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There is nothing "essential" or "vital" about Poison/"Vitamin A" - Part 2, molecular evidence

See Part 1 here.

See Part 3 here.

One argument proposed for the “necessity” of Poison/”Vitamin A” in the diet is that we have a receptor called RXR (retinoid X receptor), and because scientists named the receptor that way, we simply MUST need retinoids (Poison/”Vitamin A”) to activate it! There is also the RAR (retinoic acid receptor), which is a slightly different story yet has the same ending.

First, to define some terms.

  • Agonist - a substance which initiates a physiological response when combined with a receptor (the "key")
  • Receptor - a molecule in a cell membrane which responds specifically to a particular neurotransmitter, hormone, antigen, or other substance (the "lock")
  • Ligand - a molecule, as an antibody, hormone, or drug, that binds to a receptor (can be agonistic or antagonistic)
  • Antagonist - a substance that interferes with or inhibits the physiological action of another

Since we are trying to show that the RXR and RAR can and are activated by other things than only retinoids, we will be talking about other demonstrated agonistic ligands of the RXR and RAR.

How can we disprove that retinoids of any sort are “vital” or “essential” to human life in a molecular sense?  It’s fairly easy. We show that there are MANY other agonist ligands other than just retinoids that activate these receptors...and that the RXR can even be activated without any known agonist ligands!

Let us first show that there are MANY agonist ligands for the RXR:

Specifically note the DHA and phytanic acid, two fatty acids.  We discuss these elsewhere, and they are actually the NATURAL, INTENDED agonistic ligands for the RXR.  Oh, they also missed arachidonic acid (ARA) in that graphic, a known agonistic ligand of the RXR. Maybe you've heard of DHA and ARA being of crucial importance to visual and brain development in babies?  Does me pointing these things out mean I suggest taking fish oil?  NO, it doesn't.

Are there any other (free) fatty acids that activate the RXR?  Yes, actually, quite a few of them!

Retinoid X receptor (RXR alpha) gene expression is regulated by fatty acids and dexamethasone in hepatic cells.

Abstract
This work describes the molecular mechanism of fatty acid and hormonal modulation of retinoid X receptor (RXR alpha) in rat liver. We examined the effects of different fatty acids (myristic-, stearic-, linolenic-, oleic-, arachidonic- and tetradecylthioacetic acid (TTA)) and the synthetic glucocorticoid dexamethasone on RXR alpha mRNA and protein steady-state levels in hepatoma cells and cultured hepatocytes. Fatty acids induced the RXR alpha gene expression where TTA showed the most inductive effect (three-fold induction). Dexamethasone alone resulted in a stronger induction (up to seven-fold in hepatocytes), and in combination with fatty acids, an additive or synergistic effect was observed. The RXR alpha protein level in cultured hepatocytes showed a similar pattern of regulation, with a slight inductive effect of fatty acids and an additive or synergistic effect was observed in combination with dexamethasone. Our results indicate that the RXR alpha gene expression is under distinct regulation by fatty acids and dexamethasone acid which strongly suggests a coupling with the lipid metabolizing system and the retinoid signaling pathway.

The question after reading the above becomes, which (free) fatty acids actually DON'T stimulate the RXR?

Why is this important?  Because nearly all of the diets fed to animals in the "Vitamin A deficiency" studies had ZERO fat to begin with!  Do you see the connection now?  How can we say that it is a "Vitamin A deficiency" when they took away ALL of their FAT?  Why don't they say it is a FAT deficiency???  Moving on.

How many ligands are there for the RAR, you wonder?  Well…

RAR (Nuclear receptors) Ligands Library

7,500 Compounds

I’m working on getting that list sent to me.  7500.  Seven thousand, five hundred.

Next, what if scientists have shown that the RXR can be activated without any known agonist ligands present at all?

Vitamin A - Vitamins and Hormones, Volume 75

In addition, fluorescence studies have shown in living cells that the formation of RXR heterodimers do not depend on the presence of an exogenous RXR agonist.

What does this all mean?

It means that there are all sorts of other compounds that can do the job of Poison/”Vitamin A”, and the science shows this at the molecular level.  This is exactly how people can show up with so-called "Vitamin A Deficiency" (VAD) in their blood and still have NO symptoms, which is exactly what I demonstrated in the first part of this series.

Poison/"Vitamin A" is not a vitamin ("vital amine") and is not essential or vital to life at all.  There is nothing UNIQUE in the body that ONLY Poison/"Vitamin A" can do.

See Part 3 here.

Dr. Garrett Smith, the "Nutrition Detective"
Licensed Naturopathic Physician (NMD) in Arizona
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