Sex-specific associations of circulating testosterone levels with all-cause and cause-specific mortality

Objective: Testosterone is a critical determinant of health in both genders. However, the relationship between circulating levels of testosterone and mortality remains undetermined. Methods: We examined the associations of serum total testosterone (TT) and free testosterone (FT) with all-cause and cause-specific mortality in 154,965 men and 93,314 postmenopausal women from UK Biobank. Cox regression models were used to calculate the hazard ratios (HR) and 95% confidence intervals (CI). Given multiple testing, P < 0.005 was considered statistically significant. Results: Over a median follow-up of 8.9 (inter-quartile range, 8.3-9.5) years, we documented 5,754 deaths in men, including 1,243 (21.6%) from CVD and 2,987 (51.9%) from cancer. In postmenopausal women, 2,435 deaths occurred, including 346 (14.2%) from CVD and 1,583 (65.0%) from cancer. TT and FT concentrations were inversely associated with all-cause mortality in men, with the multivariable HR of 0.82 (95% CI: 0.75-0.91) and 0.80 (95% CI: 0.73-0.87) for the highest (Q5) versus the lowest quintile (Q1), respectively. In postmenopausal women, TT concentrations showed a positive association with all-cause mortality (HR for Q5 versus Q1 = 1.20, 95% CI: 1.06-1.37). Furthermore, higher TT and FT concentrations were associated with a lower risk of cancer mortality in men (both P for trend = 0.001), whereas TT concentrations were suggestively associated with a higher risk of cancer mortality in postmenopausal women (P for trend = 0.03). Conclusions: Our findings suggest that high levels of circulating testosterone may be beneficial for all-cause and cancer mortality in men but detrimental in postmenopausal women.

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Free testosterone and malignant melanoma risk in men: prospective analyses of testosterone and SHBG with 19 cancers in men and postmenopausal women UK Biobank

10.1101/2020.12.03.20241976 ◽

2020 ◽

Author(s):

Eleanor L. Watts ◽

Aurora Perez-Cornago ◽

Anika Knuppel ◽

Konstantinos K. Tsilidis ◽

Timothy J. Key ◽

...

Keyword(s):

Prostate Cancer ◽

Malignant Melanoma ◽

Liver Cancer ◽

Postmenopausal Women ◽

Multiple Testing ◽

Cox Regression ◽

Free Testosterone ◽

Sex Hormone Binding Globulin ◽

Total Testosterone ◽

Uk Biobank

AbstractWe investigated the associations of estimated free and total circulating testosterone and sex hormone-binding globulin (SHBG) with cancer risk in men and postmenopausal women, using a pan-cancer approach, including 19 cancers in UK Biobank.Risk was estimated using multivariable-adjusted Cox regression in up to 182,608 men and 122,112 postmenopausal women who were cancer-free at baseline. Participants diagnosed with cancer within two years of baseline were excluded. Hazard ratios (HRs) and confidence intervals (CIs) were corrected for regression dilution bias using repeat measurements. We accounted for multiple testing using the false discovery rate.In men, higher free testosterone was associated with higher risks of melanoma and prostate cancer (HR per 50 pmol/L increase=1.35, 95% CI 1.14-1.61 and 1.10,1.04-1.18, respectively). Higher total testosterone was associated with an elevated risk of liver cancer (HR per 5 nmol/L=2.45,1.56-3.84), and higher SHBG was associated with a higher risk of liver cancer (HR per 10 nmol/L=1.56,1.31-1.87) and a lower risk of prostate cancer (0.93,0.91-0.96); associations with liver cancer were attenuated after excluding early follow-up. In postmenopausal women, higher free and total testosterone and lower SHBG were associated with elevated risks of endometrial (HR per 10 pmol/L=1.59,1.32-1.90; HR per 0.5 nmol/L=1.34,1.18-1.52 and HR per 25 nmol/L=0.78,0.67-0.91, respectively) and breast cancer (1.32,1.22-1.43;1.24,1.17-1.31 and 0.88,0.83-0.94, respectively).We report a novel association of free testosterone with malignant melanoma in men; our findings also support known associations between sex hormones and risks for prostate, breast and endometrial cancers. The association with liver cancer in men may be attributable to reverse causation.

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Association of Urinary Cadmium with Cancer Mortality Is Influenced by Zinc Intake in Follow-up Study of NHANES 1988–1994 and 1999–2004 (P18-026-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz039.p18-026-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Kijoon Kim ◽

Melissa Melough ◽

Junichi Sakaki ◽

Hwayoung Noh ◽

Sung Koo ◽

...

Keyword(s):

Cancer Mortality ◽

Proportional Hazards ◽

Adult Population ◽

Positive Association ◽

Cox Proportional Hazards ◽

Toxic Heavy Metal ◽

Cox Proportional Hazards Models ◽

All Cause Mortality ◽

Risk Of Cancer

Abstract Objectives Exposure to cadmium (Cd), a toxic heavy metal, increases risk of numerous chronic diseases and overall mortality. However, little work has been conducted to examine the effect of Zn intake on the association between Cd burden and mortality. The aim of this study was to examine whether the association between urinary Cd concentration and all-cause and disease specific mortality differs by Zn intake level among a representative sample of the US adult population. Methods A total of 15,642 US adults aged 30 years and older in the National Health and Nutrition Examination Survey 1988–1994 and 1999–2004 were followed up through December 31, 2011. Participants’ Zn intake was assessed through 24-hour dietary recalls. The main outcomes included mortality from cardiovascular disease (CVD), cancer, and all causes. Using Cox proportional hazards models, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for quartiles of urinary Cd, quartiles of dietary Zn, and for quartiles of urinary Cd stratified by level of dietary Zn. Results Of 5367 total deaths that occurred over a mean follow-up of 15 years, 1194 were attributed to cancer and 1677 were attributed to CVD. After adjustment for potential confounders, positive relationships were observed between urinary Cd and all-cause mortality (HR for highest vs. lowest quartile (Q4 vs. Q1): 1.38; 95% CI: 1.14–1.68; P-trend < 0.0001) and cancer mortality (HR for Q4 vs. Q1: 1.54; 95% CI: 1.05–2.27; P-trend < 0.005), but not CVD mortality (HR for Q4 vs. Q1: 1.22; 95% CI: 0.95–1.57; P-trend = 0.0502). Negative associations were observed between dietary Zn and all-cause mortality (HR for Q4 vs. Q1: 0.88; 95% CI: 0.75–1.02; P-trend < 0.05) and cancer mortality (HR for Q4 vs. Q1: 0.82; 95% CI: 0.65–1.03, P-trend < 0.05). Among the lowest tertile of Zn consumers, there was a clear positive association between urinary Cd and cancer mortality (HR for Q4 vs. Q1: 1.79; 95% CI: 1.07–3.01), however, among the highest Zn consumers, this association was somewhat diminished (HR for Q4 vs. Q1: 1.66; 95% CI: 0.80–3.41). Conclusions These findings support existing evidence that Cd burden is associated with greater mortality, and also demonstrate that greater Zn consumption is associated with reduced risk of cancer death related to Cd. Funding Sources This study received no financial support.

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Coffee consumption and overall and cause-specific mortality: the Norwegian Women and Cancer Study (NOWAC)

European Journal of Epidemiology ◽

10.1007/s10654-020-00664-x ◽

2020 ◽

Vol 35 (10) ◽

pp. 913-924

Author(s):

Marko Lukic ◽

Runa Borgund Barnung ◽

Guri Skeie ◽

Karina Standahl Olsen ◽

Tonje Braaten

Keyword(s):

Cancer Mortality ◽

Smoking Status ◽

Coffee Consumption ◽

Inverse Association ◽

All Cause Mortality ◽

Specific Mortality ◽

Never Smokers ◽

Risk Of Cancer ◽

Filtered Coffee

Abstract Coffee consumption has previously been reported to reduce overall and cause-specific mortality. We aimed to further investigate this association by coffee brewing methods and in a population with heavy coffee consumers. The information on total, filtered, instant, and boiled coffee consumption from self-administered questionnaires was available from 117,228 women in the Norwegian Women and Cancer (NOWAC) Study. We used flexible parametric survival models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause, cardiovascular, and cancer mortality by total coffee consumption and brewing methods, and adjusted for smoking status, number of pack-years, age at smoking initiation, alcohol consumption, body mass index, physical activity, and duration of education. During 3.2 million person-years of follow-up, a total of 16,106 deaths occurred. Compared to light coffee consumers (≤ 1 cup/day), we found a statistically significant inverse association with high-moderate total coffee consumption (more than 4 and up to 6 cups/day, HR 0.89; 95% CI 0.83–0.94) and all-cause mortality. The adverse association between heavy filtered coffee consumption (> 6 cups/day) and all-cause mortality observed in the entire sample (HR 1.09; 95% CI 1.01–1.17) was not found in never smokers (HR 0.85; 95% CI 0.70–1.05). During the follow-up, both high-moderate total and filtered coffee consumption were inversely associated with the risk of cardiovascular mortality (HR 0.79; 95% CI 0.67–0.94; HR 0.80; 95% CI 0.67–0.94, respectively). The association was stronger in the analyses of never smokers (> 6 cups of filtered coffee/day HR 0.20; 95% CI 0.08–0.56). The consumption of more than 6 cups/day of filtered, instant, and coffee overall was found to increase the risk of cancer deaths during the follow-up. However, these associations were not statistically significant in the subgroup analyses of never smokers. The data from the NOWAC study indicate that the consumption of filtered coffee reduces the risk of cardiovascular deaths. The observed adverse association between coffee consumption and cancer mortality is most likely due to residual confounding by smoking.

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Dietary patterns related to total mortality and cancer mortality in the United States

Cancer Causes & Control ◽

10.1007/s10552-021-01478-2 ◽

2021 ◽

Author(s):

Marcela R. Entwistle ◽

Donald Schweizer ◽

Ricardo Cisneros

Keyword(s):

United States ◽

Dietary Patterns ◽

Cancer Mortality ◽

Cox Regression ◽

Total Mortality ◽

Principal Component ◽

The United States ◽

Red Meat ◽

Increased Risk ◽

All Cause Mortality

Abstract Purpose This study investigated the association between dietary patterns, total mortality, and cancer mortality in the United States. Methods We identified the four major dietary patterns at baseline from 13,466 participants of the NHANES III cohort using principal component analysis (PCA). Dietary patterns were categorized into ‘prudent’ (fruits and vegetables), ‘western’ (red meat, sweets, pastries, oils), ‘traditional’ (red meat, legumes, potatoes, bread), and ‘fish and alcohol’. We estimated hazard ratios for total mortality, and cancer mortality using Cox regression models. Results A total of 4,963 deaths were documented after a mean follow-up of 19.59 years. Higher adherence to the ‘prudent’ pattern was associated with the lowest risk of total mortality (5th vs. 1st quintile HR 0.90, 95% CI 0.82–0.98), with evidence that all-cause mortality decreased as consumption of the pattern increased. No evidence was found that the ‘prudent’ pattern reduced cancer mortality. The ‘western’ and the ‘traditional’ patterns were associated with up to 22% and 16% increased risk for total mortality (5th vs. 1st quintile HR 1.22, 95% CI 1.11–1.34; and 5th vs. 1st quintile HR 1.16, 95% CI 1.06–1.27, respectively), and up to 33% and 15% increased risk for cancer mortality (5th vs. 1st quintile HR 1.33, 95% CI 1.10–1.62; and 5th vs. 1st quintile HR 1.15, 95% CI 1.06–1.24, respectively). The associations between adherence to the ‘fish and alcohol’ pattern and total mortality, and cancer mortality were not statistically significant. Conclusion Higher adherence to the ‘prudent’ diet decreased the risk of all-cause mortality but did not affect cancer mortality. Greater adherence to the ‘western’ and ‘traditional’ diet increased the risk of total mortality and mortality due to cancer.

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Hormone replacement therapy in women with cancer and risk of cancer-specific mortality and cardiovascular disease: a protocol for a cohort study from Scotland and Wales

BMC Cancer ◽

10.1186/s12885-021-08065-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Úna McMenamin ◽

Blánaid Hicks ◽

Carmel Hughes ◽

Peter Murchie ◽

Julia Hippisley-Cox ◽

...

Keyword(s):

Cardiovascular Disease ◽

Hormone Replacement Therapy ◽

Venous Thromboembolism ◽

Replacement Therapy ◽

Cancer Diagnosis ◽

Hormone Replacement ◽

All Cause Mortality ◽

Specific Mortality ◽

Cancer Specific Mortality ◽

Risk Of Cancer

Abstract Background Hormone replacement therapy (HRT) is widely used and has proven benefits for women with menopausal symptoms. An increasing number of women with cancer experience menopausal symptoms but the safety of HRT use in women with cancer is unclear. There are particular concerns that HRT could accelerate cancer progression in women with cancer, and also that HRT could increase the risk of cardiovascular disease in such women. Therefore, our primary aim is to determine whether HRT use alters the risk of cancer-specific mortality in women with a range of common cancers. Our secondary objectives are to investigate whether HRT alters the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality. Methods The study will utilise independent population-based data from Wales using the SAIL databank and Scotland based upon the national Prescribing Information System. The study will include women newly diagnosed with common cancers from 2000 to 2016, identified from cancer registries. Women with breast cancers will be excluded. HRT will be ascertained using electronic prescribing in Wales or dispensing records in Scotland. The primary outcome will be time to cancer-specific mortality from national mortality records. Time-dependent cox regression models will be used to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer specific death in HRT users compared with non-users after cancer diagnosis after adjusting for relevant confounders, stratified by cancer site. Analysis will be repeated investigating the impact of HRT use immediately before cancer diagnosis. Secondary analyses will be conducted on the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality. Analyses will be conducted within each cohort and pooled across cohorts. Discussion Our study will provide evidence to inform guidance given to women diagnosed with cancer on the safety of HRT use and/or guide modifications to clinical practice.

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Association between glaucoma surgery and all-cause and cause-specific mortality among elderly patients with glaucoma: a nationwide population-based cohort study

Scientific Reports ◽

10.1038/s41598-021-96063-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sang Yeop Lee ◽

Hun Lee ◽

Ji Sung Lee ◽

Sol Ah Han ◽

Yoon Jeon Kim ◽

...

Keyword(s):

Cohort Study ◽

Elderly Patients ◽

Cox Regression ◽

Open Angle Glaucoma ◽

Glaucoma Surgery ◽

Population Based ◽

Angle Closure ◽

Charlson Comorbidity Index Score ◽

All Cause Mortality ◽

Specific Mortality

AbstractThis population-based, retrospective cohort study aimed to evaluate the association between glaucoma surgery and all-cause and cause-specific mortality among Korean elderly patients with glaucoma. A total of 16210 elderly patients (aged ≥ 60 years) diagnosed with glaucoma between 2003 and 2012 were included, and their insurance data were analyzed. The participants were categorized into a glaucoma surgery cohort (n = 487), which included individuals who had diagnostic codes for open angle glaucoma (OAG) or angle closure glaucoma (ACG) and codes for glaucoma surgery, and a glaucoma diagnosis cohort (n = 15,723), which included patients who had codes for OAG and ACG but not for glaucoma surgery. Sociodemographic factors, Charlson Comorbidity Index score, and ocular comorbidities were included as covariates. Cox regression models were used to assess the association between glaucoma surgery and mortality. The incidence of all-cause mortality was 34.76/1,000 person-years and 27.88/1,000 person-years in the glaucoma surgery and diagnosis groups, respectively. The adjusted hazard ratio (HR) for all-cause mortality associated with glaucoma surgery was 1.31 (95% confidence interval [CI], 1.05–1.62, P = 0.014). The adjusted HR for mortality due to a neurologic cause was significant (HR = 2.66, 95% CI 1.18–6.00, P = 0.018). The adjusted HRs for mortality due to cancer (HR = 2.03, 95% CI 1.07–3.83, P = 0.029) and accident or trauma (HR = 4.00, 95% CI 1.55–10.34, P = 0.004) associated with glaucoma surgery for ACG were significant as well. Glaucoma surgery was associated with an increase of mortality in elderly patients with glaucoma. In particular, the risk of mortality associated with glaucoma surgery due to neurologic causes was significant.

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Resting Heart Rate as a Predictor of Cancer Mortality: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10071354 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1354

Author(s):

Diana P. Pozuelo-Carrascosa ◽

Iván Cavero-Redondo ◽

I.M. Lee ◽

Celia Álvarez-Bueno ◽

Sara Reina-Gutierrez ◽

...

Keyword(s):

Heart Rate ◽

Cancer Mortality ◽

Meta Analysis ◽

Positive Association ◽

Cochrane Library ◽

Resting Heart Rate ◽

Potential Marker ◽

Meta Analyses ◽

Risk Of Cancer ◽

The Relationship

This work was aimed to synthetize the evidence available about the relationship between resting heart rate (RHR) and the risk of cancer mortality. A computerized search in the Medline, EMBASE, Web of Science, and Cochrane Library databases from their inception to 24 September 2020 was performed. We performed three meta-analyses: (1) cancer mortality comparing the “less than 60 bpm” and “more than 60 bpm” categories; (2) cancer mortality comparing “less than 60 bpm”, “60 to 80 bpm”, and “more than 80 bpm” categories; and (3) analysis for 10–12 and 20 bpm increase in RHR and risk of cancer mortality. Twenty-two studies were included in the qualitative review, and twelve of them met the inclusion criteria for the meta-analysis. Our results showed a positive association between RHR and the risk of cancer mortality. This association was shown in a meta-analysis comparing studies reporting mean RHR values below and above 60 bpm, when comparing three RHR categories using less than 60 bpm as the reference category and, finally, in dose response analyses estimating the effect of an increase of 10–12 bpm in RHR, both in men and in women. In conclusion, a low RHR is a potential marker of low risk of cancer mortality.

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Abstract P349: Association Of Fibroblast Growth Factor 23 With Incident Cardiovascular Disease And All-Cause Mortality In The Framingham Heart Study

Circulation ◽

10.1161/circ.129.suppl_1.p349 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Robin Haring ◽

Ramachandran S Vasan ◽

Henri Wallaschofski ◽

Lisa Sullivan ◽

Danielle Enserro

Keyword(s):

Cardiovascular Disease ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Regression Models ◽

Cox Regression ◽

Fibroblast Growth Factor 23 ◽

Positive Association ◽

Fibroblast Growth ◽

All Cause Mortality ◽

Incident Cardiovascular Disease

Objective: To investigate the association of fibroblast growth factor 23 (FGF23) with incident cardiovascular disease (CVD) and mortality risk in the general population. Methods: We evaluated 3,236 Framingham Offspring and Omni Study participants to examine the associations of serum FGF23 (measured by immunoassay) with 10-year incident CVD (N = 2,823) and all-cause mortality (N = 3,223) using multivariable Cox regression models. Results: During a median follow-up time of 10.8 years (Q1, 10.0; Q3, 11.4), 347 participants developed new-onset CVD and 412 died. Age- and sex-adjusted Cox regression models revealed a positive association of FGF23 with incident CVD (hazard ratio (HR) per unit increase in logFGF23: 1.43, 95% confidence interval (CI) 1.11-1.84) and all-cause mortality (HR 2.26, 95% CI, 1.86-2.75). After multivariable adjustment, the association of FGF23 with incident CVD was rendered non-significant (HR 1.12, 95% CI 0.86-1.46), whereas the positive association of FGF23 with all-cause mortality was maintained (HR: 1.87, 95% CI: 1.52 - 2.29). Analyses modeling FGF23 quartiles yielded similar findings (multivariable-adjusted HR Q4 vs. Q1 for incident CVD: 1.17, 95% CI: 0.87 - 1.59; for death: 1.87, 95% CI: 1.38 - 2.53). Conclusion: In our large community-based sample, serum FGF23 shows an independent positive association with all-cause mortality, but not with incident CVD risk.

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Dietary cholesterol and egg intake in relation to incident cardiovascular disease and all-cause and cause-specific mortality in postmenopausal women

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa353 ◽

2020 ◽

Author(s):

Guo-Chong Chen ◽

Li-Hua Chen ◽

Yasmin Mossavar-Rahmani ◽

Victor Kamensky ◽

Aladdin H Shadyab ◽

...

Keyword(s):

Cardiovascular Disease ◽

Postmenopausal Women ◽

Dietary Cholesterol ◽

Saturated Fat ◽

Inverse Association ◽

Egg Consumption ◽

All Cause Mortality ◽

Specific Mortality ◽

Cholesterol Intake ◽

Incident Cardiovascular Disease

ABSTRACT Background The potential cardiovascular impact of dietary cholesterol intake has been actively debated for decades. Objectives We aimed to evaluate associations of dietary cholesterol and egg intakes with incident cardiovascular disease (CVD) and all-cause and cause-specific mortality. Methods We included 96,831 US postmenopausal women aged 50–79 y without known CVD or cancer during baseline enrollment (1993–1998) of the Women's Health Initiative. Dietary information was collected using a validated FFQ. Incident CVD [i.e., ischemic heart disease (IHD) and stroke] and all-cause and cause-specific mortality were ascertained and adjudicated through February 2018. Results A total of 9808 incident CVD cases and 19,508 all-cause deaths occurred during a median follow-up of 17.8 y and 18.9 y, respectively. After multivariable adjustment for traditional risk factors and key dietary nutrients including dietary saturated fat, there were modest associations of dietary cholesterol intake with incident CVD (HRQ5versusQ1: 1.12; 95% CI: 1.03, 1.21; P-trend < 0.001) and all-cause mortality (HRQ5versusQ1: 1.09; 95% CI: 1.02, 1.15; P-trend < 0.001). Significant positive associations were also observed between dietary cholesterol and incident IHD (P-trend = 0.007), incident ischemic stroke (P-trend = 0.002), and CVD mortality (P-trend = 0.002), whereas there was an inverse association for incident hemorrhagic stroke (P-trend = 0.037) and no association for mortality from cancer, Alzheimer disease/dementia, respiratory diseases, or other causes (P-trend > 0.05). Higher egg consumption was also associated with modestly higher risk of incident CVD (P-trend = 0.004) and all-cause mortality (P-trend < 0.001), with HRs of 1.14 (95% CI: 1.04, 1.25) and 1.14 (95% CI: 1.07, 1.22), respectively, when comparing ≥1 egg/d with <1 egg/wk. Conclusions Both higher dietary cholesterol intake and higher egg consumption appeared to be associated with modestly elevated risk of incident CVD and all-cause mortality in US postmenopausal women.

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Dietary supplement use and mortality in a cohort of Swedish men

British Journal Of Nutrition ◽

10.1017/s0007114507812049 ◽

2008 ◽

Vol 99 (3) ◽

pp. 626-631 ◽

Cited By ~ 23

Author(s):

Maria Messerer ◽

Niclas Håkansson ◽

Alicja Wolk ◽

Agneta Åkesson

Keyword(s):

Dietary Supplements ◽

Dietary Supplement ◽

Cancer Mortality ◽

Inverse Association ◽

Supplement Use ◽

All Cause Mortality ◽

Dietary Supplement Use ◽

Risk Of Cancer ◽

Cvd Mortality

The use of dietary supplements has increased substantially in most industrialized countries. The aim of this study was to prospectively examine the association between use of dietary supplements and all-cause mortality, cancer mortality and CVD mortality in men. We used the population-based prospective cohort of 38 994 men from central Sweden, 45–79 years of age, with no cancer or CVD at baseline and who completed a self-administered FFQ including questions on dietary supplement use and life-style factors in 1997. During average 7.7 years of follow-up, 3403 deaths were ascertained; among them, 771 due to cancer and 930 due to CVD (during 5.9 years of follow-up). In multivariate adjusted models including all men there was no association observed between use of any dietary supplement or of multivitamins, vitamin C, vitamin E or fish oil specifically and all-cause mortality, cancer or CVD mortality. Among current smokers, regular use of any supplement was associated with statistically significant increased risk of cancer mortality: relative risk (RR) 1·46 (95 % CI 1·06, 1·99). Among men reporting an inadequate diet at baseline (assessed by Recommended Food Score), there was a statistically significant inverse association between use of any dietary supplement and CVD mortality (RR 0·72; 95 % CI 0·57, 0·91), no associations were observed among men with adequate diets. In conclusion, we cannot exclude that the use of dietary supplements is harmful for smokers. On the other hand, among men with an insufficient diet, the use of supplements might be beneficial in reducing CVD mortality.

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