Low Toxin Diet Grant Genereux's Theory Of Vitamin A Toxicity

[postman]

True.but we cant know if there were no problems though.Just lack of overt symptomatology.
You can not often find something,if you do not search for it.
Retinol is so basic that the general tendency of accelerated decay with insufficiency would go unnoticed for the
inexperienced observer.These Physicians were not trained Vitamin A scholars.

Actually yes they were, Sharman was a big vitamin A proponent and wrote many papers about it and how good it is and how necessary it is. It's more like he didn't want to report anything negative about retinol intake, that's why he didn't, that's why he was so extremely brief his report of this 2 year long study.

 

[Amazoniac]

That is all that was ever published about it from what I can tell. A conference abstract. He probably didn't want to show extensive results.

It doesn't seem comprehensive to me, seems more like whatever interesting papers Garret read that month becomes basis for the next developments in his diet. I also suspect that his whole rationale about how detox symptoms are to be avoided, that he now seemingly has gotten Grant to believe in as well, is misguided and wrong.

Now that I went back to the PubMeb page where it was indexed, you're right: [1973 Dec;32(3): 105A-106A]. So indeed, it was only published as an abstract, go figure..

Grant was making such a big deal of it that I assumed he had access to the detailed information, he spent pages addressing it (which is fine) but dismissed most of the extensive research on poison A that's available.

However, Geraldo Stern coauthored it and discussed the 'enigma' in a recent publication, not sure if you missed it:
- Anti-Peat - Grant Genereux's Theory Of Vitamin A Toxicity

You may be able to contact him through email for more details.

--
- The effect of lecithin, choline, and methionine on the vitamin A and carotene plasma levels and liver stores of young dairy calves

 

[Amazoniac]

- Handbook of Vitamins (978-0-8493-4022-2)

(a) Relationship of plasma retinol concentration to liver retinol concentration. Three portions of the curve represent the following: left, inadequate liver vitamin A to maintain a normal level of plasma retinol; middle, homeostatic regulation of plasma retinol over a range of liver retinol concentrations from ~20 to ~300 mcg/g liver; right, increasing plasma total retinol at liver concentrations greater than ~300 mcg/g, due to presence in plasma of lipoprotein-associated retinyl esters. (From Olson, J.A., J. Natl. Canc. Inst., 73, 1439, 1984. With permission.)

My post got lost during maintenance, so I'm having to repost it.

Mealtimes aside, the concentration of poisonol in circulation remains more constant than killcidiol, and these are bathing cells and gels nonstop. Consider how easy it is to double your killcidiol level in blood. Therefore we're relying on regulatory mechanisms within cells to keep their ratio decent.

Since killcidiol has activity and it's less regulated than killcitriol, if you supplement killciol without consuming enough poison A, an increased mobilization to maintain their balance is possible.

And it gets complicated because those regulatory mechanisms can be altered..

- Possible renoprotection by vitamin D in chronic renal disease: beyond mineral metabolism

"Reduced activity of 1a-hydroxylase is widely accepted to be the main cause of reduced circulating levels of 1,25(OH)2 vitamin D3 in patients with CKD.[74] In a model of experimental nephrosis, renal mRNA expression of 1a-hydroxylase is decreased and CYP24A1 is increased 3 days after induction of nephrosis, resulting in a reduction in serum levels of 1,25(OH)2 vitamin D3.[72] Therefore, in patients with CKD, vitamin D deficiency probably results from multiple factors including urinary loss of 25(OH) vitamin D3–DBP associated with proteinuria,[72] reduced activity of 1a-hydroxylase, and compromised endogenous previtamin D3 production in the skin.[73]"​

 

[Amazoniac]

Tufts University Confirms That Vitamin A Protects Against Vitamin D Toxicity by Curbing Excess Production of Vitamin K-Dependent Proteins

"[..]even modest amounts of vitamin D, whether provided by UV-light or in the diet, decrease liver stores of vitamin A; when the doses of D are larger, they decrease plasma levels of A as well. This suggests that vitamin D increases the need for and turnover of vitamin A."​

 

[Tristan Loscha]

Actually yes they were, Sharman was a big vitamin A proponent and wrote many papers about it and how good it is and how necessary it is. It's more like he didn't want to report anything negative about retinol intake, that's why he didn't, that's why he was so extremely brief his report of this 2 year long study.

That thinking about his intentions is correct,and fair use of suspicion and asking of intent.
Im still full-on spinning in a deceptive Retinol-Carousel though,haha.
But slight anectdotal mentioning of possible reduction of Convusion-frequency is interesting.
Never found a mechanical explanation though,also Convusions are no common side effect even from
Retinol-Poisoning.

 

[Tristan Loscha]

Is there a mechanistic Target explanation for alleged Retinol Epilepsy connection?

 

[Amazoniac]

- Vitamin A Blocks The Hypercalcemia From Vitamin D

⮤ Vitamin A and Osteoporosis: Experimental and Clinical Studies (author of the last, featured here)

"Osteoblasts, osteoclasts and osteocytes are the bone cells of major importance for production and maintenance of bone tissue, and for regulation of its metabolic function. The precursors of the bone cells originate from the bone marrow cavity and, when needed, move to skeletal sites for differentiation and proliferation."

"Direct stimulation of the proliferation and differentiation of osteoblastic progenitors is exerted by growth factors such as FGFs, IGF-1 and TGF-b released from the eroded bone or produced by the bone cells (29,30), and a regulatory effect of bone matrix proteins is also likely (31). Leptin was first described as neuro-endocrine inhibitor of bone formation, but may also act as an autocrine factor in bone tissue in a way that promotes bone formation (32). Mechanical stress has a positive effect on bone mass via mechanisms only partly known (33,34)."

"In 1994, WHO defined female osteoporosis as a bone mineral density (BMD) of 2.5 standard deviations or more below the mean value for healthy, young adults (43). However, low BMD alone can not explain all osteoporotic fractures (44). According to the Study of Osteoporotic Fractures, total hip BMD can predict only 28% of hip fractures (45), and elderly individuals have a several-fold increased hip fracture risk compared to young individuals with the same BMD (46). Thus, there are other factors of interest in the search for variables that explain and predict osteoporotic fractures. Among these are the intrinsic mechanical quality (material properties) of the bone tissue and its spatial distribution (geometry) (44). An increased rate of bone remodeling, apart from bringing about a loss of bone mass, is itself a risk factor for fracture, and has been proposed as a major cause of bone fragility (47). Also the quality of bone matrix and its degree of mineralization can be of importance (48,49)."

"Secondary osteoporosis can be induced by corticosteroid treatment, hyperthyroidism, alcohol abuse and skeletal malignancies, among other factors (53)."

"Calcium is important for cells throughout the body, as a co-factor for proteins, for control of neuronal excitability and as an intracellular 2nd messenger. Therefore the calcium level of the extracellular compartment is kept constant through delicate homeostasis."

"Calcium absorption and preservation in the body is not very efficient. Intestinal absorption can be as low as 15% (61), and the ability to adapt to a low calcium intake is reduced after menopause and in elderly people (62). Renal conservation of calcium also deteriorates after menopause (63)."

"The skeleton, intestine and kidney are central in the regulation of calcium homeostasis. Calcium absorption in the intestine is facilitated by vitamin D, especially under conditions of low calcium intake (64). Via a brush border calcium channel and the intracellular calcium-binding protein calbindinD9k, both largely vitamin D-dependent, calcium is actively absorbed and transported to the circulation (65). If abundant, calcium is deposited in bone tissue via mineralization. On the contrary, a low calcium level leads to an instantaneous release of PTH from the parathyroid glands. PTH increases activation of vitamin D in the kidney, with secondary positive effects on intestinal calcium absorption. PTH also increases reabsorption of calcium from the urine and mobilizes calcium via direct effects on bone (66). Via these mechanisms, the overall goal to increase serum calcium to normal is achieved. Since the need for calcium mobilization overrides other functions of the skeleton, calcium homeostasis is of major importance for the balance of bone remodeling (30)."

"Despite the usage of vitamin D for the treatment of osteoporosis and other metabolic bone diseases, the mechanism by which it is beneficial for bone is not exactly known. 1,25-(OH)2-vitamin D3 can induce differentiation of osteoclastic cells, but indirectly via osteoblastic cells (64). Interestingly, a physiological vitamin D dose inhibits bone resorption while a pharmacological dose stimulates resorption (70-72). The characteristic disease of vitamin D deficiency is rickets or, in the adult, osteomalacia, i.e. incomplete mineralization. However, the skeletal symptoms of the VDR knock-out mice – hypocalcemia and rickets – are rescued by a high calcium diet (73,74). Therefore it has been assumed that the function of vitamin D is to provide calcium levels sufficient for mineralization rather than acting directly in the mineralization process."

"Some other organs, such as the kidneys, [] have storage capacity [for poison A] (98)."

"RBP has been considered to protect the body from toxic effects of free retinol. However, RBP-knockout mice were essentially unaffected (102)."

"RA and retinol can [] be converted to retinoyl b-glucoronide and retinyl b-glucoronide, respectively, mainly in the liver and intestine (105)."

"S-REs normally increase postprandially, and there is a five-fold interindividual difference in clearance from serum (half-life 1.54-9.90 h after a single intake of 50,000 IU) (111). In cases of vitamin A intoxication, S-REs are elevated for extended periods. It is generally accepted that the normal S-RE level is <5-10% of circulating vitamin A and that S-RE >10% is an indication of chronic vitamin A toxicity (83). In absolute numbers, this corresponds to a normal value <244 nM (112)."

"In general, a major role of vitamin A is to regulate proliferation and differentiation of cells, and this is a likely role of vitamin A in bone tissue as well. Both osteoblastic and osteoclastic cells express retinoid receptors."

"The generation of mice with combined knock-outs of the retinoid receptors has emphasized the importance of vitamin A during development, but since the mutants died in utero or shortly after birth, our knowledge about how they function in the adult skeleton was hardly increased (reviewed in (129))."

"An interaction between vitamin A and D has long been suggested, in part based on clinical observations and in part on the basis of the VDR-RXR heterodimer mediating the molecular action of vitamin D. Accordingly, allosteric receptor ligand interactions have been demonstrated in vitro (118), and in vitro studies have variously indicated antagonistic, additive or synergistic interaction between the vitamins (191). The recent finding that 9-cis-RA exhibits receptor-binding activity in vivo only at pharmacological doses, and the failure to isolate 9-cis-RA in vivo (119) makes a direct ligand-mediated interaction with the VDR-RXR complex less likely, but an antagonism can arise via competition between RAR and VDR for formation of RXR heterodimers. Many other mechanisms for interaction, during intestinal absorption, transport, metabolism or storage of the vitamins, are of course possible. For example, RA can induce expression of a 24-OH-hydroxylase which is a key catabolic enzyme for 1,25-(OH)2-vitamin D3 (192)."

"A general antagonistic interaction among the fat-soluble vitamins has previously been demonstrated in the chicken (200,201). Our data suggest that a similar general interaction among fat-soluble vitamins is also present in the rat. Although the decrease in S-phylloquinone (vitamin K) only reached marginal statistical significance, an interaction between vitamin K and vitamin A seems likely. Clinical reports of bleedings and hypothrombinemia after intoxication with vitamin A and vitamin E, respectively, support this hypothesis (202,203). Vitamin D has well-known beneficial effects on the skeleton, and similar effects are proposed for vitamins K and E (204,205). Therefore, our findings suggest possible indirect mechanisms of vitamin A toxicity."

"The antagonism causing reduced serum levels of other vitamins can occur during vitamin absorption in the intestine, or during transport, storage or degradation of the vitamins. Previous studies have suggested a competitive interaction at the level of intestinal absorption (195,206), and our data are in agreement with this hypothesis (see also discussion in paper III). However, other levels of interaction must also be considered. For example the 24-OH-hydroxylase, a key catabolic enzyme for 1,25-(OH)2-vitamin D3, is up-regulated by RA (192)."

"I have shown that adverse skeletal effects of vitamin A are demonstrable in rats where no clinical signs of toxicity are evident. Although the doses are many times the “RDI” for rats, it is likely that subclinical skeletal effects may arise at much lower doses."

"It has previously been assumed from animal studies that the antagonistic action between vitamin A and D in bone is weak, since it is evident at high levels of vitamin A intake (193-195). However, at marginal dietary intake of vitamin D, the antagonistic effects occur at lower vitamin A doses (197). In vitamin D-depleted rats with a marginal dietary intake of phosphorous or calcium, the negative effect of vitamin A on bone ash was aggravated when vitamin D was added to the diet, compared to controls with a vitamin D-deficient diet (156). These data suggest that at least in certain conditions of limited intake of vitamin D and calcium and/or phosphorous, the antagonistic effect on vitamin D and other fat-soluble vitamins may also be of importance."

"In humans, these indirect effects can possibly be more pronounced in the elderly, and in other individuals with poor intake of calcium and/or vitamin D. In Scandinavia, the average daily intake of vitamin D is below recommended levels in many groups (213-216) and the limited exposure to sunlight further increases the risk for hypovitaminosis D. I hypothesize that the high intake of vitamin A in Scandinavia may further aggravate the effect of hypovitaminosis D on calcium absorption and, possibly, contribute to the high incidence of osteoporosis."​

 

[Amazoniac]

Poisoned due to careless practices, but..

- Restricting vitamin A intake increases bone formation in Zambian children with high liver stores of vitamin

"Calcium intake may have protective effects on bone even when preformed VA intake is high [10]."

"The low serum calcium concentrations are notable. Dietary intake of children in this community was documented to be low using a database for US foods [11], but Zambia does not have a good reference for calcium in their local foods that would allow adjusting this database. Furthermore, vitamin D status was suboptimal. The combination of low calcium and vitamin D does not support optimal bone health and could affect markers of bone remodeling."​

 

[postman]

Poisoned due to careless practices, but..

- Restricting vitamin A intake increases bone formation in Zambian children with high liver stores of vitamin

"Calcium intake may have protective effects on bone even when preformed VA intake is high [10]."

"The low serum calcium concentrations are notable. Dietary intake of children in this community was documented to be low using a database for US foods [11], but Zambia does not have a good reference for calcium in their local foods that would allow adjusting this database. Furthermore, vitamin D status was suboptimal. The combination of low calcium and vitamin D does not support optimal bone health and could affect markers of bone remodeling."​

How the f do Zambian kids have vitamin D deficiency? Is there any population anywhere that has adequate levels of vitamin D according to mainstream allopaths?

 

[Amazoniac]

How the f do Zambian kids have vitamin D deficiency? Is there any population anywhere that has adequate levels of vitamin D according to mainstream allopaths?

Lack of enough calcium in the diet can be a contributor.

But what do you consider an adequate level?

Spoiler

 

[Amazoniac]

- Isotretinoin and intestinal inflammation: what gastroenterologists need to know

 

[postman]

- Isotretinoin and intestinal inflammation: what gastroenterologists need to know

Retinyl acetate and retinol also cause severe intestinal inflammation.

 

[Amazoniac]

- Retinoic acid is abundantly detected in different depots of adipose tissue by SERS

Retinyl acetate and retinol also cause severe intestinal inflammation.

What to expect from poisons?

 

[Amazoniac]

- Retinol saturase modulates lipid metabolism and the production of reactive oxygen species

 

[Tristan Loscha]

Isotretinoin has a Receptor-binding Pattern that differs from Retinol proper.
The Xtreme amounts taken combined with alternate ligand-receptor relationship
has power to explain such findings,resembling Retinol-deficiency.
But i know that you guys know. just my 2c.

 

[Amazoniac]

To be honest I don't know what it means for a vitamin to be unsaturated. In terms of PUFA, I understood it as unsaturated = unstable chemical bonds so prone to rancidity upon exposure to heat, but I don't think vit A is toxic in the same way that PUFA is even though it's unsaturated.

That's because we wouldn't dare to eat grams of it a day (Saturazione, 2017).

This trash has 5 conjugated (alternated) double bonds. For a chain that aren't fully hydrogenated, having the hydrogens also alternating throughout where there are gaps (all-trans poisonol) straightens the chain, otherwise it bends (as in 9-cis poisonol, the number being the carbon position where it occurs).

- Vitamin A2 - Wikipedia
- Anti-Peat - Grant Genereux's Theory Of Vitamin A Toxicity

Below they suggest 1.5 mg of natural Dio-tocopherol for every gram of pentaenoic acid. There is a double bond in the ring and I don't know how it's affected. Poisonoids should also be more carefully protected. But if 2 mg of Dio-tocopherol was needed to stabilize a gram of it, you'd have to adjust for a consumption of someting like 1.5 mg of poisonol equivalents a day.
- Balancing Vitamins A And E

However, Raj suggests an arbitrary amount of 70 mg to prevent its destruction, which shows you how nasty this stuff is. Extremely toxic!!1

 

[Amazoniac]

Some time ago franko mentioned feeling unwell after eating contaminated foods after a while of avoidance. If it's not a learned reflex to them for being triggers to inflammation, there are alcohol-metabolizing enzymes already expressed in the stomach that may somehow inappropriately act on tiny amounts of poisonoids that are found free or are being liberated from the meal, maybe it also signals the release from liver that was conserving (?) it.

 

[Rafael Lao Wai]

Let's fully hydrogenate vitamin A to make it more saturated.

 

[Amazoniac]

Let's fully hydrogenate vitamin A to make it more saturated.

But that's what makes it useful. Will wrote a lot about this principle.

One must not forget the ease with which some aromatic hydroxyl compounds change to quinones, or even exist as both forms in equilibrium in solution and in the solid state. Since as we will describe, the quinone group can conduct chain reactions and liberate energy quite perpetually, and through its fluorescent properties this group is like other unsaturated unions between atoms and can appropriate exothermic energy evolved in its environment and either use it for activation of its own chemical processes, or hand the energy on to a suitable acceptor that can so use it, we have in these properties all that is necessary to make a virus of a suitably constructed molecule.

For example, the contaminated eyes rely on its unsaturation to rotate/bend when light hits the retina (11-cis to all-trans poisonal).

 

[Rafael Lao Wai]

But that's what makes it useful. Will wrote a lot about this principle.

​

For example, the contaminated eyes rely on its unsaturation to rotate/bend when light hits the retina (11-cis to all-trans poisonal).

I was half-joking, but thanks for the explanation. Very interesting.