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==Overview== | ==Overview== | ||
Use of multivitamin supplements in the US has increased tremendously in past decade. According to the data from National Center for Health Statistics<ref name="pmid15286019">{{cite journal |author=Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano MF |title=Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999-2000 |journal=[[American Journal of Epidemiology]] |volume=160 |issue=4 |pages=339–49 |year=2004 |month=August |pmid=15286019 |doi=10.1093/aje/kwh207 |url=}}</ref>, over 50% of adults in the United States consume dietary supplements, with approximately 35% of adults taking multivitamin supplements. Studies on multivitamin supplements have shown conflicting evidence on their effect on mortality, with | Use of multivitamin supplements in the US has increased tremendously in past decade. According to the data from National Center for Health Statistics<ref name="pmid15286019">{{cite journal |author=Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano MF |title=Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999-2000 |journal=[[American Journal of Epidemiology]] |volume=160 |issue=4 |pages=339–49 |year=2004 |month=August |pmid=15286019 |doi=10.1093/aje/kwh207 |url=}}</ref>, over 50% of adults in the United States consume dietary supplements, with approximately 35% of adults taking multivitamin supplements. Annual multivitamin and dietary supplements sales total to $ 20 billion. Studies on multivitamin supplements have shown conflicting evidence on their effect on mortality, with majority of studies showing a reduction in mortality and a few demonstrating an increase. | ||
==Mode of Action== | |||
* [[Free radical]] formation in the cell is a result of normal energy metabolism leading to oxidant stress. It may also occur as a consequence of exposure to environmental agents like cigarette [[smoking]]. | |||
* Oxidative damage to cell disrupts the normal structure and function of DNA and lipids (causing [[lipid peroxidation]]) giving rise to cancer and atherosclerosis. | |||
* [[Vitamins]], being anti-oxidants, prevent this damage caused by free radicals by antagonizing its effect, thereby preventing [[cancer]]s and [[atherosclerosis]]. | |||
==Landmark Studies== | ==Landmark Studies== | ||
===Iowa Women Health Study<ref name="pmid21987192">{{cite journal |author=Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR |title=Dietary supplements and mortality rate in older women: the Iowa Women's Health Study |journal=[[Archives of Internal Medicine]] |volume=171 |issue=18 |pages=1625–33 |year=2011 |month=October |pmid=21987192 |doi=10.1001/archinternmed.2011.445 |url=}}</ref>=== | ===Iowa Women's Health Study <ref name="pmid21987192">{{cite journal |author=Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR |title=Dietary supplements and mortality rate in older women: the Iowa Women's Health Study |journal=[[Archives of Internal Medicine]] |volume=171 |issue=18 |pages=1625–33 |year=2011 |month=October |pmid=21987192 |doi=10.1001/archinternmed.2011.445 |url=}}</ref>=== | ||
* This study assessed the long term effects of multivitamin supplements on mortality. It included 38,772 women with a mean age of 61.6 years at baseline. | * This was an observational study that assessed the long term effects of [[multivitamin]] supplements on all-cause [[mortality]]. It included 38,772 women with a mean age of 61.6 years at baseline. | ||
* The study found increase in risk of total mortality in women on dietary and vitamin supplements, with highest increase in mortality seen in women on iron supplements. In | * The study found increase in risk of total [[mortality]] in women on dietary and vitamin supplements, with highest increase in mortality seen in women on [[iron]] supplements. Calcium supplement intake was associated with a decrease in mortality. | ||
* Limitations of the study include: | |||
** [[Confounding factor]]s: [[Smoking]] status, [[alcohol]] intake, [[BMI]] and lipid levels were not excluded to minimize [[bias]]. | |||
** The study heavily relied on questionnaire | |||
** [[Compliance]] of the women taking multivitamin and mineral supplements was not considered | |||
** Although the multivitamin and dietary mineral intake patterns in these women were observed<ref name="pmid19208725">{{cite journal |author=Park K, Harnack L, Jacobs DR |title=Trends in dietary supplement use in a cohort of postmenopausal women from Iowa |journal=[[American Journal of Epidemiology]] |volume=169 |issue=7 |pages=887–92 |year=2009 |month=April |pmid=19208725 |pmc=2727219 |doi=10.1093/aje/kwn410 |url=}}</ref>, the serum levels of vitamins and minerals were not studied to correlate the occurrence of death with intake of the supplements. | |||
In contradiction to the above findings, another recent prospective longitudinal cohort study that assessed the long term effects of calcium on cardiovascular mortality demonstrated an increase in death rates from all causes and cardiovascular diseases in those on calcium supplements<ref name="pmid23403980">{{cite journal |author=Michaëlsson K, Melhus H, Warensjö Lemming E, Wolk A, Byberg L |title=Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study |journal=[[BMJ (Clinical Research Ed.)]] |volume=346 |issue= |pages=f228 |year=2013 |pmid=23403980 |pmc=3571949 |doi= |url=}}</ref>. | |||
===Physician's Health Study II (Prevention of Cancer)<ref name="pmid23162860">{{cite journal |author=Gaziano JM, Sesso HD, Christen WG, ''et al.'' |title=Multivitamins in the prevention of cancer in men: the Physicians' Health Study II randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=308 |issue=18 |pages=1871–80 |year=2012 |month=November |pmid=23162860 |doi= |url=}}</ref>=== | |||
* This was a large scale randomized, [[double-blinded]], placebo-controlled trial done on 14,641 US male physicians aged 50 years or older with 1312 men having a history of cancer. | |||
* All the subjects were then randomly assigned to receive either multivitamins or placebo and followed-up for a median of 11.2 years. The primary end points included total cancer, with other site specific cancers as secondary end points. | |||
* Compared to [[placebo]], the incidence of total [[cancer]] in men on multivitamin supplements in this study showed a modest but statistically significant reduction. | |||
===Physician's Health Study II (Cardiovascular mortality)<ref name="pmid23117775">{{cite journal |author=Sesso HD, Christen WG, Bubes V, ''et al.'' |title=Multivitamins in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=308 |issue=17 |pages=1751–60 |year=2012 |month=November |pmid=23117775 |doi=10.1001/jama.2012.14805 |url=}}</ref>=== | |||
* The above study population of 14,641 US male physicians were studied for effects of long term multivitamin supplements use on cardiovascular [[mortality]]. They were randomly assigned to multivitamins and placebo group, and followed up for a period of 11.2 years | |||
* The study demonstrated no significant effects of daily multivitamin on cardiovascular events, including total [[MI]] and total [[stroke]]. Also, there was no significant difference seen in total cardiovascular mortality in the two groups. | |||
===Physician's Health Study II (Effects of Vitamin E and Vitamin C on Cardiovascular Mortality)<ref name="pmid18997197">{{cite journal |author=Sesso HD, Buring JE, Christen WG, ''et al.'' |title=Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=300 |issue=18 |pages=2123–33 |year=2008 |month=November |pmid=18997197 |pmc=2586922 |doi=10.1001/jama.2008.600 |url=}}</ref>=== | |||
* This study also analyzed the above data to assess the effects of vitamin E and vitamin C supplements on cardiovascular mortality. | |||
* At the end of the follow-up period of 11.2 years, it was found that neither [[vitamin E]] nor [[vitamin C]] reduced the risk of major cardiovascular events. | |||
===Cancer Prevention Study - II <ref name="pmid10909952">{{cite journal |author=Watkins ML, Erickson JD, Thun MJ, Mulinare J, Heath CW |title=Multivitamin use and mortality in a large prospective study |journal=[[American Journal of Epidemiology]] |volume=152 |issue=2 |pages=149–62 |year=2000 |month=July |pmid=10909952 |doi= |url=}}</ref>=== | |||
* Another large prospective study done by [[CDC]] and National center for environmental health, included 1,063,023 men and women to determine the effects of [[multivitamins]] supplements on [[incidence]] of cardiovascular disease, cerebrovascular disease and cancer. | |||
* They compared the mortality in these healthy subjects by dividing the cohort into 4 subgroups: | |||
** Multivitamin group: Those consuming multivitamins including vitamin B12, B6, folic acid, etc. | |||
** Vitamin A, C and E group | |||
** Combination of multivitamin and vitamin A, C and E group | |||
** Non-vitamin users | |||
* The incidence of cardiovascular and cerebrovascular deaths was the same in multivitamin group and non-users, whereas it was 15% lower in those on combination of multivitamin and vitamin A, C and E. | |||
* The multivitamin and the combination group had minimal effects on overall cancer mortality. However, mortality from all cancers increased in male smokers in these groups and decreased in male non-smokers who belonged to the combination group. No such associations were seen in females. | |||
* The risk of ischemic heart disease and stroke mortality was lower in those on combination of vitamins than multivitamins alone and non-users. The risk of cancer was increased in multivitamin users who smoked than those who did not. | |||
==Other Studies== | |||
* A cohort study performed in Washington, assessed the long term effects of vitamin supplements on cardiovascular mortality using data collected from 77,719 residents of the Washington State aged 50 to 76 years by filling a questionnaire. The study demonstrated a small decrease in risk of cardiovascular mortality with [[vitamin E]] use and no effect with the use of [[vitamin C]]<ref name="pmid19596711">{{cite journal |author=Pocobelli G, Peters U, Kristal AR, White E |title=Use of supplements of multivitamins, vitamin C, and vitamin E in relation to mortality |journal=[[American Journal of Epidemiology]] |volume=170 |issue=4 |pages=472–83 |year=2009 |month=August |pmid=19596711 |pmc=2727181 |doi=10.1093/aje/kwp167 |url=}}</ref>. | |||
* A similar prospective cohort study done by Muntwyler et al.<ref name="pmid12090883">{{cite journal |author=Muntwyler J, Hennekens CH, Manson JE, Buring JE, Gaziano JM |title=Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality |journal=[[Archives of Internal Medicine]] |volume=162 |issue=13 |pages=1472–6 |year=2002 |month=July |pmid=12090883 |doi= |url=}}</ref> on 83,639 healthy US male physicians, showed no significant effects of vitamin C and vitamin E intake on increase in cardiovascular mortality. | |||
* A [[meta-analysis]] report from randomized controlled trials also showed no significant effects of multivitamin and multimineral intake on cardiovascular mortality<ref name="pmid23255568">{{cite journal |author=Macpherson H, Pipingas A, Pase MP |title=Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials |journal=[[The American Journal of Clinical Nutrition]] |volume=97 |issue=2 |pages=437–44 |year=2013 |month=February |pmid=23255568 |doi=10.3945/ajcn.112.049304 |url=}}</ref>. | |||
==References== | ==References== | ||
Latest revision as of 15:02, 8 May 2013
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]
Overview
Use of multivitamin supplements in the US has increased tremendously in past decade. According to the data from National Center for Health Statistics[1], over 50% of adults in the United States consume dietary supplements, with approximately 35% of adults taking multivitamin supplements. Annual multivitamin and dietary supplements sales total to $ 20 billion. Studies on multivitamin supplements have shown conflicting evidence on their effect on mortality, with majority of studies showing a reduction in mortality and a few demonstrating an increase.
Mode of Action
- Free radical formation in the cell is a result of normal energy metabolism leading to oxidant stress. It may also occur as a consequence of exposure to environmental agents like cigarette smoking.
- Oxidative damage to cell disrupts the normal structure and function of DNA and lipids (causing lipid peroxidation) giving rise to cancer and atherosclerosis.
- Vitamins, being anti-oxidants, prevent this damage caused by free radicals by antagonizing its effect, thereby preventing cancers and atherosclerosis.
Landmark Studies
Iowa Women's Health Study [2]
- This was an observational study that assessed the long term effects of multivitamin supplements on all-cause mortality. It included 38,772 women with a mean age of 61.6 years at baseline.
- The study found increase in risk of total mortality in women on dietary and vitamin supplements, with highest increase in mortality seen in women on iron supplements. Calcium supplement intake was associated with a decrease in mortality.
- Limitations of the study include:
- Confounding factors: Smoking status, alcohol intake, BMI and lipid levels were not excluded to minimize bias.
- The study heavily relied on questionnaire
- Compliance of the women taking multivitamin and mineral supplements was not considered
- Although the multivitamin and dietary mineral intake patterns in these women were observed[3], the serum levels of vitamins and minerals were not studied to correlate the occurrence of death with intake of the supplements.
In contradiction to the above findings, another recent prospective longitudinal cohort study that assessed the long term effects of calcium on cardiovascular mortality demonstrated an increase in death rates from all causes and cardiovascular diseases in those on calcium supplements[4].
Physician's Health Study II (Prevention of Cancer)[5]
- This was a large scale randomized, double-blinded, placebo-controlled trial done on 14,641 US male physicians aged 50 years or older with 1312 men having a history of cancer.
- All the subjects were then randomly assigned to receive either multivitamins or placebo and followed-up for a median of 11.2 years. The primary end points included total cancer, with other site specific cancers as secondary end points.
- Compared to placebo, the incidence of total cancer in men on multivitamin supplements in this study showed a modest but statistically significant reduction.
Physician's Health Study II (Cardiovascular mortality)[6]
- The above study population of 14,641 US male physicians were studied for effects of long term multivitamin supplements use on cardiovascular mortality. They were randomly assigned to multivitamins and placebo group, and followed up for a period of 11.2 years
- The study demonstrated no significant effects of daily multivitamin on cardiovascular events, including total MI and total stroke. Also, there was no significant difference seen in total cardiovascular mortality in the two groups.
Physician's Health Study II (Effects of Vitamin E and Vitamin C on Cardiovascular Mortality)[7]
- This study also analyzed the above data to assess the effects of vitamin E and vitamin C supplements on cardiovascular mortality.
- At the end of the follow-up period of 11.2 years, it was found that neither vitamin E nor vitamin C reduced the risk of major cardiovascular events.
Cancer Prevention Study - II [8]
- Another large prospective study done by CDC and National center for environmental health, included 1,063,023 men and women to determine the effects of multivitamins supplements on incidence of cardiovascular disease, cerebrovascular disease and cancer.
- They compared the mortality in these healthy subjects by dividing the cohort into 4 subgroups:
- Multivitamin group: Those consuming multivitamins including vitamin B12, B6, folic acid, etc.
- Vitamin A, C and E group
- Combination of multivitamin and vitamin A, C and E group
- Non-vitamin users
- The incidence of cardiovascular and cerebrovascular deaths was the same in multivitamin group and non-users, whereas it was 15% lower in those on combination of multivitamin and vitamin A, C and E.
- The multivitamin and the combination group had minimal effects on overall cancer mortality. However, mortality from all cancers increased in male smokers in these groups and decreased in male non-smokers who belonged to the combination group. No such associations were seen in females.
- The risk of ischemic heart disease and stroke mortality was lower in those on combination of vitamins than multivitamins alone and non-users. The risk of cancer was increased in multivitamin users who smoked than those who did not.
Other Studies
- A cohort study performed in Washington, assessed the long term effects of vitamin supplements on cardiovascular mortality using data collected from 77,719 residents of the Washington State aged 50 to 76 years by filling a questionnaire. The study demonstrated a small decrease in risk of cardiovascular mortality with vitamin E use and no effect with the use of vitamin C[9].
- A similar prospective cohort study done by Muntwyler et al.[10] on 83,639 healthy US male physicians, showed no significant effects of vitamin C and vitamin E intake on increase in cardiovascular mortality.
- A meta-analysis report from randomized controlled trials also showed no significant effects of multivitamin and multimineral intake on cardiovascular mortality[11].
References
- ↑ Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano MF (2004). "Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999-2000". American Journal of Epidemiology. 160 (4): 339–49. doi:10.1093/aje/kwh207. PMID 15286019. Unknown parameter
|month=ignored (help) - ↑ Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR (2011). "Dietary supplements and mortality rate in older women: the Iowa Women's Health Study". Archives of Internal Medicine. 171 (18): 1625–33. doi:10.1001/archinternmed.2011.445. PMID 21987192. Unknown parameter
|month=ignored (help) - ↑ Park K, Harnack L, Jacobs DR (2009). "Trends in dietary supplement use in a cohort of postmenopausal women from Iowa". American Journal of Epidemiology. 169 (7): 887–92. doi:10.1093/aje/kwn410. PMC 2727219. PMID 19208725. Unknown parameter
|month=ignored (help) - ↑ Michaëlsson K, Melhus H, Warensjö Lemming E, Wolk A, Byberg L (2013). "Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study". BMJ (Clinical Research Ed.). 346: f228. PMC 3571949. PMID 23403980.
- ↑ Gaziano JM, Sesso HD, Christen WG; et al. (2012). "Multivitamins in the prevention of cancer in men: the Physicians' Health Study II randomized controlled trial". JAMA : the Journal of the American Medical Association. 308 (18): 1871–80. PMID 23162860. Unknown parameter
|month=ignored (help) - ↑ Sesso HD, Christen WG, Bubes V; et al. (2012). "Multivitamins in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial". JAMA : the Journal of the American Medical Association. 308 (17): 1751–60. doi:10.1001/jama.2012.14805. PMID 23117775. Unknown parameter
|month=ignored (help) - ↑ Sesso HD, Buring JE, Christen WG; et al. (2008). "Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial". JAMA : the Journal of the American Medical Association. 300 (18): 2123–33. doi:10.1001/jama.2008.600. PMC 2586922. PMID 18997197. Unknown parameter
|month=ignored (help) - ↑ Watkins ML, Erickson JD, Thun MJ, Mulinare J, Heath CW (2000). "Multivitamin use and mortality in a large prospective study". American Journal of Epidemiology. 152 (2): 149–62. PMID 10909952. Unknown parameter
|month=ignored (help) - ↑ Pocobelli G, Peters U, Kristal AR, White E (2009). "Use of supplements of multivitamins, vitamin C, and vitamin E in relation to mortality". American Journal of Epidemiology. 170 (4): 472–83. doi:10.1093/aje/kwp167. PMC 2727181. PMID 19596711. Unknown parameter
|month=ignored (help) - ↑ Muntwyler J, Hennekens CH, Manson JE, Buring JE, Gaziano JM (2002). "Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality". Archives of Internal Medicine. 162 (13): 1472–6. PMID 12090883. Unknown parameter
|month=ignored (help) - ↑ Macpherson H, Pipingas A, Pase MP (2013). "Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials". The American Journal of Clinical Nutrition. 97 (2): 437–44. doi:10.3945/ajcn.112.049304. PMID 23255568. Unknown parameter
|month=ignored (help)