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

[Blossom]

Could take many years

Yes, I’m pretty sure you’re correct. I’m happy that it wasn’t high at least.
@Amazoniac, thanks for the helpful information!

 

[Amazoniac]

Gallbladders, cholecystitis, cholelithiasis...caused by excess Poison/"Vitamin A", and the body tries NOT to absorb it and Vitamin D from the diet

I remember reading about the potential issue once (they're not the only responsibles):
- Gallbladder Removal

If I'm not wrong it was gbolduev that had some posts on it as well.

 

[Tarmander]

Gallbladders, cholecystitis, cholelithiasis...caused by excess Poison/"Vitamin A", and the body tries NOT to absorb it and Vitamin D from the diet

This is pretty interesting and connecting a lot of dots in my head that might mean something. Whenever I would take TUDCA, I would get estrogenic symptoms. More gyno and swelling. It always puzzled me because I thought it would help the liver. I just wrote it off as too much detox or something. But it was possibly potentiating vitamin A.

This makes further sense in that one of the best things about this diet is a return of strength and muscle tone that has been lacking for years. I did 20 push ups yesterday and am not even really sore today. The push ups were pretty easy too. I would have had trouble doing 10 push ups when I was peak liver/OJ/etc intake more than a year ago.

More from the article: I will say that his take that the body lowering bile production at the ingestion of vitamin A and D is proof they are toxic is hyperbole. Giving credit where it is due, Gbolduev/Helen has been saying for awhile to avoid fat soluble vitamins like A and D because they shut the gallbladder down. You just have to do like 50 gall bladder flushes and then you are good...or something

 

[Blossom]

You just have to do like 50 gall bladder flushes and then you are good...or something

That sounds fun. :)

 

[InChristAlone]

Yeah gallbladder flushes suck!! I have done a few of them and every time I got incredibly nauseous all night. Guaranteed little sleep. The last time I was very pregnant and it only produced a few little green 'stones' I was amazed I could absorb all that oil well kinda horrified now that I know the stones are just a combination of the oil and bile acids. Soap stones.

 

[Kartoffel]

Giving credit where it is due, Gbolduev/Helen has been saying for awhile to avoid fat soluble vitamins like A and D because they shut the gallbladder down.

Well, that person says a lot of retarded things. Every paper I have seen has shown vitamin D to normalize bile concentrations, and that low vitamin D status promotes pathological bile problems including impaired clearance that can eventually lead to carcinogenesis.

Vitamin-D Deficiency Is Associated with Gallbladder Stasis Among Pregnant Women. - PubMed - NCBI
Vitamin D and gallstone disease-A population-based study. - PubMed - NCBI
Association between circulating vitamin D metabolites and fecal bile acid concentrations

 

[sunraiser]

This is pretty interesting and connecting a lot of dots in my head that might mean something. Whenever I would take TUDCA, I would get estrogenic symptoms. More gyno and swelling. It always puzzled me because I thought it would help the liver. I just wrote it off as too much detox or something. But it was possibly potentiating vitamin A.

This makes further sense in that one of the best things about this diet is a return of strength and muscle tone that has been lacking for years. I did 20 push ups yesterday and am not even really sore today. The push ups were pretty easy too. I would have had trouble doing 10 push ups when I was peak liver/OJ/etc intake more than a year ago.

More from the article: I will say that his take that the body lowering bile production at the ingestion of vitamin A and D is proof they are toxic is hyperbole. Giving credit where it is due, Gbolduev/Helen has been saying for awhile to avoid fat soluble vitamins like A and D because they shut the gallbladder down. You just have to do like 50 gall bladder flushes and then you are good...or something

To me it just means large supplemental doses "use up" finite bile cofactors, especially and specifically taurine, which has other uses beyond uptake of fat solubles, like helping with iron and copper uptake (and potentially being part of their disposal mechanism).

I think vitamin D via supplement has the potential to be toxic or to act only as a hormone our body is purposefully limiting, though.

With vitamin A, if a person had been estrogen dominant and storing copper for a long time then taurine would be needed to promote uptake and disposal of copper and iron, as opposed to fat solubles.

Liver for sick or chronically stressed people is awful news, in that case. Accutane is obviously going to bypass any natural means of uptake and cause problems regardless, and it's compounded by the fact skin health often corresponds with liver health...so the sect of people that can deal with the least vitamin A are being given the most.

I'm still pretty firmly in the camp of vitamin A being imperative for immune health and, via craving, being the most natural prompt as a metabolic stimulant. It may mean a person will never need liver, though.

I think your diet saves playing with extensive liver flushes and taurine and b6 balancing protocols, but I have seen both work. Liver flushing (like 15 needed) via accutane user on acne.org forum and then taurine via forum users brian/nicholas/natedawgg.

Personally I think it's the resource sparing of avoiding fat solubles that's helping you, and it any of you were to take vit D or K2 it'd set you back just as much, albeit with slightly different effects.

I'm totally at odds with Ray Peat in his suggestions to eat liver and have very high calcium and copper intakes to restore metabolic health. I think it's the cause of a lot of hardship for a lot of people around here (albeit with good intentions). It's so dangerous to revere one person as a paragon of wisdom.

 

[Amazoniac]

Every paper I have seen has shown vitamin D to normalize bile concentrations, and that low vitamin D status promotes pathological bile problems including impaired clearance that can eventually lead to carcinogenesis.

Vitamin-D Deficiency Is Associated with Gallbladder Stasis Among Pregnant Women. - PubMed - NCBI
Vitamin D and gallstone disease-A population-based study. - PubMed - NCBI
Association between circulating vitamin D metabolites and fecal bile acid concentrations

Ach ja, it likely involves various other factors for der subjectified exzess to become problematisch. Mufasa and tankas took massive amounts without noticing any issues in this regard.

OPENED inflammatology book , all there

- Dysregulated bile acid synthesis and dysbiosis are implicated in Western diet–induced systemic inflammation, microglial activation, and reduced neuroplasticity

"Like BAs [British Airways], RA regulates lipid homeostasis, insulin sensitivity, and inflammation (65, 66). Mediated through RA receptors, such as retinoic acid receptors and RXRs, RA also regulates differentiation, metabolism, and development based on genome-wide binding and gene expression profiling data (45, 67). In addition, RA has a profound effect on regulating genes involved in BA homeostasis (21). In WD-fed mice, reduced RA signaling was accompanied by dysregulated BA synthesis."

"[..]our data revealed that reduced RA signaling and dysregulated BA synthesis occurred because of WD intake."​

They discuss gut dysbiosas, liver and brain disturbances, ammonia, and other friendly stuff, in case you's interested.

So..
surrealquackwatch.org/unpoisoningwithforprofits/alarmists - Will, Smith?

 

[Amazoniac]

- The biological significance of vitamin A in humans: A review of nutritional aspects and clinical considerations

"In patients with renal insufficiency, a daily dose of 4000 IU can cause severe damage and if these patients are also alcohol consumers, then the level of damage can be even more substantial."​

 

[charlie]

- The biological significance of vitamin A in humans: A review of nutritional aspects and clinical considerations

"In patients with renal insufficiency, a daily dose of 4000 IU can cause severe damage and if these patients are also alcohol consumers, then the level of damage can be even more substantial."​

Is this a sign of renal sufficiency?

 

[Orion]

This makes further sense in that one of the best things about this diet is a return of strength and muscle tone that has been lacking for years.

Same here, seeing strength increase easily and recovery time decrease. But this is at 4 months for me, so need more time to experiment. But does seems that overload of A interferes with test/estrogen, almost as if its a key to the hardgainer lock.

 

[Tarmander]

Same here, seeing strength increase easily and recovery time decrease. But this is at 4 months for me, so need more time to experiment. But does seems that overload of A interferes with test/estrogen, almost as if its a key to the hardgainer lock.

Definitely. I am right around the 3-4 month mark as well.

 

[Amazoniac]

More functions for poison/"vitamin" A.
It's too orange, it has to be interesting.

- Retinol as electron carrier in redox signaling, a new frontier in vitamin A research (!)

"The common purpose of carotenoids and retinaldehyde is the conversion of energy from one form to another: light to chemical energy, light to nerve impulse, light to electrons, electrons to heat, and so on. Among the retinoid family, retinaldehyde alone was thought to possess the property of energy conversion, but vitamin A alcohol (retinol) was recently found capable of handling electrons as part of a specific redox-chemical reaction that controls mitochondrial energy homeostasis (23,24). In essence, two protein kinase C (PKC) isoforms, δ and ε, require retinol as indispensible co-factor for their function in mitochondria (25,26). In this organelle, activation of PKCs is not mediated by the classic diacyl-glycerol (DAG) second messenger (27), but is accomplished by an alternate redox mechanism in which retinol participates as an electron transfer agent (24,28-30). Since both PKC isoforms regulate the pyruvate dehydrogenase complex (PDHC), although opposing each other yin-yang style (25), retinol is part of a signal network that regulates the conversion of glucose to acetyl coenzyme A (CoA), and as such is fundamental to animated life. The PKC δ/ε-PDHC axis is crucial for the balanced flux of fuel entering the Krebs cycle in virtually all respiring mammalian cells, and thus retinol plays a critical role in containing the respiratory capacity within safe borders. It is becoming increasingly clear that harmful reactive oxygen species emanating from an overtaxed electron transfer chain (ETC) underlie a welter of metabolic disorders, impacting diabetes, cancer, cardiovascular disease, neurodegenerative disorders, and aging (31,32). The subject of this review is the emerging role of retinol as an electron carrier. In this vein, retinol performs a narrowly specialized task that at first glance may appear incompatible with the biological function of other retinoids, yet fits neatly into the electronic capabilities of the carotenoid/retinoid superfamily."

"Vitamin A was long thought to lack intrinsic biological activity. Its sole function was believed to be precursor of various bioactive forms, notably retinaldehyde for vision (18) and RA for transcriptional regulation (33,34). However! Vitamin A is uniquely defined as the alcohol form, retinol, and thus is distinct from other retinoids in its chemical structure and, owing to the discovery of the involvement in mitochondrial signaling, its biological function as well. A reluctance to accept bona fide biological activity for retinol can be attributed to the need for a new paradigm that would account for an intrinsic function that is radically different from the reigning retinoid acid paradigm. RA works primarily as a paracrine hormone (35). In accord, RA is elicited by one group of cells to signal the execution of a transcriptional program by another, receptive, population of cells. RA signaling is usually narrowly controlled in time and space, within a developmental field, or a regenerating tissue, for instance (36,37). To make this system work, RA receptors have evolved to high affinity in the sub-nanomolar range. Thus RA concentrations are usually exceedingly low, excess being promptly degraded by specific enzymes, exemplified by CYP26, that are strategically placed to prevent RA escaping from a designated developmental field (38). Moreover, RA production is transient."

"The evolving retinol paradigm does not share these classic attributes of hormones. Retinol is distributed via the circulation to tissues and cells at all times. In healthy animals, the liver maintains retinol in plasma at an unwavering concentration of 1.5−2 micromoles (39). [Exemplified by the level of a female specimen on the previous page] Moreover, the uptake of retinol occurs via redundant, though controlled, processes assuring that it is available to cells in relative abundance. This is the precise antithesis of a hormone. In distinction to RA, retinol does not activate the target molecules to which it binds, the members of the PCK and Raf families, for instance (29). Instead, binding of retinol primes these molecules to become responsive to redox-mediated activation signals that present an alternative to the classic, retinol-independent second-messenger pathway (40). In the case of PKCδ, which inhabits the mitochondrial intermembrane space, this signal is given by a locally activated oxidizing agent, cytochrome c3+ (24). However, without retinol this kinase activation process is impeded."

"[..]the full complexity of poison/"vitamin" A action is underappreciated to this day. For instance, while the causes of defective vision in vitamin A deficiency are now well understood, the equally dramatic loss of olfactory sensation observed by Wolbach and Howe (46) remains unexplained (47). When RA arrived on the scene and the 1920s nutritional studies were repeated, the power of RA to reverse many symptoms of the vitamin A deficiency was noted. However, several aspects of immune system dysfunction were not fully corrected with RA, but required vitamin A for reversal (48). It should be noted that vitamin A is converted in the body to RA, but the converse is not true."

"Many arguments can be made that vitamin A is more than just a precursor, as it is often said, of bioactive molecules, such as retinaldehyde in vision, or RA in gene transcription. For instance, while it is true that retinoic acid receptors [RARs and retinoic acid X receptors (RXRs)] are ubiquitously expressed, and hence most cell types evidently use RA, the majority of these consumers do not synthesize RA. Nevertheless, most cells including the RA non-producers, harbor the biochemical machinery to take up vitamin A from the circulation via specific intracellular transporters, the cellular retinol binding proteins (CRBP) (49), to convert it for storage into retinyl esters by dedicated acyl transferases [lecithin retinol acyltransferase, LRAT (50) or acyl-CoA retinol acyltransferase, ARAT (51)] and to retrieve free retinol on demand by retinyl-esterases (52)."

"Moreover, many cell types metabolize retinol into hydroxylated derivatives, including 14-hydroxy-retro-retinol (14-HRR) (53) and 13,14-dihydroxy-retinol (DHR) (54) which have in vitro growth-promoting qualities broadly similar to that of retinol, although it is unclear whether they act by a similar mechanism or what their biological relevance might be. Another retinol metabolite, anhydroretinol (AR) (55), was discovered owing to its capacity to compromise cell survival. Both 14-HRR and AR, along with retinyl esters, are evolutionarily-conserved in insect cells, suggesting physiological relevance of these compounds (and of the enzymes that generate these), although specific uses have not been investigated (56). Since RARs or RXRs emerged at the vertebrate/invertebrate boundary it is unlikely that 14-HRR or AR act as transcriptional co-activators. While these findings hint at the existence of an unknown vitamin A physiology they do not per se argue that unmodified vitamin A is bioactive. Arguments in favor of intrinsic bioactivity stem from the discovery of a large class of intracellular receptors of vitamin A, namely the serine/threonine PCK and Raf kinases (29)."

"[..]we traced the retinol-binding site to the cysteine-rich domain (CRD) that these two proteins share in common. cRaf contains one such CRD whereas PKC contains two. In fact all other members of the Raf and PKC families possess retinoid-binding sites associated with at least one of their CRDs, although the novel PKCs (δ and ε) have sites on both CRDs. The binding affinities of retinol for CRDs range from 20 to 95 nm. These values are at least two orders of magnitude lower than the (sub-nanomolar) affinity of RA for RARs. On the other hand, the estimated PKC and Raf affinities for retinol are similar to those of extracellular and cytoplasmic RBPs (RBP and CRBP, respectively), suggesting that they are in equilibrium with these major retinol transporters. Therefore, in nutritionally healthy animals at least a proportion of the Raf and PKC isoforms will always be complexed with retinol. It should however be understood that the recorded affinities relate to recombinant CRD fragments, and that the true values for the native proteins in their cellular environments may be substantially different."

"Both PKCδ and PKCε translocate from the cytosol to mitochondria, but whereas PKCδ migrates to the intermembrane space, PKCε is transported into the matrix. Despite their different locations, or perhaps by design, the two isoforms signal to a common target, the PDHC (25) (Figure 1)."

@tca300

"Proposed activation and signaling schematic of PKCδ in mitochondria. The PKCδ signalosome (described in Figure 2) is located in the intermembrane space where it is activated by interaction with the oxidized form of cytochrome c (cyt 3+). Redox activation involves the passage of at least two electrons (e−) from the PKCδ C1B zinc-finger domain (synonymous with the activation domain) to cyt 3+. The intermediary cyt 2+ molecules so formed carry the electrons to complex IV for disposal (indicated by red arrow), regenerating cyt 3+ (for details see Figure 2). Oxidation converts the globular, auto-inhibited PKCδ into the unfolded, activated kinase. Activated PKCδ up-regulates the PDHC. This is accomplished by a yet unidentified phosphatase (PDK2 P’ase) that inactivates PDK2. In the active state, PDK2 normally suppresses PDHC, but when inactivated by PKCδ this suppression is lifted, allowing PDP1,2 to activate the PDHC. PKCδ is known to be opposed Yin-Yang style by PKCε. Although the activation mode of PKCε kinase is unknown, the attractive target is PDK2. The increased output of acetyl-coenzyme A (CoA) stimulates TCA activity and increases OXPHOS, associated with increased electron flow through the ETC. High electron flow maintains a large pool of cyt c in the oxidized form, thereby keeping PKCδ active and maintaining high glucose fuel flux. When demands for OXPHOS are low, cyt 2+ prevails, curtailing PKCδ/PDHC activity and reducing fuel flux. The mechanism of PKCδ inactivation is not known, but the potential of reducing the PKC zinc-finger and refolding the kinase is presented in Figure 3. PKC, protein kinase C; PDHC, pyruvate dehydrogenase; PDK2, pyruvate dehydrogenase kinase 2; PDP 1,2, pyruvate dehydrogenase phosphatase 1,2; CoA, coenzyme A; TCA, tricarboxylic acid cycle; OXPHOS, oxidative phosphorylation; ETC, electron transfer chain."​

[Suggestion: follow with the figure]

"Although the correlations between PKCδ and PDH E1 phosphorylation patterns (60,61) identified this kinase as positive regulator of the PDHC the actual signal path was indirect. First, PKCδ is a phosphotransferase, but PDH became dephosphorylated when the PKCδ kinase was active. This implied the participation of an intermediary phosphatase. In fact, two pyruvate dehydrogenase phosphatases, PDP1 and 2, are known to directly control the PDHC E1 subunit (62,63), but both could be excluded from the PKCδ signal chain proper. A required phosphatase that is activated by PKCδ has not yet been identified. Second, the pyruvate dehydrogenase kinase isoform 2 (PDK2) (64), was identified as the intermediate target of the PKCδ signal path (23). Along with three other PDK isoforms, in its active, phosphorylated form PDK2 is a known suppressor of PDHC, acting by phosphorylating the PDHC E1 subunit (61). On the other hand, PDK2 is opposed by pyruvate dehydrogenase phosphatase 1,2 (PDP1,2) which dephosphorylates PDHC E1. Thus, PKCδ seems to function by activating PDK2 via the hypothetical, PKCδ-dependent PDK2-phosphatase. ()When PDK2 is neutralized by dephosphorylation, PDP1,2 is unopposed to activate the PDHC.()"

"In his pioneering work, Dr. Nishizuka (27) established the activation of PKC by diacyl-glygerol second messenger, and later added an alternate mechanism involving redox stress (65). Despite descriptive evidence for other family members, notably cRaf, this redox mechanism raised doubts in the minds of biologists as to the physiological purpose, as well as of chemists who worried about vulnerability of this cysteine-rich molecule towards randomly oxidizing agents. On the other hand, the activation domains of PKCs and Raf, which are synonymous with the aforementioned CRDs, are organized into zinc fingers (66-68). These folds are generally believed to stabilize tertiary protein structure as long as reducing conditions prevail, as they normally do in intact cells, but CRDs dissociate when oxidizing conditions arise systemically or locally, allowing the respective proteins to change function by rearranging form."

"Zinc-fingers are devices to maintain PKCs in the closed, that is: enzymatically inactive, form. But it is attractive to view these structures as hinges that open in order to effect kinase activation. In fact, the transition from inactive to active enzyme classically involves large-scale protein unfolding to expose targeting structures and various binding sites for substrate, ATP, and, for some isoforms, Ca2+ (71)."

"The heme of cytochrome c3+ absorbs one electron at a time. Therefore the left-behind electron of the pair to be transferred to cytochrome c3+ inevitably forms an intermediary radical, which needs to be stabilized until cytochrome c3+ is regenerated from cytochrome c2+ by cytochrome c oxidase. However, the transfer of electrons between proteins that are not in VanDerWaal’s contact (like the passage from PKCδ to cytochrome c3+) is exceedingly slow, and hence requires an electron bridge. PKC-bound retinol is proposed to perform this function. Close similarities exist with electron transfer in the ETC. This process is dictated by one-electron chemistry that mediates directional passage of electrons from NADH-CoQ reductase (complex I) or succinate-CoQ reductase (complex II) to CoQH2-cyochrome c reductase (complex III). Coenzyme Q greatly accelerates this step (76). Note that coenzyme Q toggles between different chemical forms, ubiquinone ↔ semiquinone radical ↔ ubiquinol. We propose that PKCδ employs retinol for the analogous purpose of enabling safe and efficient electron transfer to cytochrome c3+ (Figure 2). However in distinction to coenzyme Q retinol may not need to change its redox state, as the transitory electron may be stabilized by the π-electron system. While the details have to be worked out, it is known that an intact electron system is required."

"Components and assembly of the PKCδ signalosome. The PKCδ signalosome comprises the PKCδ molecule, the signal adapter p66Shc, cytochrome c and retinol (vitamin A alcohol). The interaction of P66Shc- SH2 domain with phosphotyrosine Y332 of PKCδ brings the kinase into close apposition with cytochrome c anchored to p66Shc by hydrophobic interaction. The β-ionone head of retinol binds the C1B activation domain of PKCδ and the polyene tail extends to cytochrome c. In this arrangement PKCδ is electronically coupled with cytochrome c, facilitating the transfer of electrons. Oxidation of the zinc-finger-domain destabilizes the Zn2+-coordination center, leading from the local conformation change to large-scale remodeling of the inactive, auto-inhibited protein to yield the active enzyme. PKC, protein kinase C."​

"The PDHC catalyzes the conversion of pyruvate to acetyl-CoA, the last step of glycolysis. As our evidence shows, the PKCδ signaling module positively regulates the PDHC. A survey of the literature reveals that PKCδ-signaling pathways are directly involved at several points in energy metabolism. In particular, PKCδ affects glucose transport and utilization (77), gluconeogenesis and insulin secretion (78,79), insulin signaling (80-82), insulin resistance (83), and cellular oxidative stress (84). The latter is a key factor believed to drive the metabolic syndrome (31,85,86). In addition, lipoprotein metabolism and hepatic liponeogenesis were linked to PKCδ (87). With such broad relevance to regulation of energy homeostasis it comes as no surprise that genetic or pharmacologic manipulations impairing any of the four protein components of the PKCδ signalosome undercut the mitochondrial balance, profoundly affecting life span (88,89), obesity, and especially type 2 diabetes (90). Specifically, differences in PKCδ protein expression levels strongly influenced glucose utilization in mice. In excess, PKCδ predisposed mice towards obesity and metabolic syndrome (91). It seems that chronic activation of the PKCδ signaling pathway leading to preferred glucose fuel use at the expense of fat (which goes into storage) could be a factor in increased adiposity."

"How can chronic poison/"vitamin" A excess lead to pathology? The action of two inhibitory retinoids, AR (55) and fenretinide (105) may be informative. In cell culture experiments, these retinoids caused mitochondrial stress and necrotic cell death (25,58,106-109). Both retinoids are known to bind the PKCδ activation domain with similar affinity as retinol (28), but inexplicably they caused the hyper-activation of mitochondrial PKCδ (25) leading to cell death. This was reflected in one study by high levels of ROS (58), while in another AR-treated cells became depleted of ATP to a degree that they could no longer survive (107). The paradox, why AR (or feneretinide) can substitute for retinol as activating cofactors of PKCδ, but why this mode of activation leads to cell necrosis, remains unresolved. It is noteworthy that supranormal retinol levels (above 2 micromoles) are also toxic, as the inverted U-shaped retinol dose responses indicate (25). The common denominator may be uncontrolled ROS production stimulated by the inordinately high PDHC activity. The important realization is that both the concentration and the type of retinoid determine the function of PKCδ."

"Our findings represent the beginnings of an intra-mitochondrial control system of aerobic glycolysis. To the extent that mitochondria of a given cell are separate entities the question arises how this signaling system is coordinated among these organelles. Other questions left unaddressed by this review are the interplay with the opposing PKCε signal pathway that is also dependent on retinol, and indeed the crosstalk with the myriads of extra-mitochondrial signals that control OXPHOS. Unresolved is also the problem of how PKCδ, once activated, is turned off again, as it surely needs to be, because continuous signaling is lethal (84)."

"A mechanism wherein PKCδ oscillates between active (oxidized) and silent (reduced) forms would allow for real-time regulation of the PDHC (Figure 3). Retinol would be required to catalyze both the forward and reverse reactions. Still unclear is the nature of retinoid toxicity that arises when other retinoids, such as AR, substitute for retinol. However, if this finely tuned redox system were to be upset by a retinoid with different electronic properties (i.e., with different activation energies of their π-electrons), conceivably the forward, but not the reverse, reaction might be sustained, leaving the PKCδ stuck in the activated state which causes irreversible damage."​

@haidut - Is you following this thread?

--

Is this a sign of renal sufficiency?

I don't know what they mean. If I come across something relevant, I'll leave you a comment.

 

[Vinero]

Gallbladders, cholecystitis, cholelithiasis...caused by excess Poison/"Vitamin A", and the body tries NOT to absorb it and Vitamin D from the diet

"The quickest recipe for hypercalcemia is Poison/"Vitamin A" + Hormone D by mouth + large amounts of calcium"

Damn. I have been doing that a lot in the past. Consuming Vitamins A,D and K with high calcium foods.

 

[tca300]

@Amazoniac Thank you for confirming my importance, I will be sure to share this with my wife!

 

[tankasnowgod]

"The quickest recipe for hypercalcemia is Poison/"Vitamin A" + Hormone D by mouth + large amounts of calcium"

Damn. I have been doing that a lot in the past. Consuming Vitamins A,D and K with high calcium foods.

I don't think you'd have to worry. There doesn't seem to be any basis in reality for that statement by Garrett Smith.

First off, intramuscular injections of 600,000 IU Vitamin D are much more likely to cause hypercalcemia than vitamin D taken by mouth. Second, he admits in that post that he hasn't even read beyond the title of some of the studies he's basing his claim on. Third, Smith (and Generaux) seem ignorant of Vitamin K, which will always help prevent soft tissue calcification, especially K2. So I don't think you would have any reason to worry about soft tissue calcification or hypercalcemia.

And so far, nothing that Smith has presented or suggested in any way refutes what Peat has stated in this article- Calcium and Disease: Hypertension, organ calcification, & shock, vs. respiratory energy

 

[Tarmander]

Second, he admits in that post that he hasn't even read beyond the title of some of the studies he's basing his claim on.

It was only the one article that he did not have access to.

 

[Brother John]

Gallbladders, cholecystitis, cholelithiasis...caused by excess Poison/"Vitamin A", and the body tries NOT to absorb it and Vitamin D from the diet

Good one Charlie!
Thanks, Brother John

 

[Amazoniac]

- Vitamin A and inflammatory bowel diseases: from cellular studies and animal models to human disease

"The inflammatory events related to the development of IBD involve modifications in the permeability of the epithelial cells and intestinal microbiota patterns that trigger an imbalanced immune response [13]. This imbalance leads to the activation of dendritic cells and differentiation of näive CD4+T-cells into TH1, TH2, TH9 and TH17 with the release of pro-inflammatory cytokines such as TNF-α (Tumor Necrosis Factor-α), IFN-γ, Interleukin 1β (IL-1β), IL-6, IL-9, IL-12, IL-17, and IL-23."

"In patients with UC, the inflammatory process seems to be limited to the colon and rectum and is mainly mediated by TH2 and TH9 activation mediated by NKT (Natural Killers T cells) and production of IL-4, IL-5, IL-9, and IL-13. In CD patients, the inflammation involves skipped areas from mouth to anus, and the primary immune response is modulated by TH1 and TH17 resulting in the release of IFN-γ, IL-17, and TNF-α [40-41]."

"The transcription factor RA receptor-related orphan receptor γt (RORγt) also plays a fundamental role in the IBD pathogenesis once it represents a key transcription factor which determines the differentiation of naïve TH cells into the TH17 lineage and production of IL-17A, IL-17F, IL-22, IL-23 and colony-stimulating factors from TH17, NKT, and innate lymphoid cells. The main effects of IL-17 in promoting inflammation are conducted by the induction of TNFα, IL-1β, antimicrobial peptides, and matrix metalloproteinases in surrounding cells, resulting in the recruitment of macrophages and neutrophils. RORγt also accelerates the imbalance between TH17 and Treg cells leading to autoimmune diseases [42, 43]."

"In the intestines, the levels of RA levels are much higher than in other parts of the body and may play a role in the differentiation of TH cells (TH1, TH9, and TH17). The modulation of TH cells occurs directly or by priming the DtC [Direct-to-Consumer], and depend on the inflammatory conditions [44]."

"[..]large amounts of at-RA could reduce inflammatory processes in IBD patients. However, other findings show that RALDH1A (Aldehyde dehydrogenases 1 A) mRNA was augmented in CD intestinal mucosa suggesting that the increase in the RA in the gut could contribute to the development of IBD. Maybe the high expression of ALDH1A could be a compensatory strategy to low at-RA concentrations. The absence of VA also seems to be related to poor outcomes in the presence of diarrhea [24, 54-55]."

"[..]there is evidence that metabolites of VA can augment the risk for development of IBD as shown by a study that observed that the use of isotretinoin for 12 months increased the risk of UC. RA, in contrast to its potential against inflammation, in the face of inflammatory conditions, may maintain or even aggravate intestinal inflammation [37, 66-67]. Another interesting point is that high proportions of at-RA can stimulate T-cell differentiation into TH2 leading to the release of IL-4 and IL-5 [56, 68]."

"[..]authors have found that at-RA may exert a pivotal role in the maintenance of inflammation under some pathologic conditions. TH9 cells are induced by IL-2, IL-4, and TGF-β resulting in the release of IL-9. These cells are elevated in allergy, experimental infection and UC patients [69]. Some authors investigated the effects of RA in TH9 cells under inflammatory conditions and reported that this metabolite produced an opposite role leading to the prime of CD103+ DtCs (differentiated CCR9+ and a4b7+ T cells) and resulted in the induction of IFN-γ in the presence of TH1 and TH17. Furthermore, they observed the induction of IL-17 and in the presence of TGF-β and IL-4. RA-monocyte-derived DtC inhibited IL-9 and stimulated the expression of IFN-γ. For these reasons, authors postulated that under inflammatory conditions RA plays a role in the maintenance or aggravation of the inflammatory process in the bowel [36-37]."

"RA may also act by interaction cell to cell (costimulatory pathways) or in the presence of NK cells, modulate the release of IFN-γ [70-71]. These findings show that DtC may display an inflammatory nature stimulated by RA in the presence of inflammation, that is contrary to the well-known anti-inflammatory role of VA. A possibility is that RA may devote a dual role that depends on the pathologic condition, tissue type, and its concentration. Furthermore, depending on the gut microenvironment, RA can modulate TH1, TH17, and TH9 balance [37]."​

 

[Amazoniac]

- Interaction between Vitamin D and calcium

"It is possible to live without the active vitamin D metabolite 1,25(OH)2D and vitamin D receptor[*]. However, this requires a very high calcium intake as only passive diffusion of calcium in the intestine can supply the calcium for bone mineralization in this situation. An adequate vitamin D status makes calcium intake more flexible. A low calcium intake causes a high turnover of vitamin D metabolites, due to higher production of 1,25(OH)2D and higher breakdown of vitamin D metabolites. A low calcium intake causes or aggravates vitamin D deficiency while a high calcium intake is vitamin D sparing."

* "[..]when a very high calcium and lactose diet (“rescue diet”) is given to the VDR-null mouse the rickets is cured and the bone becomes well mineralized. This shows that vitamin D is not essential for bone mineralization while the problem of low calcium absorption can be overcome with a special diet to facilitate passive diffusion [5]. The VDR-null mouse has a human analogue i.e. patients with mutations leading to inactivation of the vitamin D receptor. This causes vitamin D dependent rickets type 2 or hereditary vitamin D resistant rickets associated with alopecia and severe rickets. This rickets can be cured by calcium infusion or by a very high calcium diet [6]"​

@Jennifer @Tarmander