How To Revert Hypervitaminosis A?

[JerkyPerky]

The mononitrate will boosts nitric oxide, which is not good. Maybe this is causing issues?

Possibly? I need to read up on how nitric oxide effects blood flow/vessels.

UPDATE:

Okay, so completely cutting out salt solved the problem with the black spots completely! I believe the swelling of my liver is somewhat relieved as well since the pressure in my right side was somewhat lighter this morning. I went from about 6-8 g salt down to 1 g and will keep it there for a while and see how I progress.

I believe I've read on this forum earlier how vitamin A toxicity has an effect on membrane stability or something. This could definitely be the case. Enabling diffusion of sodium into hepatocytes/disrupting the N+kinase pumps function --> cell swelling --> loss of liver function distrupting thrombopoietin synthesis/fluid shear stress destroying platelets --> excacerbated thrombocytopenia?????

Retinol/retinoids' effect on membranes I can't fully grasp, but the sodium retention seems like a real issue.

"The hypervitaminosis A, confirmed by a significant increase in tissue concentration of the vitamin, altered the hepatic content of the above mentioned cations. While Na and Zn increased..."
Effects of acute overdose of vitamin A on the hepatic content of K, Na, Mg, Fe, Cu and Zn, in rats. - PubMed - NCBI

"The harmful effect of an excess of the vitamin A was manifested in an increased content of Na+ in erythrocytes and also in decreased stability of the cells to acid hemolytics."
Effects of acute overdose of vitamin A on the hepatic content of K, Na, Mg, Fe, Cu and Zn, in rats. - PubMed - NCBI

"These results suggest that retinoid toxicity may indeed be related to a membrane effect"
Membrane effects of retinoids: Possible correlation with toxicity - ScienceDirect

"Hypervitaminosis A induces the following changes in rat kidney: decrease in sodium and potassium excretion and an increase of urinary volume."
Changes in sodium and potassium excretion and urinary volume in rats submitted to hypervitaminosis A. - PubMed - NCBI

 

[sunraiser]

@OP

For something functional and practical your early post seems to make the most sense. Copper could well have the capacity to massively aid retinol clearance and supplementing 2-4mg copper for a few weeks won't do huge harm.

Retinol and copper work together but if you're skewed in favour of active retinol for a while without robust copper intake then it's entirely possible you'll have an artificially inflated copper need for a little while to provide balance. This is hard through diet as liver provides too much retinol to achieve such a homeostasis.

I'll post in more detail on this in future but it feels very compelling to me at the moment. I'm seeing more and more people have luck with a similar approach but I can't be certain of anything so don't consider this prescriptive.

Considering your study on page 1 perhaps it'll feel right for you to try.

I'm unsure there are any other "active" forms of nutrients in the way retinol is in nature, so it makes sense for it to have a very specific and potentially debilitating consequence but also a specific resolution mechanism that might be more challenging to achieve in the short term via tolerable diet (lots of lobster and squid might get you to those copper levels though).

This is why eating "healthy" and overriding intuition/craving can be so dangerous, particularly in the context of vitamin A.

Just to note as I can't edit it - - - - - -this is COMPLETELY and utterly a speculative idea and not something to try for more than a few days to a week to see if you notice anything positve! I didn't intend it to come across in such a prescriptive way!

 

[Travis]

Possibly? I need to read up on how nitric oxide effects blood flow/vessels.
"The hypervitaminosis A, confirmed by a significant increase in tissue concentration of the vitamin, altered the hepatic content of the above mentioned cations. While Na and Zn increased..."
Effects of acute overdose of vitamin A on the hepatic content of K, Na, Mg, Fe, Cu and Zn, in rats. - PubMed - NCBI

"The harmful effect of an excess of the vitamin A was manifested in an increased content of Na+ in erythrocytes and also in decreased stability of the cells to acid hemolytics."
Effects of acute overdose of vitamin A on the hepatic content of K, Na, Mg, Fe, Cu and Zn, in rats. - PubMed - NCBI

"These results suggest that retinoid toxicity may indeed be related to a membrane effect"
Membrane effects of retinoids: Possible correlation with toxicity - ScienceDirect

"Hypervitaminosis A induces the following changes in rat kidney: decrease in sodium and potassium excretion and an increase of urinary volume."
Changes in sodium and potassium excretion and urinary volume in rats submitted to hypervitaminosis A. - PubMed - NCBI

This is interesting because Dr. Cone in the '70s had discovered that intracellular Na⁺ is a mitotic stimulus directly correlated with cell membrane potential (Cone, 1971). Cells proliferating quickly—especially cancer cells—are found to have greatly increased Na⁺ concentrations and no other ion, except for Cl⁻, consistently changes to a significant degree. Doctor Cone had proved that mitosis can be induced using Na⁺ and that it can be prevented by increasing* the cell membrane potential. The articles above made me wonder if retinoids' effects on Na⁺ could be partially responsible for the mitosis they induce. Since sodium's ability to stimulate mitosis is such a reliable phenomenon, perhaps acting through osmotic swelling, I would imagine that increased cytosolic Na⁺must be an important factor in all cases.

[*] By the word 'increased' here I mean its absolute value, i.e. ❘Ψ❘, is increased towards greater negativity.

 

[ecstatichamster]

This is interesting because Dr. Cone in the '70s had discovered that intracellular Na⁺ is a mitotic stimulus directly correlated with cell membrane potential (Cone, 1971). Cells proliferating quickly—especially cancer cells—are found to have greatly increased Na⁺ concentrations and no other ion, except for Cl⁻, consistently changes to a significant degree. Doctor Cone had proved that mitosis can be induced using Na⁺ and that it can be prevented by increasing* the cell membrane potential. The articles above made me wonder if retinoids' effects on Na⁺ could be partially responsible for the mitosis they induce. Since sodium's ability to stimulate mitosis is such a reliable phenomenon, perhaps acting through osmotic swelling, I would imagine that increased cytosolic Na⁺must be an important factor in all cases.

[*] By the word 'increased' here I mean its absolute value, i.e. ❘Ψ❘, is increased towards greater negativity.

@Travis do you think this is the basis for the high K low Na Gershon diet? Dr. Peat seems to think that it is.

 

[Travis]

@Travis do you think this is the basis for the high K low Na Gershon diet? Dr. Peat seems to think that it is.

I think that it's certainly part of it, but the Gerson approach also provides less methionine and omega−6 fatty acids. After reading about the cell cycle and how a cell divides, I think all three factors would act in synergy to slow the mitotic rate. Polyamines are of course needed to physically unwind the dNA for replication, and fatty acid synthesis needs to provide enough lipids for a new cell membrane. Sodium comes in ostensibly to increase the osmotic pressure of the cell's interior, providing the physical force needed to expand it against the extracellular space. Of course the cytoskeleton needs to be disassembled as well—explaining taxol and methoxyestradiol—and even the rate of glucose flux plays a significant role.

What correlates even more with the cell's mitotic rate, yet easier to measure, is the cell's membrane potential. Neurons having a high cell membrane potential of approximately −70 millivolts rarely divide. This is why lipofuscin only accumulates in the interior of neurons where it can be found at 75% by volume, in centenarians, as this 'age pigment' becomes diluted in other cells through mitosis. The average run-of-the-mill cell freely divides and has a membrane potential between about −40 mV and −50 mV. Cancerous cells can be found with potentials as low as −10 mV, and sodium concentrations 300% over controls.

The sodium concentration is correlated with the membrane potential, which is expected since the separation of ions can create an electrical potential. This is predicted by the Goldman–Hodgkin–Katz equation for cell membranes, and studies on prolactin-induced calcium influx show the expected potential changes. Conversely: an electric potential can induce a repartitioning of ions, leading a person to wonder 'what causes what?' Since the electric potential is a derivative property of matter and not matter itself, the sodium concentration can be considered more fundamental—a view shared by Dr. Cone. Sodium ions have the benefit of being tangible objects, and an electric potential alone cannot cause an osmotic force.

 

[JerkyPerky]

Just to note as I can't edit it - - - - - -this is COMPLETELY and utterly a speculative idea and not something to try for more than a few days to a week to see if you notice anything positve! I didn't intend it to come across in such a prescriptive way!

Hey sunraiser,

Thanks for replying. Your idea definitely has merit.

------------------------------------------------------------------------------
This long-**** thread with 16,000 posts relating to overdose of a form of retinoic acid through accutane, has a lot of info but is way too long to read.
A moderator on the forum made a post there that summarizes copper's relation to V.A breakdown in a somewhat conside manner:

Repairing the long-term damage from Accutane

Apparently copper is related to the breakdown-protein for V.A called CYP26 through NADPH, Oxygen-availablity through SOD1 and probably by enabling iron mobility - all of which are copper-dependant processes.

"These findings suggest that a copper-deficient diet may cause defective transport of vitamin A from liver to blood. "
Modification of vitamin A metabolism in rats fed a copper-deficient diet. - PubMed - NCBI
------------------------------------------------------------------------------

My problem is most likely just an imbalance between zinc-copper-iron due to supplemental zinc and long-term defective nutrition; hopefully it's not something genetic.

I'm waiting for my doc to respond, but since it's well below the UL of copper intake I might as well add in a couple of mg of copper from food like you suggested. I haven't noticed any problems with bileflow(skin/fecal color) so I can probably eliminate any potential excess. Thanks :)

I think that it's certainly part of it, but the Gerson approach also provides less methionine and omega−6 fatty acids. After reading about the cell cycle and how a cell divides, I think all three factors would act in synergy to slow the mitotic rate. Polyamines are of course needed to physically unwind the dNA for replication, and fatty acid synthesis needs to provide enough lipids for a new cell membrane. Sodium comes in ostensibly to increase the osmotic pressure of the cell's interior, providing the physical force needed to expand it against the extracellular space. Of course the cytoskeleton needs to be disassembled as well—explaining taxol and methoxyestradiol—and even the rate of glucose flux plays a significant role.

What correlates even more with the cell's mitotic rate, yet easier to measure, is the cell's membrane potential. Neurons having a high cell membrane potential of approximately −70 millivolts rarely divide. This is why lipofuscin only accumulates in the interior of neurons where it can be found at 75% by volume, in centenarians, as this 'age pigment' becomes diluted in other cells through mitosis. The average run-of-the-mill cell freely divides and has a membrane potential between about −40 mV and −50 mV. Cancerous cells can be found with potentials as low as −10 mV, and sodium concentrations 300% over controls.

The sodium concentration is correlated with the membrane potential, which is expected since the separation of ions can create an electrical potential. This is predicted by the Goldman–Hodgkin–Katz equation for cell membranes, and studies on prolactin-induced calcium influx show the expected potential changes. Conversely: an electric potential can induce a repartitioning of ions, leading a person to wonder 'what causes what?' Since the electric potential is a derivative property of matter and not matter itself, the sodium concentration can be considered more fundamental—a view shared by Dr. Cone. Sodium ions have the benefit of being tangible objects, and an electric potential alone cannot cause an osmotic force.

Glad my case can spark some interest! My actual knowledge in biochem is dreadful so sadly you already had me lost at mitotic rate and membrane potential.

 

[Richiebogie]

According to this article from 1944, the body seems to excrete beta carotene through the skin with sweat!

Yellow staining on clothing could be carotene leaving the body.

Perhaps exercise, a few saunas, spas, baths and showers assist with this removal?

Note below, axilla = armpit!

Josephs, Hugh. "Hypervitaminosis A and carotenemia." American Journal of Diseases of Children (1944)

Histologic examination shows that the carotene is found mostly in the superficial horny layer of the skin and that its concentration is less the deeper one goes. The fact that it is present in sweat and sebaceous material has led to the hypothesis that its presence in the skin is dependent on this excretion and the subsequent rubbing of the carotene into the horny layer. Its predominant occurrence in those areas in which the horny layer is particularly thick or in which sweating is most marked (palms and soles, forehead, nasolabial folds, axillas and groins) would tend to bear out this theory.

 

[postman]

Hey sunraiser,

Thanks for replying. Your idea definitely has merit.

------------------------------------------------------------------------------
This long-**** thread with 16,000 posts relating to overdose of a form of retinoic acid through accutane, has a lot of info but is way too long to read.
A moderator on the forum made a post there that summarizes copper's relation to V.A breakdown in a somewhat conside manner:

Repairing the long-term damage from Accutane

Apparently copper is related to the breakdown-protein for V.A called CYP26 through NADPH, Oxygen-availablity through SOD1 and probably by enabling iron mobility - all of which are copper-dependant processes.
"These findings suggest that a copper-deficient diet may cause defective transport of vitamin A from liver to blood. "
Modification of vitamin A metabolism in rats fed a copper-deficient diet. - PubMed - NCBI
------------------------------------------------------------------------------

My problem is most likely just an imbalance between zinc-copper-iron due to supplemental zinc and long-term defective nutrition; hopefully it's not something genetic.

I'm waiting for my doc to respond, but since it's well below the UL of copper intake I might as well add in a couple of mg of copper from food like you suggested. I haven't noticed any problems with bileflow(skin/fecal color) so I can probably eliminate any potential excess. Thanks :)



Glad my case can spark some interest! My actual knowledge in biochem is dreadful so sadly you already had me lost at mitotic rate and membrane potential.

How did things progress? Did you experiment with copper intake?