Should I Worried About Tolerable Upper Limits Of Vitamins?

Gametime

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After looking through all the tolerable upper limits to foods, looking at vitamin A retinol for example it's around 10,000IU.. should I worried about going over on it when my diet is rich in butter, whole milk, cheese etc? I do work out how much of each I eat a day making sure I don't go over the TUL of VIT a.. Which tbh is pretty hard to do with butter/milk/cheese alone but could be done.. Something to be worried about guys? I find I am thinking about it to much when I probably shouldn't be at all!

Or TUL of VIT C, maybe selenium etc?
 

tankasnowgod

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It's gonna depend on the vitamin or mineral. As far as from eating just food, the ones with most concern are gonna be iron, zinc, copper, and manganese. Those depend on multiple factors. Liver and oysters pretty much the only foods that can deliver these toxicities, but if you eat them less than twice a week, I don't think there is much cause for concern. Problems tend to happen when people eat something like a dozen or two oysters daily for several weeks.

As far as Vitamin A, most toxicity concerns are overblown, and the TUL is really low. I think it used to be 25,000 IU or higher. Retinol in doses of 100,000 IU daily is regularly prescribed for skin issues. There was a study that followed some patients, and it took 100,000 IU for women and 200,000-300,000 IU for men for several months for toxicity symptoms to appear, and even then, it was only in some subjects. Even then, if you look at the writings of Chris Masterjohn, it may be more due to an imbalance of A/D/K2 than toxicity of the vitamins, per se.
 

Steve123

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Wow really!! 200,000 - 300,000 ! That's insane!!! I should imagine accutane is a lot of VIT a too! I serisouly can't believe 300,000 IU that's crazy stuff! Cheers though!
 

artlange

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the danger with Vit A comes from the "almost" vit A wannabes that are patented synthetic form of vit A, and probably cancer causing compounds. some of the earlier stories about the dangers of Vit A were caused by the almost synthetic patented Vit A replacements.

the same thing happened with progesterone and the "progestins" which were all synthetic patented progesterone wannabes which turned out to be estrogens in disguise.

Nothing suynthetic and slightly different compares with the original natural bio-identical Progesterone and Vit A.

Ray talked about these synthetics on some of his KMUD interviews
 

Steve123

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the danger with Vit A comes from the "almost" vit A wannabes that are patented synthetic form of vit A, and probably cancer causing compounds. some of the earlier stories about the dangers of Vit A were caused by the almost synthetic patented Vit A replacements.

the same thing happened with progesterone and the "progestins" which were all synthetic patented progesterone wannabes which turned out to be estrogens in disguise.

Nothing suynthetic and slightly different compares with the original natural bio-identical Progesterone and Vit A.

Ray talked about these synthetics on some of his KMUD interviews
Right got ya, thanks for that! So no worries at all with VIT a from foods and could probably have say 30,000iu a day with no problems (or just going over the TUL at least) with foods like butter, cheese, whole milk etc?
 

Dave Clark

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This problem isn't a good question, and I probably know the answer, but, is there any natural vitamin A supplement that is not from cod/fish oil, or does one have to just eat liver, etc. to get any natural vitamin A? Any natural vitamin A that I see in a supplement form is always fermented cod liver oil, or something like that, can't they extract natural vitamin A from a source that doesn't include PUFAs?
 

Travis

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Steroid hormones, vitamin A, eicosanoids, and vitamin D work directly on nuclear receptors to influence gene transcription. These hormones can have different effects on different cell types.

There is some epidemiological evidence that high vitamin A leads to increased bone turnover and osteoporosis in the Nordic Countries where they eat fish oil and their milk is supplemented. They get way more than you would get from normal food (sans liver).

But these findings are confounded by latitude. The people in the Nordic Countries get little vitamin D, which acts in the other direction on bone density.

High vitamin A with low vitamin D over the course of years could be an issue.
Owing to their ability to accumulate in the body, fat-soluble vitamins have a higher potential for toxicity than do water-soluble vitamins. Iron-containing vitamins are the most toxic, especially in pediatric acute ingestions. –Medscape
All supplemental iron should probably be avoided. If you eat whole food, you probably get enough iron.

Excessive iron is generally considered public enemy #2 on the Peat Forum (behind PUFAs).

Vitamin D presents less of an issue because the supplemental form is actually an inactive prohormone. It needs to be hydroxylated twice by enzymes in the body to be fully active. These steps appear to be largely regulated by parathyroid hormone.

Vitamin A's active form, retinoic acid, is not so regulated. Retinol from animal foods will turn into retinoic acid essentially without feedback, but the the retinol⇨retinoic acid derived from β-carotene is regulated by the carotene cleavage enzyme in the intestine. Not really a problem unless you megadose.

All of the B-vitamins appear safe at 10× the RDA.

Vitamin K₂ can cause heart palpitations in some people because it can substitute for CoQ₁₀ in the mitochondrial electron transport chain. Vitamin K₁ has no reported toxicity. You can search all day and not find one case of vitamin K₁ toxicity.

Vitamin E toxicity is rare and hard to accomplish. You would actually have to try very hard to poison your self with this. Mixed tocopherols are better because they have both α- and γ-tocopherols. There is much new interesting research on how γ-tocopherol works to scavenve reactive nitrogen species on the cell membrane, something α-tocopherol cannot do. Gamma tocopherol also prevents cancer better in vitro.
 
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tara

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If you eat large amounts of carrots and other sources of carotenes, and your system is not currently up to the job of converting them effectively to usable vit-A (eg hypothyroid or B12 deficient), you might get some trouble with that. It eventually shows up as an orange tinge to the skin. If that happens, time to back off.

I have a lowish tolerance for carrots and other orange veges. So I rinse my grated carrots, and while I enjoy orange coloured sweet potatoes and pumpkins from time to time, I only eat them occasionally or else I get averse.
Some people have no trouble of this kind - just a matter of watching how things affect you personally.
 

Steve123

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Steroid hormones, vitamin A, eicosanoids, and vitamin D work directly on nuclear receptors to influence gene transcription. These hormones can have different effects on different cell types.

There is some epidemiological evidence that high vitamin A leads to increased bone turnover and osteoporosis in the Nordic Countries where they eat fish oil and their milk is supplemented. They get way more than you would get from normal food (sans liver).

But these findings are confounded by latitude. The people in the Nordic Countries get little vitamin D, which acts in the other direction on bone density.

High vitamin A with low vitamin D over the course of years could be an issue.

All supplemental iron should probably be avoided. If you eat whole food, you probably get enough iron.

Excessive iron is generally considered public enemy #2 on the Peat Forum (behind PUFAs).

Vitamin D presents less of an issue because the supplemental form is actually an inactive prohormone. It needs to be hydroxylated twice by enzymes in the body to be fully active. These steps appear to be largely regulated by parathyroid hormone.

Vitamin A's active form, retinoic acid, is not so regulated. Retinol from animal foods will turn into retinoic acid essentially without feedback, but the the retinol⇨retinoic acid derived from β-carotene is regulated by the carotene cleavage enzyme in the intestine. Not really a problem unless you megadose.

All of the B-vitamins appear safe at 10× the RDA.

Vitamin K₂ can cause heart palpitations in some people because it can substitute for CoQ₁₀ in the mitochondrial electron transport chain. Vitamin K₁ has no reported toxicity. You can search all day and not find one case of vitamin K₁ toxicity.

Vitamin E toxicity is rare and hard to accomplish. You would actually have to try very hard to poison your self with this. Mixed tocopherols are better because they have both α- and γ-tocopherols. There is much new interesting research on how γ-tocopherol works to scavenve reactive nitrogen species on the cell membrane, something α-tocopherol cannot do. Gamma tocopherol also prevents cancer better in vitro.
Wow! Thanks for this Travis! Excuse my dullness but got confused on what you was referring to with Vitamin A in terms of beta carotene or actual retinol... so to confirm... It would be extremely hard to overdose on vitamin A retinol? From foods like butter/milk/ etc ..
 

Steve123

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If you eat large amounts of carrots and other sources of carotenes, and your system is not currently up to the job of converting them effectively to usable vit-A (eg hypothyroid or B12 deficient), you might get some trouble with that. It eventually shows up as an orange tinge to the skin. If that happens, time to back off.

I have a lowish tolerance for carrots and other orange veges. So I rinse my grated carrots, and while I enjoy orange coloured sweet potatoes and pumpkins from time to time, I only eat them occasionally or else I get averse.
Some people have no trouble of this kind - just a matter of watching how things affect you personally.
Right I got ya! And vitamin a retinol not an issue to be worried about at all?
 

paymanz

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There is a sweet point/optimal dose of each of them.

Toxicity is not the only concern, but there is no point to go higher than optimal dose. Bad effects is not visible immediately but they exist!

Ray peat recommendations usually are on lower side,

If I remember correctly for vitamin E his advise is 100-200iu
Zinc 15mg
B6 10mg
If you overdo vitamin e for example you lower your vitamin k levels. For example.


Another one, retinol, dosage he mentions usually is on higher widen, comparing to mainstream , but it also depends on sun exposure, vitamin d level. UV in sunlight destroys your retinol so in summer and lots of sun you need more retinol.
 

Travis

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... so to confirm... It would be extremely hard to overdose on vitamin A retinol? From foods like butter/milk/ etc ..
Yeah. The only people who overdose from from vitamin A are arctic explorers who eat polar bear liver, and people who supplement.

But it is fat-soluble so non-acute doses can build-up over time.
 
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Gametime

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Yeah. The only people who overdose from from vitamin A are arctic explorers who eat polar bear liver, and people who supplement.

But it is fat-soluble so non-acute doses can build-up over time.
Great, Thanks Travis! I know this sounds ridiculous but i do like to eat sweet pots now and again maybe once a week. The massive amount of Vitamin A in them makes me worried about overdosing on them even though i know its beta carotene.. Is there 100% no risk to overdosing on vit a beta carotene if already in that day i'm eating lots of butter, whole milk, cheese etc? Not just sweet potatoes i speak about aswell but any form of high beta carotene like cantoloup melon for example along with the raw carrot in the day and other forms of beta carotene.. is beta carotene no risk at all? Or is it just the retinol version that is possible to overdose on? I've heard a portion of beta carotene can be converted into retinol etc..? Thanks !
 

Travis

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What's the consequence?
It can help prevent congestive heart failure, and it can also cause arrhythmias in some people.

It's just a good thing to keep in mind when supplementing with vitamin K₂. Taking high doses with CoQ₁₀ might be contraindicated. Once the Gla proteins are saturated, any additional amount of vitamin K becomes redundant.

These are cool. Gamma-carboxyglutamic acid (Gla) formation is a post-translational modification that turns glutamic acid into a strong calcium chelator:

fig1.jpg

(This picture sucks. I know I should draw a better one but I'm feeling tired right now.)

These Gla proteins chelate calcium and keep it from precipitating. Rats chronically fed Warfarin have greatly calcified arteries because there are less Gla domains on the proteins. This causes calcium ions to spontaneously precipitate with phosphate in the body.

The best way to check vitamin K status is by measuring the degree of carboxylation on certain blood proteins, such as osteocalcin. This is a direct measure of its calcium-chelating ability.

Other bone structural proteins also have Gla domains, such as matrix Gla protein.
 
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Steve123

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Guys.. I took a look at that video but couldnt find a specific answer to my query.. I know this sounds ridiculous but i do like to eat sweet pots now and again maybe once a week. The massive amount of Vitamin A in them makes me worried about overdosing on them with Vitamin A even though i know its beta carotene.. Is there 100% no risk to overdosing on vit a beta carotene if already in that day i'm eating lots of butter, whole milk, cheese etc? Not just sweet potatoes i speak about aswell but any form of high beta carotene like cantoloup melon for example along with the raw carrot in the day and other forms of beta carotene.. is beta carotene no risk at all? Or is it just the retinol version that is possible to overdose on? I've heard a portion of beta carotene can be converted into retinol etc..? For some reason i have this strange fear that if i was to eat Sweet potatoes, Eggs, butter, cheese, milk, etc that i would overdose on vitamin A Mainly from the massive amounts of vitamin a in sweet potatoes, i have this weird fear that sweet potatoes paired with vit a retinol rich foods would be a problem, Please would someone re assure my crazy brain that Vitamin A in Sweet pots is BETA CAROTENE and not Retinol and its not possible to overdose on? And even ANY other beta carotene rich foods like cantoloupe melon, Carrots, Brocolli etc.. Thanks !
 

Travis

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Mainly from the massive amounts of vitamin a in sweet potatoes, i have this weird fear that sweet potatoes paired with vit a retinol rich foods would be a problem,...
I don't think so. You are probably correct in describing that thought as "weird".
Please would someone re assure my crazy brain that Vitamin A in Sweet pots is BETA CAROTENE and not Retinol and its not possible to overdose on?
I'll try. Here are some preliminary quotes from an experiment* done in 2002:
High dose β-carotene supplementation in humans does not cause any signs of hypervitaminosis A or teratogenicity (19). Therefore, the conversion of β-carotene to vitamin A must be tightly regulated through vitamin A homeostasis.
This is despite the fact that each β-carotene molecule can form two retinol molecules:
vitamin A 4.png
(Ignore the eccentric cleavage pathway. A different enzyme is responsible for this.)

Retinoic acid is the main player and works on nuclear receptors. Even retinol can be considered a precursor in a sense, but consuming β-carotene adds another layer of control over retinoic acid levels. This is because at high vitamin A intakes, the activity of this enzyme is reduced:
In rats, the conversion rate, as measured by a vitamin A growth bioassay, is 50% at low doses of β-carotene, whereas at high doses, the cleavage efficiency is less than 5% as measured by retinal accumulation in the liver storage test.
A few words about the enzyme's new name:
The conversion of β-carotene to vitamin A in human and animal tissues (6) is catalyzed by the enzyme β,β-carotene 15,15 β-monooxygenase (βCMOOX) (formerly β,β-carotene 15,15 β-dioxygenase). Biochemical characterization suggested a dioxygenase reaction mechanism (7,8). For this reason, the enzyme was termed β,β-carotene 15,15 β-dioxygenase (E C. 1.13.11.21) for many years. However, recent work by Leuenberger et al. (9) demonstrated that the cleavage of β-carotene follows a monooxygenase mechanism. We therefore use the term β,β-carotene 15,15 β--monooxygenase.
So it is now officially carotene monoxygenase, but the historical name should be kept in mind should you want to search earlier studies. This is referred to as βCMOOX throughout the article:
Subsequent findings showed that the βCMOOX activity is upregulated in rat intestine by vitamin A deficiency (22). Van Vliet et al. (23) confirmed in the same tissue that high doses of vitamin A or its precursor β-carotene decreased enzyme activity.
The authors did their own experiments. They made rats vitamin A deficient by restricting vitamin A and then fed them varying doses and types of vitamin A. The intestines were then removed from each group, homogenized, and separated by centrifugation. The fraction with the carotene cleavage enzyme (βCMOOX) was then analyzed for its ability to split β-carotene. You can ignore the eccentric cleavage products:
vitamin A 3.png

As the dose increases, the enzymatic activity decreases. Having high vitamin A levels will down-regulate this enzyme.
Application of a total of 2.1 or 4.2 μmol retinyl acetate reduced specific βCMOOX activity by 76 and 79%, respectively. [...] β-Carotene, at doses of 4.2, 8.4 and 16.8 mol reduced the specific activity of intestinal βCMOOX by 73, 72 and 79%, respectively. [...] The conversion efficiency of β-carotene to vitamin A decreases with increasing doses (21).
And this happened quickly, within a day or two. Here is a graph showing how quickly the activity of this enzyme decreased after a loading dose of trans retinoic acid:
vitamin A.png

Time course of βCMOOX regulation. Wistar and RORO rats were killed at 0, 2, 4, 8, 24 and 48 h after receiving a single oral dose of RA (2.1 mol/kg body) in 0.25 mL triacetin. Despite differences in strain, origin and feeding between the two assays, significant downregulation of intestinal βCMOOX activity by RA occurred between 24 and 48 h in both studies.
They also extracted the total RNA from two groups of chickens: one vitamin A deficient and one that was given retinol in the food. They took this extracted RNA and used a radioactive probe, a complimentary RNA strand that hybridizes selectively with the βCMOOX messenger RNA.
The probe was amplified by polymerase chain reaction from the coding sequence of βCMOOX (5` primer: 5` GGTACTTCAATTGTTGATAAAGG 3`; 3` primer: 5` TTCTGTT GCATAGACATACTTG 3`) and purified over an S-400 spin column (Amersham Biosciences, Du¨bendorf, Switzerland).
They could then see this RNA fragment after it was separated by gel electrophoresis. Radioactive elements can expose photographic plates in the dark:
vitamin A 2.png

Northern blot analysis showed markedly lower βCMOOX mRNA levels in RA-treated chickens compared with controls (Fig. 3). . Intestinal βCMOOX activity was also decreased by RA (86%).
So the RNA that encodes for the enzyme gets progressively down-regulated as the retinol or retinoic acid levels increase. The carotene cleavage enzyme is under direct genetic control. There are two classes of nuclear receptors that interact with retinoic acid: the RXR and RAR. These interact with DNA directly and can exert primary control over DNA expression. Other hormones like vitamin D, thyroid hormone, eicosanoids, androgens, mineralcorticoids, and glucocorticoids can do this too through nuclear receptors of their own (VDR, TR, PPAR, AR, MR, GR). The RNA that encodes the βCMOOX enzyme has promoter regions:
In the promoter of the mouse βCMOOX gene, we found a direct repeat with a spacing of 2 nucleotides RA responsive element (TACAGGTTCAGAAGTTCAGTCC, unpublished data). Therefore, we assume that RAR and/or RXR are responsible at least in part for the regulation that occurs in the intestines of rats and chickens.
So the DNA that produces the carotene cleavage enzyme interacts with a retinoic acid response element. These are specific sequences of DNA that the retinoic acid receptors bind to.
Additionally, RA and 9-RA, which were reported to bind RAR (33), markedly reduced βCMOOX activity in rats. Treatment with the RAR antagonist increased βCMOOX activity in rats and chickens. This is further evidence that RAR might be involved in a negative feedback regulation.
Remember that the high-retinol rats had β-carotene conversion efficiency of under 5%.†
The effective feedback regulation of RA on intestinal βCMOOX might also be involved in vitamin A homeostasis in humans, and it might explain why excessive doses of β-carotene do not cause hypervitaminosis A or teratogenicity.
Just to show how tight this feedback control is, a study was done on Filipino schoolchildren. There body stores of retinol were measured at baseline and then after 3 months of very high β-carotene fruits and vegetables. The graph is somewhat counter intuitive, since they measured the body status with radioactive retinol. This means that the higher values on the X-axis correspond to lower retinol body stores; the more tissue retinol you have, the less radio-labeled retinol you can absorb:
vitamin a 5.png
Pearson coefficient of r=−.99
What is amazing is how straight this line is. This implies that all of the children could regulate β-carotene conversion nearly perfectly. There was no apparent genetic variation out of 27 children.
Bioconversion of plant carotenoids to vitamin A varies inversely with vitamin A status;
So if you are eating "Eggs, butter, cheese, milk, etc", then I would expect your carotene cleavage enzyme (βCMOOX) to be at very low activity. The relatively high amounts of retinol from these should suppress transcription of this enzyme. So the sweet potatoes should actually be quite safe, since less than 5% would probably be converted for you.


*Bachmann, Heinrich, et al. "Feedback regulation of β, β-carotene 15, 15′-monooxygenase by retinoic acid in rats and chickens." The Journal of nutrition 132.12 (2002): 3616-3622.
†Nutr. 124: 1461S–1466S. 21. Brubacher, G. B. & Weiser, H. (1985) The vitamin A activity of betacarotene. Int. J. Vitam. Nutr. Res. 55: 5–15
Ribaya-Mercado, Judy D., et al. "Bioconversion of plant carotenoids to vitamin A in Filipino school-aged children varies inversely with vitamin A status." The American journal of clinical nutrition 72.2 (2000): 455-465.
 
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Steve123

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Travis, you are an absolute saviour. I cannot thank you enough for this, this is unbelievably helpful to me!!l You have definitely re assured me on my consumption of beta carotene rich foods!!! Can't wait to get back on sweet potatoes now and then (I know not peato but I feel good on them)
Some things I am not able to understand so well but is it true from your reply that even vitamin a retinol found in butter etc is a pre cursor meaning that it's not 100% that it will convert 100% into the form of vitamin A that is possible to overdose on? And then beta carotene is a few extra steps away from the form of retinol to overdose on aswell?
 

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