Vitamin A (retinol) reduces hepatic cancer incidence by 89%!

haidut

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I know a lot of people here avoid taking vitamin A or do so at very low doses out of fear of liver toxicity. In theory, anything that is toxic to the liver would tend to cause hepatic carcinoma in the long run. However, in the case of vitamin A (retinol) not only there seems to be no liver toxicity but a hefty dose reduced liver cancer incidence by 89%. At half the dosage, the protection was still remarkable with over 83% reduction. The form used was retinol acetate and the fact that it has many studies touting its anti-cancer effects was one of the reasons I chose it for my vitamin supplement.

http://www.ncbi.nlm.nih.gov/pubmed/6928249

"...Control mice autopsied at 12 months of age or older showed a 70% incidence of hepatomas, whereas the incidences were approximately 11, 17, and 46% in mice fed 83, 41, and 21 mg RA/kg diet, respectively."

The 83mg/kg of diet for mice translates into a human dose of 300,000+ IU per day, so that's definitely within the range of the doses of retinol for which modern medicine claims should cause liver damage.
 

Kray

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Re: Vitamin A (retinol) reduces hepatic cancer incidence by

Just saw your post here-- what about retinol acetate vs. retinol palmitate as sources for supplementation? Please address in your response to my other query from your retinol discussion. :)
 
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haidut

haidut

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Re: Vitamin A (retinol) reduces hepatic cancer incidence by

classicallady said:
Just saw your post here-- what about retinol acetate vs. retinol palmitate as sources for supplementation? Please address in your response to my other query from your retinol discussion. :)


I think both are equally good. I use acetate b/c it is easier for me to find high-purity (99%) and a lot of cancer-prevention and skin health studies in Russia were done with acetate. So, I am inclined to think there is a reason why Russian doctors chose acetate.
Anyways, I have personally tries both types and both give me very good effects on skin health and vision. At high doses (50,000 IU) I get a drop in estrogen, since vitamin A is a known aromatase inhibitor as well.
 

mouse

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Re: Vitamin A (retinol) reduces hepatic cancer incidence by

It might be related to Vitamin A increasing GNMT, as GNMT is a potent anticarcingen (in all tissue) through a mechanism that is unrelated to methylation.
 

Kray

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Re: Vitamin A (retinol) reduces hepatic cancer incidence by

haidut said:
classicallady said:
Just saw your post here-- what about retinol acetate vs. retinol palmitate as sources for supplementation? Please address in your response to my other query from your retinol discussion. :)


I think both are equally good. I use acetate b/c it is easier for me to find high-purity (99%) and a lot of cancer-prevention and skin health studies in Russia were done with acetate. So, I am inclined to think there is a reason why Russian doctors chose acetate.
Anyways, I have personally tries both types and both give me very good effects on skin health and vision. At high doses (50,000 IU) I get a drop in estrogen, since vitamin A is a known aromatase inhibitor as well.

Thanks for the information. Sorry I missed it earlier. Does either the acetate or palmitate come from fish liver sources? I have this brand on hand and don't know what form of A comes from the fish liver they use, but are they all the same source? Is fish liver not acceptable? Thanks-
http://www.iherb.com/Carlson-Labs-Vitam ... =null&ic=4
 

aguilaroja

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Re: Vitamin A (retinol) reduces hepatic cancer incidence by

haidut said:
I know a lot of people here avoid taking vitamin A or do so at very low doses out of fear of liver toxicity....However, in the case of vitamin A (retinol) not only there seems to be no liver toxicity but a hefty dose reduced liver cancer incidence by 89%. At half the dosage, the protection was still remarkable with over 83% reduction....

Yes, there's evidence about vitamin A being protective in certain animal liver cancer models. The not-so-Peaty-y melatonin in combination was found to be useful too:

http://www.ncbi.nlm.nih.gov/pubmed/10813094
Folia Biol (Praha). 2000;46(2):73-6.
Effects of retinyl acetate and melatonin on N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats. A preliminary report. Bojková B1, Kubatka P, Môciková K, Mníchová M, Ahlersová E, Ahlers I.

"The tumour incidence in the control group was 88%, in the group treated with RA 80% and in the group treated with Mel 61%. A substantial decrease in tumour incidence to 37% was noted in the group treated with RA plus Mel."


I profess mostly ignorance about Vitamin A, and am agnostic about the little I have read. While I do not agree with Dr. Peat on every topic, I have mainly abided by the understanding that there is a window of vitamin A where adequate vit. A is important and excess vit. A is concerning.

I've followed the views of Dr. Peat & Dr. Barnes that the carotenes, as unsaturated oils, are best avoided. I also avoid melatonin supplements.

As main unworthy so-called scientific works have shown, it's easy to cherry-pick or slant in any direction. To be as clear as possible: I don't think haidut is doing this, and his many lines of inquiry and experiment are admirable.

There are contexts of vitamin A action for which I have no integrated view. There seem both plenty of reasons for intrigue and for caution. Some are layed out in the vitamin A wikipedia page (I'm not saying that wikipedia is consistently a go-to resource, just that some vit. A points are raised.)

http://www.ncbi.nlm.nih.gov/pubmed/6487822
Breast Cancer Res Treat. 1984;4(3):205-8.
Stimulation by neonatal treatment with vitamin A of spontaneous mammary tumor development in GRS/A mice. Nagasawa H.

http://www.ncbi.nlm.nih.gov/pubmed/21967161
Nutr Rev. 2011 Oct;69(10):613-24. doi: 10.1111/j.1753-4887.2011.00425.x.
Vitamin A and clefting: putative biological mechanisms. Ackermans MM1, Zhou H, Carels CE, Wagener FA, Von den Hoff JW.

"Excess vitamin A can cause congenital malformations such as spina bifida and cleft palate....Excessive vitamin A may disturb all three stages of palatogenesis: 1) during shelf outgrowth, it may decrease cell proliferation and thus prevent tissue development; 2) it may prevent shelf elevation by affecting extracellular matrix composition and hydration; and 3) during shelf fusion, it may affect epithelial differentiation and apoptosis, which precludes the formation of a continuous palate."

http://www.ncbi.nlm.nih.gov/pubmed/20865785
Birth Defects Res A Clin Mol Teratol. 2010 Oct;88(10):895-905. doi: 10.1002/bdra.20721.
The neurobehavioral teratology of retinoids: a 50-year history. Adams J.

"studies demonstrated that adverse effects on postnatal behavior could be produced in animals exposed to doses of vitamin A lower than those that were teratogenic or impacted growth."

http://www.ncbi.nlm.nih.gov/pubmed/16469975
Am J Clin Nutr. 2006 Feb;83(2):191-201.
The acute and chronic toxic effects of vitamin A. Penniston KL1, Tanumihardjo SA.
"Osteoporosis and hip fracture are associated with preformed vitamin A intakes that are only twice the current RDA."

http://jid.oxfordjournals.org/content/196/7/965.long
Unraveling the Contradictions of Vitamin A and Infectious Diseases in Children
Margaret Kosek and Richard A. Oberhelman2
"Somewhat contradictory to the impact that vitamin A has on child mortality, its effects on morbidity are not consistently evident. It was reasonable to expect, given the large reductions in mortality, that vitamin A would modify the incidence and severity of the principal causes of child mortality—that is, lower respiratory tract infections, diarrhea, and malaria. Research findings, taken together, suggest that vitamin A decreases the severity and duration of diarrheal disease. However, the body of evidence does not support a protective effect of vitamin A supplementation on morbidity related to respiratory tract infections, and the evidence for malaria is too limited and contradictory for convincing conclusions to be drawn"
 

himsahimsa

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Re: Vitamin A (retinol) reduces hepatic cancer incidence by

I have seen claims that A, D and K2 must all be present and an imbalance of A relative to D will cause disease. Free living humans would probably have got A and D mostly from livers and would have always got them together. Not counting sun derived D, which comes with an off switch. I have never seen a study in which it was stated that A was controlled when observing the effects of D or vice versa. Forget K2. Most don't even discriminate it from K1. Same goes for iodine, I never see that they control for selenium. It seems oddly dopy for people who you would think would think.

I'll find some links (after a while).
 

aguilaroja

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Re: Vitamin A (retinol) reduces hepatic cancer incidence by

himsahimsa said:
I have seen claims that A, D and K2 must all be present and an imbalance of A relative to D will cause disease...I have never seen a study in which it was stated that A was controlled when observing the effects of D or vice versa.

There is little attention paid to interactions of two or three factors in most "sciences". If the science enterprises were guided by ecological scientific thinking, they would be very different.

There are bits out there about interactions, and in some cases synergies. Some generalizations that sound true deserve scrutiny. For instance,there is dogma that "B vitamins should be taken altogether" that I doubt is true, or even neutral in consequence. There are plenty of "health" "expert" "advocates" outside the Peat circle who make claims with more zeal than assessment. The claims seem less than compelling in all directions.

http://www.ncbi.nlm.nih.gov/pubmed/22149065
Nutr Cancer. 2012;64(1):57-64. doi: 10.1080/01635581.2012.630552. Epub 2011 Dec 9.
Effects of vitamin D3 and calcium supplementation on serum levels of tocopherols, retinol, and specific vitamin D metabolites.
Chai W1, Bostick RM, Ahearn TU, Franke AA, Custer LJ, Cooney RV.
"At baseline, γT levels were inversely associated with 25[OH]D (r = -0.31, P = 0.004). With vitamin D(3) plus calcium treatment, serum α-tocopherol decreased 14% (P = 0.04), whereas similar changes in γT (19% lower, P = 0.14) were observed. No significant effects were observed for D(3) supplementation on leptin or retinol levels. These results are consistent with the hypothesis that vitamin D(3) ± calcium affects serum tocopherol and 25[OH]D(2) levels"

http://www.ncbi.nlm.nih.gov/pubmed/11585356
J Bone Miner Res. 2001 Oct;16(10):1899-905.
Vitamin A antagonizes calcium response to vitamin D in man.
Johansson S1, Melhus H.

http://www.ncbi.nlm.nih.gov/pubmed/12612152
J Nutr. 2003 Mar;133(3):777-83.
Bone resorption activity of all-trans retinoic acid is independent of vitamin D in rats.
Rohde CM1, DeLuca H.

Horm Metab Res. 2009 Apr;41(4):277-80. doi: 10.1055/s-0028-1103287. Epub 2008 Dec 3.
Influence of neonatal vitamin A or vitamin D treatment on the concentration of biogenic amines and their metabolites in the adult rat brain. Tekes K1, Gyenge M, Folyovich A, Csaba G.
"Vitamin A treatment as hormonal imprinting significantly decreased 5HIAA levels in each brain region. Vitamin D imprinting significantly elevated DA only in the brainstem and HVA levels in striatum and hypothalamus."
 
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haidut

haidut

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Re: Vitamin A (retinol) reduces hepatic cancer incidence by

aguilaroja said:
haidut said:
I know a lot of people here avoid taking vitamin A or do so at very low doses out of fear of liver toxicity....However, in the case of vitamin A (retinol) not only there seems to be no liver toxicity but a hefty dose reduced liver cancer incidence by 89%. At half the dosage, the protection was still remarkable with over 83% reduction....

Yes, there's evidence about vitamin A being protective in certain animal liver cancer models. The not-so-Peaty-y melatonin in combination was found to be useful too:

http://www.ncbi.nlm.nih.gov/pubmed/10813094
Folia Biol (Praha). 2000;46(2):73-6.
Effects of retinyl acetate and melatonin on N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats. A preliminary report. Bojková B1, Kubatka P, Môciková K, Mníchová M, Ahlersová E, Ahlers I.

"The tumour incidence in the control group was 88%, in the group treated with RA 80% and in the group treated with Mel 61%. A substantial decrease in tumour incidence to 37% was noted in the group treated with RA plus Mel."


I profess mostly ignorance about Vitamin A, and am agnostic about the little I have read. While I do not agree with Dr. Peat on every topic, I have mainly abided by the understanding that there is a window of vitamin A where adequate vit. A is important and excess vit. A is concerning.

I've followed the views of Dr. Peat & Dr. Barnes that the carotenes, as unsaturated oils, are best avoided. I also avoid melatonin supplements.

As main unworthy so-called scientific works have shown, it's easy to cherry-pick or slant in any direction. To be as clear as possible: I don't think haidut is doing this, and his many lines of inquiry and experiment are admirable.

There are contexts of vitamin A action for which I have no integrated view. There seem both plenty of reasons for intrigue and for caution. Some are layed out in the vitamin A wikipedia page (I'm not saying that wikipedia is consistently a go-to resource, just that some vit. A points are raised.)

http://www.ncbi.nlm.nih.gov/pubmed/6487822
Breast Cancer Res Treat. 1984;4(3):205-8.
Stimulation by neonatal treatment with vitamin A of spontaneous mammary tumor development in GRS/A mice. Nagasawa H.

http://www.ncbi.nlm.nih.gov/pubmed/21967161
Nutr Rev. 2011 Oct;69(10):613-24. doi: 10.1111/j.1753-4887.2011.00425.x.
Vitamin A and clefting: putative biological mechanisms. Ackermans MM1, Zhou H, Carels CE, Wagener FA, Von den Hoff JW.

"Excess vitamin A can cause congenital malformations such as spina bifida and cleft palate....Excessive vitamin A may disturb all three stages of palatogenesis: 1) during shelf outgrowth, it may decrease cell proliferation and thus prevent tissue development; 2) it may prevent shelf elevation by affecting extracellular matrix composition and hydration; and 3) during shelf fusion, it may affect epithelial differentiation and apoptosis, which precludes the formation of a continuous palate."

http://www.ncbi.nlm.nih.gov/pubmed/20865785
Birth Defects Res A Clin Mol Teratol. 2010 Oct;88(10):895-905. doi: 10.1002/bdra.20721.
The neurobehavioral teratology of retinoids: a 50-year history. Adams J.

"studies demonstrated that adverse effects on postnatal behavior could be produced in animals exposed to doses of vitamin A lower than those that were teratogenic or impacted growth."

http://www.ncbi.nlm.nih.gov/pubmed/16469975
Am J Clin Nutr. 2006 Feb;83(2):191-201.
The acute and chronic toxic effects of vitamin A. Penniston KL1, Tanumihardjo SA.
"Osteoporosis and hip fracture are associated with preformed vitamin A intakes that are only twice the current RDA."

http://jid.oxfordjournals.org/content/196/7/965.long
Unraveling the Contradictions of Vitamin A and Infectious Diseases in Children
Margaret Kosek and Richard A. Oberhelman2
"Somewhat contradictory to the impact that vitamin A has on child mortality, its effects on morbidity are not consistently evident. It was reasonable to expect, given the large reductions in mortality, that vitamin A would modify the incidence and severity of the principal causes of child mortality—that is, lower respiratory tract infections, diarrhea, and malaria. Research findings, taken together, suggest that vitamin A decreases the severity and duration of diarrheal disease. However, the body of evidence does not support a protective effect of vitamin A supplementation on morbidity related to respiratory tract infections, and the evidence for malaria is too limited and contradictory for convincing conclusions to be drawn"


Yeah, I don't cherry pick on purpose. It's just that I was researching the vitamin A effects at that time and came upon that study. My take would be that if the cancer reducing effect is not a statistical error it would likely be due to a large part to the anti-estrogen effects of retinol and trans retinoic acid. Peat has written that estrogen is the biggest burden for the liver and if vitamin A can produce a measurable drop in estrogen levels that would certainly help. But there may be other pathways as well.
 

mosaic01

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The study notes that there was no difference in mammary carcinomas between controls and RA-fed mice. It also notes that retinol induced "severe damage to most articulations" (joints).

The lowest dose that only had a slight protective effect (46% vs 70%) would translate to around 80,000 IU per day for humans.

So it is clear that whatever is going on here has nothing to do with what would be considered a physiological dose by common definitions (for example, 3000 IU per day).

Since the mice would store most of the retinol in their livers, this local protective effect may relate to the ability of retinol to act as a chemotherapeutic agent in extremely large doses by killing cancer cells.

Clinical trials using retinoids exerted beneficial therapeutic effects in solid tumors such as breast cancer, cervical cancer, renal cancer, head and neck cancer, basal cell skin cancer, and prostate cancer, but the therapy response to retinoids was often limited to a small part of treated patients


Thus, this mouse study shows that retinol is a very potent poison, and like other poisons, can kill tumors.
 
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Clyde

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The study notes that there was no difference in mammary carcinomas between controls and RA-fed rats. It also notes that retinol induced "severe damage to most articulations" (joints).

The lowest dose that only had a slight protective effect (46% vs 70%) would translate to around 80,000 IU per day for humans.

So it is clear that whatever is going on here has nothing to do with what would be considered a physiological dose by common definitions (for example, 3000 IU per day).

Since the rats would store most of the retinol in their livers, this local protective effect may relate to the ability of retinol to act as a chemotherapeutic agent in extremely large doses by killing cancer cells.




Thus, this rat study shows that retinol is a very potent poison, and like other poisons, can kill tumors.
Very useful context. Thanks for digging in.
 

Richiebogie

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Reducing incidence of liver cancer sounds great.

However if it increases morbidity from multiple other causes then that may not be what you are looking for.

Might suit those with particular phobia for hepatic cancer!
 

charlie

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It also notes that retinol induced "severe damage to most articulations" (joints).
So retinol causes arthritis. This is why when people in the low toxin groups go on the diet their arthritis goes away.

Since the mice would store most of the retinol in their livers, this local protective effect may relate to the ability of retinol to act as a chemotherapeutic agent in extremely large doses by killing cancer cells.
So while it did burn away the cancer, it destroyed the joints on the way to the liver and who knows what else.
The 83mg/kg of diet for mice translates into a human dose of 300,000+ IU per day, so that's definitely within the range of the doses of retinol for which modern medicine claims should cause liver damage.
:confused2
 

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