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The "rules" of understanding Poison/"Vitamin A" toxicity in the research.

Once you understand these "rules", the Poison/"Vitamin A" research becomes much less confusing.


If Vitamin A or retinoids or carotenoids seem to show "positive results" for a disease condition in short-term in vitro (aka "petri dish") type studies, then you can be sure that in the LONG-TERM in vivo (aka "animals") type studies, Poison/"Vitamin A" completely destroys that tissue and is the CAUSE of that very problem!  This is the one that confuses most people, so let's fix that.  More examples will follow, we'll just stick hair loss for now (anything that affects appearance always gets people's attention, no?)

SHORT-TERM "helping":

"Minoxidil enhances hair growth by prolonging the anagen phase and induces new hair growth in androgenetic alopecia (AGA), whereas retinol significantly improves scalp skin condition and promotes hair growth."

Note the above is a cell (in vitro) study and is short-term.

Now, LONG-TERM destruction:

"Vitamin A

Vitamin A is a group of compounds including retinol, retinal, retinoic acid, and provitamin A carotenoids. In murine studies, dietary vitamin A has been shown to activate hair follicle stem cells [55], although its role is recognized as complex and “precise levels of retinoic acid are needed for optimal function of the hair follicle” [56].

While deficiency has not been linked to hair loss, high levels of vitamin A have. In fact, one study found that in a mouse AA model, reduction of vitamin A in the diet actually delayed hair loss onset [56].

In humans, hypervitaminosis A may result from over-supplementation and has a strong known link to hair loss with other effects such as skin, vision, and bone changes [4,8]."

Did you catch the part about how a REDUCTION of Vitamin A in the diet DELAYED hair loss?  There are no coincidences.

What is the theory on this? Vitamin A revs up cell turnover to be TOO FAST, and then the cells BURN OUT.

First, in simpler terms:…/why-excessive-vitamin-a-ca…/

"The problem is that too much Vitamin A can have detrimental effects on both the hair and body. If you take too much of it, the hair follicles will go into overdrive. This means that your hair will be reaching the end of the growth phase too quickly and falling out. If your body is unable to make new hair quickly to replace it, you can end up experiencing hair thinning and in severe cases, baldness."

Next, in more technical terms:

Allosteric Regulation of the Discriminative Responsiveness of Retinoic Acid Receptor to Natural and Synthetic Ligands by Retinoid X Receptor and DNA

"As shown in Table 1, ligand concentrations required for half-maximal activation of the reporter gene by the wt hRXRα-hRARα pair (50% effective concentration [EC50]) varied for each retinoid compared to atRA, which was chosen throughout this study as the reference ligand. Remarkably, synthetic agonists binding with a high affinity for hRARα (TTNPB, CD367, and Am580) were the most efficient at reaching 50% maximal activation, whereas atRA and 9-cis RA displayed EC50s one order of magnitude higher than those of synthetic retinoids. In contrast, these two natural stereoisomers induced higher maximal levels of reporter gene activity at 1 μM. The highest rate of activation in the presence of synthetic agonists varied from 44 to 90% compared to atRA, suggesting that maximal occupancy of hRARα by these ligands still reveals different abilities of retinoids to promote transcriptional activation. Increasing further retinoid concentrations in some cases led to a slightly higher level of reporter gene activity (10 to 15% for CD367) but in other cases inhibited cell proliferation and triggered cell death in variable ratio, resulting in an apparently decreased reporter gene activity (atRA and other synthetic retinoids)."

At first, there is more activity with increasing concentration...then as the concentration is further increased, there is less cell proliferation (cells are not increasing in number as rapidly) and CELL DEATH.  Could this also happen with not just increasing concentration, but possibly also longer exposure to Poison/"Vitamin A"?

Another example from adipose (fat) cells.

"Recently, Berry et al. [62] provided data indicating that CRABP-II [Cellular Retinoic Acid-Binding Protein-II] is highly expressed during early adipocyte differentiation but its expression is repressed during later stages. The lack of CRABP-II after early differentiation may thus explain that retinoic acid only inhibits differentiation early but not in later stages of differentiation."

The main thing to note above is that the short-term effect is the OPPOSITE of the long-term effect.  This may be part of the explanation why short-term higher-dose Poison/"Vitamin A" toxicity is associated with anorexia (a lack or loss of appetite for food) and undesired weight loss, while Chronic Insidious Vitamin A Toxicity is associated with obesity and bodyfat gain.

Think of it like this...if a person was very tired, they would have trouble getting their work done.  Let's say, out of desperation, they decide to start using a stimulant to "help" them with their drinks, tons of coffee, cocaine, amphetamines, whatever.  Over time, as the root cause of their issue has not been dealt with, and the stimulant depletes their system even more, they end up needing EVEN MORE of said stimulant to even feel normal, and they're eventually unhealthier and worse off than they were before.  Poison/"Vitamin A" does the same thing to tissues.


Rule #2 - RETINOL BINDING PROTEIN RULE (to be called the RBP RULE)

If you see a disease condition that is associated in the research with "low serum retinol" (aka low Poison/"Vitamin A" in the blood) and/or "low Retinol Binding Protein" (aka RBP), then that condition will nearly always have other connections that "cause" the decreased serum retinol and/or RBP:  zinc deficiency, Vitamin E deficiency, and protein undernutrition (there are other things than these as well, we "test, don't guess, then address" them all through my Nutritional Restoration programs).

The problems of that disease condition are absolutely related to Poison/"Vitamin A" toxicity in the LIVER, as well as other areas.  First, the liver considers one of its main evolutionary jobs to be that of hoarding Poison/"Vitamin A" within itself, to keep it out of the blood.  The short explanation is that if the liver does not have what it needs to make Retinol Binding Protein (RBP, a protein that protects the body from free retinol and its breakdown product retinoic acid), then the liver will NOT let go of the Vitamin A out into the circulation.  It will hold onto it tightly, "taking the bullets" (organ damage) in effect for the rest of the body to suffer less.  Once the liver is completely full, that's when all hell breaks loose in the body.  See Grant's book "Extinguishing the Fires of Hell", Chapter 13 for more info.

The following excerpt (the top left of this page comes from this book


Vitamin A toxicity, also called hypervitaminosis A, is a serious and even life-threatening condition. Toxicity is dose dependent; it may be acute and even fatal with very high doses of vitamin A, whereas with lower but still excessive intakes over a longer time, onset is likely to be slower but symptoms may still be severe. Signs of acute vitamin A toxicity include pseudotumor cerebri, anorexia, anemia, rough and dry skin, and bone pain. A prolonged elevation of vitamin A concentration may lead to irreversible organ damage. Manifestations of vitamin A toxicity in the reproductive period include teratogenic birth defects, including malformations of the face, nervous system, heart, and thymus gland.155 Hypervitaminosis A occurs when the amount of plasma retinol exceeds the availability of RBP to bind it, leading to unbound and elevated levels of free retinol in plasma, and formation of excess retinoid metabolites. Although there is no antidote, hypervitaminosis A may be slowly reversible by restriction of vitamin A consumption, with remediation of symptoms within a few hours to a few months. However, a patient with chronic hypervitaminosis A was reported to still experience symptoms of increased intracranial pressure and elevated serum retinol and RBP levels almost 2 months after cessation of vitamin A supplementation.156 Dietary vitamin E has displayed some therapeutic benefit in treating vitamin A toxicity,157 and 2-hydroxypropyl-β-cyclodextrin has been shown to be safe and has been used to solubilize vitamin A, which allows urinary excretion as a method of ridding retinol from the circulation.158 However, more research is needed to provide therapeutic interventions for chronic hypervitaminosis A."

Important takeaways from that article:

  • With chronic toxicity, it can be a sloooooow onset with severe problems.   Sound like anyone's health issues that you know?
  • Too much retinol without enough RBP equals toxicity.  If the liver cannot keep up production of RBP, yet the liver is completely overflowing with Poison/"Vitamin A", then the retinol will be forced to escape into the circulation with extremely damaging consequences.
  • It would appear that simply avoiding Vitamin A supplements may NOT fix people's issues (we're way ahead of that limited approach).
  • Dietary Vitamin E has been shown to be helpful in Poison/"Vitamin A" toxicity.
  • Detoxification through the kidneys/urine is one viable route of getting rid of the excess.

Let's go through some of the research on the above-mentioned nutrients and how they are needed to make RBP:

Zinc is necessary for making RBP:

"In regard to retinol-binding protein, it appears from the animal studies that zinc deficiency per se has an effect on both the plasma and liver RBP concentrations. We have hypothesized that zinc deficiency impairs RBP synthesis."

Vitamin E is correlated with RBP levels:

"We found a significant relationship between OS and the level of RBP4 (p=0.002), retinol (p=0.037) and vitamin E (p=0.007)."

Protein is necessary for making RBP (uh, it is called Retinol Binding Protein, after all!!!):

"Plasma RBP is decreased to 1.62 mg plus or minus 0.71/100 ml, or 31.1 percent of normal, in the acute stage of kwashiorkor. [kwashiorkor, aka protein malnutrition, is malnutrition produced by a severely inadequate amount of protein in the diet] RBP doubles its plasma level after 1 wk and triples after 2 wk of appropriate refeeding. The return to normal of RPB runs in close parallel with prealbumin (PA), implying that both components remain bound by 1:1 molar ratio in the PA-RBP complex. Low values recorded on admission for RBP seem to be the result of reduced liver biosynthesis. On the other hand, a high correlation persists between RBP and retinol plasma level along the successive steps of clinical recovery, suggesting that RBP acts as the limiting factor for retinol transport."

Note that very last bolded part...that RBP acts as the *limiting factor* for retinol transport.  This is what was said above.  Generally, RBP levels and serum retinol levels go up and down together, because the liver wants it this way to protect you from Poison/"Vitamin A"!

It looks like this:

  1. Liver fills up with Poison/"Vitamin A" until it can't hold any more.
  2. RBP-related nutrient deficiencies get bad enough that RBP production can't keep up with what the liver needs to make it, and it can't get rid of the Poison/"Vitamin A" fast enough.
  3. Excess retinol spills into the system, there's not enough RBP, and we have the chronic disease epidemics of our modern times.

So, let's put all that together in a Rheumatoid Arthritis (RA) example.  If you have actually read Grant's book(s), you should know by now, or at least highly suspect, that nearly ALL autoimmune conditions are likely directly caused by Poison/"Vitamin A" toxicity.  If you didn't catch that, go back and read them again with a more open mind.  We established above that zinc and Vitamin E are needed to make RBP.  Low zinc and low Vitamin E would go with low serum retinol and low RBP, in a disease that is being caused by Poison/"Vitamin A" toxicity at its heart.

Vitamins A and E, retinol binding protein and zinc in rheumatoid arthritis.

"Serum vitamins A and E levels were lower in patients with rheumatoid arthritis (RA) than in healthy controls. Low vitamin A and E levels together with a marginally lowered selenium concentration may lead to a markedly decreased antioxidant capacity and enhanced eicosanoid production in RA. Univariate linear regression analysis showed a positive correlation (r = 0.383; p less than 0.005) between serum levels of vitamin A and zinc, and between serum retinol binding protein (RBP) and zinc (r = 0.440, p less than 0.02). These findings suggest that hypovitaminosis A in RA may be mediated by decreased vitamin A transport from the liver to the blood, caused by the low level of zinc dependent hepatic retinol binding protein synthesis. In multiple linear regression analysis, the serum zinc level emerged as the most significant variable and had an independent predictive value of 15.2% for vitamin A. Variations in the serum vitamin E levels were only explained by seropositivity (predictive value of 14.2%), a finding which suggests that the decreased level of vitamin E is a constant feature in RA rather than part of the acute phase response."

Low Poison/"Vitamin A" in the serum/blood is precisely caused by a lack of nutrients needed by the liver to produce RBP (zinc and Vitamin E in this case).

To check this yourself, when you come up against the situation of low serum retinol showing up in a chronic disease:

Pubmed search for "acne serum retinol"
Acne does tend to have "low serum retinol".  So, is acne also associated with a zinc deficiency?

The next step is to go search Pubmed for:
-> [insert medical disease term] zinc deficiency <-

Yes, acne is strongly associated with a zinc deficiency in the research, and I would say that acne is another condition that looks like it is a Poison/"Vitamin A" toxicity disease masquerading as "low serum retinol" due to a zinc deficiency as a major part of it.  This process will be repeated elsewhere here, and feel free to use it yourself to prove the association.

If there are any other "rules" I figure out, I will put them here.

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