Effect of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality

Zhang, Suiliang; Chen, Tingsong; Ma, Chenyun; Meng, Yongbin; Zhang, Yufei; Chen, Yiwei; Zhou, Yuhao

doi:10.1097/md.0000000000003485

Cited by 19 publications

(16 citation statements)

References 53 publications

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“…An inverse relationship was reported for a meta-analysis of three RCTs evaluating treatment with combined supplements, including folic acid and risk for malignant melanomas (RR 0.47; 95% CI 0.23-0.94) with similar magnitudes of effect to our current MR study. However, the sample size for this analysis was very small (38 malignant melanoma cases)[55]. A meta-analysis of 13 RCTs found no association between folic acid supplementation and malignant melanoma, though results were limited by low number of cases (N = 126) and a relatively short follow up period (average 5.2 years)[19].…”

Section: Discussionmentioning

confidence: 99%

Mendelian randomisation study exploring the associations of serum folate with pan and site-specific cancers

Burrows¹,

Kazmi²,

Haycock³

et al. 2019

Preprint

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Background: Epidemiological studies report evidence for an association between folate, an essential B vitamin, and the risk of several common cancers. However, both protective and harmful effects have been reported, and effects may differ by cancer site. These associations suggest that modulating dietary folate, or its synthetic form folic acid, could be used to modify population-wide cancer risk. However, observational studies are liable to biases, including residual confounding and reverse causation, thus limiting causal inference. Using Mendelian randomisation (MR), we investigated the causal relationships of genetically determined serum folate with pan-cancer risk (all cancers excluding non-melanoma skin cancers); breast, prostate, ovarian, lung, and colorectal cancers; and malignant melanoma. Methods:Using publicly available genome-wide association study (GWAS) summary data, we identified genetic instruments to proxy serum folate levels and analysed these using GWAS summary statistics of risk of pan-cancer and six site-specific cancers available from large consortia and the population-based cohort study UK Biobank (UKBB) within a two-sample Mendelian randomisation framework. We conducted MR using the inverse variance weighted (IVW) method and the likelihood-based approach. We performed sensitivity analyses to assess potential violations of MR assumptions. Results:We identified three SNPs (rs1801133, rs1999594, rs7545014) robustly associated with serum folate in a healthy, young adult Irish population using publicly available GWAS summary data. There was little evidence that genetically increased serum folate was associated with risk of pan-cancer or six site-specific cancers. Meta-analysis showed odds ratios (OR) per standard deviation (SD) increase in log10 serum folate of 0.92 (95% confidence interval 0.78-1.07) for breast cancer, 0.87 (95% confidence interval 0.71-1.06) for prostate cancer, 0.87 (95% confidence interval 0.61-1.25) for ovarian cancer, 0.87 (95% confidence interval 0.57-1.34) for lung cancer, and 1.26 (95% confidence interval 0.84-1.88) for colorectal cancer. ORs for pan-cancers and malignant melanoma in UKBB were 0.86 (95% confidence interval 0.71-1.03) and 0.57 (95% confidence interval 0.30-1.10) respectively. The results were powered to detect modest effect sizes (>80% power [α=0.05] to detect ORs 1.1 (or its inverse 0.9) for the cancer GWAS consortia) and were consistent between the two statistical approaches used (IVW and likelihood-based). Conclusions:There is little evidence that genetically increased serum folate may affect the risk of pan-cancer and six site-specific cancers. However, we may still be underpowered to detect clinically relevant but smaller magnitude effects. Our results provide some evidence that increasing levels of circulating folate through widespread supplementation or deregulation of fortification of foods with folic acid is unlikely to lead to moderate unintended population-wide increase in cancer risk.

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Section: Discussionmentioning

confidence: 99%

Mendelian randomisation study exploring the associations of serum folate with pan and site-specific cancers

Burrows¹,

Kazmi²,

Haycock³

et al. 2019

Preprint

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“…There is growing evidence that some B vitamins, and choline may prevent the occurrence of developmental abnormalities and chronic degenerative or neoplastic diseases [102]. However, others suggest they may contribute to neoplastic diseases, exacerbate them or have no effect [103]. Heart disease is the major cause of death in the United States and for many years, physicians and researchers have been emphasizing the importance of the Mediterranean diet.…”

Section: Choline the Mediterranean Diet And Heart Diseasementioning

confidence: 99%

The Microbiota–Gut–Brain Axis Heart Shunt Part I: The French Paradox, Heart Disease and the Microbiota

Obrenovich

Siddiqui

McCloskey³

et al. 2020

Microorganisms

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It has been well established that a vegetarian and polyphenol-rich diet, including fruits, vegetables, teas, juices, wine, indigestible fiber and whole grains, provide health-promoting phytochemicals and phytonutrients that are beneficial for the heart and brain. What is not well-characterized is the affect these foods have when co-metabolized within our dynamic gut and its colonizing flora. The concept of a heart shunt within the microbiota-gut-brain axis underscores the close association between brain and heart health and the so-called “French paradox” offers clues for understanding neurodegenerative and cerebrovascular diseases. Moreover, oxidation-redox reactions and redox properties of so-called brain and heart-protective foods are underappreciated as to their enhanced or deleterious mechanisms of action. Focusing on prodromal stages, and common mechanisms underlying heart, cerebrovascular and neurodegenerative diseases, we may unmask and understanding the means to better treat these related diseases.

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“…Then vitamin B12 deficiency is directly responsible for an increased occurrence of various age-related diseases: megaloblastic macrocytic anaemia, cardiovascular diseases, neurological pathologies, and osteoporosis [10,11,13]. In parallel, the impact of folic acid supplementation on cancers (colorectal cancers in particular) remains a matter of debate [14]. To summarize, although food fortification in folic acid has been shown to decrease the occurrence of NTD, some side deleterious effects (particularly towards elderly population) are still questioned in the literature.…”

Section: Introductionmentioning

confidence: 99%

“…To summarize, although food fortification in folic acid has been shown to decrease the occurrence of NTD, some side deleterious effects (particularly towards elderly population) are still questioned in the literature. The optimal dose of folic acid supply (ranging from 0.4 to 40 mg per day used in interventional studies [14]) on the short-term and the long-term basis [11,15] capable to improve overall health status also remains a matter of debate.…”

Section: Introductionmentioning

confidence: 99%

Food matrix structure (from Biscuit to Custard) has an impact on folate bioavailability in healthy volunteers

et al. 2020

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Purpose We examined the impact of matrix food structure on post-prandial folate bioavailability (and other macronutrients) in human volunteers using a randomized, controlled, crossover experimental design. Methods Twelve healthy male volunteers (22.6 ± 0.4 years old) were offered four food models (differing in matrix structure: Custard, Pudding, Sponge cake and Biscuit) to which 1 mg of folic acid was added, according to a randomized, controlled, crossover experimental design. Plasma folates, glucose, insulin, alpha amino nitrogen and triglycerides were measured over the post-prandial period (from T0 to T480 min). Results Food matrix structure was capable of altering folate plasma availability. The highest folate availability was observed for pudding and to a lesser extent Sponge cake whereas the lowest was for the two matrices presenting extreme rheological properties: Custard (liquid) (P < 0.05 total AUC) and to a lesser extent Biscuit (hard solid) (P < 0.05, AUC 180 min). The analysis of plasma kinetics of appearance of other nutrients/metabolites helps to understand/explain the lower bioavailability of folates in Custard and Biscuit. Conclusion A least overall efficient bio-accessibility of all macronutrients and folic acid is observed in the gut lumen for Biscuit (delayed/incomplete destructuration of biscuit along the digestive tract). On the contrary, the lower folic acid absorption observed with custard does not fit with the rapid plasma appearance of other nutrients and should require further investigation.

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Effect of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality

Cited by 19 publications

References 53 publications

Mendelian randomisation study exploring the associations of serum folate with pan and site-specific cancers

Mendelian randomisation study exploring the associations of serum folate with pan and site-specific cancers

The Microbiota–Gut–Brain Axis Heart Shunt Part I: The French Paradox, Heart Disease and the Microbiota

Food matrix structure (from Biscuit to Custard) has an impact on folate bioavailability in healthy volunteers

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