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Retinol Chemical Structure
15 Sep 2017

Vitamin A Retinoids and Cancer

I’ve been struggling with the utility of retinol for cancer prevention or treatment because the published data in humans is not encouraging (Adv Nutr 2017;8:27–39.)… however I do see some encouraging data in mice (Biol. Pharm. Bull. 40, 486–494 (2017)), and I realize you have a lot of real-world experience with it that may not be published.
Do you ever use their plasma retinol levels as a guide?

Dr. Anderson:

Quick ‘Vit-A’ reply – it is complex, and nobody actually knows. One issue (similar to vitamin E and cancer) is the form makes a difference and often the studies are random and confusing as to form used. Mixed carotenoids in food perform differently than single (beta) forms. Retinol is going to be VERY different due to absorption, direct nuclear activity and other factors such as the quite common BCMO SNPs. Also “prevention” with the fat-soluble vitamins is almost always nonlinear which NO study accounts for [a quick example, clinically with fat-soluble vitamins for prevention we assess need, ramp dose up to saturation and then back off once levels are appropriate to low (or lowest required) levels for maintenance of appropriate level.] It’s not the same as many water-soluble nutrients where X mg/day is required.

Flowchart of Vitamin A Synthesis

The last point is that prevention versus therapy with a fat-soluble vitamin is a huge difference as well. There are data in active cancer that many of the fat-soluble vitamins have different therapeutic roles than they have in the preventive setting. Specifically high dose retinoids (and others like K2) can apparently be used therapeutically in some or many cancers at doses much higher than are considered safe for prevention. I see that as completely logical however since they are filling a pharmacological role in treatment whereas in prevention their role is more subtle.

Fat soluble nutrients and cancer are just different and nobody is writing about it let alone designing studies to show these subtleties. I’ve been on panels at the hospital all about this and it’s shocking the low level of critical thinking (even in the biochemists we bring in as experts) on the topic. [My medical biochemistry professor was this savant lipid biochemist who trained us very deeply in fat-soluble nutrient biochemistry which I suppose ruined me for the simplistic discussions we see in the papers published.]

Plasma Retinol can (if processed properly) be a place to start in prevention settings (not much use during retinoid based cancer treatment). It is affected by inflammation so in an infected, cancer or other inflamed person may be inaccurate. In that instance, you can correct for inflammation using the retinol-binding protein: transthyretin ratio. [PMID: 10953676]

Retinol Metabolism