Hormonal Treatment For Advanced Prostate And Breast Cancer

[boxers]

Will do, ill add psa to my next labs

 

[Braveheart]

PSA should be 4 or less. Mine was as high as 13000

There are ranges for PSA depending on age...that number 4 is a little too scary...for example someone my age (73) can have PSA 9-12 or thereabouts....can't find my reference right now but easily found on Dr Google.

 

[Obi-wan]

There are ranges for PSA depending on age...that number 4 is a little too scary...for example someone my age (73) can have PSA 10-12 or thereabouts....can't find my reference right now

There are ranges for PSA depending on age...that number 4 is a little too scary...for example someone my age (73) can have PSA 10-12 or thereabouts....can't find my reference right now

Its all about PSA acceleration

 

[Braveheart]

Its all about PSA acceleration

Exactly

 

[Travis]

This is why I take 50-100 mgs of USP Progesterone daily along with Firmagon and Xtandi

After investigating lycopene's mechanism of action, I've concluded that it's an androgen inhibitor.

The fist hint to this effect had come from an article by Dae Joong Kim in which both male and female rats had been treated with nitrosamines. He had reported approximate fourfold and fivefold reductions in tumor multiplicity and incidence, respectively, and yet 'no such effect was observed for females.'⁽¹⁾ Regardless of these sex-specific effects, Doctor Kim had explained them though 'connexin 43 mRNA' and lycopene's most-commonly-invoked mechanism: its general antioxidant nature. After reading this article, I had stopped thinking about lycopene as an antioxidant altogether.

Lycopene is quite similar to squalene, the immediate precursor from lanosterol. After a counterintuitive polycylization by lanosterol synthase, its eponymous steroid is formed. Just one enzyme is responsible for the entire polycylization, yet this does require prior epoxidation of squalene by intuitively-named squalene epoxidase. Due to structural similarity, an a priori assumption that lycopene is either: (1) an inhibitor of, or (2) substrate for at least one of these enzymes seems reasonable.

Should a person entertain the idea that lycopene is actually a substrate for lanosterol synthase they're led to a novel compound having no mention in biochemical literature. Even should it's extra-long 'tail' be docked by P₄₅₀-scc, thus simplifying the structure, the resulting compound would still be an the uncharacterized mongrel called 4β-(5-dimethyl-4-hexenyl)-progesterone—but since it doesn't actually exist you can call it anything.

Yet, the idea that lycopene is an inhibitor for either squalene epoxidase or lanosterol synthase gets support from a 1997 study on cholesterol synthesis. When added to macrophages, lycopene is incorporated at over twice the rate as β-carotene and inhibits the cellular cholesterol synthesis to a greater extent. When given to humans at a dose of 60 milligrams per day, lycopene leads to a 14% reduction of circulating cholesterol after three months.

Although lycopene is a universal cholesterol inhibitor, reductions of merely 14% cannot explain the magnitude of the reductions observed in cancer incidence rates and experimental rodent carcinogenesis; nor can cholesterol alone explain it's sex specific effects. However! lycopene's pharmacokinetic distribution does explain this effect, both of these effects, and quite easily. Lycopene concentrates approximately fifteenfold in the testes over the serum concentration, and nearly sevenfold in the adrenal glands:⁽³⁾

These are expressed in units equivalent to the micromolar (μM) concentrations used by Bianca Furman when studying lycopene's cholesterol inhibiting effect. From her dose response curve pictured above, human testicular concentrations can reach levels shown to inhibit cholesterol synthesis by 55%. Since this is the precursor for testosterone and the testes are its main organ of synthesis, this should translate into lower circulating androgens.

A forty-five percent reduction in circulating testosterone had been reported after the administration of 700·μg lycopene per day, in F344 rats, for four days.⁽⁵⁾ Circulating cortisol had also been reduced by half in Wistar rats fed lycopene—at 10·mg per kilogram, per day, for four weeks—in a separate experiment,⁽⁵⁾ perhaps not too surprising when considering its distribution in adrenal glands:

click to embiggen

Not surprisingly, lycopene had also lowered malondialdehyde—a marker for lipid peroxidation.

This antioxidant, squalene-mimicking, steroid-inhibiting, yet testicular- & andreno-concentrating carotenoid in tomatoes then can be framed primarily as a general antiandrogen and secondarily as an inhibitor of adrenocorticoid synthesis. Epidemiological studies do not disappoint, obviously, as it had been statistical correlations that had formed the impetus for most subsequent lycopene research. Dose-dependent reductions in prostate cancer have been consistently observed as far back as 1999,⁽⁶⁾ effects not observed with other carotenoids:

Is this effect observed in females? you bet it's not. Not only is there no consistent relationship between female cancers and lycopene, the results can sometimes go the opposite way.⁽⁷⁾ This is a consistent observation, and there are many more studies highlighting this general trend:

Lycopene appears on all counts to be more than merely a biomarker for general fruit & vegetable intake; and in fact, lycopene bears little correlation to general fruit & vegetable intake (r=.11) due to tomato sauce being such a versatile and ubiquitous dietary element.⁽⁸⁾ Lycopene also concentrates in the human prostate gland.

'Lycopene concentrations vary greatly among tissues, with the highest concentrations observed in the adrenal gland and testes. Lycopene is also highly concentrated in the prostate and, in some men, is present at levels comparable to those that are biologically active in vitro.' ―Gann​

Since lycopene appears to inhibit universal androgen synthesis in testes, and also steroid synthesis in the prostate, it could work synergistically with epigallocatechin gallate: a water-soluble green tea catechol that blocks the androgen receptor in low micromolar concentrations.⁽⁹⁾

And besides oleamide, derived via olive oil, lycopene could also help explain that stereotypical Italian psychology.

[1] Kim, Dae Joong. "Chemoprevention by lycopene of mouse lung neoplasia after combined initiation treatment with DEN, MNU and DMH." Cancer letters (1997)
[2] Fuhrman, Bianca. "Hypocholesterolemic effect of lycopene and β-carotene is related to suppression of cholesterol synthesis and augmentation of LDL receptor activity in macrophages." Biochemical and biophysical research communications (1997)
[3] Stahl, Wilhelm. "Cis–trans isomers of lycopene and β-carotene in human serum and tissues." Archives of biochemistry and biophysics (1992)
[4] Campbell, Jessica. "Serum testosterone is reduced following short-term phytofluene, lycopene, or tomato powder consumption in F344 rats." The Journal of nutrition (2006)
[5] Eze, Ejike Daniel. "Lycopene attenuates diabetes-induced oxidative stress in Wistar rats." Journal of Diabetes and Endocrinology (2018)
[6] Gann, Peter. "Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis." Cancer research (1999)
[7]Vecchia, Carlo La. "Tomatoes, lycopene intake, and digestive tract and female hormone-related neoplasms." Experimental Biology and Medicine (2002)
[8] Giovannucci, Edward. "Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature." Journal of the national cancer institute (1999)
[9] Siddiqui, Imtiaz. "Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer." The FASEB Journal (2011)​

 

[Braveheart]

After investigating lycopene's mechanism of action, I've concluded that it's an androgen inhibitor.

The fist hint to this effect had come from an article by Dae Joong Kim in which both male and female rats had been treated with nitrosamines. He had reported approximate fourfold and fivefold reductions in tumor multiplicity and incidence, respectively, and yet 'no such effect was observed for females.'⁽¹⁾ Regardless of these sex-specific effects, Doctor Kim had explained them though 'connexin 43 mRNA' and lycopene's most-commonly-invoked mechanism: its general antioxidant nature. After reading this article, I had stopped thinking about lycopene as an antioxidant altogether.

View attachment 9676

Lycopene is quite similar to squalene, the immediate precursor from lanosterol. After a counterintuitive polycylization by lanosterol synthase, its eponymous steroid is formed. Just one enzyme is responsible for the entire polycylization, yet this does require prior epoxidation of squalene by intuitively-named squalene epoxidase. Due to structural similarity, an a priori assumption that lycopene is either: (1) an inhibitor of, or (2) substrate for at least one of these enzymes seems reasonable.

Should a person entertain the idea that lycopene is actually a substrate for lanosterol synthase they're led to a novel compound having no mention in biochemical literature. Even should it's extra-long 'tail' be docked by P₄₅₀-scc, thus simplifying the structure, the resulting compound would still be an the uncharacterized mongrel called 4β-(5-dimethyl-4-hexenyl)-progesterone—but since it doesn't actually exist you can call it anything.

Yet, the idea that lycopene is an inhibitor for either squalene epoxidase or lanosterol synthase gets support from a 1997 study on cholesterol synthesis. When added to macrophages, lycopene is incorporated at over twice the rate as β-carotene and inhibits the cellular cholesterol synthesis to a greater extent. When given to humans at a dose of 60 milligrams per day, lycopene leads to a 14% reduction of circulating cholesterol after three months.

View attachment 9677

Although lycopene is a universal cholesterol inhibitor, reductions of merely 14% cannot explain the magnitude of the reductions observed in cancer incidence rates and experimental rodent carcinogenesis; nor can cholesterol alone explain it's sex specific effects. However! lycopene's pharmacokinetic distribution does explain this effect, both of these effects, and quite easily. Lycopene concentrates approximately fifteenfold in the testes over the serum concentration, and nearly sevenfold in the adrenal glands:⁽³⁾

View attachment 9678

These are expressed in units equivalent to the micromolar (μM) concentrations used by Bianca Furman when studying lycopene's cholesterol inhibiting effect. From her dose response curve pictured above, human testicular concentrations can reach levels shown to inhibit cholesterol synthesis by 55%. Since this is the precursor for testosterone and the testes are its main organ of synthesis, this should translate into lower circulating androgens.

A forty-five percent reduction in circulating testosterone had been reported after the administration of 700·μg lycopene per day, in F344 rats, for four days.⁽⁵⁾ Circulating cortisol had also been reduced by half in Wistar rats fed lycopene—at 10·mg per kilogram, per day, for four weeks—in a separate experiment,⁽⁵⁾ perhaps not too surprising when considering its distribution in adrenal glands:

View attachment 9679 View attachment 9680 View attachment 9681 click to embiggen

Not surprisingly, lycopene had also lowered malondialdehyde—a marker for lipid peroxidation.

This antioxidant, squalene-mimicking, steroid-inhibiting, yet testicular- & andreno-concentrating carotenoid in tomatoes then can be framed primarily as a general antiandrogen and secondarily as an inhibitor of adrenocorticoid synthesis. Epidemiological studies do not disappoint, obviously, as it had been statistical correlations that had formed the impetus for most subsequent lycopene research. Dose-dependent reductions in prostate cancer have been consistently observed as far back as 1999,⁽⁶⁾ effects not observed with other carotenoids:

View attachment 9682

Is this effect observed in females? you bet it's not. Not only is there no consistent relationship between female cancers and lycopene, the results can sometimes go the opposite way.⁽⁷⁾ This is a consistent observation, and there are many more studies highlighting this general trend:

View attachment 9683

Lycopene appears on all counts to be more than merely a biomarker for general fruit & vegetable intake; and in fact, lycopene bears little correlation to general fruit & vegetable intake (r=.11) due to tomato sauce being such a versatile and ubiquitous dietary element.⁽⁸⁾ Lycopene also concentrates in the human prostate gland.

'Lycopene concentrations vary greatly among tissues, with the highest concentrations observed in the adrenal gland and testes. Lycopene is also highly concentrated in the prostate and, in some men, is present at levels comparable to those that are biologically active in vitro.' ―Gann​

Since lycopene appears to inhibit universal androgen synthesis in testes, and also steroid synthesis in the prostate, it could work synergistically with epigallocatechin gallate: a water-soluble green tea catechol that blocks the androgen receptor in low micromolar concentrations.⁽⁹⁾

And besides oleamide, derived via olive oil, lycopene could also help explain that stereotypical Italian psychology.

[1] Kim, Dae Joong. "Chemoprevention by lycopene of mouse lung neoplasia after combined initiation treatment with DEN, MNU and DMH." Cancer letters (1997)
[2] Fuhrman, Bianca. "Hypocholesterolemic effect of lycopene and β-carotene is related to suppression of cholesterol synthesis and augmentation of LDL receptor activity in macrophages." Biochemical and biophysical research communications (1997)
[3] Stahl, Wilhelm. "Cis–trans isomers of lycopene and β-carotene in human serum and tissues." Archives of biochemistry and biophysics (1992)
[4] Campbell, Jessica. "Serum testosterone is reduced following short-term phytofluene, lycopene, or tomato powder consumption in F344 rats." The Journal of nutrition (2006)
[5] Eze, Ejike Daniel. "Lycopene attenuates diabetes-induced oxidative stress in Wistar rats." Journal of Diabetes and Endocrinology (2018)
[6] Gann, Peter. "Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis." Cancer research (1999)
[7]Vecchia, Carlo La. "Tomatoes, lycopene intake, and digestive tract and female hormone-related neoplasms." Experimental Biology and Medicine (2002)
[8] Giovannucci, Edward. "Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature." Journal of the national cancer institute (1999)
[9] Siddiqui, Imtiaz. "Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer." The FASEB Journal (2011)​

Wow!!

 

[Inaut]

@Travis palm oil is quite high in lycopene, vitamin e in the form of tocotrienols, and mostly saturated fat...Do you approve of it’s use?

 

[Travis]

@Travis palm oil is quite high in lycopene, vitamin e in the form of tocotrienols, and mostly saturated fat...Do you approve of it’s use?

I think so. Before I had starting catching hints of lycopene's pronounced sex-specific effects, I had read some articles on prenylation: I had the suspicion that just like menaquinone-7, tocotrienols, and coenzyme Q₁₀—which also have long prenyl 'tails'—the carotenoid lycopene would also associate with the mitochondria. This does appear to be the case, and much research has been devoted dealing with its general antioxidant & mitochondrial effects:

i.e. Sandhir, Rajat. "Lycopene prevents 3-nitropropionic acid-induced mitochondrial oxidative stress and dysfunctions in nervous system." Neurochemistry international (2010)
i.e. Hantz, Holly. "Physiologically attainable concentrations of lycopene induce mitochondrial apoptosis in human prostate cancer cells." Experimental biology and medicine (2005)
i.e. Qu, Mingyue. "Lycopene protects against trimethyltin-induced neurotoxicity [...] by inhibiting the mitochondrial apoptotic pathway." Neurochemistry international (2011)
i.e. Yi, Fang. "Lycopene protects against MPP+-induced cytotoxicity by maintaining mitochondrial function in SH-SY5Y cells." Neurochemical research (2013)
i.e. Yue, Rongchuan. "Lycopene protects against [...] apoptosis by preventing mitochondrial dysfunction in primary neonatal mouse cardiomyocytes." PloS one (2012)​

Coenezyme Q₁₀ occupies a central role in the mitochondrial electron transport chain. These molecules are commonly believed to orient themselves having their long prenyl 'tails' somewhat 'buried' into the membrane, and with their 'head' groups arrayed along the surface—about what you'd predict based on solubility considerations alone, as in the diagrammatic representation of the micelle. Menaquinone-7 is very similar in structure to coenzyme Q₁₀—having both the long prenylated 'tail' and a paraquinone 'head'—so there should be little surprise that it has been shown to freely-substitute for it in the mitochondrial electron transport chain:

[1] Kurosu, Michio. "Vitamin K₂ in electron transport system: are enzymes involved in vitamin K₂ biosynthesis promising drug targets?." Molecules (2010)
[2] Newton, N. A. "The function of menaquinone (vitamin K₂) in Escherichia coli K-12." Biochimica et Biophysica Acta (BBA)-General Subjects (1971)
[2] Vos, Melissa. "Vitamin K₂ is a mitochondrial electron carrier that rescues pink1 deficiency." Science (2012)​

Since tocotrienols are nearly identical to both coenzyme Q₁₀ and menaquinone-7, I think it is fair to assume that tocotrienols are in fact the mitochondrial membrane-bound form vitamin E—identical in function to those having tocopherol 'tails' yet differing in intracellular locality. This does appear to be the case, and there are literally dozens of studies proving α,γ-tocotrienol–mitochondria interactions.

Lycopene could also associate with the mitochondria, to some degree, but since it lacks a 'head' group who really cares? In addition, lycopene appears to have more salient functions in inhibiting cholesterol synthesis.

So after reading a little about tocotrienols, I am under the impression that they're even more important than the tocopherols. There are many cancer studies using tocotrienols, and all the ones that I've seen show good results.

Just like its molecular cousins—i.e. γ-tocopherol and γ-carboxyethyl hydroxychroman—gamma-tocotrienol would also be expected to adduct-with and remove NO₂ and ONOO⁻. Alpha-tocopherol, α-CEHC, and α-tocopherol lack this function yet are slightly more efficient and safely capturing and storing free radical electrons.

[4] Cooney, Robert. "Gamma-tocopherol detoxification of nitrogen dioxide: superiority to alpha-tocopherol." Proceedings of the National Academy of Sciences (1993)
[5] Christen, Stephan. "γ-Tocopherol traps mutagenic electrophiles such as NOx and complements α-tocopherol:" Proceedings of the National Academy of Sciences (1997)​

Palm oil has tocotrienols having all four 'head' groups, and has a good fatty acid profile besides. For these two reasons, I would place palm oil near the very top of my food oil list.

 

[Mito]

There are ranges for PSA depending on age..

The Mayo Clinic’s age adjusted range is 2.0 (< 40 yrs old) to 7.2 (>80 yrs old)

Its all about PSA acceleration

PSA test - Mayo Clinic
Variations of the PSA test
Your doctor might use other ways of interpreting PSA results before deciding whether to order a biopsy to test for cancerous tissue. These other methods are intended to improve the accuracy of the PSA test as a screening tool.

Researchers continue to investigate variations of the PSA test to determine whether they provide a measurable benefit.

Variations of the PSA test include:

• PSA velocity. PSA velocity is the change in PSA levels over time. A rapid rise in PSA may indicate the presence of cancer or an aggressive form of cancer. However, recent studies have cast doubt on the value of PSA velocity in predicting a finding of prostate cancer from biopsy.
• Percentage of free PSA. PSA circulates in the blood in two forms — either attached to certain blood proteins or unattached (free). If you have a high PSA level but a low percentage of free PSA, it may be more likely that you have prostate cancer.
• PSA density. Prostate cancers can produce more PSA per volume of tissue than benign prostate conditions can. PSA density measurements adjust PSA values for prostate volume. Measuring PSA density generally requires an MRI or transrectal ultrasound.