOL54); fatigue (Fatigue Severity Scale, FSS; and Modified Fatigue Impact Scale, MFIS); mood (Hospital Anxiety and Depression Scale, HADS); and cognitive function (Perceived Deficits Questionnaire, PDQ). Results: During the 12 months, the HB group experienced improvement in scores for mental QoL (MSQOL54 - Mental, 0.24, 95% CI 0.01, 0.47; p = 0.04), fatigue (Total MFIS, -7.26, 95% CI -13.3,-1.18; p = 0.02), and perceived cognitive function (Total PDQ, PDQ-Attention, PDQ-Promemory, and PDQ-Planning, p ≤ 0.03 for all). A between-group difference was observed only for PDQ-Planning (p = 0.048). Non-inferiority analysis revealed that the 12-month changes in means for the HB group were not worse than those for the SOC group with respect to fatigue (FSS, p = 0.02), mood (HDS-Anxiety, p = 0.02; HADS-Depression, p < 0.0001), physical QoL (MSQOL54 - Physical, p = 0.02), or cognitive dysfunction (Total PDQ, p = 0.01). Conclusion: The multimodal lifestyle intervention for individuals newly diagnosed with CIS or RRMS, who voluntarily decline DMTs, did not yield patient-reported outcomes worse than those observed in the SOC group regarding perceived mental quality of life, mood, fatigue, and cognitive function. Trial Registration: clinicaltrials.gov identifier: NCT04009005.

Untargeted serum metabolomic profiles and breast density in young women.

PURPOSE OF THE STUDY: Breast density is an established risk factor for breast cancer. However, little is known about metabolic influences on breast density phenotypes. We conducted untargeted serum metabolomics analyses to identify metabolic signatures associated with breast density phenotypes among young women. METHODS: In a cross-sectional study of 173 young women aged 25-29 who participated in the Dietary Intervention Study in Children 2006 Follow-up Study, 449 metabolites were measured in fasting serum samples using ultra-high-performance liquid chromatography-tandem mass spectrometry. Multivariable-adjusted mixed-effects linear regression identified metabolites associated with magnetic resonance imaging measured breast density phenotypes: percent dense breast volume (%DBV), absolute dense breast volume (ADBV), and absolute non-dense breast volume (ANDBV). Metabolite results were corrected for multiple comparisons using a false discovery rate adjusted p-value (q). RESULTS: The amino acids valine and leucine were significantly inversely associated with %DBV. For each 1 SD increase in valine and leucine, %DBV decreased by 20.9% (q = 0.02) and 18.4% (q = 0.04), respectively. ANDBV was significantly positively associated with 16 lipid and one amino acid metabolites, whereas no metabolites were associated with ADBV. Metabolite set enrichment analysis also revealed associations of distinct metabolic signatures with %DBV, ADBV, and ANDBV; branched chain amino acids had the strongest inverse association with %DBV (p = 0.002); whereas, diacylglycerols and phospholipids were positively associated with ANDBV (p ≤ 0.002), no significant associations were observed for ADBV. CONCLUSION: Our results suggest an inverse association of branched chain amino acids with %DBV. Larger studies in diverse populations are needed.

Association of type 2 diabetes mellitus with dementia-related and non-dementia-related mortality among postmenopausal women: A secondary competing risks analysis of the women's health initiative.

INTRODUCTION: Alzheimer's disease (AD) and AD-related dementias (ADRD) are leading causes of death among older adults in the United States. Efforts to understand risk factors for prevention are needed. METHODS: Participants (n = 146,166) enrolled in the Women's Health Initiative without AD at baseline were included. Diabetes status was ascertained from self-reported questionnaires and deaths attributed to AD/ADRD from hospital, autopsy, and death records. Competing risk regression models were used to estimate the cause-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for the prospective association of type 2 diabetes mellitus (T2DM) with AD/ADRD and non-AD/ADRD mortality. RESULTS: There were 29,393 treated T2DM cases and 8628 AD/ADRD deaths during 21.6 (14.0-23.5) median (IQR) years of follow-up. Fully adjusted HRs (95% CIs) of the association with T2DM were 2.94 (2.76-3.12) for AD/ADRD and 2.65 (2.60-2.71) for the competing risk of non-AD/ADRD mortality. DISCUSSION: T2DM is associated with AD/ADRD and non-AD/ADRD mortality. HIGHLIGHTS: Type 2 diabetes mellitus is more strongly associated with Alzheimer's disease (AD)/AD and related dementias (ADRD) mortality compared to the competing risk of non-AD/ADRD mortality among postmenopausal women. This relationship was consistent for AD and ADRD, respectively. This association is strongest among participants without obesity or hypertension and with younger age at baseline, higher diet quality, higher physical activity, higher alcohol consumption, and older age at the time of diagnosis of type 2 diabetes mellitus.

Diet-induced changes in functional disability are mediated by fatigue in relapsing-remitting multiple sclerosis: A secondary analysis of the WAVES randomized parallel-arm trial.

Background: People with multiple sclerosis (MS) often report dietary modifications; however, evidence on functional outcomes remains sparse. Objective: Evaluate the impact of the low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets on functional disability among people with relapsing-remitting MS. Methods: Baseline-referenced MS functional composite (MSFC) scores were calculated from nine-hole peg-test (NHPT), timed 25-foot walk, and oral symbol digit modalities test (SDMT-O) collected at four study visits: (a) run-in, (b) baseline, (c) 12 weeks, and (d) 24 weeks. Participants were observed at run-in and then randomized at baseline to either the Swank (n = 44) or Wahls (n = 43) diets. Results: Among the Swank group, MSFC scores significantly increased from -0.13 ± 0.14 at baseline to 0.10 ± 0.11 at 12 weeks (p = 0.04) and 0.14 ± 0.11 at 24 weeks (p = 0.02). Among the Wahls group, no change in MSFC scores was observed at 12 weeks from 0.10 ± 0.11 at baseline but increased to 0.28 ± 0.13 at 24 weeks (p = 0.002). In both groups, NHPT and SDMT-O z-scores increased at 24 weeks. Changes in MSFC and NHPT were mediated by fatigue. Discussion: Both diets reduced functional disability as mediated by fatigue. Trial Registration: Clinicaltrials.gov Identifier: NCT02914964.

Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality.

Importance: Approximately 65% of adults in the US consume sugar-sweetened beverages daily. Objective: To study the associations between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality. Design, Setting, and Participants: A prospective cohort with 98 786 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative from 1993 to 1998 at 40 clinical centers in the US and were followed up to March 1, 2020. Exposures: Sugar-sweetened beverage intake was assessed based on a food frequency questionnaire administered at baseline and defined as the sum of regular soft drinks and fruit drinks (not including fruit juice); artificially sweetened beverage intake was measured at 3-year follow-up. Main Outcomes and Measures: The primary outcomes were (1) liver cancer incidence, and (2) mortality due to chronic liver disease, defined as death from nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% CIs for liver cancer incidence and for chronic liver disease mortality, adjusting for potential confounders including demographics and lifestyle factors. Results: During a median follow-up of 20.9 years, 207 women developed liver cancer and 148 died from chronic liver disease. At baseline, 6.8% of women consumed 1 or more sugar-sweetened beverage servings per day, and 13.1% consumed 1 or more artificially sweetened beverage servings per day at 3-year follow-up. Compared with intake of 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more servings per day had a significantly higher risk of liver cancer (18.0 vs 10.3 per 100 000 person-years [P value for trend = .02]; adjusted HR, 1.85 [95% CI, 1.16-2.96]; P = .01) and chronic liver disease mortality (17.7 vs 7.1 per 100 000 person-years [P value for trend <.001]; adjusted HR, 1.68 [95% CI, 1.03-2.75]; P = .04). Compared with intake of 3 or fewer artificially sweetened beverages per month, individuals who consumed 1 or more artificially sweetened beverages per day did not have significantly increased incidence of liver cancer (11.8 vs 10.2 per 100 000 person-years [P value for trend = .70]; adjusted HR, 1.17 [95% CI, 0.70-1.94]; P = .55) or chronic liver disease mortality (7.1 vs 5.3 per 100 000 person-years [P value for trend = .32]; adjusted HR, 0.95 [95% CI, 0.49-1.84]; P = .88). Conclusions and Relevance: In postmenopausal women, compared with consuming 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more sugar-sweetened beverages per day had a higher incidence of liver cancer and death from chronic liver disease. Future studies should confirm these findings and identify the biological pathways of these associations.

Evaluation of a web-based program for the adoption of wellness behaviors to self-manage fatigue and improve quality of life among people with multiple sclerosis: A randomized waitlist-control trial.

BACKGROUND: Wellness is a promising area of research in multiple sclerosis (MS); however, considerable questions remain regarding the efficacy of behavioral interventions to improve wellness and which delivery methods yield favorable results. OBJECTIVE: To evaluate the efficacy of a wellness intervention consisting of diet, stress reduction techniques, sleep hygiene, and exercise, delivered via a 7-week web-based program with no tailored intervention support (e.g., counseling or resources) from the study team, on quality of life (QoL) and fatigue among people with MS. METHODS: Individuals (n = 100) with self-reported physician's diagnosis of relapsing-remitting MS or clinically isolated syndrome were recruited to enroll in this randomized waitlist-control trial consisting of three timepoints at 0, 12, and 24 weeks. Participants were randomized to begin the intervention at baseline (INT; n = 51) or to a waitlist to begin the intervention after the 12-week timepoint (WLC; n = 49), and both groups were followed for 24 weeks. RESULTS: At 12-weeks, 95 participants (46 INT and 49 WLC) completed the primary endpoint and 86 (42 INT and 44 WLC) completed the 24-week follow-up. Compared to baseline, the INT group had a significant increase in physical QoL (5.43 ± 1.85; P = 0.003) at 12-weeks which was maintained at 24-weeks. Physical QoL values in the WLC group did not significantly increase between weeks 12 and 24 (3.24 ± 2.03; P = 0.11); however, physical QoL values significantly improved compared to week 0 values (4.00 ± 1.87; P = 0.033). Neither group had significant changes in mental QoL. The INT group had a mean baseline to 12-week change of ­5.06 ± 1.79 (P = 0.005) for MFIS and -0.68 ± 0.21 (P = 0.002) for FSS, both of which were maintained at 24-weeks. The 12- to 24-week changes for the WLC group were -4.50 ± 1.81 (P = 0.013) for MFIS and -0.44 ± 0.17 (P = 0.011) for FSS. At 12-weeks, the INT group had significantly greater reductions in fatigue compared to the WLC (P = 0.009 for both MFIS and FSS). There were no between-group mean differences for physical or mental QoL, but a significantly higher proportion of participants had clinically significant improvement in physical QoL in the INT group (50%) compared to the WLC group (22.5%) at 12-weeks (P = 0.006). The 12-week intervention effect was similar during the active intervention phase (i.e., baseline to 12 weeks for INT and 12 to 24 weeks for WLC) in each group. Course completion rates significantly differed between groups with 47.9% of the INT group and 18.8% of the WLC group completing the course (P = 0.01). CONCLUSION: A wellness intervention delivered via a web-based program, without tailored support, resulted in significant improvements in fatigue compared to control. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05057676.

Association Between the Healthy Lifestyle Index and Risk of Multimorbidity in the Women's Health Initiative.

BACKGROUND: Multimorbidity, defined as the presence of 2 or more chronic health conditions, is increasingly common among older adults. The combination of lifestyle characteristics such as diet quality, smoking status, alcohol intake, physical activity (PA), sleep duration, and body fat as assessed by body mass index (BMI) or waist circumference, and risk of multimorbidity are not well understood. OBJECTIVES: We investigated the association between the healthy lifestyle index (HLI), generated by combining indicators of diet quality, smoking, alcohol, PA, sleep amount, and BMI, and risk of multimorbidity, a composite outcome that included cardiovascular disease (CVD), diabetes, cancer, and fracture. METHODS: We studied 62 037 postmenopausal women aged 50-79 years at enrollment in the Women's Health Initiative, with no reported history of CVD, diabetes, cancer, or fracture at baseline. Lifestyle characteristics measured at baseline were categorized and a score (0-4) was assigned to each category. The combined HLI (0-24) was grouped into quintiles, with higher quintiles indicating a healthier lifestyle. Multivariable adjusted estimates of hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of developing multimorbidity were obtained using Cox proportional hazard models. RESULTS: Over an average follow-up period of 16.3 years, 5 656 women developed multimorbidity. There was an inverse association between the HLI levels and risk of multimorbidity (compared to the HLI_1st quintile: HR_2nd quintile = 0.81 95% CI 0.74-0.83, HR_3rd quintile = 0.77 95% CI 0.71-0.83, HR_4th quintile = 0.70 95% CI 0.64-0.76, and HR_5th quintile = 0.60 95% CI 0.54-0.66; p trend < .001). Similar associations were observed after stratification by age or BMI categories. CONCLUSIONS: Among postmenopausal women, higher levels of the HLI were associated with a reduced risk of developing multimorbidity.

Associations of dietary cholesterol and fat, blood lipids, and risk for dementia in older women vary by APOE genotype.

INTRODUCTION: Whether apolipoprotein E's (APOE's) involvement in lipid metabolism contributes to Alzheimer's disease (AD) risk remains unknown. METHODS: Incident probable dementia and cognitive impairment (probable dementia+mild cognitive impairment) were analyzed in relation to baseline serum lipids (total, low-density lipoprotein [LDL], high-density lipoprotein [HDL], non-HDL cholesterol, total-to-HDL, LDL-to-HDL, remnant cholesterol, and triglycerides) using Mendelian randomization in 5358 postmenopausal women from the Women's Health Initiative Memory Study. We also examined associations of baseline dietary cholesterol and fat with lipids based on APOE status. RESULTS: After an average of 11.13 years, less favorable lipid levels related to greater dementia and cognitive impairment risk. Dementia (odds ratio [OR] = 3.13; 95% confidence interval [CI]: 2.31 to 4.24) and cognitive impairment (OR = 2.38; 95% CI: 1.85 to 3.06) risk were greatest in relation to higher remnant cholesterol levels. Greater cholesterol consumption related to poorer lipids in APOE4+ compared to APOE3 carriers. DISCUSSION: APOE4+ carriers consuming more cholesterol had less favorable lipids, which were associated with greater dementia and cognitive impairment risk. HIGHLIGHTS: Less favorable serum lipids were associated with higher dementia incidence. Mendelian randomization findings suggest causality between lipids and dementia. Lipid levels in older women may be clinical indicators of dementia risk. APOE4 carriers had poorest lipid profiles in relation to cholesterol consumption. APOE risk for dementia may be modifiable through lipid management.

Dietary omega-6/omega-3 fatty acids and risk of prostate cancer; Is there any potential interaction by organophosphate insecticides among the agricultural health study population.

BACKGROUND: In the United States (US), the average annual increase in the incidence of prostate cancer (PCa) has been 0.5% between 2013 and 2017. Although some modifiable factors have been identified as the risk factors for PCa, the effect of lower ratio of omega-6 to omega-3 fatty acids intake (N-6/N-3) remains unknown. Previous studies of the Agricultural Health Study (AHS) reported a significant positive association between PCa and selected organophosphate pesticides (OPs) including terbufos and fonofos. OBJECTIVE: The aim of this study was to evaluate the association between N-6/N-3 and PCa and any interaction between N-6/N-3 and 2 selected OPs (i.e., terbufos and fonofos) exposure. DESIGN AND PARTICIPANTS: This case-control study, nested within a prospective cohort study, was conducted on a subgroup of the AHS population (1193 PCa cases and 14,872 controls) who returned their dietary questionnaire between 1999 and 2003 MAIN OUTCOME MEASURES: PCa was coded based on the International Classification of Diseases of Oncology (ICD-O-3) definitions and obtained from the statewide cancer registries of Iowa (2003-2017) and North Carolina (2003-2014). STATISTICAL ANALYSIS: Multivariate logistic regression analysis was applied to obtain the odds ratios adjusted (aORs) for age at dietary assessment (years), race/ethnicity (white, African American, other), physical activity (hours/week), smoking (yes/no), terbufos (yes/no), fonofos (yes/no), diabetes, lycopene intake (milligrams/day), family history of PCa, and the interaction of N-6/N-3 with age, terbufos and fonofos. Pesticide exposure was assessed by self-administrated questionnaires collecting data on ever/never use of mentioned pesticides during lifetime as a yes/no variable. Assessing the P value for the interaction between pesticides and N-6/N-3, we used the continuous variable of "intensity adjusted cumulative exposure" to terbufos and fonofos. This exposure score was based on duration, intensity and frequency of exposure. We also conducted a stratified regression analysis by quartiles of age. RESULTS: Relative to the highest N-6/N-3 quartile, the lowest quartile was significantly associated with a decreased risk of PCa (aOR=0.61, 95% CI: 0.41-0.90), and quartile-specific aORs decreased toward the lowest quartile (Ptrend=<0.01). Based on the age-stratified analysis, the protective effect was only significant for the lowest quartile of N-6/N-3 among those aged between 48 and 55 years old (aORs=0.97, 95% CI, 0.45-0.55). Among those who were exposed to terbufos (ever exposure reported as yes in the self-report questionnaires), lower quartiles of N-6/N-3 were protective albeit nonsignificant (aORs: 0.86, 0.92, 0.91 in quartiles 1,2, and 3, respectively). No meaningful findings were observed for fonofos and N-6/N-3 interaction. CONCLUSION: Findings showed that lower N-6/N-3 may decrease risk of PCa among farmers. However, no significant interaction was found between selected organophosphate pesticides and N-6/N-3.

Association of serum homocysteine, folate, and vitamin B12 and mood following the Swank and Wahls elimination dietary interventions in relapsing-remitting multiple sclerosis: Secondary analysis of the WAVES trial.

BACKGROUND: Depression and anxiety are common psychiatric comorbidities among people with multiple sclerosis (MS). Emerging data suggest abnormal serum homocysteine, vitamin B12, and folate levels in people with MS, which are related to a range of neurological disorders, including mood and mental illnesses. Evidence suggests that dietary interventions could affect mood disorders via several pathways. This study aimed to evaluate the impact of the low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets, along with a supplement regimen, on mood as assessed by Hospital Anxiety and Depression Scale (HADS), and Mental Health Inventory (MHI). The secondary objective was to identify changes in serum levels of homocysteine, folate, and vitamin B12 and the association and mediation effects between their changes and HADS and MHI scores and their subscales among people with relapsing-remitting MS (RRMS). METHODS: In a previously conducted randomized parallel-arm trial, participants with RRMS (n = 77) were randomly allocated to either the Swank or Wahls diets at baseline and followed for 24 weeks. Blood was drawn at four study visits spaced 12 weeks apart: (1) run-in, (2) baseline, (3) 12 weeks, and (4) 24 weeks. Serum vitamin B12, folate, and homocysteine were analyzed. HADS and MHI questionnaires were also completed by participants at the four study visits to assess symptoms of depression and anxiety, behavioral control and positive affect respectively. RESULTS: Significant improvement in severity of depression (HADS-D) and anxiety (HADS-A) symptoms, MHI total, and MHI subscores were seen at 12 and 24 weeks in each diet group. Further, a significant within-group reduction in serum homocysteine and a significant increase in serum vitamin B12 level were observed in both groups at 12 and 24 weeks compared to corresponding baseline values (p ≤ 0.05 for all). All participants exceeded the analytical maximum threshold for folate of 20 nmol/L at 12 and 24 weeks. Changes in serum levels of homocysteine and vitamin B12 were not associated with and did not mediate changes in HADS depression, anxiety, MHI total and four subscales scores (p > 0.05). CONCLUSION: Participants on both Swank and Wahls dietary interventions, including folate and vitamin B12 supplements, showed significant improvement in mood. However, the favorable effects of both diets on mood were not associated with or mediated by the effect of the diets on serum levels of homocysteine, folate, and vitamin B12 (p > 0.05).

Supplemental B-Vitamins and Risk of Upper Gastrointestinal Cancers in the Women's Health Initiative.

B-vitamins contribute to DNA synthesis, maintenance, and regulation. Few studies have examined associations of supplemental sources of B-vitamins with the incidence of upper gastrointestinal (GI) cancers [including gastric (GCA) and esophageal (ECA) cancers]; the only prior study to comprehensively examine such intakes reported potential elevated risks of ECA. We examined 159,401 postmenopausal women, ages 50-79 years at baseline, including 302 incident GCA and 183 incident ECA cases, over 19 years of follow-up within the Women's Health Initiative observational study and clinic trials. Adjusted Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations of supplemental B-vitamins [riboflavin (B2), pyridoxine (B6), folic acid (B9), or cobalamin (B12)] with GCA and ECA risk, respectively. Although HRs were generally below 1.0, we observed no statistically significant associations between supplemental intakes of any of the evaluated B-vitamins with the risk of GCA or ECA. As the first prospective study to comprehensively assess these associations, our findings do not corroborate prior research indicating potential harm from supplemental B-vitamin intake for upper GI cancer risk. This study adds evidence that supplemental intakes of B-vitamins may be used by postmenopausal women without regard to their relationship with upper GI cancer risk.

Perspective: Organic food consumption during pregnancy and the potential effects on maternal and offspring health.

Pregnancy represents a critical window for both maternal and child health. Previous studies have shown that the consumption of an organic diet during pregnancy can reduce pesticide exposure compared with the consumption of a conventional diet. It is possible that this could, in turn, improve pregnancy outcomes, because maternal pesticide exposure during pregnancy has been associated with increased risk of pregnancy complications. Organic foods are produced by methods that comply with organic standards, generally restricting the use of agrochemicals, such as synthetic pesticides. In the past few decades, the global demand for organic foods has increased drastically, driven in large part by consumer beliefs that organic foods provide benefits to human health. However, the effects of organic food consumption during pregnancy on maternal and child health have not been established. This narrative review aims to summarize current evidence regarding the consumption of organic foods during pregnancy and the potential effects on short- and long-term health outcomes in mothers and offspring. We performed a comprehensive literature search and identified studies investigating the association between organic food consumption during pregnancy and health outcomes in mothers and their offspring. The outcomes identified from the literature search included pre-eclampsia, gestational diabetes mellitus, hypospadias, cryptorchidism, and otitis media. Although existing studies suggest that consumption of organic foods (overall or a specific kind) during pregnancy may have health benefits, further investigation to replicate the findings in other populations is needed. Moreover, because these previous studies have all been observational and thus may be limited by the potential for residual confounding and reverse causation, causal inference cannot be established. We argue that the next necessary step in this research is a randomized trial to test the efficacy of organic diet intervention in pregnancy on maternal and offspring health.

Association of Artificially Sweetened Beverage Consumption and Urinary Tract Cancers in the Women's Health Initiative Observational Study.

Background: Insufficient data exist to conclude whether consumption of artificially sweetened beverages is associated with a higher risk of urinary tract cancers. Objective: We sought to investigate whether urinary tract cancer incidence differed among women who consumed various amounts of artificially sweetened beverages. Design setting and participants: This was a secondary analysis of data from the Women's Health Initiative Observational Study, a multicenter longitudinal prospective study of the health of 93 676 postmenopausal women with a mean follow-up time of 13.5 yr. Women were identified at 40 clinical centers across the USA and enrolled from 1993 to 1998. Women between the ages of 50 and 79 yr were enrolled. We included women who answered questions about artificially sweetened beverage consumption and reported no prior urinary tract cancer diagnoses. The frequency of artificially sweetened beverage consumption was categorized as follows: rare artificially sweetened beverage consumption (never to fewer than one serving per week), frequent consumption (one to six servings per week), and daily consumption (more than one servings per day). Outcome measurements and statistical analysis: The incidence of urinary tract cancer reported during subsequent visits until February 28, 2020 was recorded. Demographic characteristics were compared between those with varying levels of artificially sweetened beverage consumption. Descriptive statistics were used to report the rates of urinary tract cancer diagnosis, and Cox regression models were constructed to determine hazard ratios and adjust for potential confounders. Results and limitations: We identified 80 388 participants who met the inclusion criteria. Most participants (64%) were infrequent consumers of artificially sweetened beverages, with 13% (n = 10 494) consuming more than one servings per day. The incidence of urinary tract cancers was low, with only 804 cases identified. Cox regression models showed that frequent artificially sweetened beverage consumption was associated with a higher risk of kidney cancer (adjusted hazard ratio 1.34, 95% confidence interval 1.03-1.75). There was no significant association between artificially sweetened beverage intake and bladder cancer. Conclusions: Frequent consumption of artificially sweetened beverages may be associated with a higher risk of kidney cancer among postmenopausal women. Patient summary: A secondary analysis of the Women's Health Initiative Observational Study showed that higher consumption of artificially sweetened beverages was associated with a higher risk of kidney cancer.

A comparison of associations of body mass index and dual-energy x-ray absorptiometry measured percentage fat and total fat with global serum metabolites in young women.

OBJECTIVE: Body mass index (BMI) does not directly measure adiposity, whereas dual-energy x-ray absorptiometry (DXA) provides valid direct estimates of adiposity. Therefore, this study evaluated usefulness of BMI as a measure of adiposity in serum metabolomics studies. METHODS: A cross-sectional analysis was conducted of 202 women aged 25 to 29 years in the Dietary Intervention Study in Children Follow-Up Study. Heights and weights were measured, and body composition was quantified using clinical DXA protocols. Serum metabolomic profiling was performed by liquid chromatography-tandem mass spectrometry. Partial correlations of BMI, percentage fat (%FAT), and total fat (TOTFAT) with log transformed serum metabolites were calculated. RESULTS: There was significant overlap in the 93 metabolites that correlated with BMI, %FAT, and/or TOTFAT; 9 differently correlated with BMI and %FAT, whereas 15 differently correlated with BMI and TOTFAT. Even for these metabolites, absolute differences were modest. Metabolite set enrichment analysis identified diacylglycerol and sphingolipid metabolism as overrepresented among metabolites significantly correlated with all three measures of adiposity. CONCLUSIONS: BMI can be a good proxy for DXA measured %FAT and TOTFAT in descriptive metabolomic studies of healthy, young White women. Larger studies in more diverse populations are needed to endorse more generalized conclusions.

Efficacy of Diet on Fatigue and Quality of Life in Multiple Sclerosis: A Systematic Review and Network Meta-analysis of Randomized Trials.

BACKGROUND AND OBJECTIVE: Emerging evidence suggests a role for diet in multiple sclerosis (MS) care; however, owing to methodological issues and heterogeneity of dietary interventions in preliminary trials, the current state of evidence does not support dietary recommendations for MS. The objective of this study was to assess the efficacy of different dietary approaches on MS-related fatigue and quality of life (QoL) through a systematic review of the literature and network meta-analysis (NMA). METHODS: Electronic database searches were performed in May 2021. Inclusion criteria were (1) randomized trial with a dietary intervention, (2) adults with definitive MS based on McDonald criteria, (3) patient-reported outcomes for fatigue and/or QoL, and (4) minimum intervention period of 4 weeks. For each outcome, standardized mean differences (SMDs) were calculated and included in random effects NMA to determine the pooled effect of each dietary intervention relative to each of the other dietary interventions. The protocol was registered at PROSPERO (CRD42021262648). RESULTS: Twelve trials comparing 8 dietary interventions (low-fat, Mediterranean, ketogenic, anti-inflammatory, Paleolithic, fasting, calorie restriction, and control [usual diet]), enrolling 608 participants, were included in the primary analysis. The Paleolithic (SMD -1.27; 95% CI -1.81 to -0.74), low-fat (SMD -0.90; 95% CI -1.39 to -0.42), and Mediterranean (SMD -0.89; 95% CI -1.15 to -0.64) diets showed greater reductions in fatigue compared with control. The Paleolithic (SMD 1.01; 95% CI 0.40-1.63) and Mediterranean (SMD 0.47; 95% CI 0.08-0.86) diets showed greater improvements in physical QoL compared with control. For improving mental QoL, the Paleolithic (SMD 0.81; 95% CI 0.26-1.37) and Mediterranean (SMD 0.36; 95% CI 0.06-0.65) diets were more effective compared with control. However, the NutriGRADE credibility of evidence for all direct comparisons is very low because of most of the included trials having high or moderate risk of bias, small sample sizes, and the limited number of studies included in this NMA. DISCUSSION: Several dietary interventions may reduce MS-related fatigue and improve physical and mental QoL; however, because of the limitations of this NMA, which are driven by the low quality of the included trials, these findings must be confirmed in high-quality, randomized, controlled trials.

Comparison of the Ketogenic Ratio of Macronutrients With the Low-Carbohydrate Diet Score and Their Association With Risk of Type 2 Diabetes in Postmenopausal Women: A Secondary Analysis of the Women's Health Initiative.

BACKGROUND: Previous attempts to identify low-carbohydrate diets (LCDs) in epidemiological studies relied on the LCD Score, which is unable to identify ketogenic dieters. Ketogenic ratios of macronutrients are clinical equations proposed to predict ketogenic diets; however, their utility in epidemiological studies is unknown. OBJECTIVE: To determine the number of participants consuming a ketogenic diet, compare ketogenic ratios to the LCD Score, and evaluate their association with type 2 diabetes mellitus (T2DM). DESIGN: Secondary analysis of the Women's Health Initiative with 17.9 ± 6.03 years of follow-up. Baseline food frequency questionnaires were used to calculate the ketogenic ratio as follows: (0.9 × grams fat + 0.46 × grams protein) / (0.1 × grams fat + 0.58 × grams protein + grams net carbohydrate), a value ≥1.5 is the minimum threshold for a ketogenic diet. PARTICIPANTS/SETTING: One hundred twenty-five nine hundred eighty-two postmenopausal women without diabetes (aged 50 to 79 years) enrolled in the multicenter Women's Health Initiative observational study and clinical trials were included. MAIN OUTCOME MEASURES: Risk of self-reported incident T2DM. STATISTICAL ANALYSES PERFORMED: Cox proportional hazards models, adjusted for age, race, ethnicity, education, income, health insurance, relationship status, geographic region, Women's Health Initiative study component, female hormone use, smoking status, alcohol use, recreational physical activity, total energy intake, diet quality, body mass index, hyperlipidemia, and hypertension, were used to compare hazard ratios and 95% CIs for T2DM among quintiles of the ketogenic ratio. RESULTS: A total of 18,775 incident cases of T2DM occurred. The median ketogenic ratio was 0.35 (interquartile range 0.28 to 0.42) and 15 individuals (0.01%) exceeded the threshold for a ketogenic diet. Higher ketogenic ratio quintiles were associated with increased risk of T2DM in a dose-dependent manner. Comparing extreme quintiles of the ketogenic ratio, the hazard ratio for diabetes was 1.24 (95% CI 1.18 to 1.31; Ptrend < 0.001) in fully adjusted models. Similarly, comparing extreme quintiles, the hazard ratio for diabetes was 1.36 (95% CI 1.29 to 1.43; Ptrend < 0.001) for the LCD Score and 1.13 (95% CI 1.07 to 1.19; Ptrend < 0.001) for the simplified ketogenic ratio in fully adjusted models. CONCLUSIONS: Increasing ketogenic ratio values are associated with increased risk of T2DM and align well with LCD Scores; however, too few participants consumed a ketogenic diet to determine its association with T2DM.