Fish - a scoping review for Nordic Nutrition Recommendations 2023.

The aim of this scoping review was to conduct evidence-based documentation between fish intake and health outcomes for food-based dietary guidelines (FBDGs) in the Nordic Nutrition Recommendations (NNR) 2023. For most health outcomes, the evidence for fish oil and n-3 long chain (LC) polyunsaturated fatty acids (PUFA) supplementation was included when examining evidence between fish intake and health. In this review, conclusions from qualified systematic reviews (qSR) approved by NNR2023 are included. In addition, conclusions of a de novo systematic reviews on the topic of n-3 LC-PUFA, asthma, and allergy are included. Finally, a systematic literature search was performed limited to systematic reviews and meta-analysis published between 2011 and September 2021. In total, 21 papers from the systematic literature search, four qSR, and eight reports were included addressing the association between fish intake, fish oil, and n-3 LC-PUFA supplementation on several health outcomes. These included cardiovascular disease (CVD), type 2 diabetes, cancers (colorectal, breast, and prostate), metabolic syndrome, obesity, mortality, cognition and mental health, pregnancy-related outcomes (preterm birth and birth weight), and outcomes specific for children (neurodevelopment, and risk of food allergies, and asthma). In addition, intermediate risk factors such as blood lipids, glucose, C-reactive protein, and blood pressure were reviewed. Based on current evidence, fish consumption can have beneficial effects to prevent coronary heart disease (CHD) and stroke incidence, and lower mortality from CVD, CHD, myocardial infarction (MI), and stroke, as well as total mortality risk. In addition, fish consumption is beneficial for preventing cognitive decline in adults (e.g. dementia and Alzheimer's disease). Fish intake may also prevent metabolic syndrome, supported by an observed association between fish intake and reduction in plasma triglycerides and increase in high-density lipoprotein (HDL) cholesterol levels. Data from fish oil and n-3 LC-PUFA supplementation studies supports the conclusions on the effects of fish consumption on most of the health outcomes.

Calcium - a scoping review for Nordic Nutrition Recommendations 2023.

The aim of this scoping review was to conduct evidence-based documentations between calcium (Ca) intake and health outcomes for updating dietary reference values (DRVs) and food-based dietary guidelines (FBDGs) in the sixth edition of Nordic Nutrient Recommendations (NNR2023). The systematic literature search was limited to reviews on human data published between 2011 and June 2021. Systematic reviews (SRs) and original publications of relevance for this scoping review were included. A common practice of designing studies on health outcomes related to Ca supplement intake is to examine combined Ca and vitamin D, and therefore, a combination of Ca with vitamin D (CaD) was included in this review. In total, 27 studies addressing the association between dietary or supplemental Ca on bone health, bone mineral density (BMD), pregnancy-related outcomes, cardiovascular diseases (CVD), cancers, obesity, and mortality were reviewed. SRs showed that both dietary and supplemental Ca intakes were positively associated with BMD, but evidence did not support the benefit in fracture prevention. Current evidence did not support that Ca or CaD supplementation increases risk of coronary heart disease or all-cause mortality in older adults, but that Ca may be beneficial for hypertension, especially in young people. Increasing Ca intake may be beneficial during pregnancy, especially for those at high risk of pre-eclampsia due to ethnicity, age, high BMI, and those with low baseline Ca intake. The associations between high Ca intake and cancers were varied, with strong evidence that high consumption of dairy products is protective against colorectal cancer and limited-suggestive evidence that dairy products and diets high in Ca might also be protective against breast cancer. Moreover, there is limited-suggestive evidence that dairy products and diets high in Ca increase the risk of prostate cancer. Based on current evidence, Ca intake is beneficial or neutral in relation to most of the outcomes evaluated in this review. Data from the Nordic countries show that average Ca intake is around the same as previously recommended by NNR. However, the average Ca intake in the Baltic countries is below the recommendations.

Dietary patterns in adolescence and risk of colorectal cancer: a population-based study.

PURPOSE: To study whether dietary patterns in adolescence are associated with risk of colorectal cancer (CRC). METHODS: Food frequency data were obtained from the AGES-Reykjavik study, conducted between 2002 and 2006, which included 5,078 (58% women) participants with mean age of 77 (± 5.8) years. Principal component analysis was used to identify dietary patterns. Participants were followed through linkage to the Icelandic Cancer Registry. Multivariable Cox models were used to calculate hazard ratios (HR) of CRC and 95% confidence interval (CI) by dietary patterns. RESULTS: During the follow-up period (mean 8.2 years), 136 participants (75 women and 61 men) were diagnosed with CRC. The main dietary pattern in adolescence was characterized by high intake of traditional food items consumed in the earlier half of the twentieth century, namely, salted or smoked meat and fish, milk, offal, rye bread, and oatmeal. Compared to the lowest tertile, the middle tertile of this pattern was associated with increased risk of CRC (HR 1.63, 95% CI 1.04-2.57), while the highest tertile was not statistically associated with CRC (HR 1.48, 95% CI 0.93-2.37), except among women (HR 2.06, 95% CI 1.11-3.84). CONCLUSION: These data suggest that strong adherence to a traditional Icelandic diet in adolescence might increase the risk of CRC, particularly among women. More research is need on the association between food items and dietary patterns of relevance to CRC at different points in the life cycle.

Randomized Trial for Weight Loss Using a Digital Therapeutic Application.

BACKGROUND: Smartphones present a near-ubiquitous channel through which structured lifestyle change can reduce risk or progression of the most common noncommunicable diseases. We explored whether a digital structured lifestyle program enhances weight loss. METHODS: We randomized overweight and obese participants attending a four-month lifestyle change program to either standard weekly coaching sessions (controls), or standard treatment supplemented with a digital therapeutic mobile application (intervention). Changes in body mass index after four months were the main outcome measure. Odds ratios of achieving 5% weight loss were estimated with unconditional logistic regression. RESULTS: Of 234 eligible persons, 146 (62%) agreed to participate, were block-randomized, showed up for the baseline measures, and constituted the intention-to-treat (ITT) sample (n = 95 intervention group, n = 51 control group). In the intervention group, 70 (74%) downloaded the mobile application and completed the program (intervention per-protocol). Significant weight loss and BMI reduction were observed for both the intention-to-treat intervention group (P < 0.05, P = 0.01) and the per-protocol intervention group (P < 0.0001, P < 0.0001). For the intervention per-protocol group, the odds ratio of achieving 5% weight loss, compared to not treated per-protocol, was 3.3 (95% CI 1.3-8.2), adjusting for age and weight at baseline.Attendance to weekly coaching sessions decreased by 18% during the program in the control group while it increased by 3% amongst the per-protocol group (P = 0.004). CONCLUSIONS: These preliminary findings support the benefit of a digital therapeutic to enhance weight reduction and attendance in a structured lifestyle change program. Larger trials of longer duration are needed to confirm these findings.

Growth Rate in Childhood and Adolescence and the Risk of Breast and Prostate Cancer: A Population-Based Study.

Growth rate is regulated by hormonal pathways that might affect early cancer development. We explored the association between rate of growth in height from ages 8 to 13 years (childhood) and from age 13 to attainment of adult height (adolescence), as measured at study entry, and the risk of breast or prostate cancer. Participants were 2,037 Icelanders born during 1915-1935, who took part in the Reykjavik Study, established in 1967. Height measurements were obtained from school records and at study entry. We used multivariable Cox regression models to calculate hazard ratios with 95% confidence intervals of breast and prostate cancer by rates of growth in tertiles. During a mean follow-up of 66 years (women) and 64 years (men), 117 women were diagnosed with breast cancer and 118 men with prostate cancer (45 with advanced disease). Women in the highest growth-rate tertile in adolescence had a higher risk of breast cancer (hazard ratio = 2.4, 95% confidence interval: 1.3, 4.3) compared with women in the lowest tertile. A suggestive inverse association was observed for highest adolescent growth rate in men and advanced prostate cancer: hazard ratio = 0.4, 95% confidence interval: 0.2, 1.0. Rapid growth, particularly in adolescence may affect cancer risk later in life.

Vitamin D status and current policies to achieve adequate vitamin D intake in the Nordic countries.

Aims: Nordic countries share fairly similar food culture and geographical location as well as common nutrition recommendations. The aim of this paper was to review the latest data on vitamin D status and intake and to describe the national supplementation and food fortification policies to achieve adequate vitamin D intake in the Nordic countries. Methods: The data are based on results derived from a literature search presented in a workshop held in Helsinki in November 2018 and completed by recent studies. Results: Vitamin D policies and the implementation of the recommendations differ among the Nordic countries. Vitamin D fortification policies can be mandatory or voluntary and widespread, moderate or non-existent. Vitamin D supplementation recommendations differ, ranging from all age groups being advised to take supplements to only infants. In the general adult population of the Nordic countries, vitamin D status and intake are better than in the risk groups that are not consuming vitamin D supplements or foods containing vitamin D. Non-Western immigrant populations in all Nordic countries share the problem of vitamin D insufficiency and deficiency. Conclusions: Despite the common nutrition recommendations, there are differences between the Nordic countries in the implementation of the recommendations and policies to achieve adequate vitamin D intake and status. There is a need for wider Nordic collaboration studies as well as strategies to improve vitamin D status, especially in risk groups.

Type 2 diabetes and obesity in midlife and breast cancer risk in the Reykjavik cohort.

PURPOSE: As obesity and type 2 diabetes (T2D) have been increasing worldwide, we investigated their association with breast cancer incidence in the Reykjavik Study. METHODS: During 1968-1996, approximately 10,000 women (mean age = 53 ± 9 years) completed questionnaires and donated blood samples. T2D status was classified according to self-report (n = 140) and glucose levels (n = 154) at cohort entry. A linkage with the Icelandic Cancer Registry provided breast cancer incidence through 2015. Cox regression with age as time metric and adjusted for known confounders was applied to obtain hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Of 9,606 participants, 294 (3.1%) were classified as T2D cases at cohort entry while 728 (7.8%) women were diagnosed with breast cancer during 28.4 ± 11.6 years of follow-up. No significant association of T2D (HR 0.95; 95% CI 0.56-1.53) with breast cancer incidence was detected except among the small number of women with advanced breast cancer (HR 3.30; 95% CI 1.13-9.62). Breast cancer incidence was elevated among overweight/obese women without (HR 1.18; 95% CI 1.01-1.37) and with T2D (HR 1.35; 95% CI 0.79-2.31). Height also predicted higher breast cancer incidence (HR 1.03; 95% CI 1.02-1.05). All findings were confirmed in women of the AGES-Reykjavik sub-cohort (n = 3,103) who returned for an exam during 2002-2006. With a 10% T2D prevalence and 93 incident breast cancer cases, the HR for T2D was 1.18 (95% CI 0.62-2.27). CONCLUSIONS: These findings in a population with low T2D incidence suggest that the presence of T2D does not confer additional breast cancer risk and confirm the importance of height and excess body weight as breast cancer risk factors.

Body fat distribution on computed tomography imaging and prostate cancer risk and mortality in the AGES-Reykjavik study.

BACKGROUND: The World Cancer Research Fund classifies as "strong evidence" the link between obesity and the risk of advanced prostate cancer. In light of the different hormonal profiles associated with where adipose is stored, this study investigated the role of objectively measured body fat distribution and the risk of clinically relevant prostate cancer. METHODS: This was a prospective study of 1832 men in the Age, Gene/Environment Susceptibility-Reykjavik study. From 2002 to 2006, participants underwent baseline computed tomography imaging of fat deposition, bioelectric impedance analysis, and measurement of body mass index (BMI) and waist circumference. Men were followed through linkage with nationwide cancer registries for the incidence of total (n = 172), high-grade (Gleason grade ≥8; n = 43), advanced (≥cT3b/N1/M1 at diagnosis or fatal prostate cancer over follow-up; n = 41), and fatal prostate cancer (n = 31) through 2015. Cox regression was used to evaluate the association between adiposity measures and prostate cancer outcomes. RESULTS: Among all men, visceral fat (hazard ratio [HR], 1.31 per 1-standard deviation [SD] increase; 95% confidence interval [CI], 1.00-1.72) and thigh subcutaneous fat (HR, 1.37 per 1-SD increase; 95% CI, 1.00-1.88) were associated with risk of advanced and fatal disease, respectively. Among men who were leaner based on BMI, visceral fat was associated with both advanced and fatal disease. BMI and waist circumference were associated with a higher risk of advanced and fatal disease. No adiposity measures were associated with total or high-grade disease. CONCLUSIONS: Specific fat depots as well as BMI and waist circumference were associated with the risk of aggressive prostate cancer, which may help to elucidate underlying mechanisms and target intervention strategies.

Pre-diagnostic 25-hydroxyvitamin D levels and survival in cancer patients.

PURPOSE: Our main aim was to explore whether pre-diagnostic circulating levels of 25-hydroxyvitamin D (25(OH)D) among older individuals with cancer were associated with overall and cancer-specific survival after diagnosis. DESIGN: We used data from the Reykjavik-AGES Study on participants (n = 4,619) without cancer at entry, when blood samples were taken for 25(OH)D standardized measurements. The association with cancer risk, all-cause- and cancer-specific mortality was assessed among those later diagnosed with cancer, comparing four 25(OH)D categories, using 50-69.9 nmol/L as the reference category. RESULTS: Cancer was diagnosed in 919 participants on average 8.3 years after blood draw. No association was observed between the reference group and other 25(OH)D groups and total cancer incidence. Mean age at diagnosis was 80.9 (± 5.7) years. Of those diagnosed, 552 died during follow-up, 67% from cancer. Low pre-diagnostic levels of 25(OH)D < 30 nmol/L were significantly associated with increased total mortality (HR: 1.39, 95% CI 1.03, 1.88) and non-significantly with cancer-specific mortality (HR: 1.33, 95% CI 0.93, 1.90). Among patients surviving more than 2 years after diagnosis, higher pre-diagnostic 25(OH)D levels (≥ 70 nmol/L) were associated with lower risk of overall (HR: 0.68, 95% CI 0.46, 0.99) and cancer-specific mortality (HR: 0.47, 95% CI 0.26, 0.99). CONCLUSIONS: Among elderly cancer patients, low pre-diagnostic serum 25(OH)D levels (< 30 nmol/L) were associated with increased overall mortality.

Hip fractures among older people in Iceland between 2008 and 2012.

INTRODUCTION: Hip fractures are a serious injury especially among older people, mainly caused by falls and women have a higher risk. The authors studied gender differences in hip fractures, marital status, waiting times for surgery and mortality in an older population. METHODS: Data was obtained for all 67 years and older admitted with hip fractures to an Emergency Department (ED) in Iceland 2008-2012. The associations of covariates with mortality were analyzed using multivariable logistic regression. RESULTS: The study included 1053 patients; covering 80% of hip fractures in Iceland during the study period, 72% were women. Men were more often married (51% vs. 23%) (P < 0.001). Average waiting time was men vs. women 21.5 h/18.9 h (p = 0.003). Mortality within 12 months was men 36% vs. women 21% (Odds Ratio (OR); 2.30, 95% Confidence Interval (CI); 1.66-3.18). Higher mortality rates were observed in older age-groups compared to 67-79 years old, i.e.80-89 years: OR 1.80 (95% CI 1.25-2.60) and 90-109 years: OR 4.52 (95% CI 2.91-7.01). Waiting time was not associated with 12-months mortality risk after adjustment. CONCLUSION: Although women constitute the majority of elderly with hip fractures, men had higher mortality in our study. Further reserach that examine factors affecting gender difference will likey be of benefit and associated changes to the care already dleivered in the ED may improve mortality.

Dietary intake is associated with risk of multiple myeloma and its precursor disease.

The etiology of monoclonal gammopathy of undetermined significance (MGUS), the precursor state of multiple myeloma (MM), is mostly unknown and no studies have been conducted on the effect of diet on MGUS or progression from MGUS to MM. We aimed to explore the association between common foods and MGUS and progression to MM. Data from the population-based AGES Study (N = 5,764) were utilized. Food frequency questionnaire was used to assess dietary intake during adolescence, midlife, and late life. Serum protein electrophoresis and serum free light-chain assay was performed to identify MGUS (n = 300) and LC-MGUS cases (n = 275). We cross linked our data with the Icelandic Cancer Registry to find cases of MM in the study group. We found that intake of fruit at least three times per week during adolescence was associated with lower risk of MGUS when compared to lower fruit consumption (OR = 0.62, 95% CI 0.41-0.95). We additionally found that intake of fruit at least three times per week during the late life period was associated with decreased risk of progressing from MGUS to MM (HR = 0.34, 95% CI 0.13-0.89) when compared to lower intake. Adolescent intake of fruit may reduce risk of MGUS, whereas fruit intake after MGUS onset may reduce risk of progressing to MM. Our findings suggest that diet might alter the risk of developing MGUS and progression to MM.

Correction: Dietary habits in adolescence and midlife and risk of breast cancer in older women.

[This corrects the article DOI: 10.1371/journal.pone.0198017.].

Dietary habits in adolescence and midlife and risk of breast cancer in older women.

Recent studies indicate that lifestyle factors in early life affect breast cancer risk. We therefore explored the association of high consumption of meat, milk, and whole grain products in adolescence and midlife, on breast cancer risk. We used data from the population based AGES-Reykjavik cohort (2002-2006), where 3,326 women with a mean age of 77 years (SD 6.0) participated. For food items and principal component derived dietary patterns we used Cox proportional models to calculate multivariate hazard ratios (HR) with 95% confidence intervals (95% CI). During a mean follow-up of 8.8 years, 97 women were diagnosed with breast cancer. For both adolescence and midlife, daily consumption of rye bread was positively associated with breast cancer (HR 1.7, 95% CI 1.1-2.6 and HR 1.8, 95% CI 1.1-2.9, respectively). In contrast, persistent high consumption of oatmeal was negatively associated with breast cancer (0.4, 95% CI 0.2-0.9). No association was found for other food items or dietary patterns that included rye bread. High rye bread consumption in adolescence and midlife may increase risk of late-life breast cancer whilst persistent consumption of oatmeal may reduce the risk.

Midlife metabolic factors and prostate cancer risk in later life.

Metabolic syndrome is associated with several cancers, but evidence for aggressive prostate cancer is sparse. We prospectively investigated the influence of metabolic syndrome and its components on risk of total prostate cancer and measures of aggressive disease in a cohort of Icelandic men. Men in the Reykjavik Study (n = 9,097, enrolled 1967-1987) were followed for incident (n = 1,084 total; n = 378 advanced; n = 148 high-grade) and fatal (n = 340) prostate cancer until 2014. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for (1) measured metabolic factors at cohort entry (body mass index (BMI), blood pressure, triglycerides, fasting blood glucose) and (2) a metabolic syndrome score (range 0-4) combining the risk factors: BMI ≥30 kg/m2 ; systolic blood pressure (SBP) ≥130 or diastolic blood pressure (DBP) ≥85 mm Hg or taking antihypertensives; triglycerides ≥150 mg/dl; fasting blood glucose ≥100 mg/dl or self-reported type 2 diabetes. Hypertension and type 2 diabetes were associated with a higher risk of total, advanced, high-grade, and fatal prostate cancer, independent of BMI. Neither BMI nor triglycerides were associated with prostate cancer risk. Higher metabolic syndrome score (3-4 vs 0) was associated with a higher risk of fatal prostate cancer (HR 1.55; 95% CI: 0.89, 2.69; p trend = 0.08), although this finding was not statistically significant. Our findings suggest a positive association between midlife hypertension and diabetes and risk of total and aggressive prostate cancer. Further, metabolic syndrome as a combination of factors was associated with an increased risk of fatal prostate cancer.

Early Life Residence, Fish Consumption, and Risk of Breast Cancer.

Background: Little is known about fish intake throughout the life course and the risk of breast cancer.Methods: We used data on the first residence of 9,340 women born 1908 to 1935 in the Reykjavik Study as well as food frequency data for different periods of life from a subgroup of the cohort entering the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study (n = 2,882).Results: During a mean follow-up of 27.3 years, 744 women were diagnosed with breast cancer in the Reykjavik Study. An inverse association of breast cancer was observed among women who lived through the puberty period in coastal villages, compared with women residing in the capital area [HR, 0.78; 95% confidence interval (CI), 0.61-0.99]. In the subgroup analysis of this Icelandic population, generally characterized by high fish intake, we found an indication of lower risk of breast cancer among women with high fish consumption (more than 4 portions per week) in adolescence (HR, 0.71; 95% CI, 0.44-1.13) and midlife (HR, 0.46; 95% CI, 0.22-0.97), compared with low consumers (2 portions per week or less). No association was found for fish liver oil consumption in any time period, which could be due to lack of a reference group with low omega-3 fatty acids intake in the study group.Conclusions: Our findings suggest that very high fish consumption in early to midlife may be associated with a reduced risk of breast cancer.Impact: Very high fish consumption in early adulthood to midlife may be associated with decreased risk of breast cancer. Cancer Epidemiol Biomarkers Prev; 26(3); 346-54. ©2016 AACR.

Health Behavior and Metabolic Risk Factors Associated with Normal Weight Obesity in Adolescents.

OBJECTIVE: To explore health behaviors and metabolic risk factors in normal weight obese (NWO) adolescents compared with normal weight lean (NWL) peers. DESIGN AND METHODS: A cross-sectional study of 18-year-old students (n = 182, 47% female) in the capital area of Iceland, with body mass index within normal range (BMI, 18.5-24.9 kg/m2). Body composition was estimated via dual energy X-ray absorptiometry, fitness was assessed with maximal oxygen uptake (VO2max) during treadmill test, dietary intake through 24-hour recall, questionnaires explained health behavior and fasting blood samples were taken. NWO was defined as normal BMI and body fat >17.6% in males and >31.6% in females. RESULTS: Among normal weight adolescents, 42% (n = 76) were defined as NWO, thereof 61% (n = 46) male participants. Fewer participants with NWO were physically active, ate breakfast on a regular basis, and consumed vegetables frequently compared with NWL. No difference was detected between the two groups in energy- and nutrient intake. The mean difference in aerobic fitness was 5.1 ml/kg/min between the groups in favor of the NWL group (p<0.001). NWO was positively associated with having one or more risk factors for metabolic syndrome (Odds Ratio OR = 2.2; 95% confidence interval CI: 1.2, 3.9) when adjusted for sex. High waist circumference was more prevalent among NWO than NWL, but only among girls (13% vs 4%, p = 0.019). CONCLUSIONS: High prevalence of NWO was observed in the study group. Promoting healthy lifestyle with regard to nutrition and physical activity in early life should be emphasized regardless of BMI.

Fish and fish-liver oil consumption in adolescence and midlife and risk of CHD in older women.

OBJECTIVE: To study the association of fish and fish-liver oil consumption across the lifespan with CHD later in life among Icelandic women, with special emphasis on the effects of consumption in adolescence. DESIGN: Prevalence association study. Logistic regression was used to estimate odds ratios and 95 % confidence intervals of CHD according to fish or fish-liver oil exposure. Models were adjusted for age, education, concurrent diet and other known risk factors. SETTING: The study was nested within the AGES-Reykjavik Study, conducted in Reykjavik, Iceland. SUBJECTS: Participants were 3326 women aged 66-96 years, with available information on CHD status at entry to the study and information on fish and fish-liver oil consumption during midlife and adolescence. Dietary habits were assessed retrospectively using a validated FFQ. RESULTS: CHD was identified in 234 (7·9 %) women. Compared with women with no intake of fish-liver oil in adolescence or midlife, women who consumed fish-liver oil at least three times weekly in adolescence or in midlife had a decreased risk of CHD (OR=0·62; 95 % CI 0·45, 0·85 and OR=0·68; 95 % CI 0·50, 0·94, respectively). No associations were observed between fish intake (>2 portions/week v. ≤2 portions/week) in adolescence or midlife and CHD in this population with high fish intake. CONCLUSIONS: Fish-liver oil consumption, from early life, may reduce the risk of CHD in older women. Lifelong nutrition may be of importance in the prevention of CHD in older women.

Physical Activity from Early Adulthood and Risk of Prostate Cancer: A 24-Year Follow-Up Study among Icelandic Men.

Physical activity in adult life may reduce prostate cancer risk. Data are scarce on the role of activity during early adulthood, as well as combined recreational and occupational physical activity on prostate cancer risk and mortality. We undertook a prospective study of 8,221 Icelandic men (born 1907 to 1935) in the population-based Reykjavik Study. At enrollment, between 1967 and 1987, the men provided information on regular recreational physical activity since the age of 20 years as well as current occupational activity. Through linkage to nationwide cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality through 2009. We used Cox models to calculate the relative risk of prostate cancer by level of physical activity. During a mean follow-up of 24.8 years, 1,052 men were diagnosed with prostate cancer, of whom 349 had advanced disease (stage 3+ or prostate cancer death). Neither recreational nor occupational physical activity was, independently or combined, associated with overall or localized prostate cancer. Compared with physically inactive men, we observed a nonsignificant lower risk of advanced prostate cancer [HR, 0.67; 95% confidence interval (CI), 0.42-1.07] among men reporting both recreational and occupational physical activities (P value for interaction = 0.03). Awaiting confirmation in larger studies with detailed assessment of physical activity, our data suggest that extensive physical activity beginning in early adulthood may reduce the risk of advanced prostate cancer.