Table 1.
Characteristics of included studies.
| First author, year, Study ID, country | Sample size (Randomised (R), analysed (A)) | Vitamin D3 dosing regimen, galenics | Vitamin D3 daily or non-daily bolus | Intervention period [years] | No of cancer deaths in treatment period | Risk ratio for cancer mortality (95% CI) in treatment period |
|---|---|---|---|---|---|---|
|
| ||||||
| Trivedi et al. (2003) UK | R = A = 2686 | 100,000 IU Q4M (15 doses total), capsule | Bolus | 5 | 135 | 0.86 (0.61–1.20) |
| Wactawski-Wende et al. (2006), Jackson et al., (2003, 2006),Chlebowski et al. (2008),Chacko et al. (2011), WHI (NCT00000611), US | R = A = 36,282a | 400 IU/d + 1000 mg Ca/d, chewable tablet | Daily | 7 | 726 | 0.89 (0.77–1.03) |
| Avenell et al. (2012) Grant et al. (2005) RECORD (ISRCTN51647438), UK | R = A = 2675b | 800 IU/d, 1000 mg Ca/d, both/d, tablet | Daily | 2–5.2 | 88c | 0.83 (0.55–1.26)c |
| Baron et al. (2015) VitDCa Polyp Prevention Study (NCT00153816), US | R = 835d | 1000 IU/d, 1200 mg Ca/d, both/d, tablet | Daily | 3–5 | 5e | 1.44 (0.24–8.63)e |
| Martineau et al. (2015) ViDiCO (NCT00977873), UK | R = A = 240 | 120,000 IU Q2M, Vigantol oil | Bolus | 1 | 2 | 0.97 (0.06–15.29)f |
| Witte et al. (2016) VINDICATE (NCT01619891), UK | R = 223; A = 163 | 4000 IU/d, tablet | Daily | 1 | 5 g | 0.25 (0.03–2.44)g |
| Akiba et al. (2018) AMATERASU 4 (UMIN000001869), Japan | R = 155 h; A = 144 | 1200 IU/d, capsule | Daily | 1 | 2i | 1.01 (0.06–15.10)i |
| Manson et al. (2019) VITAL (NCT01169259), US | R = A = 25,871 | 2000 IU/d, n - 3 fatty acids 1 g/d, both/d, capsule | Daily | 5 | 341 | 0.83 (0.67–1.02) |
| Scragg et al. (2018) ViDA (ACTRN12611000402943) New Zealand | R = 5110; A = 5108 | Initial dose of 200,000 IU, then 100,000 IU/m, soft-gel capsule | Bolus | 3.3j | 60k | 0.99 (0.60–1.64)k |
| Urashima et al. (2019) AMATERASU 5 (UMIN000001977) Japan | R = A = 417 | 2000 IU/d, capsule | Daily | 5 | 62 | 1.09 (0.58–2.01) |
| Sudfeld et al. (2020) ToV4 (NCT01798680), Tanzania | R = A = 4000 | 50,000 IU/wk for first month of ART, then 2000 IU/d, “supplements” | Daily | 1 | 8l | 1.01 (0.25–4.02)l |
| Chatterjee et al. (2021) D2dCA (NCT01942694), US | R = A = 2385 | 4000 IU/d, soft-gel | Daily | 3 | 6 m | 0.23 (0.03–1.96)m |
| Neale et al. (2022)D-Health (ACTRN12613000743763), Australia | R = 21,315; A = 21,310 | 60,000 IU/m, gel capsule | Bolus | 5 | 452 n | 1.15 (0.96–1.39)n |
| Virtanen et al. (2022) FIND (NCT01463813), Finland | R = A = 2495 | 3200 IU/d, pills | Daily | 5 | 36 m, o | 0.90 (0.38–2.13)m, o |
| 1600 IU/d, pills | 5 | 36 m, o | 1.36 (0.63–2.97)m, o | |||
| Both intervention arms combined | 5 | 36 m, o | 1.13 (0.56–2.30)m, o | |||
Abbreviations: /d, /wk, /m per day/week/month; ART antiretroviral therapy; Ca calcium; COD cause of death; FU follow-up; m month; OS overall survival; P placebo; Q2M / Q4M every 2 / 4 months; RR relative risk; VD vitamin D3; VDS Vitamin D3 supplementation; y year
Vitamin D3 was inseparably combined with calcium.
5292 participants were randomised to vitamin D3 and calcium combined.
Derived from IPD analysis to restrict FU to intervention period. During the long-term FU, a total of 156 cancer deaths were recorded (HR (95 % CI): 0.85 (0.68–1.06)).
Regarding the two-group randomisation (2GR), women could elect to be randomly assigned to receive either calcium or calcium plus vitamin D3 (584 randomised, 540 analysed). Regarding the full factorial randomisation (FFR), all other patients were randomly assigned to receive one of the four regimens (1675 randomised, 1548 analysed). 835 refers to FFR.
Unpublished data. During the entire trial duration, 17 cancer deaths were recorded (HR (95 % CI): 0.40 (0.14–1.14)). Vitamin D3 combined with calcium yielded in 10 cancer deaths during the intervention period (HR (95% CI): 2.29 (0.59–8.86)) and a total of 30 cancer deaths during the entire trial duration (HR (95 % CI): 0.87 (0.43–1.79)).
HR extracted from “Zhangyou Guo et al. (2022) Association between vitamin D supplementation and cancer incidence and mortality: A trial sequential meta-analysis of randomised controlled trials, Critical Reviews in Food Science and Nutrition, DOI: 10.1080/10408398.2022.2056574”.
Unpublished data. 5 cancer deaths were among cause of death I, one cancer death among cause of death II. Only cause of death I was included in the analysis. Risk ratio was self-calculated based on provided data.
Eight patients from placebo arm did not receive allocated intervention.
Self-calculated based on provided clinical data.
Median
Excluded those who died of cancer diagnosed before randomisation.
Unpublished data. Note of author: Nearly all deaths were HIV related. We had eight deaths coded as attributable to cancers. However, these are based on verbal autopsy and rather incomplete medical records.
Unpublished data.
Underlying cause of death available for 889/1100. 452/889 died of cancer.
During the entire trial duration, 43 cancer deaths were recorded (HR (95% CI): 1.23 (0.59–2.56) for 1600 IU/d, 1.07 (0.50–2.28) for 3200 IU/d, 1.15 (0.60–2.21) for both dosages combined)