Vitamin Mortality Meta-Analyses

[ Because nearly this entire page is based on meta-analyses, I'm ignoring my typical custom of coloring evidence from then. ]

This is a collection of meta-analyses examining the effect of vitamins on measures of mortality. I've ignored studies examining effects specifically on sick people, studies on specifically infants or pregnant women, or studies specifically on low-income countries.

TODO: Finish Schwingshackl. I've only covered all-cause and cardiovascular mortality.

Multivitamins

Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials Macpherson

Randomized and controlled primary or secondary prevention trials were considered appropriate for review. To limit heterogeneity between the included trials, the following inclusion criteria were enforced: the trial must have been randomized and controlled, the participants must have been supplemented with a daily MVMM formulation in at least one study arm, the MVMM must have been taken orally and administered as a monotherapy within the treatment arm, the supplementation must have taken place for $1 y, and the cohort must not have been institutionalized or have had a terminal illness (tertiary prevention). Furthermore, each trial must have reported on the number of deaths in both the control and MVMM groups, or these data must have been made available on request. As recommended (14, 15), studies without deaths were excluded from the analyses

SubgroupMetricLowHigh
allall-cause mortality0.941.02
primary prevention trialsall-cause mortality0.891.00
high-income countriesall-cause mortality0.951.04
allcancer mortality0.881.04
allvascular mortality0.931.09

Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a protocol for a systematic review and network meta-analysis of primary prevention trials. Schwingshackl

Studies were included if they met the following criteria: 1) randomized controlled design (identical placebo or no intervention) or trials of one supplement compared with another; 2) minimum intervention period of 12 mo; 3) primary prevention trial (defined as trials with the first occurrence of a chronic disease as the primary outcome); 4) mean age ≥18 y; 5) an intervention that used dietary supplements defined according to the Directive 2002/46/EC of the European Parliament and of the Council of 10 June 2002. The following dietary supplements were included according to previous systematic reviews and meta-analyses on dietary supplements and chronic diseases (9, 12, 16): vitamins [β-carotene; vitamins A, E, C (ascorbic acid), and D (cholecalciferol, ergocalciferol)]; B vitamins (thiamin, riboflavin, niacin, pyridoxine, cobalamin, folic acid); supplements containing a combination of different vitamins; FAs (n–3 FAs [EPA, DHA, α-linolenic acid (18:3n−3)]; n–6 FAs [linoleic acid (18:2n−6)]; monounsaturated fat (olive oil); minerals (magnesium, calcium, selenium, potassium, iron, zinc, copper, iodine); multiminerals; supplements containing combinations of both vitamins and minerals; protein (amino acids); fiber (psyllium, inulin, cellulose); probiotics; prebiotics; and synbiotics; 6) oral intake (modalities of supplement intake such as liquid, pill, capsule, tablet, drops, ampoule, powdered); and 7) assessment of clinical outcomes (“primary”: all-cause mortality; “secondary”: cardiovascular mortality, cancer mortality, cardiovascular incidence, and cancer incidence).

...

The exclusion criteria were as follows: 1) studies with a dietary or drug co-intervention that was not applied in all intervention or placebo and control groups; 2) studies with intravenous or parenteral administration of vitamins or minerals; 3) pregnant or lactating women; 4) mean age ≥70 y; 5) >75% of sample size assigned to secondary prevention trials [defined as trials undertaken to prevent recurrences or exacerbations of a disease that has already been diagnosed, such as in cancer survivors; survivors of myocardial infarction, stable or unstable angina pectoris, acute coronary insufficiency, coronary artery disease (verified by coronary angiography), stroke, hemodialysis, or chronic kidney disease; and subjects with the following diseases: gastrointestinal, neurological, ocular, dermatologic, rheumatoid, endocrinologic]; and 6) follow-up time not reported.

Vitamin D

95% confidence intervals of the effect of vitamin D on all-cause mortality.

Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a protocol for a systematic review and network meta-analysis of primary prevention trials. Schwingshackl

SubgroupMetricLowHigh
anyall-cause mortality0.831.01
Vitamin D aloneall-cause mortality0.043.20
Vitamin D with othersall-cause mortality0.831.01
dose < 500 IU/dall-cause mortality0.831.01
dose ≥ 500 IU/dall-cause mortality0.391.45
anycardiovascular mortality0.761.09
Vitamin D alonecardiovascular mortality0.017.96
Vitamin D with otherscardiovascular mortality0.411.76

Vitamin D supplements and cancer incidence and mortality: a meta-analysis Keum

To be included, studies had to be a RCT providing information on the effect of vitamin D supplementation (with or without calcium supplementation) on total cancer incidence or mortality. When there were several publications from the same trial, the publication most fully covering the intervention period was selected.

SubgroupMetricLowHigh
allcancer incidence0.941.06
allcancer mortality0.780.98

The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis Bolland

We excluded cluster randomised trials, trials of hydroxylated vitamin D or vitamin D analogues, trials that included other interventions only in the vitamin D group, trials of fortified dairy products, and trials in populations with chronic comorbidity other than osteoporosis or frailty (appendix).

SubgroupMetricLowHigh
vitamin D without calciumheart attacks or ischaemic heart disease0.861.13
vitamin D with calciumheart attacks or ischaemic heart disease0.861.63
allheart attacks or ischaemic heart disease0.931.13
vitamin D without calciumstroke or cerebrovascular disease0.921.30
vitamin D with calciumstroke or cerebrovascular disease0.871.13
allstroke or cerebrovascular disease0.901.13
vitamin D without calciumcancer0.831.17
vitamin D with calciumcancer0.671.18
allcancer0.931.05
allheart attacks0.911.17
allischaemic heart disease or cardiovascular disease0.781.62
allstroke0.881.13
allcerebrovascular disease0.821.34
vitamin D without calciumfractures0.881.08
vitamin D with calciumfractures0.850.99
allfractures0.881.02
vitamin D without calciumhip fractures0.971.27
vitamin D with calciumhip fractures0.740.96
allhip fractures0.861.08
vitamin D without calciumall-cause mortality0.921.01
vitamin D with calciumall-cause mortality0.891.02
allall-cause mortality0.931.00

Meta-analysis of long-term vitamin D supplementation on overall mortality Zheng

Types of studies. Randomized controlled trials evaluating an intervention with vitamin D were identified as part of the review, while review articles, commentaries, letters, observational studies were excluded.

Interventions. The intervention group was restricted to vitamin D alone or in combination with calcium treatment; the control group was placebo, no treatment or calcium only therapy. Studies of patients receiving active vitamin D and intramuscular injection of vitamin D were excluded from the review.

Outcome. The number of deaths was reported separately for the vitamin D treatment group and the control group. For articles with a large sample size, if the number of deaths was not reported by treatment, we tried to contact the authors to obtain the missing data.

SubgroupMetricLowHigh
< 3 year follow-upall-cause mortality0.971.12
≥ 3 year follow-upmortality0.900.98
womenall-cause mortality0.831.00
younger than 80all-cause mortality0.880.97
older than 80all-cause mortality0.901.04
dose ≤ 800 IUall-cause mortality0.890.98
dose > 800 IUall-cause mortality0.891.03
baseline of 25-hydroxyvitamin D less than 500 nmol/lall-cause mortality0.890.98
baseline of 25-hydroxyvitamin D greater than 500 nmol/lall-cause mortality0.891.03
treatment with cholecalcifrlall-cause mortality0.890.97
treatment with ergocalciferolall-cause mortality0.901.06
vitamin D with calciumall-cause mortality0.880.99
calciumall-cause mortality0.911.03
vitamin D aloneall-cause mortality0.861.00
allcancer mortality0.790.98
allcardiovascular mortality0.811.02

Extraskeletal effects of vitamin D in older adults: cardiovascular disease, mortality, mood, and cognition Barnard

Publications had to include patients ≥65 years of age who had ≥1 recorded measurement of 25(OH)D or were receiving vitamin D supplementation.

Note: This study examined a lot of hypotheses. I skipped many.

SubgroupMetricLowHigh
allall-cause mortality0.831.01
women less than 70all-cause mortality0.791.01
women 70 or olderall-cause mortality0.801.12
women 70 or olderCV0.781.32
women 70 or oldercoronary artery0.711.47
women 70 or oldercerebrovascular0.722.01
women 70 or oldercancer deaths0.651.12

Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials Autier

For an article to be included in our analysis, it must have met the following criteria:

  1. To represent the principal published report on a randomized controlled trial evaluating an intervention with vitamin D. The addition of calcium supplements in the intervention group and the absence of a placebo for vitamin D in the control group (ie, an open-label trial) were not exclusion criteria.
  2. To be independent from other studies to avoid giving double weight to estimates derived from the same trial.
  3. To have deaths from any cause reported separately for the intervention and the control groups. If in an article the number of all-cause deaths was not reported by treatment group, we tried to contact corresponding authors to obtain the missing information.
  4. To have subjects randomized to the intervention and control groups on an individual basis. Cluster randomization (eg, a nursing home taken as a randomization unit) was not valid because mortality in a specific cluster could be increased by a health event (eg, an influenza epidemic) affecting this cluster and not the others.
  5. To have sufficient information to allow adequate estimation of the relative risks (RRs) and 95% confidence intervals (CIs) (ie, crude data or adjusted RRs and standard errors, 95% CIs, or P values) to estimate mortality risk after vitamin D intake vs placebo or control.
SubgroupMetricLowHigh
allall-cause mortality0.870.99
follow-up ≥ 3 yearsall-cause mortality0.831.01
follow-up < 3 yearsall-cause mortality0.831.10
dose ≥ 800 IU/dall-cause mortality0.851.03
dose between 300 and 799 IU/dall-cause mortality0.821.03
placebo-controlled trialsall-cause mortality0.860.98
non-placebo-controlled trialsall-cause mortality0.841.45
vitamin D and calciumall-cause mortality0.861.01
vitamin D onlyall-cause mortality0.781.06
D3 and not D2all-cause mortality0.870.98

Antioxidants

Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials

We included randomized and quasi-randomized trials (if a system involving dates of admission, odd or even date of birth, or hospital record numbers were used for the allocation of patients, these studies are known as quasi-randomized) that randomized participants to supplementation with antioxidants (β-carotene, vitamins A, C, E, α-tocopherol, and selenium, as different combinations or separately) versus placebo and reported the incidence or mortality of prostate cancer. We included participants from the general population, mainly with non-prostate diseases, and at high risk of developing prostate cancer.

We excluded studies in which prepared food containing antioxidant vitamins or selenium was given rather than a unique supplement of antioxidant vitamins or selenium. We also excluded studies in which the outcomes were not clearly defined. We excluded reviews letters, commentaries, and editorials if they did not contain original data

Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis Bardia

Eligible studies were trials with a minimum of 1 year of followup and that randomly assigned participants—who had no history of cancer (except skin cancer) nor precancerous lesions—to receive antioxidants or placebo. Eligible antioxidants were beta carotene, selenium, zinc, vitamin C (ascorbic acid), vitamin E (α-tocopherol), and lycopene alone or in combination with other antioxidant supplements, administered by mouth or parenterally. Ineligible trials used antioxidant supplements with undisclosed components or sought antioxidant supplementation through dietary increases in vegetables, fruits, or fiber. Also, trials reporting only site-specific cancer incidence or only cancer mortality, but not overall cancer incidence, were excluded.

SubgroupMetricLowHigh
allcancer incidence0.941.04
allcancer mortality0.921.15

Reexamination of a meta-analysis of the effect of antioxidant supplementation on mortality and health in randomized trials Biesalski

This study starts with nearly the same sources as Mortality in randomized trials of antioxidant supplements for primary and secondary, but the authors conduct different analyses. They do not compute any new confidence intervals.

Effect of antioxidant vitamin supplementation on cardiovascular outcomes: a meta-analysis of randomized controlled trials Effect of antioxidant vitamin supplementation on cardiovascular outcomes: a meta-analysis of randomized controlled trials

We restricted our research based on randomized controlled trials, which contributed less confounding and bias than based on observational studies. All completed trials evaluating the effects of antioxidant vitamin on cardiovascular outcomes as compared to placebo, and providing at least 1 outcome as follows: major cardiovascular events, myocardial infarction, stroke, total death, or cardiac death.

SubgroupMetricLowHigh
allcardiovascular events0.961.03
allheart attacks0.921.04
allstroke0.931.05
allall-cause mortality0.981.07
allcardiac events0.971.07
allrevascularization risk0.951.05
allcoronary heart disease0.871.05
allangina0.901.07
allcongestive heart failure0.961.19
all≥ 10000 patients0.911.05
all< 10000 patients0.881.14
allmean age ≥ 600.921.13
allmean age < 600.821.10
allmen0.891.11
allwomen0.811.06
allmen and women0.901.20
allhealthy population0.891.05
allhigh risk for cardiovascular events0.921.10
allfollow-up ≥ 6 months0.921.07
allfollow-up < 6 months 0.871.08
allJadad score ≥ 40.921.06
allJadad sore < 40.841.11

Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis

I can't find access to this.

Do antioxidants prevent colorectal cancer? A meta-analysis Pais

I can't find access to this.

Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm? Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm?

We considered for inclusion primary and secondary prevention randomized clinical trials in adults (aged ≥ 18 years) comparing beta-carotene, vitamin A, vitamin C, vitamin E, and selenium at any dose, duration, and route of administration versus placebo. The antioxidants could have been administered separately or in any combination, or in combination with other vitamins or trace elements without antioxidant function. Concomitant interventions were allowed when used equally in all the intervention groups of the trial.

For the present study we selected only the randomized primary or secondary prevention trials with low risk of bias where beta-carotene, vitamin A, and vitamin E were compared with placebo.

The analysis was done on a per-vitamin basis, so see those sections on this page for the metrics.

Beta carotene

Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials

SubgroupMetricLowHigh
anyprostate cancer0.901.05
beta-carotene and retinyl palmitateprostate cancer0.901.16
anyprostate cancer mortality0.871.65
beta-carotene and retinyl palmitateprostate cancer mortality0.591.19

Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a protocol for a systematic review and network meta-analysis of primary prevention trials. Schwingshackl

SubgroupMetricLowHigh
anyall-cause mortality0.961.09
beta-carotene aloneall-cause mortality1.021.10
beta-carotene with othersall-cause mortality0.921.11
dose < 30 mg/dall-cause mortality0.901.07
dose ≥ 30 mg/dall-cause mortality1.031.18
anycardiovascular mortality0.921.10
beta-carotene alonecardiovascular mortality0.931.16
beta-carotene with otherscardiovascular mortality0.841.09
dose < 30 mg/dcardiovascular mortality0.851.10
dose ≥ 30 mg/dcardiovascular mortality0.931.21

Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis Bardia

SubgroupMetricLowHigh
allcancer incidence1.001.12
smokerscancer incidence1.031.18
nonsmokerscancer incidence0.921.10
allcancer mortality0.981.37

Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm? Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm?

SubgroupMetricLowHigh
Beta carotene, aloneall-cause mortality1.021.10
anyall-cause mortality1.011.09
dose ≤ 9.6 mgall-cause mortality0.691.17
dose > 9.6 mgall-cause mortality1.021.09

A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease Mente

TODO

SubgroupMetricLowHigh
Beta carotene supplementsall-cause mortality0.921.09

Vitamin E

95% confidence intervals of the effect of vitamin E on all-cause mortality.

Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials

SubgroupMetricLowHigh
anyprostate cancer0.851.08
vitamin E + seleniumprostate cancer0.921.19
anyprostate cancer mortality0.581.24

Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a protocol for a systematic review and network meta-analysis of primary prevention trials. Schwingshackl

SubgroupMetricLowHigh
anyall-cause mortality0.991.05
Vitamin E aloneall-cause mortality0.991.06
Vitamin E with othersall-cause mortality0.321.06
dose < 500 IU/dall-cause mortality0.891.07
dose ≥ 500 IU/dall-cause mortality0.951.06
anycardiovascular mortality0.800.96
Vitamin E alonecardiovascular mortality0.790.98
Vitamin E with otherscardiovascular mortality0.801.00
dose < 500 IU/dcardiovascular mortality0.760.99
dose ≥ 500 IU/dcardiovascular mortality0.771.01

Vitamin E supplementation and mortality in healthy people: a meta-analysis of randomised controlled trials Curtis

To be included, studies had to meet pre-specified selection criteria as follow.

  1. Be a randomised, placebo-controlled trial with
    • an intervention period of ≥6 months;
    • no intervention co-supplements, i.e. other antioxidants or medications, concurrently with vitamin E unless balanced by a corresponding control arm that also included the additional antioxidant, supplement or medication
  2. Investigate the effect of any dose of synthetic (dl-alphatocopherol) or natural (d-alpha-tocopherol) oral vitamin E supplementation;
  3. Include adult men and/or non-pregnant women;
  4. Trial participants must be in good general health. On this basis, we included the following:
    • Trials in which participants were recruited from the general population;
    • Trials in which participants had non-systemic medical conditions, such as knee osteoarthritis;
    • Trials in which otherwise healthy participants had risk factors for CVD, such as smoking, hypercholesterolaemia or atherosclerosis;
    • Trials in which participants had chronic conditions, such as diabetes mellitus without serious comorbidities or complications.
  5. Be undertaken in highly or very highly developed countries, defined according to the United Nations Human Development Index;
  6. The number of deaths was available for intervention and control groups, and mortality was either a pre-specified primary or secondary outcome, or the methods indicated complete follow-up of participants or full ascertainment of deaths.

The following types of trials were excluded:

  • Trials that selected patients on the basis of having a serious disease that may result in lower life expectancy, such as cancer, recent myocardial infarction, chronic infectious disease, Alzheimer’s disease or end stage renal disease;
  • Trials undertaken in developing countries, due to the higher likelihood of participants having underlying nutritional deficiencies;
  • Trials where no deaths were reported.
SubgroupMetricLowHigh
allall-cause mortality0.971.05
syntheticall-cause mortality0.961.05
naturalall-cause mortality0.961.08
< 400all-cause mortality0.971.07
≥ 400all-cause mortality0.941.05
< 3 yearsall-cause mortality0.461.58
≥ 3 yearsall-cause mortality0.971.05
mortality was pre-specifiedall-cause mortality0.971.05
mortality was not pre-specifiedall-cause mortality0.401.26
parallel group studyall-cause mortality0.681.58
factorial studyall-cause mortality0.971.05
high study qualityall-cause mortality0.961.05
medium/low study qualityall-cause mortality0.961.08

A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease Mente

SubgroupMetricLowHigh
Vitamin E supplementsall-cause mortality0.841.01

Meta-analysis: low-dose intake of vitamin E combined with other vitamins or minerals may decrease all-cause mortality Meta-analysis: low-dose intake of vitamin E combined with other vitamins or minerals may decrease all-cause mortality

The following inclusion criteria were used to select studies for this analysis (1) RCTs evaluating the efficacy of vitamin E; (2) assessment of vitamin E intake alone or combined with at least one of the following vitamins or minerals, which have been largely reported to interact with vitamin E: vitamin C, β-carotene, selenium and zinc; (3) a study sample limited to men or non-pregnant women; (4) minimal vitamin E supplementation and a follow-up period of 1 y; and (5) a minimum of 10 deaths in trial...Trials with a Jadad score of 4 or more were included.

SubgroupMetricLowHigh
allall-cause mortality0.891.06
dose < 400 IU/dall-cause mortality0.860.98
dose ≥ 400 IU/dall-cause mortality0.812.03
age < 65 y oldall-cause mortality0.841.04
age ≥ 65 y oldallall-cause mortality0.941.19
people without probably or confirmed diseasesall-cause mortality0.860.99
unhealthy individuals with probably or confirmed diseasesmortality0.861.21
short follow-upall-cause mortality0.871.15
long follow-upall-cause mortality0.941.03
vitamin E aloneall-cause mortality0.971.04
vitamin E alone; dose < 400 IU/dall-cause mortality0.961.05
vitamin E alone; dose ≥ 400 IU/dall-cause mortality0.951.06
vitamin E alone; age < 65all-cause mortality0.971.04
vitamin E alone; age ≥ 65all-cause mortality0.921.09
vitamin E alone; people without probably or confirmed diseasesall-cause mortality0.971.05
vitamin E alone; unhealthy individuals with probably or confirmed diseasesall-cause mortality0.931.06
vitamin E alone; short follow-upall-cause mortality0.881.06
vitamin E alone; long follow-upall-cause mortality0.981.05

Bayesian model averaging in meta-analysis: vitamin E supplementation and mortality Berry

TODO

Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis Bardia

SubgroupMetricLowHigh
allcancer incidence0.941.04
mencancer mortality0.971.12

Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm? Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm?

SubgroupMetricLowHigh
vitamin E, aloneall-cause mortality0.981.05
anyall-cause mortality1.001.05
dose ≤ 15 mgall-cause mortality0.513.46
dose > 15 mgall-cause mortality1.001.05

Vitamin E and all-cause mortality: a meta-analysis Abner

Inclusion criteria were (1) peer review (indicated by publication in a peer-reviewed journal), (2) randomized treatment conditions, (3) comparator arms, (4) adult participants (excluding pregnant women), (5) parallel or factorial designs, and (6) the assignment of participants to supplemental vitamin E, taken orally, alone or in combination with other drugs and supplements for at least one year (Figure 1).

SubgroupMetricLowHigh
anyall-cause mortality0.981.02
double-blind; placebo-controlledall-cause mortality0.991.03

The role of vitamin E in the prevention of cancer: a meta-analysis of randomized controlled trials The role of vitamin E in the prevention of cancer: a meta-analysis of randomized controlled trials.

Data sources were randomized controlled trials (RCTs) in which outcomes related to cancer prevention that were associated with the intake of vitamin E supplements alone or with other supplements were compared to a control group (placebo or control). Participants in studies were adults of either sex (18 years or older). Types of interventions were vitamin E alone or with other supplements versus placebo or no intervention. Supplementation was in capsule or tablet form, to be consumed by mouth.

SubgroupMetricLowHigh
anyall-cause mortality0.961.03
anycancer mortality0.951.09
anycancer incidence0.941.02
anystomach cancer0.901.15
anylung cancer0.881.19
anycolorectal cancer0.811.12
anyprostate cancer0.740.96
anybreast cancer0.901.10
anyesophageal cancer0.881.14
anyhematological cancer0.711.33
anyurinary tract cancer0.841.84
vitamin E aloneall-cause mortality0.941.05
vitamin E alonecolorectal cancer0.791.39
vitamin E aloneprostate cancer0.701.06
vitamin E alonetotal cancer0.901.12
vitamin E alonecancer mortality0.831.26
vitamin E with other supplementsall-cause mortality0.961.03
vitamin E with other supplementstotal cancer0.921.01
vitamin E with other supplementscancer mortality0.931.08
vitamin E with other supplementsprostate cancer0.670.93
dose ≥ 300 mg/dall-cause mortality0.971.06
dose ≥ 300 mg/dcancer mortality0.921.17
dose ≥ 300 mg/dcancer incidence0.921.05
dose ≥ 300 mg/dlung cancer0.811.16
dose ≥ 300 mg/dprostate cancer0.791.11
dose < 300 mg/dall-cause mortality0.921.02
dose < 300 mg/dcancer mortality0.901.06
dose < 300 mg/dcancer incidence0.911.01
dose < 300 mg/dstomach cancer0.841.10
dose < 300 mg/dlung cancer0.851.10
dose < 300 mg/dprostate cancer0.550.87

Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality Miller

Our prespecified inclusion criteria were 1) random allocation of participants, 2) use of vitamin E supplementation alone or combined with other vitamins or minerals, 3) presence of a control or placebo group, 4) study sample limited to men or nonpregnant women, 5) duration of vitamin E supplementation and follow-up longer than 1 year, and 6) occurrence of at least 10 deaths in the trial.

SubgroupMetricLowHigh
anyall-cause mortality0.981.04
dose < 400 IU/dall-cause mortality0.961.01
dose ≥ 400 IU/dall-cause mortality1.011.07
"adjusted for other vitamins or minerals"all-cause mortality0.1.
Figure 3 shows that Vitamin E supplements are probably net-positive at low doses but net-negative at higher doses. While Vitamin E being net-beneficial at low doses wasn't statistically significant, the overall trend was.

Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease Shekelle

SubgroupMetricLowHigh
vitamin E aloneall-cause mortality0.841.10
vitamin E alonecardiovascular mortality0.801.19
vitamin E in combinationcardiovascular mortality0.811.32
vitamin E alonefatal heart attacks0.741.27
vitamin E in combinationfatal heart attacks0.771.37
vitamin E alonenonfatal heart attacks0.511.02
vitamin E in combinationnonfatal heart attacks0.891.1.0

The role of vitamin E in the prevention of coronary events and stroke. Meta-analysis of randomized controlled trials The role of vitamin E in the prevention of coronary events and stroke. Meta-analysis of randomized controlled trials

I couldn't find the text of this study.

Vitamin A

95% confidence intervals of the effect of vitamin A on all-cause mortality. I suspect the two diverging results are due to the effect of trials in developing countries.

Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a protocol for a systematic review and network meta-analysis of primary prevention trials. Schwingshackl

SubgroupMetricLowHigh
anyall-cause mortality0.971.16
Vitamin A aloneall-cause mortality0.811.65
Vitamin A with othersall-cause mortality0.911.20
dose < 25,000 IU/dall-cause mortality0.841.08
dose ≥ 25,000 IU/dall-cause mortality1.041.21
anycardiovascular mortality0.781.21
Vitamin A alonecardiovascular mortality0.661.09
Vitamin A with otherscardiovascular mortality0.921.24

Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age

Randomised controlled trials (RCTs) and cluster-RCTs evaluating the effect of synthetic VAS in children aged six months to five years living in the community. We excluded studies involving children in hospital and children with disease or infection. We also excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods, or beta-carotene supplementation.

TODO: Fill in ?s
SubgroupMetricLowHigh
anyall-cause mortality0.830.93
?all-cause mortality0.750.92
?all-cause mortality0.810.97
Asiaall-cause mortality0.840.96
Africaall-cause mortality0.750.98
Latin Americaall-cause mortality0.147.08
6 - 12 months oldall-cause mortality0.430.82
1 year to 5 years oldall-cause mortality0.570.81
boysall-cause mortality0.891.04
girlsall-cause mortality0.840.97
countries with high child mortalityall-cause mortality0.840.94
countries with low child mortalityall-cause mortality0.147.08
anydiarrhea mortality0.790.98
?diarrhea mortality0.610.95
anymeasles mortality0.691.11
?measles mortality0.521.37
anymeningitis mortality0.171.88
?meningitis mortality0.22153.23
anylower respiratory tract infection mortality0.861.12
?lower respiratory tract infection mortality0.401.10
anymeasles0.820.87
?measles0.890.96
anymeasles0.370.67
anymalaria incidence0.600.88
?malaria prevalence0.411.28
anylower respiratory tract infection0.921.06
?lower respiratory tract infection0.891.04
?lower respiratory tract infection0.450.81
anyBitot's spots0.330.53
?Bitot's spots0.330.56
anynight blindness0.170.52
anyxerophthalmia0.701.03
?xerophthalmia0.721.07
anyvomiting1.442.69
anybulging fontanelle0.742.08
anyvitamin A deficiency0.650.78
anyvitamin A serum levels0.220.30
anyvitamin A serum levels0.370.53

Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm? Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm?

SubgroupMetricLowHigh
vitamin A, aloneall-cause mortality0.831.68
anyall-cause mortality0.971.18
dose ≤ 800 µgall-cause mortality0.651.69
dose > 800 µgall-cause mortality0.971.19

Vitamin A supplementation in infectious diseases: a meta-analysis Glasziou

A report was dropped from further analysis if the study did not include concurrent controls or contained no original data or if the report did not address mortality, respiratory disease, or diarrhoea. Several trials that looked at cancer prevention were not considered within the scope of this analysis. On the basis of these initial broad criteria, clearly irrelevant articles were discarded after consideration by a single reviewer.

...

Papers that did not include a control group, were not randomised, did not allow calculation of "intention to treat" results, or did not collect information on mortality or the incidence of respiratory or gastrointestinal infection were excluded.

SubgroupMetricLowHigh
anyall-cause mortality0.620.79
children in hospitals with measlesall-cause mortality0.150.77
children in hospitals with measlesrespiratory mortality0.100.85
community studiesall-cause mortality0.640.86
community trialsdiarrhoeal mortality0.500.76
community trialsmeasles mortality0.230.87
community trialsmortality besides diarrhea, respiratory causes, orr measles0.510.85

Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis

Types of trials—Randomised controlled trials including cluster trials and factorial trials were included irrespective of publication status or language.

Types of participants—At the time of recruitment, children had to be aged 6 months to 5 years and apparently healthy. Children in hospital at the time of recruitment were excluded.

Types of interventions—Included studies examined synthetic oral vitamin A supplementation compared with no treatment or placebo, irrespective of dose or frequency. Studies of food fortification and β carotene supplementation were excluded as their effects can differ.

TODO: Record cause-specific mortality and morbidities.
SubgroupMetricLowHigh
completed trialsall-cause mortality0.690.83
completed trials lasting more than 13 monthsall-cause mortality0.640.88
complete and incomplete trialsall-cause mortality0.840.94
Asiaall-cause mortality0.610.79
Africaall-cause mortality0.730.98
Latin Americaall-cause mortality0.147.08
6-12 months oldall-cause mortality0.430.82
1-5 years oldall-cause mortality0.570.82
boysall-cause mortality0.660.97
girlsall-cause mortality0.650.95
small frequent dosesall-cause mortality0.300.71
doses every 4-6 monthsall-cause mortality0.720.90
one-time doseall-cause mortality0.520.83

Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age

TODO

B Vitamins

Meta-analysis of B vitamin supplementation on plasma homocysteine, cardiovascular and all-cause mortality Huang

Studies were eligible for inclusion if (1) the study design was a randomized controlled trial; (2) the relative risk (RR) or the number of events for CVD, coronary heart disease (CHD), stroke, and/or all-cause mortality that occurred during the study was reported by intervention and control groups; (3) the intervention was B vitamins; and (4) there was no limitation on the intervention duration.

SubgroupMetricLowHigh
anyCVD0.941.03
anyCHD0.921.05
anyheart attacks0.901.05
anystrokes0.820.95
anycardiovascular mortality0.911.02
anyall-cause mortality0.951.04

A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease Mente

SubgroupMetricLowHigh
folate supplementsall-cause mortality0.911.06

Vitamin C

Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials

SubgroupMetricLowHigh
anyprostate cancer0.911.06
anyprostate cancer mortality0.922.29

Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a protocol for a systematic review and network meta-analysis of primary prevention trials. Schwingshackl

SubgroupMetricLowHigh
anyall-cause mortality0.911.05
Vitamin C aloneall-cause mortality0.911.11
Vitamin C with othersall-cause mortality0.911.05
dose < 500 IU/dall-cause mortality0.831.04
dose ≥ 500 IU/dall-cause mortality0.931.09
anycardiovascular mortality0.821.13
Vitamin C alonecardiovascular mortality0.831.35
Vitamin C with otherscardiovascular mortality0.801.12
dose < 500 IU/dcardiovascular mortality0.681.12
dose ≥ 500 IU/dcardiovascular mortality0.841.26

Adjuvant administration of vitamin C improves mortality of patients with sepsis and septic shock: a systems review and meta-analysis Adjuvant administration of vitamin C improves mortality of patients with sepsis and septic shock: a systems review and meta-analysis

We included trials with the following features:

  1. Type of trials: randomized controlled clinical trials and retrospective studies.
  2. Population: trials included adult population with sepsis or septic shock.
  3. Intervention: patients submitted to vitamin C for sepsis therapy.
  4. Comparison: placebo for sepsis therapy.
  5. Outcome: the primary outcome was 28-day mortality.

Trials with the following features were excluded:

  1. They were not published in English.
  2. They were not published as original articles.
  3. They did not use adult patients.
  4. They did not administrate vitamin C for sepsis therapy.
  5. They included no data on mortality in patients with sepsis or septic shock.
  6. Full-text articles were not available.
SubgroupMetricLowHigh
allall-cause mortality0.161.73
dose > 50 mg/kg/d, severe sepsis patientsall-cause mortality0.160.94
dose < 50 mg/kg/d, severe sepsis patientsall-cause mortality0.283.58
severe sepsis patientsall-cause mortality0.261.09
septic shock patientsICU duration4.911.98

A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease Mente

SubgroupMetricLowHigh
Vitamin C supplementsall-cause mortality0.701.25

Efficacy of vitamin C supplements in prevention of cancer: a meta-analysis of randomized controlled trials Efficacy of vitamin C supplements in prevention of cancer: a meta-analysis of randomized controlled trials

We included only RCTs that both reported the efficacy of vitamin C supplementation on cancer prevention and compared an intervention group with a control group. The main outcome measures included cancer incidence and mortality.

SubgroupMetricLowHigh
anycancer incidence0.951.05
< 500 mgall-cause mortality0.911.05
≥ 500 mgall-cause mortality0.951.10
Vitamin C onlyall-cause mortality0.951.10
Combination with other supplementsall-cause mortality0.911.04
follow-up < 7 yearsall-cause mortality0.921.07
follow-up ≥ 7 yearsall-cause mortality0.941.07
high methodological qualityall-cause mortality0.911.05
low methodological qualityall-cause mortality0.951.10
anycancer incidence0.951.05
anycancer mortality0.961.17
funded by non-pharmaceuticalall-cause mortality0.602.40
funded by pharmaceuticalall-cause mortality0.961.07
maleall-cause mortality0.621.20
femaleall-cause mortality0.961.23
never smokedall-cause mortality0.951.18
former smokerall-cause mortality0.901.11
current smokerall-cause mortality0.641.47
Chinaall-cause mortality0.901.24
USAall-cause mortality0.951.10
Franceall-cause mortality0.771.07
UKall-cause mortality0.891.08
anyrespiratory cancer0.731.53
anyhaematological cancer0.871.28
anyskin mortality0.811.11
anystomach mortality0.931.51
anyesophageal mortality0.781.24
anycccolorectal mortality0.641.10
anybreast mortality0.871.25
anypancreas mortality0.583.20
anygenitourinary mortality0.761.02
anyprostate mortality0.901.14
anybladder mortality0.531.34
anyuterine mortality0.491.48
anyovary mortality0.361.93
anythyroid mortality0.632.97
anyoral mortality0.132.00
anycentral nervous system mortality0.553.42

Folic Acid

Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a protocol for a systematic review and network meta-analysis of primary prevention trials. Schwingshackl

SubgroupMetricLowHigh
anyall-cause mortality0.751.23
Folic acid aloneall-cause mortality0.601.99
Folic acid with othersall-cause mortality0.032.22
dose < 500 IU/dall-cause mortality0.385.79
dose ≥ 500 IU/dall-cause mortality0.591.41
Folic acid alone, dose ≥ 5 mg/dcardiovascular mortality0.661.53

Efficacy of folic acid supplementation in stroke prevention: a meta-analysis Efficacy of folic acid supplementation in stroke prevention: a meta-analysis

TODO

Vitamin K

All the meta-analyses I found relating vitamin K to mortality were conducted on ill people being treated with vitamin K antagonists.

Keum, N., & Giovannucci, E. (2014). Vitamin D supplements and cancer incidence and mortality: a meta-analysis. British journal of cancer, 111(5), 976-980. https://doi.org/10.1038/bjc.2014.294 Zheng, Y., Zhu, J., Zhou, M., Cui, L., Yao, W., & Liu, Y. (2013). Meta-analysis of long-term vitamin D supplementation on overall mortality. PLoS One, 8(12). https://doi.org/10.1371/journal.pone.0082109 Autier, P., & Gandini, S. (2007). Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Archives of internal medicine, 167(16), 1730-1737. https://dx.doi.org/10.1001/archinte.167.16.1730 Bolland, Mark J., et al. "The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis." The lancet Diabetes & endocrinology 2.4 (2014): 307-320. https://doi.org/10.1016/S2213-8587(13)70212-2 Barnard, K., & Colón-Emeric, C. (2010). 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W., & Myung, S. K. (2015). Efficacy of vitamin C supplements in prevention of cancer: a meta-analysis of randomized controlled trials. Korean journal of family medicine, 36(6), 278. https://dx.doi.org/10.4082%2Fkjfm.2015.36.6.278 Glasziou, P. P., & Mackerras, D. E. (1993). Vitamin A supplementation in infectious diseases: a meta-analysis. Bmj, 306(6874), 366-370. https://doi.org/10.1136/bmj.306.6874.366 Mayo-Wilson, E., Imdad, A., Herzer, K., Yakoob, M. Y., & Bhutta, Z. A. (2011). Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis. Bmj, 343, d5094. https://doi.org/10.1136/bmj.d5094 Jiang, L., Yang, K. H., Tian, J. H., Guan, Q. L., Yao, N., Cao, N., ... & Yang, S. H. (2010). Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials. 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