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

[Tarmander]

+ vitamin C supplement right?

did he stop using olive oil?

Not according to the interview I did with him yesterday. It will be up next wednesday.
Edit: I think he has tried things like brazil nuts and olive oil but his current diet is the five things.

 

[Blossom]

Not according to the interview I did with him yesterday. It will be up next wednesday.
Edit: I think he has tried things like brazil nuts and olive oil but his current diet is the five things.

Thanks for doing the interview. I’m looking forward to listening.

 

[postman]

Grant has five things he eats with an occasional apple: Beef, Rice, Black beans, water, salt

He said the first year on his diet he ate nothing but rice and beef.

 

[Amazoniac]

Interesting. Aren't you worried that dropping stuff like fruits will reduce your glucaric acid? Dr Garret Smith thinks that it's really important for getting rid of retinoic acid that's why he created a superfood list. Apples and cauliflower and many fruits are on the top of that list so that's why I include one serving at least of a superfood daily. Also mushrooms have zero vitamin A. Cacao makes me feel bad and increases my detox symptoms considerably.

Dr. Smith's public post about glucaric acid vv

Glucarate/glucaric acid

You're just being volunteer guinea pigs for someone that has no clue about what he's doing. This is something to would do the worry about instead, but also the lines from the graph on the previous page for looking like scary tentacles.

- Calcium-D-Glucarate | Thorne Research

- d-Glucaric acid content of various fruits and vegetables and cholesterol-lowering effects of dietary d-glucarate in the rat
- Effect of calcium glucarate on β-glucuronidase activity and glucarate content of certain vegetables and fruits

- The Influence Of Intestinal Bacteria Upon The Thyroid Gland (1923) "gluc"

- Ray Peat Email Exchanges - Ray Peat Forum Wiki "gluca"

If the body fails for whatever reason to glucuronide it, it has multiple backup routes for excretion that won't require this. Recycling of what's eliminated in bile is a normal process, it can happen to other forms as well, the way to prevent reabsorption is not through such compounds, it's by having some fiber in the diet and avoiding constipation.

The guy posts random links that support both poisonoids and glucarates as therapeutic agents with some similar properties. In considering useful the application of glucarates, he has to be validating retinoids as well; they weren't being employed to curb the damage of poisonoids, but to amplify their effect in lower doses so that toxic amounts aren't needed.

 

[Amazoniac]

In one of the experiments he posted, calcium glucarate was added to the diet in a concentration of 1.8%.

- Third study on the food consumption and eating habits of the French population | ANSES (I could've picked a worthless country instead, but this was the most convenient result)

"On average, French people consume 2.9 kg of food per day, i.e. around 2200 kcal, 50% of which come from beverages."​

- Contribution of Water from Food and Fluids to Total Water Intake: Analysis of a French and UK Population Surveys

If a person consumes 800 g of dry food a day, it would require the equivalent of 8 g of glucarate a day.

From the second link above, there can be 600 mg per apple (not discounting the core weight) and 250 mg in a cup of cauliflower (wow is leaching?), pushing the values high for these two major non-contaminated sources, but please verify if values are correct.
You can argue that those were therapeutic ranges, but why is it being used to make a case?

It was probably something like: 'me spots glucuronidation as excretion, me remedies it'.

- Retinoyl β-Glucuronide: A Biologically Active Interesting Retinoid


For you to admit what he proposes, you have to be operating under the assumption that it's somehow impacted in the body (when not occult and evading immunity). And if this is enough to sustain the inflammation in spite of a diet that's adequate in all other aspects, why would you 'ramp up' detox instead of allowing it to be disposed in a more controlled manner over time?

The elevation of calcitriol in autoimmune conditions is followed by a lowering of calcidiol. Why can't it happen with retinoic acid as well regardless if the body is struggling to eliminate it? Just because one of the metabolites is high, doesn't mean that everything is. And what if this increase is to maintain a reasonable ratio between them? How does it start?

If you have a latent infection and you pound only poisonoids without broad support, it's possible that you'll select microorganisms that can withstand or thrive on whatever it induces. Mucosal problems are common in this thread: gut, lungs, skin. If I'm not wrong, Grant has mentioned severe IBS. When you can't get rid of the problem, you have to adapt and learn to live in peace with it, so why this tolerance only develops once poisonoids are out? There's the heightened response, but is it maladaptive or doing what it should? What are the long-term consequences of immunosuppression and being too permissive (ignoring other consequences)?

Table 2 here provides an estimation of total body stores, about 590 mg of poisonol. It can take a loong time to run out of it in someone whose rate of utilization is low for whatever reason. Perhaps it applies to people like Grant that have a conditions in which its metabolism is affected, tending towards conservation irrespective of needs. Regarding the tentacle graph, the slowest utilization reported at the end was 0.05 mg/d, imagine how long it could last if it didn't decreased much throughout depletion, especially if he started from a place of accumulation if his consumption wasn't matching the excretion. Regardless of what it is, it's something else that needs to be fix'd, there is nothing inherited wrong with the poison, living in persimmon is just a risky band aids solution.

Is the consumption of broth bone encouraged since calcium supplementation is not? How else can you be getting enough of it in this inflammatory state if a variety of good sources are excluded? Dairy is unsuitable for human consumption, leafy greens are toxic, what are you left with? Beans? The poison depletion must help in preserving it, but I think that the deprivation might eventually be narrowing your choices where the solution that offers no challenge is to extend the deprivation by eating less food, suppress more and slow down further, etc. The risk is not only in developing problems in the longer-term, but in case of an adverse event that requires fast use of resources for correction.

I wonder if some gurus here had a past of chronic elevation of paratyphoid hormone.

If you're consuming plenty of calcium in the diet, even when it's being excreted without much use, there will be the signal to stop bone dissolution from excess poisonoids since no more is needed in circulation. It should also help in easing inflammation.


How is iodine in this story given that weaseeds is out of the question?

What about protein that makes it protective in these cases? In other words, if this was a stacking tower game with the entire complex being a protein, which blocks would you take out first and vvhv?


- Light | plantphys.info

Spoiler

- Chlorophyll Or Chlorophyllin

 

[Amazoniac]

does anyone know if vitamin A has a oxidation temperature given that it’s unsaturated or does it not oxidize in the same way as a unsaturated fat does

- Factors Influencing the Chemical Stability of Carotenoids in Foods

I haven't read about this in details because it was intimidating. The simpler part is comparing before and after to find out how much remains intact, but it's more challenging to know what it's being degraded to.

"[..]although mucus plays a critical role in protecting the intestinal barrier, vitamin A has a negative effect on mucus production by goblet cells, which conversely increased under VAD conditions (160). Enhanced mucus production is further promoted by IL-13 produced by the expanded ILC2 population in the absence of vitamin A (160). Therefore, although an insufficiency of vitamin A greatly impairs the adaptive Th2 response, it equally increases the passive barrier protection and the innate ILC2 response and thus maintains or even increases control of nematode infections (160) (Figure 3)."

- Nutrients direct immune balance

"So, what is the benefit of shifting to an enhanced ILC2-mediated response during vitamin A deficiency? ILC2s have an important role in protection against nutrient-consuming helminth infections. Indeed, the authors [link below] found that, compared with controls, both vitamin A-deficient mice and mice treated with retinoic acid inhibitors exhibited enhanced protection against infection with Trichuris muris.

This enhanced protection was associated with an increased frequency of IL-13-producing ILC2s and was independent of adaptive immune cells. Furthermore, as type 2 immunity is associated with tissue repair and increased mucus production, this could improve barrier integrity.

This study shows that nutrient deficiency is not associated with a global immunosuppression, but instead can result in the specific activation of a distinct branch of barrier immunity. Furthermore, it emphasizes the role of ILCs as important mediators of intestinal immune homeostasis."​

- Adaptation of Innate Lymphoid Cells to a Micronutrient Deficiency Promotes Type 2 Barrier Immunity (!)

 

[Pompadour]

In the last publication (Adaptation of Innate Lymphoid Cells to a Micronutrient Deficiency Promotes Type 2 Barrier Immunity), the authors say that low vitamin A makes body to switch to Type 2 immunity and "Type 2 immunity and in particular IL-13 is associated with tissue repair, increased mucus production, and physiological responses all aimed at reinforcing barrier integrity and defense".
Can this switch be beneficial in some health conditions? Maybe that is wgy people feel better on low A diet?

 

[thomas200]

Gave in last night.
had (a LOT of) cereal, cheese cake, and burrito w/ guac&cheese. I don't feel as bad as i expected too though. My sleep was slightly worse but still good overall

 

[schultz]

I'm surprised Grant does not take this opportunity to do additional blood testing. I know he says that it's not possible in Canada, but he could travel to the United States and order almost any test he wants.

I live in Canada. A friend of mine goes to an independent lab to get his hormones and stuff tested. I think it's relatively new but I don't remember the name of it.

It's because the truth is in it.

You're right, @Amazoniac has posted quite a bit.

 

[Amazoniac]

In the last publication (Adaptation of Innate Lymphoid Cells to a Micronutrient Deficiency Promotes Type 2 Barrier Immunity), the authors say that low vitamin A makes body to switch to Type 2 immunity and "Type 2 immunity and in particular IL-13 is associated with tissue repair, increased mucus production, and physiological responses all aimed at reinforcing barrier integrity and defense".
Can this switch be beneficial in some health conditions? Maybe that is wgy people feel better on low A diet?

But I guess that's in response to becoming susceptible from the nutrient deprivation: it's a bright side of a delicate situation (and without considering other functions that can be compromised). Given that people here notice improvements after a few days of decontaminating their diets, it can't be the main explanation, however it wouldn't be surprising if this solution of avoiding the heightened reaction involved some sort of immunosuppression.

From the first link:

"As ILC3s are important for the immune response against bacterial infections, the authors examined the effect of vitamin A on immunity to Citrobacter rodentium infection. Both wild-type vitamin A-deficient mice and mice treated with the retinoic acid inhibitor showed increased susceptibility to infection compared with control mice."​

And the entire part from the second:

"A corollary of our findings is that differential levels of vitamin A could promote different classes of barrier immunity with physiological levels of vitamin A associated with ILC3 responses, while reduced levels associated with enhanced innate type 2 immunity. Indeed, both WT VAI mice and mice treated with RAi displayed enhanced susceptibility and pathology to C. rodentium compared to control mice, a phenotype associated with impaired Th1, Th17 and ILC3 responses (Fig. 3A–D and Fig. S18A–E). Treatment with RAi of Rag1−/− mice in which ILC are the dominant source of IL-22[22] dramatically increased pathology and mortality following infection, an effect reversed by exogenous delivery of IL-22 (Fig. 3E–K). This observation provides a potential explanation for the profound susceptibility to gastrointestinal bacterial infections observed in children suffering from vitamin A deficiency[23,24]."

"Our work suggests that vitamin A and its metabolite RA, functions as a dietary alarm signal allowing the host to immunologically respond to its nutritional state. Contrary to the current paradigm, we show that nutrient deficiency is not associated with global immunosuppression but rather can selectively activate a distinct arm of barrier immunity. Notably we found that ILC2 act as primary sensors of dietary stress able to compensate for the collapse of adaptive immunity in settings of nutrient deprivation. Type 2 immunity and in particular IL-13 is associated with tissue repair, increased mucus production, and physiological responses all aimed at reinforcing barrier integrity and defense[33,34]. Further enhanced type 2 responses are clearly beneficial in the context of exposure to worms that have been partners throughout human evolution and still represent the major form of parasitic infection worldwide. Since nematodes compete with the host for nutritional resources reinforcement of anti-helminth immunity can provide a substantial advantage to the host. Thus, in settings of malnutrition, a rapid switch to type 2 barrier immunity imposed by vitamin A deficiency may represent a powerful adaptation of the immune system to transiently promote host survival in the face of dominant barrier exposures. Such a strategy leaves the host vulnerable to potential encounters with acute diarrheal pathogens but could provide a survival strategy to temporarily reduce the pressure from its constitutive evolutionary partners, worms and commensals, in settings of nutritional deprivation."​

By the way, there's an impostor around: @Pompidoux.


--
- The Importance of Meeting Calcium Needs with Foods

Spoiler: Terma has good posts, by expanding you agree

 

[Keon]

of course

Where can we find the interview?

 

[Pompadour]

By the way, there's an impostor around: @Pompidoux.

:)

 

[Tarmander]

Enjoy

https://quaxpodcast.com/2019/08/ep-26-interview-grant-genereux-vitamin-a-is-a-poison/

Edit: If you look up 'Quax' on any podcast player you can get it there too

 

[postman]

Enjoy

https://quaxpodcast.com/2019/08/ep-26-interview-grant-genereux-vitamin-a-is-a-poison/

Edit: If you look up 'Quax' on any podcast player you can get it there too

nice, good job

 

[thomas200]

anyone have info on food poisoning if it speeds up/slows down detox?

i think i mightve eaten some bad beef..

 

[Amazoniac]

Enjoy

https://quaxpodcast.com/2019/08/ep-26-interview-grant-genereux-vitamin-a-is-a-poison/

Edit: If you look up 'Quax' on any podcast player you can get it there too

Guru, thanks you for sharing. You sound human, no offense. He seems to be a cool dude.

I wished this podcast was aired around the time that they were discovering it in retina, could've spared George Wald and Otto Warburg of fruitless research. Given that he received a share of the Nobel prize in 1967 for it, invalidating their work will be a big deal. Little did they know back that it's a matter of poison affinity for the eye.
- Visual Pigment Molecules and Retinol Isomers: the Work of George Wald

He mentioned something about original experiments being worthless based on an idea that insidious poisonoic acid in casein somehow killed the animals. This form is used nowadays to keep lab animals relatively functional in spite of critical reserves, so that at any moment that they decide to remove it, there's rapid induction of issues, leaving less margin for adaptation for example.

Grant barely takes what he proposes seriously (with the exception of pushing through his limits), so there isn't much to comment. According to his words, it's a toxin but the body must have evolved means to handle it.

 

[postman]

I wished this podcast was aired around the time that they were discovering it in retina, could've spared George Wald and Otto Warburg of fruitless research. Given that he received a share of the Nobel prize in 1967 for it, invalidating their work will be a big deal. Little did they know back that it's a matter of poison affinity for the eye.

So I assume you make sure to get extra PUFAs because how essential they are to the brain?

 

[Amazoniac]

So I assume you make sure to get extra PUFAs because how essential they are to the brain?

How low you can go on each without getting compromised? Excluding exceptional cases.

 

[Amazoniac]

- Anti-Peat - Grant Genereux's Theory Of Vitamin A Toxicity
⮤ [23] Control of oxidative phosphorylation by vitamin A illuminates a fundamental role in mitochondrial energy homoeostasis

"The physiology of two metabolites of vitamin A is understood in substantial detail: poisonaldehyde functions as the universal chromophore in the vertebrate and invertebrate eye; poisonoic acid regulates a set of vertebrate transcription factors, the poisonoic acid receptor superfamily. The third member of this retinoid triumvirate is poisonol. While functioning as the precursor of retinaldehyde and retinoic acid, a growing body of evidence suggests a far more fundamental role for retinol in signal transduction. Here we show that retinol is essential for the metabolic fitness of mitochondria. When cells were deprived of retinol, respiration and ATP synthesis defaulted to basal levels. They recovered to significantly higher energy output as soon as retinol was restored to physiological concentration, without the need for metabolic conversion to other retinoids. Retinol emerged as an essential cofactor of protein kinase C (PKC), without which this enzyme failed to be activated in mitochondria. Furthermore, retinol needed to physically bind PKC, because mutation of the retinol binding site rendered PKC unresponsive to Rol, while retaining responsiveness to phorbol ester. The PKC/retinol complex signaled the pyruvate dehydrogenase complex for enhanced flux of pyruvate into the Krebs cycle. The baseline response was reduced in vitamin A-deficient lecithin:retinol acyl transferase-knockout mice, but this was corrected within 3 h by intraperitoneal injection of vitamin A; this suggests that vitamin A is physiologically important. These results illuminate a hitherto unsuspected role of vitamin A in mitochondrial bioenergetics of mammals, acting as a nutritional sensor. As such, retinol is of fundamental importance for energy homeostasis. The data provide a mechanistic explanation to the nearly 100-yr-old question of why vitamin A deficiency causes so many pathologies that are independent of retinoic acid action."

"The accumulated evidence presented in Figs. 1–4 indicates the existence of a signal pathway anchored by the complex of PKCd and retinol that controls pyruvate utilization by the PDH complex. The capacity of retinol to prime PKCd for activation by redox action is strongly supported by the evidence that retinol must be present in the medium and must physically bind PKCd. Mutation of the retinol binding sites located in the zinc-finger domains (39) silences the PKCd signal pathway. Of considerable interest, although at first glance counterintuitive, is the lack of selectivity of PKC for retinoids, allowing several natural retinol metabolites to act as coactivators as well. Their binding was predictable because the affinity of PKCd zinc-finger domains for retinol, retinoic acid, and anhydroretinol was known to be similar in magnitude (7). However, functional selectivity is established by bioavailability, retinol being the only retinoid systemically available at the concentration needed to drive PKCd activation. Retinol circulates in plasma at a constant concentration of 1 to 2 uM, matching the effective dose of 2 uM required for PKC coactivation. Other retinoids (e.g., retinoic acid) circulate at concentrations 3 orders of magnitude lower or not at all (anhydroretinol and retinal) (40). Further evidence that retinol is active in the PKCd signal path, regardless of whether other retinoids can mimic retinol in pharmacological experiments, was the responses of isolated mitochondria in short-term experiments when reaction times were too brief to permit appreciable metabolism of retinol. In fact, no metabolites were detected in isolated mitochondria or MEFs incubated for 15 min with retinol (Fig. 2B). It is also important to recall that retinol functions as a survival factor (26, 41). In contrast, despite initial stimulation of the PDH complex, the exposure of cells to anhydroretinol for longer than 2 h causes a fatal energy crisis (13)."

"Bioenergetics is fundamental to all cells (46). In view of this tenet, it is puzzling why metabolic regulation by the pathway described in this report depends on retinol that vertebrates cannot synthesize de novo. In limiting vitamin A to nutritional sources, there must be an evolutionary advantage of such import as to override the physiological needs for vitamin A in vision and retinoic acid-dependent transcription. The answer may lie in the scenario that finite amounts of vitamin A are subject to depletion during periods of severe starvation when an organism is forced to conserve energy. Our observation that in the absence of vitamin A energy generation by respiration adapts downwards appears relevant in this context. Accumulation of triglycerides in the livers of vitamin A-deficient mice (47) may also signify a metabolic switch to fat for energy generation to offset limited utilization of pyruvate from glycolytic sources. It is also predictable that chronic deviations of vitamin A transport will lead to metabolic disease. Recent observations that the circulating levels of retinol binding protein 4, the major transporter of vitamin A in plasma, are elevated in obesity illuminate this point (48)."​

Not bad for a toxin.

@postman, if it was possible to extract all poisonoids and the PUFAs that you have in mind from the body, knowing that your dietary intake was going to be null afterwards for one of them, which would you pick? In the worst case of both being toxic, with those oils you can at least compensate with synthesis.

--
- Infection and Autoimmunity: Chapter 10. Infection, Autoimmunity, and Vitamin D (Marshall alert)

"The standard of care for most autoimmune and inflammatory conditions is immunosuppression. Commonly used immunosuppressive treatments include corticosteroids, methotrexate, and tumor necrosis factor-Diokine antagonists. While these therapeutic options often provide short-term symptom palliation, they have poor long-term associations with stability and relapse. Indeed, no definitive studies have identified corticosteroids capable of enhancing long-term prognosis or reducing mortality rates. For example, Gottlieb et al. reported that in sarcoidosis, steroid use leads to relapse and contributes to prolongation of disease by delaying resolution.[54] To date there have been nearly 150 clinical trials testing prospective agents designed to block inflammation in patients with sepsis, and all have failed.[55]"

"Most immunosuppressive medications were developed to slow what is historically believed to be an overactive immune response [might be]. However, as the inflammation and autoantibodies associated with these conditions are becoming increasingly tied to infection, the efficacy of these drugs must be reexamined. By slowing the immune response, immunosuppressive medications cause a decrease in inflammation and cytokine release. While this decrease in inflammation may allow a patient to feel better in the short term, the immune system may well become compromised to a point where it can no longer correctly maintain microbiome homeostasis. This exacerbates the underlying disease state and leaves patients more vulnerable to the acquisition of new pathogens."​

--
The claim that there's no 'global immunosuppression' is repeated here:
- The Science Behind The Coimbra Protocol

 

[Tarmander]

Guru, thanks you for sharing. You sound human, no offense. He seems to be a cool dude.

I wished this podcast was aired around the time that they were discovering it in retina, could've spared George Wald and Otto Warburg of fruitless research. Given that he received a share of the Nobel prize in 1967 for it, invalidating their work will be a big deal. Little did they know back that it's a matter of poison affinity for the eye.
- Visual Pigment Molecules and Retinol Isomers: the Work of George Wald

He mentioned something about original experiments being worthless based on an idea that insidious poisonoic acid in casein somehow killed the animals. This form is used nowadays to keep lab animals relatively functional in spite of critical reserves, so that at any moment that they decide to remove it, there's rapid induction of issues, leaving less margin for adaptation for example.

Grant barely takes what he proposes seriously (with the exception of pushing through his limits), so there isn't much to comment. According to his words, it's a toxin but the body must have evolved means to handle it.

I am indeed Human.

There are many inconsistencies here.

such as: The Adverse Effects of Alcohol on Vitamin A Metabolism

It seems that the true path to retinol destruction is whiskey. So we would assume that alcoholics have very low rates of auto immunity right? Yet things are unclear, even in that paper.

So lots of things need explaining eventually.