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

[Anders86]

I'm not sure what you have in mind, but since most of the substances that you listed don't just lower serotonin directly, they could eventually address the cause of diversion of nutrients and normalize those. Extra folate along with the other B-vitamins that you plan to take isn't a quick fix, it's part of a sustainable approach in my opinion.

There are various aspects to consider that could make them fail. Example, if someone consumes 50 g of collagen a day with the suggestion of making it a decent portion of your protein intake, how could it not lead to argininosis? Are there factors in meat (such as zinc) that when consumed together prevent this? Will these be included when it's consumed in itolasion? Are there contaminants in case it's a collagen product (such as fluoride)? And so on.
It's preferable to only include the next set when you've familiarized with one of them, otherwise the chances of becoming impractical increase markedly.

Yeah I'm sorry I wasn't all that clear. When I feel I have high Homocysteine I feel sluggish, constipated and edematous. If I take Folate or TMG I usually get an acutely liver flush and lowered Homocysteine resulting in acute bowel movement, mood lift, less bloat etc. But these effects do not apply to chronic use.

Diet is 2-3L 1% Milk, 1,5-2L OJ, 60-80g Collagen, 2 Eggs, 30-40g Coconut Oil, 0-15g Cacao Butter and about 150g Sugar.

It should fit someone with MTHFR, but gut is hard to balance and keep balanced. Often when I feel discomfort in gut I also feel discomfort in the state of now, making me think serotonin has been a bigger factor for my gut/health than I realized, and probably deserves as much attention as estrogen. A body low on estrogen and serotonin should keep liver and gut flowing, but an imbalance would keep liver and gut shut either high in estrogen or serotonin.

Progesterone and Vitamin E does wonder for my estrogen, but my body cloggs way to easy under stress and then estrogen rises sharply again, and I feel it`s because of my gut stopping as Serotonin is being produced, increasing endotoxin and this negative loop starts yet again.

So I`m going to focus heavily on an anti serotonin and anti estrogen regime, hopefully giving me a flow state I would believe would benefit methylation and regulate homocysteine levels. I`m also curious on how effective the anti fibrotic effects from Meterogoline and Lisuride can be. And I`m dropping DHEA..

Sorry to drop these awkward posts on you @Amazoniac but I always appreciate your comments

 

[thomas200]

decided to cheat and ate 3 big slices of pizza. Hope i don't feel like death tomorrow

 

[Blossom]

decided to cheat and ate 3 big slices of pizza. Hope i don't feel like death tomorrow

Let us know! On Father’s Day I ate homemade lasagna as a guest which someone made Gluten free especially for me. I thought everything was going to be fine but after 24-48 hours it was obvious that I should probably not do that again! It wasn’t too bad -my gut seems to have healed a lot in the past year but it still doesn’t seem optimal for me.

 

[Cirion]

I had wondered if Mexican Coke contained vitamin A but didn’t investigate. I just don’t drink it anymore.

Yeah I mean even if it doesn't have VA, in my opinion mexican cola is too much liquid for the calories. Excess liquid seems problematic in its own ways. I prefer juice concentrate with a tiny added bit of water because this is the only way to get liquid calories with only a few oz of liquid.

 

[Cirion]

White grape juice would be a lot lower than concord. It also depends on the threshold one aims for. While I have stopped worrying about going super low A, I do find that colorful fruits and vegetables (esp vegetables) are bad for me metabolically and generally avoid them. Tomatoes and berries are exceptions for me I don't notice such a bad response from those. Liver pate was fine for a few times, but I got tired of it fast. I don't crave it anymore so I do not eat it. I think that not everyone as the same needs for each vitamin/mineral and that you have to figure out for yourself how to properly support your body chemistry.

What is white grape juice anyway? I have never seen a white grape before?

But, that's good to know. Maybe I'll try to find some white grape juice so I can keep drinking grape juice but lower VA further.

Yeah veggies often can have VERY high VA, so even if just moderate reduction is the goal, veggies aren't really compatible with this.

Crazy, because a very high end facility I used to go to regularly (We're talking $10,000-almost $100,000 a yr depending on level of care) advised lots of colorful fruits and veggies. Shows that even "best of the best" nutritional "experts" think eating ultra high VA is the solution to health issues. I'm almost definitely cancelling my contract with them (mostly focusing on personal training) as even just that is almost $4,000 a yr... that's $4,000 I could be investing/saving anyway. To be honest, my current personal trainer is lackluster too anyway, he is rather thin and lanky and even he has admitted he is not happy with his androgen levels. Lol, this was the same trainer who thought I was on steroids the last time I was in optimal health and increased my bench by 50% (Not newbie gains BTW) in one month lol via actually applying a lot of "Peat" principles like high carb intake. The truth is, "once the apprentice now the master" to quote Darth Vader in this case, when you know more than your trainer, its time to move on LOL.

As Robert Kiyosaki said in his book rich dad poor dad - Listen to people who have DONE what you want to do only... not those who don't do what they preach...

I was just thinking more about the whole VA thing and liver health and a light bulb went off further - I had already mentioned that the liver has a max storage capacity for toxins. What if it has a max storage capacity for everything including beneficial things like glucose but that toxins can invade the glucose storage space? I am wondering if the liver actually has a priority for toxins over glucose in a desperate attempt to keep the body from being poisoned at all costs, even at the cost of storing fuel. This would help explain why once the liver is extremely toxic, you have lost your ability to store glucose and thus can not even fast more than a couple hrs without a stress response, and thus as VA (and/or other toxins) are finally purged, you finally can store glucose again and things finally start to improve in your whole body as cellular glucose and CO2 is finally normalized and thus the "180 degree turn back to good health" finally begins. Ray has suggested the liver actually has the max potential of 12 or even 16 hrs fasting with no stress response, in a perfectly healthy individual, presumably with an extremely healthy liver. Doing some thought experiments this would suggest that the liver has a total storage capacity for ALL things, whether its bad things (toxins), or good things (glucose). The more toxins that are removed, the more good stuff we can store (glucose) and that there is no dedicated storage site for toxins vs. glucose (what I originally thought was the case). Now it all makes sense to me why purging the toxins is of critical importance, because not only are toxins bad in general (poisoning the body) but they are also removing fuel from your body! A double health whammy. I am just glad I don't drink alcohol now LOL.

In addition, I've also opted for a virtually zero fat diet not just to avoid fat soluble absorption but also to de-fat the liver.

 

[Amazoniac]

Does isotretinoin have effect on vitamin D physiology and bone metabolism in acne patients?

Spoiler

"Kang et al. showed that addition of 9-cis-RA or all-trans-RA to 1,25(OH)2D caused a synergistic increase in 24-OHase mRNA in human skin (20). The stimulation of CYP24A1 with the treatment of isotretinoin may explain the fall in 25OHD levels in the present study. The decrease in 25OHD would ultimately lead to a decrease in serum Ca and increase in serum PTH and BAP levels. The increase in the levels of 1,25(OH)2D in our study may be caused by the stimulation of CYP27B1 by increased serum levels of PTH."

"[..]isotretinoin causes a status similar to osteomalacia in acne patients with only 3 months of treatment."

 

[thomas200]

Let us know! On Father’s Day I ate homemade lasagna as a guest which someone made Gluten free especially for me. I thought everything was going to be fine but after 24-48 hours it was obvious that I should probably not do that again! It wasn’t too bad -my gut seems to have healed a lot in the past year but it still doesn’t seem optimal for me.

Surprisingly woke up feeling energized, even with only 3 hours of sleep (woke up because of an earthquake), and just felt good overall throughout the day. I haven't felt any negative effects of the pizzas but probably because it was a one time thing

I went ahead and got about 3 hours of sun in total today. ive been feeling great the whole day, i'll continue with about an hour a day and update on how i feel

Edit: just realized how many times i said "day" in that lol..

 

[thomas200]

In addition, I've also opted for a virtually zero fat diet not just to avoid fat soluble absorption but also to de-fat the liver.

Wait don't you need fat to dump A??

 

[Cirion]

Wait don't you need fat to dump A??

All I know is that I don't do well with dietary fat in my diet in regards to temps/pulses or overall mood/energy levels.

 

[RWilly]

I'm thinking that people with high iron may be more susceptible to vitamin A toxicity.

"The results reveal that the low serum 25-OHD concentration in patients with hemochromatosis is directly related to the extent of iron loading and it is improved by venesection therapy." Low serum 25-hydroxyvitamin D in hereditary hemochromatosis: relation to iron status. - PubMed - NCBI

Low vitamin D puts vitamin A out of balance.

I think we can thank iron fortification for many of these issues.

 

[RWilly]

All I know is that I don't do well with dietary fat in my diet in regards to temps/pulses or overall mood/energy levels.

Ditto.

 

[Cirion]

So, looking more into mexican colas - I think I found a reason to stop drinking them even besides the possibility of vitamin A. Phosphoric acid. Amazoniac has a thread talking about how negative aminos, salt, and phosphoric acid are the three primary causes of acidity in the body. I am quite certain I am quite acidic, so, I think it's time to shelve the colas. I also have a lot of salt, which probably also needs to stop, but maybe I'll replace it with some baking soda so I do still get sodium.

 

[RWilly]

So, looking more into mexican colas - I think I found a reason to stop drinking them even besides the possibility of vitamin A. Phosphoric acid. Amazoniac has a thread talking about how negative aminos, salt, and phosphoric acid are the three primary causes of acidity in the body. I am quite certain I am quite acidic, so, I think it's time to shelve the colas. I also have a lot of salt, which probably also needs to stop, but maybe I'll replace it with some baking soda so I do still get sodium.

Keep in mind that salt has to be balanced with potassium.

 

[Cirion]

Keep in mind that salt has to be balanced with potassium.

I don't think it's that simple. I frequently get 10 grams of potassium a day after all.

More accurately, sodium must be balanced with potassium. There's a major problem with salt, and its the chloride aspect, not so much sodium. Plus from what amazoniac wrote in his thread, chloride is 3x more absorbable than sodium in the form of sodium chloride.

So from now on I'm probably gonna focus on sodium bicarbonate (baking soda) for my sodium needs.

I don't think any amount of potassium can balance out the phosphoric acid, sulfur, or chloride if the intake of one or all 3 is too high.

 

[Amazoniac]

All varies, but..

Desirable intake:
- Poison A: 800 mcg PAE/d
- Venom D: 50 mcg/d

Total body stores:
- Poison A: 590,000 mcg (from one of the linked articles)
- Venom D: 375 mcg (Vitamin D3 Distribution and Status in the Body)

Many factors affect their metabolism, but the contrast is starting nevertheless.


--
What follows is related to poison A behavior in the body (including reserves), a compartmental model originally proposed in the 19th century, 1998 to be more precise, and authors have been honing it since then.

- Development of a compartmental model describing the dynamics of vitamin A metabolism in men

They rely on radiolabel'd poison:
- Anti-Peat - Grant Genereux's Theory Of Vitamin A Toxicity (referenced in one of the articles as well)

In an experiment..

Plasma kinetics of vitamin A in humans after a single oral dose of [8,9,19-13C]retinyl palmitate​

..they poisoned volunteers with radiolabeled poisonyl palmitate, a single high-dose of it (30 mg, the equivalent to 16.5 mg or 55,000 IU of poisonol) to make it clearer for detection, so it already started bad because we know that this by itself carries its problems, yet it's still useful to have an idea of how the toxin behaves over time.

Information from a single participant judged to represent best the average response to the toxin was detailed.

Spoiler

Then, the researchers in question here, based on what's known about the metabolism of this toxin, attempted to develop a system identifying every step of the process according to changes in blood values described above, comparing its behavior, to finally predict its course. The goal was (and is) to be able to estimate the situational burden of a person without requiring extensive testing.

They propose multiple compartments, each representing one step in its metabolism, from mouth to long-term storage pool with a slow turnover. Storage is extravascular [] and mostly liver; there's also an extra compartment with faster turnover that doesn't contain much poison, they left this for last to either consider or disconsider it without affecting the rest (hence its dashed lines), it gains importance when the total body stores (TBS) are low. Search for "pool" here:

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

Both the slow and fast turnover pools exchange with blood, which is where they sample the radiolabel'd poisons. If blood remains relatively stable, whatever leaves the system has to be replenished by internal pools, which in turn is influenced by dietary intake, especially because it takes a while for the ingested dose to be reallocated, so it can be a confounder and it's the main theme of the following articles. When reasonable intakes of the poison are considered, the interpretation is affected so all values are modified, an example is the drastic drop in disposal r4t3 in the estimates.


Anyway, hopefully this saved some time in case you want to read them in detail.

- Addition of Vitamin A Intake Data during Compartmental Modeling of Retinol Kinetics in Theoretical Humans Leads to Accurate Prediction of Vitamin A Total Body Stores and Kinetic Parameters in Studies of Reasonable Duration

"Since model-based compartmental analysis (1) was first applied to study vitamin A kinetics in rats (2), and then later in humans (3), investigators have recognized the importance of study duration in the accurate prediction of model parameters. For example, if vitamin A total body stores (TBS) are high, very long experiments (∼400 d) may be required (4). When a study is found to be too short for modeling to accurately define the true terminal slope of the tracer response curve, model-predicted vitamin A disposal rate (DR) will be overestimated, as will vitamin A intake, because modeling as typically applied to the vitamin A system assumes a steady state (i.e., functional input equals output). Importantly, when DR is overestimated, vitamin A stores will be underestimated (4), both at higher and at lower levels of vitamin A status."​

↳ [7] Inclusion of Vitamin A Intake Data Provides Improved Compartmental Model-Derived Estimates of Vitamin A Total Body Stores and Disposal Rate in Older Adults

"In addition to study length and sampling protocol, there may be other ways to improve the identification of the terminal slope of the plasma retinol isotope response curve. Recently, a modeling challenge (specifically, a terminal slope that approached zero) that occurred during our work with López-Teros et al. in Mexican children (12) led us to the idea of using information on participants’ dietary vitamin A intake to constrain that slope to a non-zero value in the final steady state model. That is, because modeling, as it has been applied to the vitamin A system, assumes a steady state, constraining the value for input (dietary vitamin A intake × fractional absorption of vitamin A) also constrains the output. Reflecting back on the results of Cifelli et al. (10), we hypothesized that including an estimate of intake in the modeling data stream might provide the extra information needed to generate more realistic predictions of intake, DR, TBS, days of stores, and other kinetic parameters. Here, we reanalyzed the data from (17, 18) that were presented in (10) and demonstrate the advantage of including vitamin A intake data when modeling is used to estimate vitamin A TBS and DR in a kinetic study of less-than-optimal length. This approach enhances the power of model-based compartmental analysis for studying the kinetics of vitamin A and it can potentially be applied to other nutrients."

Spoiler: Table 2. Model predictions and estimated liver vitamin A for population data sets

1 µmol = 286 µg

1 EV: considering only the slow turnover extravascular pool
2 EV: considering the slow and fast turnover extravascular pools
2 EV DI: considering the slow and fast turnover extravascular pools and a reasonable dietary intake as PAE

I haven't gotten over the idea of the liver weight as 3% of body weight used for the calculations to define the current RDA.

↳ [10] Kinetic Analysis Shows that Vitamin A Disposal Rate in Humans Is Positively Correlated with Vitamin A Stores

"Because one of the determinants of the dietary requirements for VA is VA utilization, it is important to determine the factors that influence VA turnover and disposal. Previous work in humans and rats has demonstrated that different nutritional (5,6), environmental (7,8), and disease conditions (9–12) alter VA homeostasis. Studies in rats have established that, as VA intake and stores increased, there was a parallel increase in VA utilization (13). Similarly, Hicks et al. (14) reported that biliary VA disposal was higher in rats with high hepatic stores of the vitamin. When VA turnover was quantified in rats with low, marginal, and high liver VA stores by Green et al. (15), the results showed that VA disposal and turnover were different among the groups, suggesting that VA kinetics responds to changes in dietary VA intake. Finally, Kelley and Green (16) investigated the factors that influence VA disposal in VA-adequate rats under conditions of low VA intake. The authors showed that, if liver stores were adequate, VA disposal was not decreased to compensate for low VA intake as long as plasma retinol concentration was normal, suggesting that VA disposal is also influenced by plasma retinol concentrations."

"Although these studies have delineated some of the underlying mechanisms governing VA turnover in rats, only a few studies (17–19) have examined VA kinetics in humans. For instance, Sauberlich et al. (17) showed that VA disposal is related to total body stores, noting that both plasma VA concentration and utilization rate decreased during depletion to conserve VA when intake was low. More recently, von Reinersdorff et al. (18,19) utilized a stable isotope method to describe and quantify the absorption and metabolism of retinyl palmitate in men. A compartmental model developed to fit data for 1 of the subjects predicted that retinol recycling through plasma was substantially higher than the VA disposal rate (19), as has also been shown in rats (20)."

"In this study, both the Chinese and U.S. subjects were VA adequate. However, serum retinol concentrations were significantly higher in the U.S. adults than in Chinese adults. Based on these results, we hypothesize that, as VA stores increase, there is a parallel increase in serum VA concentrations, which results in increased VA disposal rate as observed in rat models (15,16). In contrast, as VA stores decrease over time, such as during VA deficiency, there will be a decrease in serum retinol concentrations that will result in decreased VA disposal rate to conserve VA. This hypothesis is supported by the findings of Sauberlich et al. (17), who showed that both plasma retinol concentrations and disposal decreased over time during VA depletion. Thus, differences in VA nutriture will lead to changes in VA kinetics that will alter VA disposal rate to either conserve VA (VA deficiency) or prevent excessive accumulation of VA (VA sufficiency) even when VA levels are adequate."

"[..]a variety of techniques have been employed to attempt to determine the effect of dietary VA and VA status on the turnover and disposal of VA so that dietary requirements may be accurately estimated. Because the recommended daily allowances are set to meet the requirements for nearly all healthy individuals in a given age and gender group, this study was conducted to better understand VA kinetics in 2 groups of well-nourished individuals (Chinese vs. Americans). To our knowledge, this is the first study to use model-based compartmental analysis to examine whole-body VA kinetics for the purpose of determining the effect of VA stores on VA turnover and disposal rate in humans. The results of our work demonstrate that VA disposal rate is strongly associated with VA stores, suggesting that VA stores are a major determinant of VA disposal rate in well-nourished humans."

Spoiler: Figure 4A

The greater the reserves, the higher the disposal rate tends to be.

 

[Amazoniac]

On the labeled carbons:

- Retinoid Nomenclature

- The Biology and Chemistry of Lutein and Zeaxanthin
- Beta-carotene 15,15'-dioxygenase - Wikipedia

 

[RWilly]

Also, it looks like hepatic copper and hepatic vitamin A stores may have an inverse relationship.

Modification of vitamin A metabolism in rats fed a copper-deficient diet. - PubMed - NCBI

 

[Amazoniac]

I forgot to add that the Disposal Rate in Table 2 above is 75% of the supposed amount ingested, so they assume a 'steady state' where whatever is irreversibly lost is being replenished. This ties in with the odservation of increased or decreased disposal depending on the burden of the person.

--
Just because the water becomes pigmented after a herb infusion, doesn't mean that contaminants are responsible for it, and when they is, it must not be a lot. Using whole leaves and a thicker filter should protect the water further. It's worth trying the broths as well.

- Identification, quantification and availability of carotenoids and chlorophylls in fruit, herb and medicinal teas

"For the infusion studies, selected on the initial screening results, 25 teas were used to make infusions (Fig. 5). Only lutein was detected in the infusions; chlorophylls, chlorophyll degradation products, and other carotenoids were not detected in any of the infusions. These pigments are known to have poor solubility in cold water, but this study also shows that they are essentially insoluble in hot water as well."

"It is clear that high pigment content in the dry teas (Fig. 1) does not mean high pigment release into the infusions. It is clear from this study that only lutein is available in the infusions and that there are other factors that affect its release from the dry material into the tea as seen from the non-linear relationship between lutein content in the dry tea and the percentage in the infusion (Fig. 5). There are several possible physico-chemical factors that could affect the release from the dry teas and the solubility of lutein from the different teas: (i) the basically poor solubility of lutein in water (cold or hot) and the saturation value for hot water, (ii) the dry tea matrix structure, and (iii) other phytochemicals, such as phenolics, that may increase or decrease the solubilisation of lutein. It is also known that the duration of extraction affects the contents of some bioactive compounds. Generally for teas the highest pigment levels were detected after extraction for 12 h in a Thermos bottle and the lowest levels were reported for 10 min extraction with boiling water at room temperature (Raal and Kuznetsova, 2007). Clearly, compared with richer sources of carotenoids such as fruits and vegetables, the teas in general are not a major dietary source of lutein, but regular consumption of some teas could still lead to a significant contribution of total lutein in the diet (Hart and Scott, 1995). It was also clear that the type of water used, other than ultra-pure water, had minimal effects on the availability of lutein in the infusions (Table 3)."​

 

[RWilly]

Where things always get messy for me is the acute phase response, which can make serum markers high or low depending on inflammation.

Vitamin A deficiency and the acute phase response among HIV-1-infected and -uninfected women in Kenya. - PubMed - NCBI

Serum retinol, the acute phase response, and the apparent misclassification of vitamin A status in the third National Health and Nutrition Examination Survey

Effect of the in ̄ammatory response on trace element and vitamin status

 

[Dolomite]

I don't have the full text. It looks like vitamin a will circulate for a long time for many people.

Severe hypervitaminosis A in siblings: evidence of variable tolerance to retinol intake. - PubMed - NCBI

A 2-year-old boy had signs and symptoms of chronic hypervitaminosis A. A course of increasing severity led to eventual death. A younger brother later had similar clinical features. Chicken liver spread containing up to 420 IU/g vitamin A was the likely source of intoxication. Markedly elevated circulating retinyl ester levels have persisted in the surviving sibling for 3 subsequent years despite severe restriction of vitamin A intake. A therapeutic trial of the carbohydrate-derived complexing agent 2-hydroxypropyl-beta-cyclodextrin was initiated. Circulating retinyl esters transiently increased during the infusion (from 407 to 4791 micrograms/dL), and urinary total vitamin A excretion, undetectable before infusion, increased to 23 micrograms/dL after infusion. The frequency of hypervitaminotic episodes has decreased somewhat in the 2 years since the infusion, probably related to dietary vitamin A restriction. The occurrence of this syndrome in two brothers, while a sister ingesting the same diet remains completely healthy, suggests an inherited variance in tolerance to vitamin A intake.