I. The curve of disease risk and gene expression level. II. Disease risk and vitamin D intake. III. Risk reduction and vitamin D intakes. Note: “?” means “unknown” and/or “not sure”. The grid represents the “buffering” capacity of VDR to risk of mal-function of other particular gene sets’ genetic mutations. Intake more than 140nM of VD3 may largely have “bad” effects. a: Type 1-Gene-Set 1: potentially a “standard” curve; it shows evident effects with a vitamin D intake less than 70 nM. The risk curve for VDR+ Gene-Set 1 means the risk alongside deficiency in expression of both sets of genes.
Type 2-Gene-Set 2: A documented clinical cancer-related curve. An intake of <30 nM and > 70 nM intake has positive effects; but an intake of 30 nM-70 nM has negative effects. This group follows a U-shape [1,23,24]. However, somewhat consistently for this type, mutant animals have neither null alleles nor known loss/gain of function alleles, but only some animals with daf-12 RNAi feeding on DAF-12/VDR (rh274, gain of function) have a weak multi-vulval phenotype in our observations [25]. The multi-vulva may somewhat be considered an incomplete/imperfect cancer model in C. elegans.
Type3-Gene-Set 3: VDR has almost no effect at low vitamin D concentrations and intakes but becomes effective when vitamin D intake is more than 50 nM (or 70 nM in different study populations)
Type 4-Gene-Set 4: This has a very limited window of low vitamin D concentrations with positive effects; all other doses produce negative effects. b: Type 5-Gene-Set 1” to Type 8–Gene-Set 4”: VDR and vitamin D intake generally have positive effects.
