Table 1.

Main characteristics of the RCTs included in meta-analyses

First author, year, country, reference	Trial name, population (%M), age at baseline	Primary end point of trial, follow-up period	Contrast for RR	Cancer incidence: RR (95% CI), (n case/n total)	Cancer mortality: RR (95% CI), (n case/n total), total mortality: RR (95% CI), (n case/n total)	25(OH)D level (nmol/l)a: baseline--> follow-up	Inclusion/ exclusion criteria regarding Vit D supplement/ treatment
Trivedi 2003 UK[37]	NA General population (76%) 75 years	Fracture Total mortality 5 years	Vit D3 versus placebo Vit D3: 100 000 IU/4 m (∼833 IU/d)	1.09 (0.86, 1.36) (188/1345) versus (173/1341)	0.86 (0.61, 1.20) (63/1345) versus (72/1341) *Total death 0.74, 1.06) (224/1345) versus (247/1341)	Intervention: NA --> 74 at 4y Control: NA --> 53 at 4y	Excluded Current users of Vit D supplement
Wactawski-Wende 2006 USA[34] LaCroix 2009 USA[35]	Calcium plus vitamin D trial (from WHI) Postmenopausal women (0%) 62 years	Hip fracture 7 years (up to 9.7 years)	Vit D3+Ca versus placebo Vit D3: 400 IU/d Ca (carbonate): 1000 mg/d	0.98 (0.91, 1.05) (1634/18 176) versus (1655/18 106)	0.89 (0.77, 1.03) (344/18176) versus (382/18106) *Total death 0.91 (0.83, 1.01) (744/18176) versus (807/18106)	Intervention: 42 --> 54 at 2 years Control: 42 --> NA	Excluded current users of Vit D supplement (≥ 600 IU/d); Calcitriol
Lappe 2007 USA[33]	NA postmenopausal women (0%) 67 years	Fracture 4 years	Vit D3+Ca versus Ca Vit D3: 1100 IU/d Ca: (carbonate) 1500 mg/d or (citrate) 1400 mg/d	0.76 (0.38, 1.55) (13/446) versus (17/445) After 1 year exclusion: 0.55 (0.24, 1.28)a	NA	Intervention: 72 --> 96 at 1 year Control: 72 --> 71 at 1 year	Not specified
Sanders 2010 Australia [38]	Vital D study postmenopausal women (0%), 76 years	Fracture 3–5 years with 1 year post-intervention follow-up	Vit D3 versus placebo Vit D3: 500 000 IU/year (∼1370 IU/d)	0.70 (0.27, 1.82) (7/1131) versus (10/1125)	NA *Total death 0.85 (0.56, 1.28) (40/1131) versus (47/1125)	Intervention: 53 --> 58 at trial end Control: 45 --> 38 at trial end	Excluded current users of Vit D supplement (≥400 IU/d); calcitriol
Avenell 2012 UK[41]	RECORD general population (15%) 77 years	Fracture 2–5.2 years with 3 years post-intervention follow-up	Vit D3 (w, w/o Ca) versus no Vit D3 (w, w/o Ca) Vit D3: 800 IU/d Ca (carbonate): 1000 mg/d	1.07 (0.92, 1.25) (338/2649) versus (315/2643)	0.85 (0.68, 1.06) (151/2649) versus (178/2643) *Total death 0.93 (0.85, 1.02) (836/2649) versus (881/2643)	Intervention: 38 --> 62 at 1 year Control: 38 --> 44 at 1 year	Excluded current users of Vit D supplement (200 IU/d); those with past treatment with Vit D metabolite or Vit D injection
Baron 2015 USA[40]	NA individuals with history of colorectal adenomas (63%) 58 years	Colorectal adenomas 3.7 years (range: 3–5 years)	Vit D3 (w, w/o Ca) versus no Vit D3 (w, w/o Ca) Vit D3: 1000 IU/d Ca (carbonate): 1200 mg/d	0.77( 0.53, 1.12) (47/1130) versus (61/1129)	NA *Total death 1.25 (0.59, 2.66) (15/1130) versus (12/1129)	Intervention: 61 --> 81 at trial end Control: 61 --> NA	Limited nonprotocol supplement of Vit D up to 1000 IU/d
Jorde 2016 Norway[39]	Tromso Vitamin D and T2DM trial individuals with impaired fasting glucose and/or impaired glucose tolerance 62 years	Type 2 diabetes 5 years	Vit D3 versus placebo Vit D3: 20 000 IU/week (∼2857 IU/d)	1.50 (0.69, 3.26) (15/256) versus (10/255)	NA	Intervention: 60 --> 122 at trial end Control: 61 --> 67 at trial end	Limited nonprotocol supplement of Vit D (including cod liver oil) up to 400 IU/d
Lappe 2017 USA[27]	NA postmenopausal women (0%) 65 years	Total cancer excluding nonmelanoma skin cancers 4 years	Vit D3+Ca versus placebo Vit D3: 2000 IU/d Ca (carbonate): 1500 mg/d	0.70 (0.47–1.02) (45/1102) versus (64/1095) After 1 year exclusion: 0.65 (0.42, 0.99)a	NA *Total death 0.77 (0.29, 2.07) (7/1102) versus (9/1095)	Intervention: 83 --> 106 at trial end Control: 82 --> 77 at trial end	Limited nonprotocol supplement of Vit D up to 800 IU/d
Manson 2018 USA[28]	VITAL general population including African-Americans by 20% (49%) 67 years	Total invasive cancer Major cardiovascular events 5.3 years (range: 3.8–6.1 years)	Vit D3 (w, w/o omega-3 fatty acids) versus no Vit D3 (w, w/o omega-3 fatty acids) Vit D3: 2000 IU/d Omega-3 fatty acids: 1 g/d	0.96 (0.88–1.06) (793/12 927) versus (824/12 944) After 2 year exclusion 0.94 (0.83, 1.06)b	0.83 (0.67–1.02) (154/12 927) versus (187/12 944) After 1 year exclusion 0.79 (0.63, 0.99)b After 2 year exclusion 0.75 (0.59, 0.96)c *Total death 0.99 (0.87, 1.12) (485/12 927) versus (493/12 944)	Intervention: 75 --> 105 at 1 year Control: 75--> 73 at 1 year	Limited nonprotocol supplement of Vit D up to 800 IU/d
Scragg 2018 New Zealand[29]	ViDA study general population(58%) 66 years	CVD 3.3 years (range: 2.5–4.2 years)	Vit D3 versus placebo Vit D3: Initial bolus of 200 000 IU followed by 100 000 IU/m (∼3279 IU/d)	(0.81–1.25) (165/2558) versus (163/2550) After 1 year exclusion: 0.95 (0.74, 1.23)	0.99 (0.60, 1.64) (30/2558) versus (30/2550) *Total death 0.94 (0.69, 1.27) (75/2558) versus (80/2550)	Intervention: 64 --> 120–135 at 0.5–3 years Control: 63 --> 70–85 at 0.5–3 years	Excluded current users of Vit D supplement including cod liver oil (>600 IU/d if aged 50–70 years; >800 IU/d if aged 71–84 years)

^aTo convert to ng/ml, divide by 2.5.

^bExcluded events occurring within the first year of randomization.

^cExcluded events occurring within the first 2 years of randomization.

Abbreviations: Ca, calcium; d, day; IU, international unit, M, male; m, month; n, number; NA, not available; Vit, vitamin; w, with; w/o, without.