Journal
NUTRIENTS
Volume 14, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/nu14091689
Keywords
machine learning; multivariate adaptive regression splines; vitamin D; 25(OH)D; parathyroid hormone; digestive tract cancer; RCT
Categories
Funding
- Ministry of Education, Culture, Sports, Science, and Technology in the Japan-Supported Program for the Strategic Research Foundation at Private Universities
- JSPS KAKENHI [20H03537]
- Grants-in-Aid for Scientific Research [20H03537] Funding Source: KAKEN
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This study used machine learning method MARS to explore the threshold levels of serum 25-hydroxyvitamin D and found that vitamin D supplementation improved bone health and 5-year relapse-free survival in patients with low baseline levels, but not in those with high baseline levels.
Some controversy remains on thresholds for deficiency or sufficiency of serum 25-hydroxyvitamin D (25(OH)D) levels. Moreover, 25(OH)D levels sufficient for bone health might differ from those required for cancer survival. This study aimed to explore these 25(OH)D threshold levels by applying the machine learning method of multivariable adaptive regression splines (MARS) in post hoc analyses using data from the AMATERASU trial, which randomly assigned Japanese patients with digestive tract cancer to receive vitamin D or placebo supplementation. Using MARS, threshold 25(OH)D levels were estimated as 17 ng/mL for calcium and 29 ng/mL for parathyroid hormone (PTH). Vitamin D supplementation increased calcium levels in patients with baseline 25(OH)D levels <= 17 ng/mL, suggesting deficiency for bone health, but not in those >17 ng/mL. Vitamin D supplementation improved 5-year relapse-free survival (RFS) compared with placebo in patients with intermediate 25(OH)D levels (18-28 ng/mL): vitamin D, 84% vs. placebo, 71%; hazard ratio, 0.49; 95% confidence interval, 0.25-0.96; p = 0.04. In contrast, vitamin D supplementation did not improve 5-year RFS among patients with low (<= 17 ng/mL) or with high (>= 29 ng/mL) 25(OH)D levels. MARS might be a reliable method with the potential to eliminate guesswork in the estimation of threshold values of biomarkers.
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