Prevention of Advanced Cancer by Vitamin D3 Supplementation: Interaction by Body Mass Index Revisited

Brenner, Hermann; Kuznia, Sabine; Laetsch, Clarissa; Niedermaier, Tobias; Schöttker, Ben

doi:10.3390/nu13051408

Cited by 3 publications

(5 citation statements)

References 27 publications

(37 reference statements)

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“…While cholecalciferol supplementation did not show any benefits in cancer prevention on the primary outcomes, subgroup analyses sometimes indicated the potential for a more stratified and targeted strategy. In the case of the VITAL trial, several authors underlined a statistically significant reduction in cancer incidence among participants with BMI ≤ 25 and a marginally significant reduction among Black people [ 10 , 11 ]. Most certainly, subgroup analyses can provide valuable exploratory results.…”

Section: Discussionmentioning

confidence: 99%

“…After the publication of two more large RCTs with null results this year, the hopes for a reduction in cancer mortality via cholecalciferol supplementation, mainly fueled by a marginally significant reduction reported in the VITAL study, have faded [ 9 ]. The VITAL study did not find significant benefits regarding invasive cancer or cancer mortality with vitamin D supplementation [ 10 ], but secondary analyses pointed to certain promising alternative outcomes and subpopulations that might benefit [ 11 ]. In contrast, no statistically significant results were found in the Australian D-Health trial.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D in Cancer Prevention: Gaps in Current Knowledge and Room for Hope

2022

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Intensive epigenome and transcriptome analyses have unveiled numerous biological mechanisms, including the regulation of cell differentiation, proliferation, and induced apoptosis in neoplastic cells, as well as the modulation of the antineoplastic action of the immune system, which plausibly explains the observed population-based relationship between low vitamin D status and increased cancer risk. However, large randomized clinical trials involving cholecalciferol supplementation have so far failed to show the potential of such interventions in cancer prevention. In this article, we attempt to reconcile the supposed contradiction of these findings by undertaking a thorough review of the literature, including an assessment of the limitations in the design, conduct, and analysis of the studies conducted thus far. We examine the long-standing dilemma of whether the beneficial effects of vitamin D levels increase significantly above a critical threshold or if the conjecture is valid that an increase in available cholecalciferol translates directly into an increase in calcitriol activity. In addition, we try to shed light on the high interindividual epigenetic and transcriptomic variability in response to cholecalciferol supplementation. Moreover, we critically review the standards of interpretation of the available study results and propose criteria that could allow us to reach sound conclusions in this field. Finally, we advocate for options tailored to individual vitamin D needs, combined with a comprehensive intervention that favors prevention through a healthy environment and responsible health behaviors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Vitamin D in Cancer Prevention: Gaps in Current Knowledge and Room for Hope

2022

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“…Those reductions included incident cancer in those with healthy weights [BMIs <25 kg/m2], probably because increasing BMI increases the vitamin D intakes needed to correct deficiency x1-4] fold]. [94,36] Significant falls in autoimmune disease were found overall, and a significant reduction in cancer mortality, by up to ~40%, from the 3 rd year of the study onwards. [95,96] Thus, a general condemnation of vitamin D supplementation from VITAL results is not justified.…”

Section: Than Any Others Remains Unacceptable Since Deficiency Increa...mentioning

confidence: 99%

“…Indeed, priority was called for in following up the effect on cancer mortality in a report on findings from VITAl data. [94] Furthermore, the possibility of being able to detect health benefits in the VITAL trial were reduced, even in deficient subjects, since volunteers were told at recruitment that they could take personal vitamin D supplements at up to 800 IU/day. This feature makes the lack of assessment of vitamin D status at the end of the study especially regrettable since achieved vitamin D status has emerged as an important determinant of many health outcomes.…”

Section: Than Any Others Remains Unacceptable Since Deficiency Increa...mentioning

confidence: 99%

Vitamin D deficiency in British South Asians, a persistent but avoidable problem associated with many health risks (including rickets, T2DM, CVD, COVID-19 and pregnancy complications): the case for correcting this deficiency

Boucher

2022

Endocrine Connections

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High vitamin D deficiency rates, with rickets and osteomalacia, have been common in south Asians (SAs) arriving in Britain since the 1950s with preventable infant deaths from hypocalcaemic status-epilepticus and cardiomyopathy. Vitamin D deficiency increases common SA disorders (type 2 diabetes and cardiovascular disease), recent trials and non-linear Mendelian randomisation studies having shown deficiency to be causal for both disorders. Ethnic minority, obesity, diabetes and social deprivation are recognised COVID-19 risk factors but vitamin D deficiency isn’t, despite convincing mechanistic evidence of it. Adjusting analyses for obesity/ethnicity abolishes vitamin D deficiency in COVID-19 risk prediction but both factors lower serum 25(OH)D specifically. Social deprivation inadequately explains increased ethnic-minority COVID-19 risks. SA vitamin D deficiency remains uncorrected after 70 years, official bodies using ‘education’, ‘assimilation’ and ‘diet’ as ‘proxies’ for ethnic differences and increasing pressures to assimilate. Meanwhile, English rickets was abolished from ~1940 by free ‘welfare foods’ (meat, milk, eggs, cod-liver-oil), for all pregnant/nursing mothers and young children (<5 years old). Cod-liver-oil was withdrawn from antenatal clinics from 1994 (for excessive vitamin A teratogenicity), without alternative provision. The take-up of 2006 ‘Healthy-Start’ scheme food-vouchers for low-income families with young children (<3 years old) has been poor, being inaccessible and poorly publicized. COVID-19 pandemic advice for UK adults in ‘lockdown’ was ‘400 IU vitamin D/day’, inadequate for correcting the deficiency seen winter/summer at 17.5%/5.9% in White, 38.5%/30% in Black and 57.2%/50.8% in SA people in representative UK Biobank subjects when recruited ~14 years ago and remaining similar in 2018. Vitamin D inadequacy worsens many non-skeletal health risks. Not providing vitamin D for preventing SA rickets and osteomalacia continues to be unacceptable, as deficiency-related health risks increase ethnic health disparities, while abolishing vitamin D deficiency would be easier and more cost-effective than correcting any other factor worsening ethnic minority health in Britain

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“…The paper by Dr. Brenner and colleagues [4] discusses the potentially protective effects of vitamin D 3 supplementation against cancer mortality, particularly in relation to body mass index. The VITAL study, which included over 25,000 participants, found that vitamin D 3 supplementation was effective in reducing cancer incidence and advanced cancer for normal-weight participants, but this impact did not occur in overweight or obese participants.…”

mentioning

confidence: 99%