Abstract
Purpose
Vitamin-mineral and dietary supplements (VMDS) are taken by a large fraction of the population. Whether their long-term consumption impacts mortality and cardiovascular disease (CVD) has seldom been studied.
Methods
Prospective study from a population-based cohort from Lausanne, Switzerland. Participants were categorized as non-users (no consumption at baseline and first follow-up), persistent users (consumption at baseline and follow-up), and occasional users (consumption either at baseline or follow-up). Incidence of CVD and of total mortality was assessed after the first follow-up.
Results
Data from 4261 participants (57.4 ± 10.4 years, 55% females) was used. Median follow-up was 9 years (interquartile range 7.0–9.2) After multivariable analysis, no association was found between VMDS use and total mortality: hazard ratio and (95% confidence interval) 0.95 (0.71–1.28) and 0.83 (0.55–1.26) for occasional and persistent consumers, respectively, CVD mortality: 1.00 (0.47–2.11) and 1.30 (0.53–3.18), or CVD events: 0.96 (0.72–1.27) and 0.95 (0.64–1.42). Similar findings were obtained after inverse probability weighting, using only vitamin-mineral supplement users, or considering only participants at baseline. When CVD events were split into coronary heart disease (CHD) or stroke, persistent use of VMDS was associated with a higher risk of CHD in females: 3.12 (1.52–6.41), p = 0.002, but not in males, 0.25 (0.03–1.82), p = 0.171, p for interaction < 0.05. No association was found between VMDS use and incidence of stroke in both sexes.
Conclusion
We found no association between vitamin and dietary supplement use and total or CVD mortality, or CVD events. The higher risk of CHD for persistent use in females should be further explored.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00394-025-03593-1.
Keywords: Mortality, Cardiovascular disease, Vitamin supplements, Prospective study
Introduction
Vitamin and dietary supplements are taken by a large fraction of the population, based on the belief of their beneficial effects on health. According to the 2011–2014 National Health and Nutrition Examination Survey, half (52%) of US adults reported using at least one dietary supplement and almost one-third (31%) reported using a vitamin-mineral supplement [1]. Vitamin and dietary supplements are also very common in the Swiss population, one-fifth of adults consuming them [2].
Despite the current belief that vitamin or dietary supplements improve health status, the evidence is different. Most studies on vitamin D failed to find any protective effect against cardiovascular disease (CVD) [3, 4], while a possible effect against cardiac failure was suggested [5]. No effect of vitamin C on CVD was found in a Cochrane review [6], but studies conducted in Asian populations showed a beneficial effect of vitamin C intake on the risk of stroke among smokers [7] and on total mortality [8]. Similarly, no effect of vitamin K [9] or vitamin B3 (niacin) in CVD prevention could be demonstrated [10], but the number and quality of the studies were low. In 2022, the US Preventive Task Force updated its recommendations for vitamin and dietary supplements issued in 2014 [11] and concluded that vitamin and mineral supplementation was associated with little or no benefit of preventing CVD or death [12, 13].
In previous publications, we have shown that vitamin supplement users have a better health [14] and a better dietary intake [15] than non-users, suggesting that the beneficial association between vitamin supplement use and health might be biased by a healthier lifestyle. We have also shown that vitamin supplement consumption does not lead to better fitness [16], and that the quality of some vitamin supplements in Switzerland failed to comply with the legal recommendations [17].
We have previously shown that vitamin supplement consumption is an irregular pattern, a sizable fraction of consumers discontinuing consumption and vice versa [2]. Whether long-term vitamin-mineral ± dietary supplement use has any effect on mortality or CVD has seldom been studied.
Hence, we aimed to assess if long-term vitamin-mineral ± dietary supplement consumption influences cardiovascular disease and mortality. We expected to replicate the lack of association reported previously [12, 13].
Methods
Study setting
The CoLaus|PsyCoLaus study is a population-based study investigating the epidemiology and genetic determinants of psychiatric and cardiovascular disease in Lausanne, Switzerland [18]. Briefly, a representative sample was collected through a simple, non-stratified random sampling of 19,830 individuals (35% of the source population) aged between 35 and 75. The baseline study was conducted between June 2003 and May 2006; the first follow-up was performed between April 2009 and September 2012; the second follow-up was performed between May 2014 and April 2017 and the third follow-up was performed between April 2018 and May 2021. Median follow-up time was 5.4 (average 5.6, range 4.5–8.8) years for the first follow-up, 10.7 (average 10.9, range 8.8–13.6) years for the second follow-up, and 14.5 (average 14.6, range 13.2–17.3) for the third follow-up.
Death and cardiovascular events
During the follow-up period, first incident CVD events and deaths were prospectively collected and independently adjudicated according to established recommendations and similar definitions detailed elsewhere [19]. Details of the adjudication procedure are provided in the supplementary information.
Vitamin / dietary supplement consumption
Participants reported all medicines and vitamin, or dietary supplements prescribed or bought over the counter. Vitamin-mineral and dietary supplement use were assessed for the baseline and the first follow-up. Vitamin and mineral supplements were defined according to the Swiss compendium (compendium.ch/home/fr, assessed June 2017). If the supplements were not listed in the Swiss compendium, further searches on the internet were conducted. Due to wide differences in the composition of Swiss vitamin and mineral supplements [17] and to inaccurate reporting (i.e., reporting “multivitamins from producer X” that manufactures six different types of multivitamins), it was not possible to assess the amounts of vitamins and minerals consumed by participants. Dietary supplements were defined as any other supplement that could not be considered as a VMS, such as plant extracts not considered as phytotherapy by the Swiss compendium, cod liver oil, shark cartilage or amino acids, for example. Participants were categorized as non-users (no consumption at baseline and follow-up), persistent users (consumption at baseline and follow-up), and occasional users (consumption either at baseline or follow-up) [2].
Other covariates
A list of covariates potentially associated with vitamin or dietary supplement use was selected based on previous findings [14, 20]. Smoking was self-reported and categorized as never, former (irrespective of the time since quitting smoking) and current. Education was categorized into high (university), middle (high school) and low (apprenticeship + mandatory). Marital status was defined as living alone (single, divorced, widowed) or living with a partner. Nationality was defined as Swiss or other. Alcohol consumption was defined as consumer/not consumer. At baseline, physical activity was assessed by a single question querying the number of 20-min periods of vigorous physical activity performed per week, and participants were considered as sedentary if they responded “never”. In the first follow-up, physical activity was assessed by a questionnaire validated in the population of Geneva [21], and sedentary status was defined as spending more than 90% of the daily energy in activities below moderate- and high-intensity (defined as requiring at least 4 times the basal metabolic rate) [22]. Sedentary behaviour was preferred to other types of physical activity as it was the sole measure that was not overestimated when compared to accelerometry [23]. At baseline, no information regarding dietary intake was collected. In the first follow-up, dietary intake was assessed using a validated food frequency questionnaire validated in the population of Geneva [24] and the Mediterranean diet score according to Trichopoulou et al. [25] was computed to assess dietary quality.
Body weight and height were measured with participants barefoot and in light indoor clothes. Body weight was measured in kilograms to the nearest 100 g using a Seca® scale (Hamburg, Germany). Height was measured to the nearest 5 mm using a Seca® (Hamburg, Germany) height gauge. Body mass index was calculated and categorized as normal (< 25 kg/m2), overweight ≥ 25 and < 30 kg/m2) and obese ≥ 30 kg/m2).
Blood pressure (BP) was measured using an Omron® HEM-907 automated oscillometric sphygmomanometer after at least a 10-min rest in a seated position, and the average of the last two measurements was used. Hypertension was defined by a SBP ≥ 140 mm Hg or a DBP ≥ 90 mm Hg or presence of antihypertensive drug treatment.
Total cholesterol was assessed by CHOD-PAP, with maximum inter and intra-batch CVs of 1.6% and 1.7%, respectively. HDL-cholesterol was assessed by CHOD-PAP + PEG + cyclodextrin, with maximum inter and intra-batch CVs of 3.6% and 0.9%, respectively. Hypolipidemic drugs were considered if they were listed in the official list of drugs of Switzerland. Glucose was assessed by glucose dehydrogenase, with maximum inter and intra-batch CVs of 2.1% and 1.0%, respectively. Diabetes mellitus (DM) was defined as fasting plasma glucose ≥ 7.0 mmol/L and/or presence of oral hypoglycaemic or insulin treatment.
Inclusion and exclusion criteria
Participants were considered as eligible if they participated in the first follow-up. Participants were excluded if they 1) did not participate in subsequent follow-up after the first one; 2) presented with previous CVD; 3) had missing data regarding supplements, and 4) had missing data for any covariate. As sedentary behaviour was missing in a sizable fraction of the sample, it was not considered as an exclusion criterion.
Ethical statement
The institutional Ethics Committee of the University of Lausanne, which afterwards became the Ethics Commission of Canton Vaud (www.cer-vd.ch) approved the baseline CoLaus study (reference 16/03). The approval was renewed for the first (reference 33/09), the second (reference 26/14) and the third (reference PB_2018-000408) follow-ups. The approval for the entire CoLaus|PsyCoLaus study was confirmed in 2021 (reference PB_2018-00038, 239/09). The full decisions of the CER-VD can be obtained from the authors upon request. The study was performed in agreement with the Helsinki declaration and its former amendments, and in accordance with the applicable Swiss legislation. All participants gave their signed informed consent before entering the study.
Statistical analysis
Statistical analyses were conducted using Stata v.16.1 (Stata Corp, College Station, TX, USA). Descriptive results were expressed as number of participants (percentage) for categorical variables and as average ± standard deviation or median [interquartile range] for continuous variables. Between-group comparisons for baseline characteristics were conducted using chi-square for categorical variables and student’s t-test, analysis of variance (ANOVA) or Kruskal–Wallis test for continuous variables.
Overall and CVD-related mortality and incidence of all CVD events were visualized as Kaplan-Meyer curves. Bivariate and multivariable associations between vitamin-mineral ± dietary supplement use and the outcomes of interest were assessed using Cox model for overall mortality and Fine-Gray competing risk model for cardiovascular disease, using non-cardiac mortality as competing event (21). Multivariable analyses were adjusted for sex, age, nationality, education (high, middle, low), marital status (living with a partner, living alone), smoking (never, former, current), body mass index categories (normal, overweight, obese), alcohol consumption (yes, no), Mediterranean diet score (continuous), hypertension (yes, no), diabetes (yes, no), and hypolipidemic drug treatment (yes, no). All confounders were evaluated at the first follow-up. Visual examination of the plots of the Scaled Schoenfeld residuals showed no violation of the proportional hazards assumption.
Several sensitivity analyses were conducted. The first one used inverse probability weighting to consider participants excluded from the main analysis. Briefly, logistic regression was used to estimate the likelihood of being included for each participant, and the inverse of predicted probability was then used for the survival analyses. The second one included only participants with sedentary behaviour data and adjusted for sedentary behaviour, 1) unweighted and 2) with inverse probability weighting. The third used only vitamin-mineral supplement (non) users, 1) unweighted; 2) with inverse probability weighting, and 3) including only participants with sedentary behaviour data and adjusting for sedentary behaviour. The fourth used baseline data; in this case, only users and non-users were considered, and no adjustment on dietary quality was performed. The fifth stratified the analysis by sex, and an interaction term was included between vitamin-mineral ± dietary supplement use (never, alternate, and persistent) and sex. The sixth separated coronary heart disease and stroke, and analyses were conducted overall and stratified by sex, with an interaction term as before. Statistical significance was considered for a two-sided test with p < 0.05.
Results
Sample characteristics
Out of the 6′733 initial participants, 5′064 were considered as eligible, and 803 were excluded. The reasons for exclusion are summarized in supplementary Fig. 1 and the characteristics of included and excluded participants are listed in supplementary Table 1. Excluded participants were older, more frequently male, of lesser education, current smokers, obese, and presenting with hypertension or diabetes.
Association of vitamin-mineral ± dietary supplement use with overall mortality and cardiovascular disease
Overall, two thirds (66.8%) of the participants did not consume vitamin-mineral ± dietary supplements between the baseline and the first follow-up, and less than one in eleven (8.7%) reported consuming vitamin-mineral ± dietary supplements at both study periods. Their clinical characteristics are summarized in Table 1. Never consumers were younger, less frequently female, born in Switzerland, living alone, of normal weight, took less frequently hypolipidemic drugs, had lower levels of total and HDL cholesterol andwere more frequently current smokers.
Table 1.
Characteristics of participants according to vitamin-mineral ± dietary supplement use, CoLaus|PsyCoLaus study, Lausanne, Switzerland
| Never | Occasional | Persistent | P-value | |
|---|---|---|---|---|
| N (%) | 2846 (66.8) | 1044 (24.5) | 371 (8.7) | |
| Age (years) | 56.1 ± 10.2 | 58.9 ± 10.4 | 63.9 ± 9.4 | < 0.001 |
| Female (%) | 1313 (46.1) | 733 (70.2) | 301 (81.1) | < 0.001 |
| Born in Switzerland (%) | 1735 (61.0) | 706 (67.6) | 273 (73.6) | < 0.001 |
| Educational level (%) | 0.029 | |||
| High | 646 (22.7) | 228 (21.9) | 70 (18.9) | |
| Middle | 726 (25.5) | 287 (27.5) | 123 (33.2) | |
| Low | 1472 (51.8) | 528 (50.6) | 178 (48.0) | |
| Living alone (%) | 1120 (39.4) | 508 (48.7) | 194 (52.3) | < 0.001 |
| Smoking status (%) | < 0.001 | |||
| Never | 1158 (40.7) | 466 (44.6) | 150 (40.4) | |
| Former | 1034 (36.3) | 388 (37.2) | 164 (44.2) | |
| Current | 654 (23.0) | 190 (18.2) | 57 (15.4) | |
| Body mass index (kg/m2) | 26.4 ± 4.5 | 25.5 ± 4.5 | 24.8 ± 4.5 | < 0.001 |
| BMI categories (%) | < 0.001 | |||
| Normal | 1168 (41.0) | 542 (51.9) | 212 (57.1) | |
| Overweight | 1174 (41.3) | 351 (33.6) | 118 (31.8) | |
| Obese | 504 (17.7) | 151 (14.5) | 41 (11.1) | |
| Alcohol consumption (%) | 2375 (83.7) | 861 (82.6) | 292 (78.9) | 0.062 |
| Sedentary behaviour (%) § | 1371 (56.6) | 493 (54.6) | 209 (64.1) | 0.012 |
| Mediterranean score | 3.9 ± 1.5 | 4.0 ± 1.5 | 4.0 ± 1.4 | 0.416 |
| Hypertension (%) | 1125 (39.5) | 375 (35.9) | 151 (40.7) | 0.089 |
| Systolic BP (mm Hg) | 126 ± 17 | 124 ± 18 | 127 ± 18 | 0.032 |
| Diastolic BP (mm Hg) | 79 ± 11 | 77 ± 10 | 76 ± 11 | < 0.001 |
| Diabetes (%) | 300 (10.5) | 77 (7.4) | 35 (9.4) | 0.012 |
| Hypolipidemic drugs (%) | 397 (14.0) | 172 (16.5) | 83 (22.4) | < 0.001 |
| Total cholesterol (mmol/L) | 5.72 ± 1.00 | 5.76 ± 1.02 | 5.86 ± 1.05 | 0.040 |
| HDL cholesterol (mmol/L) | 1.60 ± 0.45 | 1.74 ± 0.49 | 1.82 ± 0.47 | < 0.001 |
BMI, body mass index, BP, blood pressure
§ sample sizes are 2421, 903 and 326 for never, occasional, and persistent, respectively. Results are expressed as number of participants (percentage) for categorical variables and as average ± standard deviation for continuous variables. Between-group comparisons performed using chi-square for categorical variables and analysis of variance for continuous variables
After a median 9 years of follow-up (interquartile range: 7.0–9.2), 326 deaths (of which 52 due to CVD) and 321 CVD events were recorded. Total mortality and incidence of cardiovascular disease according to vitamin-mineral ± dietary supplement use are indicated in Fig. 1 and Table 2 and the associations between vitamin-mineral ± dietary supplement use and overall mortality and CVD are summarized in Table 3. Compared to never users, no statistical differences were found for occasional or persistent users for all outcomes considered.
Fig. 1.
overall and CVD-related mortality and all cardiovascular events according to never, alternate, and persistent vitamin mineral ± dietary supplement use, CoLaus|PsyCoLaus study, Lausanne, Switzerland
Table 2.
Total mortality and incidence of cardiovascular disease according to vitamin-mineral ± dietary supplement use, CoLaus|PsyCoLaus study, Lausanne, Switzerland
| Person-years | Failures | Rate (95% CI) | |
|---|---|---|---|
| Mortality | |||
| Never | 22,778.0 | 215 | 9.4 (8.3–10.8) |
| Occasional | 8424.5 | 78 | 9.3 (7.4–11.6) |
| Persistent | 2951.6 | 33 | 11.2 (7.9–15.7) |
| Cardiovascular death | |||
| Never | 22,778.0 | 33 | 1.4 (1.0–2.0) |
| Occasional | 8424.5 | 12 | 1.4 (0.8–2.5) |
| Persistent | 2951.6 | 7 | 2.4 (1.1–5.0) |
| Cardiovascular disease | |||
| Never | 22,244.6 | 216 | 9.7 (8.5–11.1) |
| Occasional | 8267.5 | 73 | 8.8 (7.0–11.1) |
| Persistent | 2862.6 | 32 | 11.2 (7.9–15.8) |
Results are expressed as mortality or incidence rate per 1000 person-years
Table 3.
association between vitamin-mineral ± dietary supplement use and total mortality or incidence of cardiovascular disease, CoLaus|PsyCoLaus study, Lausanne, Switzerland
| Bivariate | P-value | Multivariable | P-value | |
|---|---|---|---|---|
| Mortality | ||||
| Never | 1 (ref) | 1 (ref) | ||
| Occasional | 0.98 (0.75—1.27) | 0.860 | 0.95 (0.71—1.28) | 0.744 |
| Persistent | 1.23 (0.85—1.77) | 0.276 | 0.83 (0.55—1.26) | 0.392 |
| CVD mortality | ||||
| Never | 1 (ref) | 1 (ref) | ||
| Occasional | 1.00 (0.51—1.93) | 0.989 | 1.00 (0.47—2.11) | 0.993 |
| Persistent | 1.68 (0.74—3.79) | 0.215 | 1.30 (0.53—3.18) | 0.570 |
| CVD events | ||||
| Never | 1 (ref) | 1 (ref) | ||
| Occasional | 0.91 (0.70—1.19) | 0.498 | 0.96 (0.72—1.27) | 0.764 |
| Persistent | 1.17 (0.81—1.69) | 0.414 | 0.95 (0.64—1.42) | 0.797 |
CVD, cardiovascular disease. Results are expressed as bivariate or multivariable-adjusted hazard ratios and (95% confidence intervals). Analysis conducted using Cox regression for total mortality and CVD events, and Fine-Gray competing risk regression for CVD mortality. Multivariable analysis adjusted for sex, age, nationality, education (high, middle, low), marital status (living with a partner, living alone), smoking (never, former, current), body mass index categories (normal, overweight, obese), alcohol consumption (yes, no), Mediterranean diet score (continuous), hypertension (yes, no), diabetes (yes, no) and hypolipidemic drug treatment (yes, no)
Sensitivity analyses
The results of the analysis using inverse probability weighting are provided in supplementary Table 2. A trend towards a higher mortality risk for persistent users was observed on bivariate analysis, but no association was found after multivariable analysis. Restricting the analysis to participants with sedentary behaviour data led to similar findings (supplementary Table 3).
The clinical characteristics according to vitamin-mineral supplement use are summarized in supplementary Table 4. Overall, most participants did not consume vitamin-mineral supplements between the two survey periods. Never consumers shared the same characteristics as in Table 1. Total mortality and incidence of cardiovascular disease according to vitamin-mineral supplement use are provided in supplementary Table 5, and the associations between vitamin-mineral supplement use and overall mortality and CVD are summarized in supplementary Table 6. Compared to never users, no statistical differences were found for occasional or persistent users for all outcomes considered. Similar findings were obtained when inverse probability weighting was applied (supplementary Table 7) or when the analysis was restricted to participants with sedentary behaviour data (supplementary Table 8).
Of the 6733 participants with baseline data, 1375 (20.4%) were excluded for the analysis between vitamin-mineral ± dietary supplement use and outcomes starting at baseline. The characteristics of included and excluded participants are summarized in supplementary Table 9 and the characteristics of participants according to vitamin-mineral ± dietary supplement use are indicated in supplementary Table 10. After a median follow-up of 14.4 years (interquartile range 11.2–14.7 years), 687 deaths (of which 116 due to CVD) and 575 CVD events occurred (supplementary Table 11). The associations between vitamin-mineral ± dietary supplement use and overall mortality and CVD are summarized in supplementary Table 12. No significant association was found between vitamin-mineral ± dietary supplement use and all outcomes.
When analyses were stratified by sex, a lower risk of overall mortality was found for persistent users among females, while no association was found for males, p for interaction 0.011. No association between vitamin-mineral + dietary supplement use and CVD mortality or CVD events was found (supplementary tables 13 to 16).
When events were split into coronary heart disease or stroke, no association was found for the overall sample (supplementary tables 17 and 18). When analysis was stratified by sex, persistent use was associated with a higher risk of coronary heart disease in females (supplementary Table 19, p for interaction < 0.05) while no association was found for males. No association between vitamin-mineral + dietary supplement use and stroke was found for both sexes (supplementary Table 19).
Discussion
In this population-based, prospective study, we found no association between the use of multivitamin and dietary supplements and total or CVD mortality or CVD, in people that have no vitamin deficit. The lower overall mortality risk of persistent use among females should be further explored.
Association of vitamin-mineral ± dietary supplement use with overall mortality and cardiovascular disease
Most studies so far assessed the effect of vitamin-mineral ± dietary supplements on CVD or mortality using a single time point assessment of supplement consumption. Our results add further information to the prior literature regarding the effect of supplements on CVD. Indeed, several studies recently published concluded that vitamin and mineral supplementation was associated with little or no benefit in preventing cancer, CVD, and death [12, 26]. The O’Connor’s Vitamin and Mineral Supplements for the Primary Prevention of Cardiovascular Disease and Cancer study, found in 2022 that there was little to no association in vitamin and mineral supplementation and preventing CVD and death [12]. Similar patterns were seen in the Sesso’s Multivitamins in the prevention of cancer and cardiovascular disease study, proving that multivitamin-multimineral use neither significantly affected all-cause mortality nor reduced the incidence of total cancer [26]. The United States Preventive Services Task Force recommendations concluded that “the current evidence is insufficient to assess the balance of benefits and harms of the use of multivitamin supplements for the prevention of CVD or cancer” [13].
The supposedly beneficial effects of vitamin-mineral ± dietary supplements on CVD or on mortality are likely explained by the healthier lifestyle of users [14], such as a healthier diet [15]. For instance, the Leisure World Cohort Study found no association between antioxidant vitamin use and total mortality, the initially observed associations being considerably attenuated after adjustment for confounders [27]. Although a Chinese study reported a protective effect of antioxidant vitamin use on CVD but not on cancer mortality [28], a meta-analysis of seventy-eight randomized trials found no evidence to support antioxidant supplements for primary or secondary prevention, with beta-carotene and vitamin E even showing a tendency to increase mortality [29]. Overall, our results confirm mostly of the existing literature that neither regular nor intermittent vitamin-mineral ± dietary supplements are associated with decreased risk of total mortality, CVD mortality, or CVD events. The lower overall mortality risk observed in females could be due to a lower incidence of cancer, as it has been suggested by the SU.VI.MAX study [30]. It could also be due to a better dietary intake and a better health management among females relative to males. Conversely, when the analysis was split into coronary heart disease and stroke, a higher risk of coronary heart disease was found among persistent users in females, but not in males, while no association was found with stroke. The reasons for such an association can only be hypothesized. Females may use vitamin or dietary supplements to manage their cardiovascular risk factors [31], thus leading to a lesser control. Another hypothesis would be that some dietary supplements either possess cardiovascular modifying properties or are contaminated by potentially cardiohazardous products [32]. Dietary supplements can also interact with prescribed drugs [33], and excess consumption of vitamin-mineral supplements might lead to body accumulation and possible intoxication, with potentially deleterious effects [34, 35]. Overall, our results suggest that, in females, persistent use of vitamin-mineral ± dietary supplements might bring some benefits regarding mortality, at the expense of an increased risk of coronary heart disease. It would be important that other studies could replicate our findings.
Implications for clinical practice
These findings confirm the lack of association between multivitamin and dietary supplement use and CVD events or overall mortality in males. Neither the US [12, 13] nor the European [36] guidelines recommend multivitamin and/or dietary supplements as a preventive measure against CVD. Hence, for the time being, doctors should refrain from prescribing multivitamin and/or dietary supplements as a preventive measure against CVD.
Strengths and limitations
This is one of the few prospective studies conducted in a European country, which assessed the effect of vitamin-mineral supplement use, with and without association with dietary supplements. To our knowledge, it is also the only one that assessed the effect of persistent, occasional, and never use of vitamin-mineral ± dietary supplement use on CVD events, CVD- and total mortality.
Our study also has some limitations. First, it was conducted in a single location, and results might not be generalizable to other settings due to the differences in vitamin-mineral or dietary supplements. Still, it is unlikely that the differences in vitamin-mineral supplements be of such magnitude that they will change the findings. Second, it was not possible to precisely assess the composition of all vitamin-mineral and dietary supplements, due to lack of precise information provided by the participants, and to the large variability of vitamin-mineral supplements available in Switzerland [17]. Still, our results suggest that, irrespective of their composition, vitamin-mineral and dietary supplements do not protect from CVD, a finding also reported elsewhere [12, 13]. Third, and due to the previous limitation, it was not possible to assess if persistent users always consumed the same supplement or had switched to another one. Fourth, it was not possible to confirm if persistent users consumed the supplements throughout the whole follow-up period. Still, our results indicate that a higher vitamin-mineral ± dietary supplement use does not protect from CVD. Finally, a sizable fraction of the initial sample had to be excluded; even though the results were similar after inverse probability weighting, results should be considered with caution. Still, they replicate findings from previous studies [12, 13].
Conclusion
In this population-based prospective study, we found no association between vitamin-mineral ± dietary supplement use and total or CVD mortality or CVD. Consumption of vitamin-mineral ± dietary supplements to prevent CVD is not recommended.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
The authors would like to thank all the people who participated in the recruitment of the participants, data collection and validation, particularly Nicole Bonvin, Yolande Barreau, Mathieu Firmann, François Bastardot, Julien Vaucher, Panagiotis Antiochos, Cédric Gubelmann, Marylène Bay and Benoît Delabays. The CoLaus|PsyCoLaus study was supported by research grants from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, the Swiss National Science Foundation (grants 33CSCO-122661, 33CS30-139468, 33CS30-148401, 33CS30_177535 and 3247730_204523) and the Swiss Personalized Health Network (grant 2018DRI01). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
Author contributions
Rosa Lourenço: investigation, formal analysis, writing – original draft, visualization. Pedro Marques-Vidal: conceptualization, data curation, validation, writing – review & editing, supervision.
Funding
Open access funding provided by University of Lausanne.
Data availability
The data of CoLaus|PsyCoLaus study used in this article cannot be fully shared as they contain potentially sensitive personal information on participants. According to the Ethics Committee for Research of the Canton of Vaud, sharing these data would be a violation of the Swiss legislation with respect to privacy protection. However, coded individual-level data that do not allow researchers to identify participants are available upon request to researchers who meet the criteria for data sharing of the CoLaus|PsyCoLaus Datacenter (CHUV, Lausanne, Switzerland). Any researcher affiliated to a public or private research institution who complies with the CoLaus|PsyCoLaus standards can submit a research application to research.colaus@chuv.ch or research.psycolaus@chuv.ch. Proposals requiring baseline data only, will be evaluated by the baseline (local) Scientific Committee (SC) of the CoLaus and PsyCoLaus studies. Proposals requiring follow-up data will be evaluated by the follow-up (multicentric) SC of the CoLaus|PsyCoLaus cohort study. Detailed instructions for gaining access to the CoLaus|PsyCoLaus data used in this study are available at www.colaus-psycolaus.ch/professionals/how-to-collaborate/.
Declarations
Conflict of interest
The authors report no conflict of interest.
Declaration of generative artificial intelligence (AI) in scientific writing
The authors indicate that they did not use generative AI when writing their manuscript.
References
- 1.Cowan AE, Jun S, Gahche JJ, Tooze JA, Dwyer JT, Eicher-Miller HA, Bhadra A, Guenther PM, Potischman N, Dodd KW, Bailey RL (2018) Dietary supplement use differs by socioeconomic and health-related characteristics among U.S. adults, NHANES 2011(-)2014. Nutrients. 10.3390/nu10081114 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Marques-Vidal P, Vollenweider P, Waeber G (2017) Trends in vitamin, mineral and dietary supplement use in Switzerland. The CoLaus study. Eur J Clin Nutr 71(1):122–127. 10.1038/ejcn.2016.137 [DOI] [PubMed] [Google Scholar]
- 3.Barbarawi M, Kheiri B, Zayed Y, Barbarawi O, Dhillon H, Swaid B, Yelangi A, Sundus S, Bachuwa G, Alkotob ML, Manson JE (2019) Vitamin D supplementation and cardiovascular disease risks in more than 83000 individuals in 21 randomized clinical trials: a meta-analysis. JAMA Cardiol 4(8):765–776. 10.1001/jamacardio.2019.1870 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Gordon D, Copeland T, D’Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, Buring JE, Group VR (2019) Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 380(1):33–44. 10.1056/NEJMoa1809944 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Ford JA, MacLennan GS, Avenell A, Bolland M, Grey A, Witham M, Group RT (2014) Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis. Am J Clin Nutr 100(3):746–755. 10.3945/ajcn.113.082602 [DOI] [PubMed] [Google Scholar]
- 6.Al-Khudairy L, Flowers N, Wheelhouse R, Ghannam O, Hartley L, Stranges S, Rees K (2017) Vitamin C supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 3:CD011114. 10.1002/14651858.CD011114.pub2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Uesugi S, Ishihara J, Iso H, Sawada N, Takachi R, Inoue M, Tsugane S (2017) Dietary intake of antioxidant vitamins and risk of stroke: the Japan public health center-based prospective study. Eur J Clin Nutr 71(10):1179–1185. 10.1038/ejcn.2017.71 [DOI] [PubMed] [Google Scholar]
- 8.Wang SM, Fan JH, Taylor PR, Lam TK, Dawsey SM, Qiao YL, Abnet CC (2018) Association of plasma vitamin C concentration to total and cause-specific mortality: a 16-year prospective study in China. J Epidemiol Commun Health 72(12):1076–1082. 10.1136/jech-2018-210809 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Hartley L, Clar C, Ghannam O, Flowers N, Stranges S, Rees K (2015) Vitamin K for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 9:CD011148. 10.1002/14651858.CD011148.pub2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Schandelmaier S, Briel M, Saccilotto R, Olu KK, Arpagaus A, Hemkens LG, Nordmann AJ (2017) Niacin for primary and secondary prevention of cardiovascular events. Cochrane Database Syst Rev 6:CD009744. 10.1002/14651858.CD009744.pub2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Moyer VA, Force USPST (2014) Vitamin, mineral, and multivitamin supplements for the primary prevention of cardiovascular disease and cancer: U.S. Preventive services task force recommendation statement. Ann Intern Med 160(8):558–564. 10.7326/M14-0198 [DOI] [PubMed] [Google Scholar]
- 12.O’Connor EA, Evans CV, Ivlev I, Rushkin MC, Thomas RG, Martin A, Lin JS (2022) Vitamin and mineral supplements for the primary prevention of cardiovascular disease and cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 327(23):2334–2347. 10.1001/jama.2021.15650 [DOI] [PubMed] [Google Scholar]
- 13.U. S. Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, Cabana M, Chelmow D, Coker TR, Davis EM, Donahue KE, Doubeni CA, Jaen CR, Kubik M, Li L, Ogedegbe G, Pbert L, Ruiz JM, Stevermer J, Wong JB (2022) Vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer: US preventive services task force recommendation statement. Jama 327(23):2326–2333. 10.1001/jama.2022.8970 [DOI] [PubMed] [Google Scholar]
- 14.Marques-Vidal P, Pecoud A, Hayoz D, Paccaud F, Mooser V, Waeber G, Vollenweider P (2009) Prevalence and characteristics of vitamin or dietary supplement users in Lausanne, Switzerland: the CoLaus study. Eur J Clin Nutr 63(2):273–281. 10.1038/sj.ejcn.1602932 [DOI] [PubMed] [Google Scholar]
- 15.Patriota P, Guessous I, Marques-Vidal P (2020) Dietary patterns according to vitamin supplement use. A cross-sectional study in Switzerland. Int J Vitam Nutr Res. 10.1024/0300-9831/a000679 [DOI] [PubMed] [Google Scholar]
- 16.Fingeret M, Vollenweider P, Marques-Vidal P (2019) No association between vitamin C and E supplementation and grip strength over 5 years: the Colaus study. Eur J Nutr 58(2):609–617. 10.1007/s00394-018-1646-9 [DOI] [PubMed] [Google Scholar]
- 17.Droz N, Marques-Vidal P (2014) Multivitamins/multiminerals in Switzerland: not as good as it seems. Nutr J 13:24. 10.1186/1475-2891-13-24 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Firmann M, Mayor V, Vidal PM, Bochud M, Pecoud A, Hayoz D, Paccaud F, Preisig M, Song KS, Yuan X, Danoff TM, Stirnadel HA, Waterworth D, Mooser V, Waeber G, Vollenweider P (2008) The CoLaus study: a population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome. BMC Cardiovasc Disord 8:6. 10.1186/1471-2261-8-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Beuret H, Hausler N, Nanchen D, Mean M, Marques-Vidal P, Vaucher J (2021) Comparison of Swiss and European risk algorithms for cardiovascular prevention in Switzerland. Eur J Prev Cardiol 28(2):204–210. 10.1177/2047487320906305 [DOI] [PubMed] [Google Scholar]
- 20.Marques-Vidal P, Arveiler D, Evans A, Montaye M, Ruidavets JB, Haas B, Yarnell J, Bingham A, Ferrieres J, Amouyel P, Ducimetiere P (2000) Characteristics of male vitamin supplement users aged 50–59 years in France and Northern Ireland: the PRIME study. Prospective epidemiological study of myocardial infarction. Int J Vitam Nutr Res 70(3):102–109. 10.1024/0300-9831.70.3.102 [DOI] [PubMed] [Google Scholar]
- 21.Bernstein M, Sloutskis D, Kumanyika S, Sparti A, Schutz Y, Morabia A (1998) Data-based approach for developing a physical activity frequency questionnaire. Am J Epidemiol 147(2):147–154. 10.1093/oxfordjournals.aje.a009427 [DOI] [PubMed] [Google Scholar]
- 22.Bernstein MS, Morabia A, Sloutskis D (1999) Definition and prevalence of sedentarism in an urban population. Am J Public Health 89(6):862–867. 10.2105/ajph.89.6.862 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Verhoog S, Gubelmann C, Guessous I, Bano A, Franco OH, Marques-Vidal P (2019) Comparison of the physical activity frequency questionnaire (PAFQ) with accelerometry in a middle-aged and elderly population: The CoLaus study. Maturitas 129:68–75. 10.1016/j.maturitas.2019.08.004 [DOI] [PubMed] [Google Scholar]
- 24.Beer-Borst S, Costanza MC, Pechere-Bertschi A, Morabia A (2009) Twelve-year trends and correlates of dietary salt intakes for the general adult population of Geneva. Switzerland Eur J Clin Nutr 63(2):155–164. 10.1038/sj.ejcn.1602922 [DOI] [PubMed] [Google Scholar]
- 25.Trichopoulou A, Costacou T, Bamia C, Trichopoulos D (2003) Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 348(26):2599–2608. 10.1056/NEJMoa025039 [DOI] [PubMed] [Google Scholar]
- 26.Sesso HD, Manson JE, Aragaki AK, Rist PM, Johnson LG, Friedenberg G, Copeland T, Clar A, Mora S, Moorthy MV, Sarkissian A, Carrick WR, Anderson GL, Group CR (2022) Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa supplement and multivitamin outcomes study (COSMOS) randomized clinical trial. Am J Clin Nutr 115(6):1490–1500. 10.1093/ajcn/nqac055 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Paganini-Hill A, Kawas CH, Corrada MM (2015) Antioxidant vitamin intake and mortality: the Leisure world cohort study. Am J Epidemiol 181(2):120–126. 10.1093/aje/kwu294 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Zhao LG, Shu XO, Li HL, Zhang W, Gao J, Sun JW, Zheng W, Xiang YB (2017) Dietary antioxidant vitamins intake and mortality: a report from two cohort studies of Chinese adults in Shanghai. J Epidemiol 27(3):89–97. 10.1016/j.je.2016.10.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG (2012) Gluud C (2012) Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 3:CD007176. 10.1002/14651858.CD007176.pub2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, Roussel AM, Favier A, Briancon S (2004) The SU.VI.MAX study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med 164(21):2335–2342. 10.1001/archinte.164.21.2335 [DOI] [PubMed] [Google Scholar]
- 31.Rodondi PY, Degoumois F, Marques-Vidal P, Rodondi N (2016) Is it possible to decrease cholesterol levels with dietary supplements? Rev Med Suisse 12(508):451–453 [PubMed] [Google Scholar]
- 32.Cohen PA, Ernst E (2010) Safety of herbal supplements: a guide for cardiologists. Cardiovasc Ther 28(4):246–253. 10.1111/j.1755-5922.2010.00193.x [DOI] [PubMed] [Google Scholar]
- 33.Bush TM, Rayburn KS, Holloway SW, Sanchez-Yamamoto DS, Allen BL, Lam T, So BK, de Tran H, Greyber ER, Kantor S, Roth LW (2007) Adverse interactions between herbal and dietary substances and prescription medications: a clinical survey. Altern Ther Health Med 13(2):30–35 [PubMed] [Google Scholar]
- 34.Byard RW, Musgrave I, Maker G, Bunce M (2017) What risks do herbal products pose to the Australian community? Med J Aust 206(2):86–90. 10.5694/mja16.00614 [DOI] [PubMed] [Google Scholar]
- 35.Friedman NA, Cantrell FL (2022) Mind the gap: Bromism secondary to internet-purchased supplements. Am J Emerg Med. 10.1016/j.ajem.2022.08.005 [DOI] [PubMed] [Google Scholar]
- 36.Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Back M, Benetos A, Biffi A, Boavida JM, Capodanno D, Cosyns B, Crawford C, Davos CH, Desormais I, Di Angelantonio E, Franco OH, Halvorsen S, Hobbs FDR, Hollander M, Jankowska EA, Michal M, Sacco S, Sattar N, Tokgozoglu L, Tonstad S, Tsioufis KP, van Dis I, van Gelder IC, Wanner C, Williams B, Societies ESCNC, Group ESCSD (2021) 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 42(34):3227–3337. 10.1093/eurheartj/ehab484 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data of CoLaus|PsyCoLaus study used in this article cannot be fully shared as they contain potentially sensitive personal information on participants. According to the Ethics Committee for Research of the Canton of Vaud, sharing these data would be a violation of the Swiss legislation with respect to privacy protection. However, coded individual-level data that do not allow researchers to identify participants are available upon request to researchers who meet the criteria for data sharing of the CoLaus|PsyCoLaus Datacenter (CHUV, Lausanne, Switzerland). Any researcher affiliated to a public or private research institution who complies with the CoLaus|PsyCoLaus standards can submit a research application to research.colaus@chuv.ch or research.psycolaus@chuv.ch. Proposals requiring baseline data only, will be evaluated by the baseline (local) Scientific Committee (SC) of the CoLaus and PsyCoLaus studies. Proposals requiring follow-up data will be evaluated by the follow-up (multicentric) SC of the CoLaus|PsyCoLaus cohort study. Detailed instructions for gaining access to the CoLaus|PsyCoLaus data used in this study are available at www.colaus-psycolaus.ch/professionals/how-to-collaborate/.