Circulating vitamin C and the risk of cardiovascular diseases: A Mendelian randomization study
The impact of vitamin C supplementation on the risk of cardiovascular diseases (CVDs) remains uncertain with inconsistent evidence obtained from observational studies and randomized clinical trials (RCTs). We aimed to assess possible causal associations of vitamin C with major CVD events as well as...
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| Veröffentlicht in: | Nutrition, metabolism, and cardiovascular diseases metabolism, and cardiovascular diseases, 2021-07, Vol.31 (8), p.2398-2406 |
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| container_title | Nutrition, metabolism, and cardiovascular diseases |
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| creator | Zhu, Jiahao Ling, Yuxiao Tse, Lap A. Kinra, Sanjay Li, Yingjun |
| description | The impact of vitamin C supplementation on the risk of cardiovascular diseases (CVDs) remains uncertain with inconsistent evidence obtained from observational studies and randomized clinical trials (RCTs). We aimed to assess possible causal associations of vitamin C with major CVD events as well as their risk factors using Mendelian randomization (MR) design.
Nine genetic variants associated with vitamin C at genome-wide significance (p |
| doi_str_mv | 10.1016/j.numecd.2021.04.023 |
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Nine genetic variants associated with vitamin C at genome-wide significance (p < 5 × 10−8) were used as instrumental variables to predict plasma vitamin C levels. The primary outcomes were coronary artery disease (Ncase = 122,733 and Ncontrol = 424,528), atrial fibrillation (Ncase = 60,620 and Ncontrol = 970,216), heart failure (Ncase = 47,309 and Ncontrol = 930,014), and ischemic stroke (Ncase = 40,585 and Ncontrol = 406,111). Several CVD risk factors were also evaluated in secondary analyses. Two-sample MR analyses were performed using the inverse variance weighted method, with several sensitivity analyses. Genetically determined higher levels of plasma vitamin C were not significantly associated with any of the four examined CVD events. Likewise, there is no convincing evidence for the associations between genetically determined vitamin C and CVD risk factors, including higher blood lipids, higher blood pressure, and abnormal body composition. Sensitivity analyses using different analytical approaches yielded consistent results. Additionally, MR assumptions did not seem to be violated.
This MR study does not support a causal protective role to circulate vitamin C levels on various types of CVD events. In combination with previous RCT results, our findings suggest that vitamin C supplementation to increase circulating vitamin C levels may not help in CVD prevention.
•The evidence for the effect of vitamin C supplementation on the risk of cardiovascular diseases is inconsistent.•Genetically determined vitamin C levels were not related to the risk of coronary artery disease, atrial fibrillation, heart failure, and stroke.•Genetically determined vitamin C levels were not related to blood lipids, blood pressure, and body composition.</description><identifier>ISSN: 0939-4753</identifier><identifier>EISSN: 1590-3729</identifier><identifier>DOI: 10.1016/j.numecd.2021.04.023</identifier><language>eng</language><publisher>Elsevier B.V</publisher><subject>Cardiovascular diseases ; Mendelian randomization ; Risk factors ; Vitamin C</subject><ispartof>Nutrition, metabolism, and cardiovascular diseases, 2021-07, Vol.31 (8), p.2398-2406</ispartof><rights>2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c339t-1c2d55375d8513175efeda734ff4913fab8fd29e6f22de044d01589c5f9429ef3</citedby><cites>FETCH-LOGICAL-c339t-1c2d55375d8513175efeda734ff4913fab8fd29e6f22de044d01589c5f9429ef3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0939475321002167$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids></links><search><creatorcontrib>Zhu, Jiahao</creatorcontrib><creatorcontrib>Ling, Yuxiao</creatorcontrib><creatorcontrib>Tse, Lap A.</creatorcontrib><creatorcontrib>Kinra, Sanjay</creatorcontrib><creatorcontrib>Li, Yingjun</creatorcontrib><title>Circulating vitamin C and the risk of cardiovascular diseases: A Mendelian randomization study</title><title>Nutrition, metabolism, and cardiovascular diseases</title><description>The impact of vitamin C supplementation on the risk of cardiovascular diseases (CVDs) remains uncertain with inconsistent evidence obtained from observational studies and randomized clinical trials (RCTs). We aimed to assess possible causal associations of vitamin C with major CVD events as well as their risk factors using Mendelian randomization (MR) design.
Nine genetic variants associated with vitamin C at genome-wide significance (p < 5 × 10−8) were used as instrumental variables to predict plasma vitamin C levels. The primary outcomes were coronary artery disease (Ncase = 122,733 and Ncontrol = 424,528), atrial fibrillation (Ncase = 60,620 and Ncontrol = 970,216), heart failure (Ncase = 47,309 and Ncontrol = 930,014), and ischemic stroke (Ncase = 40,585 and Ncontrol = 406,111). Several CVD risk factors were also evaluated in secondary analyses. Two-sample MR analyses were performed using the inverse variance weighted method, with several sensitivity analyses. Genetically determined higher levels of plasma vitamin C were not significantly associated with any of the four examined CVD events. Likewise, there is no convincing evidence for the associations between genetically determined vitamin C and CVD risk factors, including higher blood lipids, higher blood pressure, and abnormal body composition. Sensitivity analyses using different analytical approaches yielded consistent results. Additionally, MR assumptions did not seem to be violated.
This MR study does not support a causal protective role to circulate vitamin C levels on various types of CVD events. In combination with previous RCT results, our findings suggest that vitamin C supplementation to increase circulating vitamin C levels may not help in CVD prevention.
•The evidence for the effect of vitamin C supplementation on the risk of cardiovascular diseases is inconsistent.•Genetically determined vitamin C levels were not related to the risk of coronary artery disease, atrial fibrillation, heart failure, and stroke.•Genetically determined vitamin C levels were not related to blood lipids, blood pressure, and body composition.</description><subject>Cardiovascular diseases</subject><subject>Mendelian randomization</subject><subject>Risk factors</subject><subject>Vitamin C</subject><issn>0939-4753</issn><issn>1590-3729</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kM1KAzEUhYMoWKtv4CJLNzPmt9O4EErxDypudB1icqOpM5mazBTq0_gsPplTxrWrC4dzPrgfQueUlJTQ2eW6jH0D1pWMMFoSURLGD9CESkUKXjF1iCZEcVWISvJjdJLzmhBeES4mSC9Dsn1tuhDf8DZ0pgkRL7GJDnfvgFPIH7j12JrkQrs1ed9N2IUMJkO-wouf70eIDupgIk7DrG3C10BrI85d73an6MibOsPZ352il9ub5-V9sXq6e1guVoXlXHUFtcxJySvp5pJyWknw4EzFhfdCUe7N69w7pmDmGXNAhHCEyrmy0isxxJ5P0cXI3aT2s4fc6SZkC3VtIrR91myAz4RQkg1VMVZtanNO4PUmhcaknaZE733qtR596r1PTYQefA6z63EGwxvbAElnGyBacCGB7bRrw_-AX0XQgiw</recordid><startdate>20210722</startdate><enddate>20210722</enddate><creator>Zhu, Jiahao</creator><creator>Ling, Yuxiao</creator><creator>Tse, Lap A.</creator><creator>Kinra, Sanjay</creator><creator>Li, Yingjun</creator><general>Elsevier B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20210722</creationdate><title>Circulating vitamin C and the risk of cardiovascular diseases: A Mendelian randomization study</title><author>Zhu, Jiahao ; Ling, Yuxiao ; Tse, Lap A. ; Kinra, Sanjay ; Li, Yingjun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c339t-1c2d55375d8513175efeda734ff4913fab8fd29e6f22de044d01589c5f9429ef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Cardiovascular diseases</topic><topic>Mendelian randomization</topic><topic>Risk factors</topic><topic>Vitamin C</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhu, Jiahao</creatorcontrib><creatorcontrib>Ling, Yuxiao</creatorcontrib><creatorcontrib>Tse, Lap A.</creatorcontrib><creatorcontrib>Kinra, Sanjay</creatorcontrib><creatorcontrib>Li, Yingjun</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Nutrition, metabolism, and cardiovascular diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Jiahao</au><au>Ling, Yuxiao</au><au>Tse, Lap A.</au><au>Kinra, Sanjay</au><au>Li, Yingjun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Circulating vitamin C and the risk of cardiovascular diseases: A Mendelian randomization study</atitle><jtitle>Nutrition, metabolism, and cardiovascular diseases</jtitle><date>2021-07-22</date><risdate>2021</risdate><volume>31</volume><issue>8</issue><spage>2398</spage><epage>2406</epage><pages>2398-2406</pages><issn>0939-4753</issn><eissn>1590-3729</eissn><abstract>The impact of vitamin C supplementation on the risk of cardiovascular diseases (CVDs) remains uncertain with inconsistent evidence obtained from observational studies and randomized clinical trials (RCTs). We aimed to assess possible causal associations of vitamin C with major CVD events as well as their risk factors using Mendelian randomization (MR) design.
Nine genetic variants associated with vitamin C at genome-wide significance (p < 5 × 10−8) were used as instrumental variables to predict plasma vitamin C levels. The primary outcomes were coronary artery disease (Ncase = 122,733 and Ncontrol = 424,528), atrial fibrillation (Ncase = 60,620 and Ncontrol = 970,216), heart failure (Ncase = 47,309 and Ncontrol = 930,014), and ischemic stroke (Ncase = 40,585 and Ncontrol = 406,111). Several CVD risk factors were also evaluated in secondary analyses. Two-sample MR analyses were performed using the inverse variance weighted method, with several sensitivity analyses. Genetically determined higher levels of plasma vitamin C were not significantly associated with any of the four examined CVD events. Likewise, there is no convincing evidence for the associations between genetically determined vitamin C and CVD risk factors, including higher blood lipids, higher blood pressure, and abnormal body composition. Sensitivity analyses using different analytical approaches yielded consistent results. Additionally, MR assumptions did not seem to be violated.
This MR study does not support a causal protective role to circulate vitamin C levels on various types of CVD events. In combination with previous RCT results, our findings suggest that vitamin C supplementation to increase circulating vitamin C levels may not help in CVD prevention.
•The evidence for the effect of vitamin C supplementation on the risk of cardiovascular diseases is inconsistent.•Genetically determined vitamin C levels were not related to the risk of coronary artery disease, atrial fibrillation, heart failure, and stroke.•Genetically determined vitamin C levels were not related to blood lipids, blood pressure, and body composition.</abstract><pub>Elsevier B.V</pub><doi>10.1016/j.numecd.2021.04.023</doi><tpages>9</tpages></addata></record> |
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| source | Elsevier ScienceDirect Journals |
| subjects | Cardiovascular diseases Mendelian randomization Risk factors Vitamin C |
| title | Circulating vitamin C and the risk of cardiovascular diseases: A Mendelian randomization study |
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