Vitamin A As A Powerful Treatment For Cancer

[haidut]

The use of vitamin a for leukemia-type cancers is nothing new and has been considered first-line therapy for decades. However, this study found out that activated vitamin A (all-trans-retinoic-acid, ATRA) blocks multiple vital cancer development pathways (in many cancer types) and also eliminates cancer stem cells - especially in cancers that are aggressive or treatment-resistant. I need to get access to the study to see what dose they used in the animal model of breast cancer, but it probably was not high otherwise they would have mentioned it in the press release as a factor limiting the "drug" usefulness.
I think this study is a big confirmation of Peat's ideas on the importance of vitamin A for metabolism and its multiple protective effects in a number of conditions including cancer. I'd venture a guess that a large part of its beneficial effects are due to its powerful anti-estrogenic properties.

It's kind of scary just how right the man is on some of the stuff he wrote about decades ago

http://www.sciencedaily.com/releases/20 ... 125651.htm
http://www.nature.com/nm/journal/vaop/n ... .3839.html

"...Their surprising discovery demonstrates that the vitamin A derivative ATRA (all-trans retinoic acid), a treatment for APL that is considered to be the first example of modern targeted cancer therapy, can block multiple cancer-driving pathways and, at the same time, eliminate cancer stem cells by degrading the Pin1 enzyme. Reported online in Nature Medicine, these novel findings suggest a promising new way to fight cancer -- particularly cancers that are aggressive or drug resistant."

 

[schultz]

Yah it is remarkable how often he is right.

Sometimes people will question Peat's ideas and think that he is just making things up because there seems to be no direct studies corroborating a few of his theories. What they fail to understand is that the man has read a ton of studies and has made connections in those studies to other things he has read. Combining this with his great understanding of science and open-mindedness, Ray can come up with brilliant conclusions on topics that haven't even been directly studied. It may take mainstream science 20, 30 or 40 years to aptly demonstrate some of this stuff.

Given the number of awesome studies you have posted this year Haidut, things are looking quite hopeful! Keep posting this stuff because I enjoy reading it and definitely appreciate it.

 

[haidut]

Yah it is remarkable how often he is right.

Sometimes people will question Peat's ideas and think that he is just making things up because there seems to be no direct studies corroborating a few of his theories. What they fail to understand is that the man has read a ton of studies and has made connections in those studies to other things he has read. Combining this with his great understanding of science and open-mindedness, Ray can come up with brilliant conclusions on topics that haven't even been directly studied. It may take mainstream science 20, 30 or 40 years to aptly demonstrate some of this stuff.

Given the number of awesome studies you have posted this year Haidut, things are looking quite hopeful! Keep posting this stuff because I enjoy reading it and definitely appreciate it.

Thanks, I'll try to keep it up. Lately it seems that pro-Peat studies are popping up everywhere. Maybe it's an indication of a general trend that medicine and science in general is starting to find the right path.

 

[Such_Saturation]

Wow check this: Retinoic acid treatment enhances lipid oxidation and inhibits lipid biosynthesis capacities in the liver of mice.

 

[haidut]

Wow check this: Retinoic acid treatment enhances lipid oxidation and inhibits lipid biosynthesis capacities in the liver of mice.

Very interesting, especially the part about RA activating UCP-2. So, I guess we can add vitamin A to the list of mitochondrial uncouplers? Any info on the dosage for mice?

 

[Such_Saturation]

It says all trans retinoic acid 10 or 100 mg/kg body weight during the 4 days before they were killed and for lipoprotein analysis an intermediate dose of 50 mg ATRA per kg of body weight per day.

 

[haidut]

It says all trans retinoic acid 10 or 100 mg/kg body weight during the 4 days before they were killed and for lipoprotein analysis an intermediate dose of 50 mg ATRA per kg of body weight per day.

So, that means 0.71mg/kg (10mg/kg in mice) or 7.14mg/kg (100mg/kg) for the 4 days.
The 50mg/kg ATRA translates to 3.57mg/kg for a human.
This means that the 10mg/kg is probably safe and usable in humans since it would translate to about 230,000 IU daily for 4 days. The other doses would be too high and probably toxic when taken daily.

 

[Such_Saturation]

I think I can see old-school bodybuilders back in the Sixties eating liver every day, seems like their sort of thing.

 

[haidut]

I think I can see old-school bodybuilders back in the Sixties eating liver every day, seems like their sort of thing.

Liver and eggs makes for a powerful androgenic steroid

 

[Such_Saturation]

I think I can see old-school bodybuilders back in the Sixties eating liver every day, seems like their sort of thing.

Liver and eggs makes for a powerful androgenic steroid

Oh yes I noticed

 

[TreasureVibe]

Would fish liver oil-derived vitamin A be oxidized like fish oil?

"...Their surprising discovery demonstrates that the vitamin A derivative ATRA (all-trans retinoic acid), a treatment for APL that is considered to be the first example of modern targeted cancer therapy, can block multiple cancer-driving pathways and, at the same time, eliminate cancer stem cells by degrading the Pin1 enzyme. Reported online in Nature Medicine, these novel findings suggest a promising new way to fight cancer -- particularly cancers that are aggressive or drug resistant."

This to me sounds very relevant, the ability to kill cancer stem cells.

 

[Amazoniac]

- From epidemiology and neurometabolism to treatment: Vitamin D in pathogenesis of glioblastoma Multiforme (GBM) and a proposal for Vitamin D + all-trans retinoic acid + Temozolomide combination in treatment of GBM

Here we review tumoricidal efficacy of Vitamin D analogues in glioblastoma multiforme (GBM) and potential synergisms with retinoic acid and temozolomide based on epidemiological and cellular studies. Epidemiological data suggest that winter birth is associated with higher risk of GBM, and GBM debulking in the winter enhanced mortality, which may relate with lower exposure to sunlight essential to convert cholecalciferol to Vitamin D. Comparative studies on blood bank specimens revealed that higher prediagnosis levels of calcidiol are associated with lower risk of GBM in elderly men. Supplemental Vitamin D reduced mortality in GBM patients in comparison to nonusers. Expression of Vitamin D Receptor is associated with a good prognosis in GBM. Conversely, Vitamin D increases glial tumor synthesis of neutrophins NGF and NT-3, the low affinity neurotrophin receptor p75NTR, IL-6 and VEGF, which may enhance glioma growth. Antitumor synergisms between temozolomide and Vitamin D and Vitamin D with Vitamin A derivatives were observed. Hence, we hypothesize that Calcitriol + ATRA (All-Trans Retinoic Acid) + Temozolomide – CAT combination might be a safer approach to benefit from Vitamin D in the management of high-grade glial tumors. Adding acetazolomide to this protocol may reduce the risk of pseudotumor cerebri, as both Vitamin D and Vitamin A excess may cause intracranial hypertension; this approach may provide further benefit as acetazolomide also exhibits anticancer activity."

They're now getting into specifics:

- Retinoids in the treatment of glioma: a new perspective

Spoiler

"Retinoid signaling is often compromised early in carcinogenesis, which has suggested a causal role for reduced vitamin A in tumor development.25 Hence, supplementation with pharmacologic doses of retinoids was thought to provide an effective treatment by correcting an underlying deficiency."

"Many [..] studies using neuronal and glial cell cultures [..] point to the beneficial effects of retinoic acid, suggesting that future therapeutic approaches should focus on the activation of retinoic acid signaling.30 In fact, retinoic acid has become the standard treatment for acute promyelocytic leukemia and has improved the complete remission rate.31 However, in general, supplementary vitamin A using retinyl esters or synthetic retinoids has only temporary benefits in cancer treatment and these appear to be outweighed over time by toxic effects, notably the occasionally fatal “retinoic acid syndrome” characterized by respiratory distress, pulmonary infiltrates, fever, hypotension, weight gain, renal failure, and leg edema.32–34"

"The alternative hypothesis suggested here is that alterations in retinoid metabolism associated with increased retinoid accumulation, expression, and toxicity induced by, eg, cigarette smoking, the use of hair dyes, irradiation, and exposure to certain chemicals and viruses, may be a common pathway for the development of many forms of cancer. In the case of gliomas, excessive and/or repeated exposure of the glial cells to retinoic acid due to the aforementioned risk factors, as well as traumatic brain injury, may result in alterations in the expression of retinoid receptor isotypes characterized by increased expression of RARα and reduced expression of RARβ."

"For instance, studies suggest associations between prior head injury and meningioma in men,9 between smoking unfiltered cigarettes and an increased risk of adult glioma,10,11 and a null or inverse association between glioma and alcohol consumption.12 An international case-control study showed an inverse association between allergic diseases and glioma, but not with meningioma.13 With regard to viral etiologies, during the 1950s and 1960s live polio vaccines were contaminated with simian monkey virus (SV40), and a case-control study of children with medulloblastoma showed that significantly more cases than controls had been exposed to SV40.14 A cohort study in Germany similarly indicated that exposure to SV40 in childhood was associated with a slightly higher risk of glioblastoma and medulloblastoma.15 However, a later study reported no difference in brain tumor risk between exposed and nonexposed groups.16"

"Two possible explanations are suggested for the temporary beneficial effects of retinoic acid analogs. First, the drugs could induce feedback inhibition to the endogenous synthesis of retinoic acid in the target tissues. For instance, Barua et al52 found that a single oral dose of retinoic acid (0.167 mM) in corn oil given to six healthy human subjects was associated with a mean decline in serum retinol levels of approximately 20% within one hour which lasted for 24 hours. The concept of feedback inhibition of retinol (and retinoic acid synthesis) is consistent with the notion that increased endogenous expression of retinoid rather than deficiency is associated with the pathogenesis of cancer. Thus, retinoic acid had opposite effects on a human glioblastoma cell line (GL-15) depending on its concentration. At low doses (0.01–1 μM), retinoic acid increased the proliferation of GL-15 cells via activation of a constitutively present signal transduction factor (STAT-3), whereas at higher concentrations (5–10 μM), retinoic acid inhibited GL-15 proliferation, induced apoptosis, and failed to activate STAT-3.53"

"A second possibility is that the modest therapeutic success of synthetic retinoic acid analogs could be due to their induction of increased RARβ expression, which is eventually repressed by other factors, possibly a corrective increase in the RARα isotype of the retinoic acid receptors. Indeed, there is evidence that RARβ is required for the antiproliferative effect exerted by retinoids and that RARβ is a potential tumor suppressor agent.54 This brings us to the concept that imbalances in the expression of retinoic acid receptor isotypes may contribute to oncogenesis."

"Although little is known about the postulated increase in RARα, there is growing evidence for the existence of RARβ underexpression in cancer []."

"RARβ is unique among the members of retinoic acid receptor isotype family because its gene expression is lost during the early development of numerous tumors. RARβ also has a demonstrated unique role as a tumor suppressor protein and regulator of retinoid inhibition of cell proliferation in several types of cancer. RARβ-deficient mice also display abnormalities in the vitreous body in the eyes and impaired abilities in locomotion and motor coordination. RARβ2, in particular, is suppressed at early stages of carcinogenesis, so agonists can be expected to be useful only in combination with agents that can reverse the silencing of RARβ2.54 What causes RARβ2 silencing? It is proposed that the silencing agent is RARα, due to excessive and prolonged exposure to retinoic acid. If this is the case, a RARα antagonist in combination with a RARβ agonist might be effective in the treatment of glioma and possibly other tumors."

"A more targeted approach involving the different isotypes and isoforms of the retinoic acid receptor and retinoid X receptor appears to be needed for treating cancer. If the present hypothesis is correct, and RARα is involved in tumor pathogenesis, then administration of retinoic acid analogs would be expected ultimately to worsen the disease. A more effective approach suggested by the hypothesis would be to combine an RARα antagonist with an RARβ agonist. However, no study to date has examined the impact of an RARα antagonist as a potential treatment for cancer. As noted, treatment strategies to date involving retinoids have been based on the supposition that a retinoid deficiency contributes to the development of cancer."

"RARα and RARβ are functionally interdependent in that, if RARα is antagonized, endogenous beta signaling is not activated, an effect that could be overcome by providing exogenous RARβ agonist.60 Hence, the proposed use of an RARα antagonist in cancer treatment would require simultaneous supplementation with an RARβ agonist."

"It remains for future research to determine whether these specifications will be met by the proposed combination of an RARα antagonist and an RARβ agonist for the treatment of glioma."

- Minocycline in Treating Glioblastoma Multiforme: Far beyond a Conventional Antibiotic

Spoiler

"RAs have been shown to be physiologically controlling regulators of embryonic development, vision, fertility, bone-forming, hematopoiesis, differentiation, and growth [86]. The RA function is primarily regulated by members of the subfamily of RA receptor (R) α, RARβ, and RARγ, which belong to the superfamily of transcription factors in the nuclear receptor [87]. Overexpression of RARγ plays a role in the growth and differentiation of tumor cells through nongenomic activation of the PI3K/Akt and NF-κB signaling pathways [88, 89]. RARs have also been identified as cell growth modulators, differentiation, and apoptosis [90]. Abnormal expression and function of RARs, in particular, are frequently involved in cancer growth, inflammation, and development [91]. It has been shown that the anti-inflammatory effects of minocycline are mediated by RAR signaling [92]. Furthermore, Regan et al. have shown that the growth-inhibitory mechanism of minocycline on human prostate cancer cells was through triggering the RAR signaling pathway [93]."