Starch And Fat ?

[Westside PUFAs]

I like California white jasmine rice.

I do too. Sometimes I actually crave brown rice but only soaked CA brown rice. I soak it in a bowl for at least 24 hours. It's a unique taste and smell. The soaking also gets rid of arsenic.

 

[Travis]

Do you think the add iron can be “washed off” the rice to some extent by rinsing in water before and after cooking?

Only before: I would think as soon as the rice gets soft, positive pressure from the hot water would physically force the iron into the grain and infuse it with that element. We need to stay free of age spots—lipofuscin—and other inclusion bodies such Lewy bodies and neurofibrillary tangles. Although aluminum should probably be considered the causative agent for the latter two, it displaces iron which could play a formative role. (Both iron and aluminum are commonly found together in inclusion bodies, together with proteins and reactive aldehydic fatty acid remnants polymerized together). Polyunsaturated fatty acids in the brain—and especially in the brain—cannot be avoided as they seem somewhat necessary, but you would think that dietary restriction would lead to lower levels in that area.

I would assume that dementia, at its worse, can largely be avoided by minimizing those three aforementioned; restricting those would leave homocysteine as the biggest factor, which is derived exclusively from methionine. And of course, restricting methionine also restricts the formation of polyamines—powerful small molecule growth factors, which act to physically stabilize/unravel DNA—absolutely essential for cell division. Polyamines are, by the way, the most likely reason why prostate cancer is the number one cancer in the West: The prostate synthesizes high amounts of polyamines for both sperm and seminal fluid, ostensibly for the intention of unraveling and/or stabilizing DNA in the ova—should it get there. The enzymes which synthesize polyamines are temporally upregulated in a manner which reflects the cell cycle. Androgens stimulate polyamine synthesis in the prostate—probably why they are associated with cancer in that organ; polyamines are the downstream mediator.

Polyamines can also be synthesized by arginine and lysine. Methylglyoxal would then, of course, act to inhibit the production polyamines—concomitant with nitric oxide inhibition—by transforming arginine into imidazalone. The anticancer effect of methylglyoxal could be partially be the result of decreased cell division resulting from its ability to disable arginine, thereby preventing excessive polyamine formation.

 

[raypeatclips]

Thank you Travis for your posts about wheat, very interesting.


Are you saying that polyamines are synthesized when someone ejaculates? From this you could say that reducing ejaculation would limit the polyamines and the damage they cause?

Polyamines are, by the way, the most likely reason why prostate cancer is the number one cancer in the West: The prostate synthesizes high amounts of polyamines for both sperm and seminal fluid, ostensibly for the intention of unraveling and/or stabilizing DNA in the ova—should it get there. The enzymes which synthesize polyamines are temporally upregulated in a manner which reflects the cell cycle. Androgens stimulate polyamine synthesis in the prostate—probably why they are associated with cancer in that organ; polyamines are the downstream mediator.[/QUOTE]

Are you saying what polyamines are synthesized when someone ejaculates? From this you could say that reducing ejaculation would limit the polyamines and the damage they cause?

 

[lollipop]

I like California white jasmine rice.

Me too. That is what I eat.

 

[Travis]

'In addition, they draw attention to the role of the leukotriene class of eicosanoids in human breast cancer cell growth.' ―Rose​

Are you saying what polyamines are synthesized when someone ejaculates? From this you could say that reducing ejaculation would limit the polyamines and the damage they cause?

Quite the opposite: The two largest epidemiological studies ever conducted on the subject had noticed the trend of reduced prostate cancer risk with increased ejaculation. The concentration of polyamines increase, over time, in the seminal fluid where they are stabilized by citric acid.

Giles, G. G. "Sexual factors and prostate cancer." BJU international (2003)
Leitzmann, Michael F. "Ejaculation frequency and subsequent risk of prostate cancer." Jama (2004)
Steele, Robert. "Sexual factors in the epidemiology of cancer of the prostate." Journal of chronic diseases (1971)
​

Polyamines explain cell division, cancer, and the correlations between it and androgens in a straightforward and unambiguous manner; however, there are eicosanoids to consider as well. I'm not sure if polyamines can explain the studies which have found extremely strong correlations, risk ratios as high at ten, between tissue linoleic acid concentrations and prostate cancer. But since prostaglandins work through the PPAR receptors, and PPAR receptors increase growth, you'd have to wonder whether or not prostaglandins increase polyamines or accelerate the cell cycle in yet a different way. Dozens of experimental rat, fat‐feeding studies have been conducted since the '60s which single‐out linoleic acid as the most carcinogenic—by far. Thus: the idea that cancer is associated with 'high‐fat diets' is somewhat of a misnomeric, or inaccurate, phrase—especially considering the fact that stearic acid has been found consistently found protective in said studies.

'The growth inhibition by stearic acid is also in agreement with the effect of this saturated fatty acids on cultured rat mammary carcinoma cells and the suppression of tumor development in C3H mice fed high levels of stearic acid contained in linseed oil.' ―Rose​

Review articles which have compiled the sum total of results obtained from scores of early rat‐feeding studies of the '60s, '70s. and '80s, had singled‐out linoleic acid. Nearly each study taken individually concludes the same:

Carroll, K. K. "Effects of level and type of dietary fat on incidence of mammary tumors induced in female Sprague-Dawley rats by 7, 12-dimethylbenzanthracene." Lipids (1971)
Godley, Paul A. "Biomarkers of essential fatty acid consumption and risk of prostatic carcinoma." Cancer Epidemiology and Prevention Biomarkers (1996)
Fay, Michael P. "Effect of different types and amounts of fat on the development of mammary tumors in rodents: a review." Cancer Research (1997)
Welsch, Clifford W. "Relationship between dietary fat and experimental mammary tumorigenesis: a review and critique." Cancer research (1992)
Ip, Clement. "Requirement of essential fatty acid for mammary tumorigenesis in the rat." Cancer Research (1985)​

Put perhaps it's premature to single‐out prostaglandins, as many other eicosanoids are produced from linoleate‐derived arachidonic acid. The enzyme lipoxygenase produces leukotriene B₄, another problematic lipid hormone. Ray Peat talks of the ability of eicasanoids to displace estrogen from binding sites, another relevant mechanism. Finding the intermediate between arachidonic acid to cell proliferation could take us a bit further in understanding cancer—especially diet‐induced cancer. I vaguely recall David Rose doing studies on this:

'Diets rich in olive oil or palm oil may not contain levels of linoleic acid sufficient for optimal mammary tumor development.' ―Clifford​

click to embiggen​

'The effects of the three inhibitors on PC-3 cell growth paralleled those in Figure 8, Piroxicam exhibited relatively little growth suppression (7%), despite being an effective inhibitor of prostaglandin E, production (48% of control), whereas indomethacin was more active at the same molar concentration. Particularly significant biologically were the effects of esculetin, which was the most active inhibitor of cell growth (58% of control) but did not inhibit prostaglandin E, secretion by the cells.' ―Rose​

David Rose had shown a reduction in cancer by using cyclooxygenase inhibitors, such as the oft‐used and widely‐accepted (as such) indomethacin (in which he spells with an 'h'—a letter most people drop when writing 'indometacin'). But since lipoxygenase inhibitor esculetin caused a greater inhibition, he essentially concludes this anti‐cancer effect is largely the result of lowered leukotriene B₄ production. Indomethacin also inhibits lipoxygenase, to a degree, but piroxicam only inhibits cyclooxygenase.

'We found that indomethacin inhibited growth of the MDA-MB-231 human breast cancer cell line in culture, but only at concentrations of 56 μM or higher, whereas prostaglandin E synthesis by these cells was suppressed effectively by as little as 2.8-28 μM of the inhibitor. These results suggest that indomethacin was inhibitory only when present at concentrations sufficient to impair leukotriene synthesis ( a conclusion supported by the efficacy of esculetin, a selective lipoxygenase inhibitor in suppressing MDA-ME-23 1 cell growth).' ―Rose​

But I wouldn't implicate leukotriene B₄ based on this alone. What David Rose fails to realize is that esculetin, his lipoxygenase inhibitor, is a very powerful glyoxylase I inhibitor as well—which could be expected to raise methylglyoxal concentrations and inhibit cancer in this way. In fact, escolutin is one of the most powerful glyoxylase I inhibitors ever assayed for such (save for Thornally's impractical glutathione analogue, lapachol, β-lapachone, hinokitiol, and baicalein).

'The results from our experiments with pharmacological inhibitors of eicosanoid synthesis imply that prostate cancer cell growth is dependent primarily on leukotriene production, but also to a lesser degree, on normal prostaglandin synthesis.' ―Rose​

click to embiggen​

'We have therefore examined the ab initio wavefunction data and the relevant maps and compared these with the same data for the substrate A and the enediol intermediate E. The most effective inhibitor so far is the substituted coumarin esculetin, and the MEP map is given in Figure 8.' ―Thomson​

Knowing whether or not these cell proliferation effects are mediated through a prostaglandin or a leukotriene is practically irrelevant, since so much evidence has plainly shown linoleic acid (or a product thereof) is the most carcinogenic dietary fatty acid. However: knowing the biochemical pathway could suggest further ways to prevent or treat cancer; natural enzyme inhibitors and dietary restrictions/additions could then become evident.

Thomson, Colin. "Theoretical investigations of the structure of potential inhibitors of the enzyme glyoxalase‐I." International Journal of Quantum Chemistry (1983)
Rose, David P. "Effects of fatty acids and eicosanoid synthesis inhibitors on the growth of two human prostate cancer cell lines." The Prostate (1991)​

David Rose does appear to be correct despite the supporting role methylglyoxal could play by using esculetin on a cell: Esculetin does inhibit the enzyme lipoxygenase as well, reduces leukotriene B₄ production, and prevents cancer cell proliferation at low concentrations. Leukotriene B₄ has been shown involved in cell proliferation and cancer by others, which appears to have its own specific receptors besides PPARα: leukotriene B₄ receptor 1 and leukotriene B₄ receptor 2.

Chan, Chi-Chung. "Leukotriene B4 and 12-hydroxyeicosatetraenoic acid stimulate epidermal proliferation in vivo in the guinea pig." Journal of investigative dermatology (1985)
Ihara, Aya. "Blockade of leukotriene B4 signaling pathway induces apoptosis and suppresses cell proliferation in colon cancer." Journal of pharmacological sciences (2007)
Seo, Ji-Min. "Leukotriene B4 receptor-2 promotes invasiveness and metastasis of ovarian cancer cells through STAT3." Journal of Biological Chemistry (2012)​

Of the two leukotriene B₄ receptors, type two (BLT2) is highly involved in cancer progression. Studies have shown that this receptor—acting through its ligands leukotriene B₄ (a 5‐lipoxygenase product), hydroxyeicosatetraenoic acid (a 12‐lipoxygenase product), and hydroxyheptadecatrienoic acid (a thromboxane remnant)—acts to upregulate the mRNA and protein for the androgen receptor; we have come full circle, since the androgen receptor increases ornithine decarboxylase expression and polyamine production. The study below illustrates this nicely:

Lee, Jin-Wook. "Androgen receptor is up-regulated by a BLT2-linked pathway to contribute to prostate cancer progression." Biochemical and biophysical research communications (2012)
Kim, Eun-Young. "BLT2 promotes the invasion and metastasis of aggressive bladder cancer cells through a reactive oxygen species-linked pathway." Free Radical Biology and Medicine (2010)
​

The androgen receptor can be upregulated or downregualted at will by using either an agonist of (CAY10583), or an antagonist of (LY255283) the leukotriene B₄ receptor (type 2). Below are some Western blots (protein separation via gel electrophoresis) and Northern blots (mRNA separation via gel electrophoresis) which illustrate this nicely, takem from Jin‐Wook (2012), as well as immunohistological images and polymerase chain reaction data taken from Kim (2010):

click to embiggen​

And this is a common finding, and has been replicated by others. Kim had even shown that a leukotriene B₄ receptor inhibitor (LY255283) caused a 'great reduction' on tumors implanted into mice.

'In this study, immunohistochemical examination showed that the leukotriene B4 receptor BLT2 is overexpressed in advanced malignant bladder cancers in proportion to advancing stages, with high prognostic significance. Blockade of BLT2 with the specific antagonist LY255283 or small‐interfering RNA knockdown significantly suppressed the invasiveness of highly aggressive bladder cancer cells.' ―Kim​

So cancer has been shown to be caused by linoleic acid, of all fats, since the '60s—a time when it had been known that all eicosanoids were dependent on this fatty acid (through the formation of arachidonic acid). It took David Rose to later prove directly that eicosanoids increased cancer cell growth, and to implicate leukotriene B₄ specifically. More modern research has since traced the pathway to the leukotriene B₄ receptor (type 2), which ostensibly achieves its carcinogenic effect by upregualting the androgen receptor⟶which upregualtes ornithine decarboxylase with subsequent polyamine synthesis. So reading headlines about how PPARγ ligands inhibit cancer should present no paradox, as the proliferative effects of linoleic acid seem mediated primarily through the leukotriene B₄ receptor (type 2).

'However, nordihydroguaiaretic acid also antagonizes leukotriene B4 binding to its receptor, which may also contribute to its efficacy when present at a low dose. These effects of the lipoxygenase inhibitors are consistent with the report that nordihydroguaiaretic acid suppresses nitrosomethylurea-induced rat mammary carcinogenesis.' ―Rose​

Of all eicosanoids, the prostaglandins get the most attention. However: the thromboxanes and leukotrienes certainly can have considerable effects on the cell—as can arachidonic acid itself.

And below is another David Rose study showing that leukotrienes, and not prostaglandins, are very likely the primary cause of linoleic acid‐induced cancer:

Rose, David P. "Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture." Cancer research (1990)​

This study also shows that 5‐lipoxygenase inhibitor nordihydroguaiaretic acid is more powerful than indomethacin, and even esculetin, in inhibiting cancer cell proliferation. This molecule can be found in the plant Larrea tridentata.

'Piroxicam, which inhibits only cyclooxygenase, exhibited no suppressive effect on cell proliferation after 6 days of culture, although there was some inhibition of thymidine incorporation into the cells after 3 days of exposure to the drug. This absence of growth suppression again has a parallel in chemically induced rat mammary carcinogenesis. Carter et al. found that, while indomethacin inhibited tumor development, the cyclooxygenase inhibitor carprofen had no such effect, although it was at least as effective in reducing mammary' epithelial cell prostaglandin E₂ levels.' ―Rose
​

I would imagine that reducing linoleic acid and methionine from the diet would essentially eliminate the risk of prostate cancer. Steve Jobs, although mostly a low‐methionine vegan, was still consuming quite a bit of linoleic acid—most likely (he was soy‐eater). The eicosanoid pathway could be why inflammation can stimulate cancer, in some cases, and also implies that allergenic cytokines such as interferon‐γ and interleukin‐1β could perhaps do likewise. So besides reducing Peat‐nonfriendly biomolecules such as linoleic acid, tryptophan, and methionine, eliminating allergenic foods should also be a priority. Growth hormone—secreted in response to tryptophan—and prolactin can also increase polyamine synthesis. Growth hormone has been shown to increase ornithine decarboxylase activity 30‐fold:

Jänne, Juhani. "On the stimulation of ornithine decarboxylase and RNA polymerase activity in rat liver after treatment with growth hormone." Biochimica et Biophysica Acta (1969)
Russel, Diane. "Growth hormone induction of ornithine decarboxylase in rat liver." Endocrinology (1970)
​

I think polyamines should be considered primary simply because there is nothing downstream of them; polyamines have no receptor. Polyamines physically interact with the DNA strands themselves, facilitating replication that cannot be achieved without. William Koch, PhD, implicated amines derived from protein in the etiology of cancer nearly a century ago; I think it's fair to consider these as his main focus, and for good reason.

'Then the anoxia, plus the intestinal diamines, the virus or some other carcinogen from the food or from an old scar with a buried infection, are the other elements that are needed. The blow may not be avoided, the scar may be identified and removed and the bowel can be trained to not produce the diamines that serve as a vanguard to the neoplastic change.' ―Koch
​

Fermentation can turn the amino acids lysine and arginine into diamines, which can be then polymerized into polyamines. Soy sauce has an unusually high amount of polyamines.

'The polyamine profile of soy sauces was quite different from that of soybeans, indicating that these polyamines were produced through the fermentation process.' ―Okamoto​

click to embiggen​

'In Japan, based on data from 8 population-based cancer registries, stomach cancer accounted for 31% of all new cancer cases in males and 22% in females in 1985–89; the stomach remains the leading tumor site. Japan is the only country where mass screening for stomach cancer has been a national policy (encouraged since 1966) and has been included in the Health Services Law for the Aged since 1983.' ―Lambert​

The soybean is particularly high in polyamines to begin with, even before fermentation. These facts, in part, could explain the consistently high stomach cancer rates found in Japan—an observation which had, perhaps a bit naïvely, been historically attributed to sodium chloride.

Koch, William. "Prevention of cancer, allergy, and infection." (1961)
Lambert, René. "Incidence and mortality from stomach cancer in Japan, Slovenia and the USA." International journal of cancer (2002)
Okamoto, Akiko. "Polyamine content of ordinary foodstuffs and various fermented foods." Bioscience, biotechnology, and biochemistry (1997)​

 

[Koveras]

'In addition, they draw attention to the role of the leukotriene class of eicosanoids in human breast cancer cell growth.' ―Rose​

Quite the opposite: The two largest epidemiological studies ever conducted on the subject had noticed the trend of reduced prostate cancer risk with increased ejaculation. The concentration of polyamines increase, over time, in the seminal fluid where they are stabilized by citric acid.

Giles, G. G. "Sexual factors and prostate cancer." BJU international (2003)
Leitzmann, Michael F. "Ejaculation frequency and subsequent risk of prostate cancer." Jama (2004)
Steele, Robert. "Sexual factors in the epidemiology of cancer of the prostate." Journal of chronic diseases (1971)
​

Polyamines explain cell division, cancer, and the correlations between it and androgens in a straightforward and unambiguous manner; however, there are eicosanoids to consider as well. I'm not sure if polyamines can explain the studies which have found extremely strong correlations, risk ratios as high at ten, between tissue linoleic acid concentrations and prostate cancer. But since prostaglandins work through the PPAR receptors, and PPAR receptors increase growth, you'd have to wonder whether or not prostaglandins increase polyamines or accelerate the cell cycle in yet a different way. Dozens of experimental rat, fat‐feeding studies have been conducted since the '60s which single‐out linoleic acid as the most carcinogenic—by far. Thus: the idea that cancer is associated with 'high‐fat diets' is somewhat of a misnomeric, or inaccurate, phrase—especially considering the fact that stearic acid has been found consistently found protective in said studies.

'The growth inhibition by stearic acid is also in agreement with the effect of this saturated fatty acids on cultured rat mammary carcinoma cells and the suppression of tumor development in C3H mice fed high levels of stearic acid contained in linseed oil.' ―Rose​

Review articles which have compiled the sum total of results obtained from scores of early rat‐feeding studies of the '60s, '70s. and '80s, had singled‐out linoleic acid. Nearly each study taken individually concludes the same:

Carroll, K. K. "Effects of level and type of dietary fat on incidence of mammary tumors induced in female Sprague-Dawley rats by 7, 12-dimethylbenzanthracene." Lipids (1971)
Godley, Paul A. "Biomarkers of essential fatty acid consumption and risk of prostatic carcinoma." Cancer Epidemiology and Prevention Biomarkers (1996)
Fay, Michael P. "Effect of different types and amounts of fat on the development of mammary tumors in rodents: a review." Cancer Research (1997)
Welsch, Clifford W. "Relationship between dietary fat and experimental mammary tumorigenesis: a review and critique." Cancer research (1992)
Ip, Clement. "Requirement of essential fatty acid for mammary tumorigenesis in the rat." Cancer Research (1985)​

Put perhaps it's premature to single‐out prostaglandins, as many other eicosanoids are produced from linoleate‐derived arachidonic acid. The enzyme lipoxygenase produces leukotriene B₄, another problematic lipid hormone. Ray Peat talks of the ability of eicasanoids to displace estrogen from binding sites, another relevant mechanism. Finding the intermediate between arachidonic acid to cell proliferation could take us a bit further in understanding cancer—especially diet‐induced cancer. I vaguely recall David Rose doing studies on this:

'Diets rich in olive oil or palm oil may not contain levels of linoleic acid sufficient for optimal mammary tumor development.' ―Clifford​

View attachment 7552 View attachment 7553 View attachment 7551 click to embiggen​

'The effects of the three inhibitors on PC-3 cell growth paralleled those in Figure 8, Piroxicam exhibited relatively little growth suppression (7%), despite being an effective inhibitor of prostaglandin E, production (48% of control), whereas indomethacin was more active at the same molar concentration. Particularly significant biologically were the effects of esculetin, which was the most active inhibitor of cell growth (58% of control) but did not inhibit prostaglandin E, secretion by the cells.' ―Rose​

David Rose had shown a reduction in cancer by using cyclooxygenase inhibitors, such as the oft‐used and widely‐accepted (as such) indomethacin (in which he spells with an 'h'—a letter most people drop when writing 'indometacin'). But since lipoxygenase inhibitor esculetin caused a greater inhibition, he essentially concludes this anti‐cancer effect is largely the result of lowered leukotriene B₄ production. Indomethacin also inhibits lipoxygenase, to a degree, but piroxicam only inhibits cyclooxygenase.

'We found that indomethacin inhibited growth of the MDA-MB-231 human breast cancer cell line in culture, but only at concentrations of 56 μM or higher, whereas prostaglandin E synthesis by these cells was suppressed effectively by as little as 2.8-28 μM of the inhibitor. These results suggest that indomethacin was inhibitory only when present at concentrations sufficient to impair leukotriene synthesis ( a conclusion supported by the efficacy of esculetin, a selective lipoxygenase inhibitor in suppressing MDA-ME-23 1 cell growth).' ―Rose​

But I wouldn't implicate leukotriene B₄ based on this alone. What David Rose fails to realize is that esculetin, his lipoxygenase inhibitor, is a very powerful glyoxylase I inhibitor as well—which could be expected to raise methylglyoxal concentrations and inhibit cancer in this way. In fact, escolutin is one of the most powerful glyoxylase I inhibitors ever assayed for such (save for Thornally's impractical glutathione analogue, lapachol, β-lapachone, hinokitiol, and baicalein).

'The results from our experiments with pharmacological inhibitors of eicosanoid synthesis imply that prostate cancer cell growth is dependent primarily on leukotriene production, but also to a lesser degree, on normal prostaglandin synthesis.' ―Rose​

View attachment 7555View attachment 7554View attachment 7557 click to embiggen​

'We have therefore examined the ab initio wavefunction data and the relevant maps and compared these with the same data for the substrate A and the enediol intermediate E. The most effective inhibitor so far is the substituted coumarin esculetin, and the MEP map is given in Figure 8.' ―Thomson​

Knowing whether or not these cell proliferation effects are mediated through a prostaglandin or a leukotriene is practically irrelevant, since so much evidence has plainly shown linoleic acid (or a product thereof) is the most carcinogenic dietary fatty acid. However: knowing the biochemical pathway could suggest further ways to prevent or treat cancer; natural enzyme inhibitors and dietary restrictions/additions could then become evident.

Thomson, Colin. "Theoretical investigations of the structure of potential inhibitors of the enzyme glyoxalase‐I." International Journal of Quantum Chemistry (1983)
Rose, David P. "Effects of fatty acids and eicosanoid synthesis inhibitors on the growth of two human prostate cancer cell lines." The Prostate (1991)​

David Rose does appear to be correct despite the supporting role methylglyoxal could play by using esculetin on a cell: Esculetin does inhibit the enzyme lipoxygenase as well, reduces leukotriene B₄ production, and prevents cancer cell proliferation at low concentrations. Leukotriene B₄ has been shown involved in cell proliferation and cancer by others, which appears to have its own specific receptors besides PPARα: leukotriene B₄ receptor 1 and leukotriene B₄ receptor 2.

Chan, Chi-Chung. "Leukotriene B4 and 12-hydroxyeicosatetraenoic acid stimulate epidermal proliferation in vivo in the guinea pig." Journal of investigative dermatology (1985)
Ihara, Aya. "Blockade of leukotriene B4 signaling pathway induces apoptosis and suppresses cell proliferation in colon cancer." Journal of pharmacological sciences (2007)
Seo, Ji-Min. "Leukotriene B4 receptor-2 promotes invasiveness and metastasis of ovarian cancer cells through STAT3." Journal of Biological Chemistry (2012)​

Of the two leukotriene B₄ receptors, type two (BLT2) is highly involved in cancer progression. Studies have shown that this receptor—acting through its ligands leukotriene B₄ (a 5‐lipoxygenase product), hydroxyeicosatetraenoic acid (a 12‐lipoxygenase product), and hydroxyheptadecatrienoic acid (a thromboxane remnant)—acts to upregulate the mRNA and protein for the androgen receptor; we have come full circle, since the androgen receptor increases ornithine decarboxylase expression and polyamine production. The study below illustrates this nicely:

Lee, Jin-Wook. "Androgen receptor is up-regulated by a BLT2-linked pathway to contribute to prostate cancer progression." Biochemical and biophysical research communications (2012)
Kim, Eun-Young. "BLT2 promotes the invasion and metastasis of aggressive bladder cancer cells through a reactive oxygen species-linked pathway." Free Radical Biology and Medicine (2010)
​

The androgen receptor can be upregulated or downregualted at will by using either an agonist of (CAY10583), or an antagonist of (LY255283) the leukotriene B₄ receptor (type 2). Below are some Western blots (protein separation via gel electrophoresis) and Northern blots (mRNA separation via gel electrophoresis) which illustrate this nicely, takem from Jin‐Wook (2012), as well as immunohistological images and polymerase chain reaction data taken from Kim (2010):

View attachment 7559View attachment 7558View attachment 7556 click to embiggen​

And this is a common finding, and has been replicated by others. Kim had even shown that a leukotriene B₄ receptor inhibitor (LY255283) caused a 'great reduction' on tumors implanted into mice.

'In this study, immunohistochemical examination showed that the leukotriene B4 receptor BLT2 is overexpressed in advanced malignant bladder cancers in proportion to advancing stages, with high prognostic significance. Blockade of BLT2 with the specific antagonist LY255283 or small‐interfering RNA knockdown significantly suppressed the invasiveness of highly aggressive bladder cancer cells.' ―Kim​

So cancer has been shown to be caused by linoleic acid, of all fats, since the '60s—a time when it had been known that all eicosanoids were dependent on this fatty acid (through the formation of arachidonic acid). It took David Rose to later prove directly that eicosanoids increased cancer cell growth, and to implicate leukotriene B₄ specifically. More modern research has since traced the pathway to the leukotriene B₄ receptor (type 2), which ostensibly achieves its carcinogenic effect by upregualting the androgen receptor⟶which upregualtes ornithine decarboxylase with subsequent polyamine synthesis. So reading headlines about how PPARγ ligands inhibit cancer should present no paradox, as the proliferative effects of linoleic acid seem mediated primarily through the leukotriene B₄ receptor (type 2).

'However, nordihydroguaiaretic acid also antagonizes leukotriene B4 binding to its receptor, which may also contribute to its efficacy when present at a low dose. These effects of the lipoxygenase inhibitors are consistent with the report that nordihydroguaiaretic acid suppresses nitrosomethylurea-induced rat mammary carcinogenesis.' ―Rose​

Of all eicosanoids, the prostaglandins get the most attention. However: the thromboxanes and leukotrienes certainly can have considerable effects on the cell—as can arachidonic acid itself.

And below is another David Rose study showing that leukotrienes, and not prostaglandins, are very likely the primary cause of linoleic acid‐induced cancer:

Rose, David P. "Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture." Cancer research (1990)​

This study also shows that 5‐lipoxygenase inhibitor nordihydroguaiaretic acid is more powerful than indomethacin, and even esculetin, in inhibiting cancer cell proliferation. This molecule can be found in the plant Larrea tridentata.

'Piroxicam, which inhibits only cyclooxygenase, exhibited no suppressive effect on cell proliferation after 6 days of culture, although there was some inhibition of thymidine incorporation into the cells after 3 days of exposure to the drug. This absence of growth suppression again has a parallel in chemically induced rat mammary carcinogenesis. Carter et al. found that, while indomethacin inhibited tumor development, the cyclooxygenase inhibitor carprofen had no such effect, although it was at least as effective in reducing mammary' epithelial cell prostaglandin E₂ levels.' ―Rose
​

I would imagine that reducing linoleic acid and methionine from the diet would essentially eliminate the risk of prostate cancer. Steve Jobs, although mostly a low‐methionine vegan, was still consuming quite a bit of linoleic acid—most likely (he was soy‐eater). The eicosanoid pathway could be why inflammation can stimulate cancer, in some cases, and also implies that allergenic cytokines such as interferon‐γ and interleukin‐1β could perhaps do likewise. So besides reducing Peat‐nonfriendly biomolecules such as linoleic acid, tryptophan, and methionine, eliminating allergenic foods should also be a priority. Growth hormone—secreted in response to tryptophan—and prolactin can also increase polyamine synthesis. Growth hormone has been shown to increase ornithine decarboxylase activity 30‐fold:

Jänne, Juhani. "On the stimulation of ornithine decarboxylase and RNA polymerase activity in rat liver after treatment with growth hormone." Biochimica et Biophysica Acta (1969)
Russel, Diane. "Growth hormone induction of ornithine decarboxylase in rat liver." Endocrinology (1970)
​

I think polyamines should be considered primary simply because there is nothing downstream of them; polyamines have no receptor. Polyamines physically interact with the DNA strands themselves, facilitating replication that cannot be achieved without. William Koch, PhD, implicated amines derived from protein in the etiology of cancer nearly a century ago; I think it's fair to consider these as his main focus, and for good reason.

'Then the anoxia, plus the intestinal diamines, the virus or some other carcinogen from the food or from an old scar with a buried infection, are the other elements that are needed. The blow may not be avoided, the scar may be identified and removed and the bowel can be trained to not produce the diamines that serve as a vanguard to the neoplastic change.' ―Koch
​

Fermentation can turn the amino acids lysine and arginine into diamines, which can be then polymerized into polyamines. Soy sauce has an unusually high amount of polyamines.

'The polyamine profile of soy sauces was quite different from that of soybeans, indicating that these polyamines were produced through the fermentation process.' ―Okamoto​

View attachment 7561 click to embiggen​

'In Japan, based on data from 8 population-based cancer registries, stomach cancer accounted for 31% of all new cancer cases in males and 22% in females in 1985–89; the stomach remains the leading tumor site. Japan is the only country where mass screening for stomach cancer has been a national policy (encouraged since 1966) and has been included in the Health Services Law for the Aged since 1983.' ―Lambert​

The soybean is particularly high in polyamines to begin with, even before fermentation. These facts, in part, could explain the consistently high stomach cancer rates found in Japan—an observation which had, perhaps a bit naïvely, been historically attributed to sodium chloride.

Koch, William. "Prevention of cancer, allergy, and infection." (1961)
Lambert, René. "Incidence and mortality from stomach cancer in Japan, Slovenia and the USA." International journal of cancer (2002)
Okamoto, Akiko. "Polyamine content of ordinary foodstuffs and various fermented foods." Bioscience, biotechnology, and biochemistry (1997)​

Do you think supplementing with ornithine is risky re:polyamines?

 

[Westside PUFAs]

Steve Jobs

He did a lot of soldering with lead and was known for being a maniac to people working with him. Negative stress.

These facts, in part, could explain the consistently high stomach cancer rates found in Japan—an observation which had, perhaps a bit naïvely, been historically attributed to sodium chloride.

They eat a lot of fish.

"Worldwide, stomach cancer is more common in Japan, China, Southern and Eastern Europe, and South and Central America."

Not much soy consumption in those other areas.

 

[Wagner83]

That a nightshade can produce a steroid analogue isn't especially uncommon: ashwagandha, Piper cubeba, and the yam Dioscorea composita all produce steroid‐like glycosides. Unfortunately: the mineralcorticoid potatoes are the common varieties in the West, but the yams can be had at a premium. I don't think that solanine is especially damaging if you know what's going on; it has a short half‐life and doesn't seem to have significant effects other than those on the mineralcorticoid receptor.

Nishie, K. "Pharmacology of solanine." Toxicology and applied pharmacology (1971)
Bushway, Rodney J. "α-Chaconine and α-solanine content of potato products and their stability during several modes of cooking." Journal of Agricultural and Food Chemistry (1981)

Interesting, I never tried yams but checking their nutritional contents, carbs, fibers etc.. I will definitely try them, they have less interesting minerals and proteins than potatoes though, so if the bad effects of potatoes are only short lived and not serious then I may give them a try again. What do you mean by "I don't think that solanine is especially damaging if you know what's going on"? Do you have some special tricks to annihilate or reduce their deleterious effects (besides peeling)? Short-lived damage twice a day sounds like it could be an issue, I have seen quite a few people online claim nightshades were no-no for them.
About enriched grains, I live in Europe and I'm not sure they can enrich grains without saying so on the package. I get jasmine rice from Thailand as I said it seems ok in its effects, I'm not sure about the iron content but at the end of the day I need to eat something!

 

[Amazoniac]

https://www.westonaprice.org/health...getarian2-the-eating-disorders-of-steve-jobs/

As a $5 an hour technician at Atari, he was known as “a hippie with b.o.” and “impossible to deal with.” He clung to the belief that his fruit-heavy vegetarian diet would prevent not just mucus but also body odor. As Isaacson writes “It was a flawed theory.”

The strange eating habits of Steve Jobs - NBC News

Jobs also believed that his commitment to vegan diets meant his body was flushed of mucus -- and that it meant he was free from body odor, so he didn't need to wear deodorant or shower regularly. Unsurprisingly, the book quotes former coworkers saying that he was very, very wrong.

https://raypeatforum.com/community/threads/body-odor.4359/page-2#post-268117

 

[Travis]

He did a lot of soldering with lead...

'Lead is only weakly mutagenic...' ―Steenland​

While true that lead is classified as a 'possible human carcinogen' by the IARC, this classification was given largely as a result of large doses of lead acetate in animals. Even with the large doses, and increased solubility of the acetate salt, the carcinogenicity wasn't particularly profound.

'However, almost all these studies used one form of lead (lead acetate, a soluble salt), chosen for ease of administration, given orally, subcutaneously, or intraperitoneally, usually at very high doses. Most human exposure to lead, on the other hand, is to lead oxides or lead fumes which are inhaled.' ―Steenland

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'Exclusion of that study yields a combined lung cancer RR of 1.14. There is little evidence of increased risk of kidney cancer (combined RR 1.01) or brain cancer (combined RR=1.06).' ―Steenland​

In humans, epidemiologically, there is little direct association between lead and cancer—even for individuals found working at lead smeltering plants. Even in the lungs, the main organ in which people are exposed, I wouldn't consider the risk great.

Polyamines, on the other hand, are highly mutagenic. The splicing of orthinine decarboxylase next to keratin‐5 DNA leads to increased enzymatic expression on this organ only. This is a common device used to examine effects on the skin, and appears reliable. Mice whose DNA had been modified in the manner were found with greatly increased polyamine concentrations on the skin.

Moreover, these mice were much more sensitive to dimethylbenzanthracene‐induced cancers, and were even victims of spontaneous skin cancers:

'Transgenic mice with ornithine decarboxylase targeted to hair follicle keratinocytes were much more sensitive than littermate controls to initiation with a single low dose of carcinogen; in fact, such mice no longer required treatment with tumor promoters for tumors to develop.' ―O'Brien​

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​

'Among inbred mouse strains, the C57BL/6 strain is usually considered resistant to tumor promotion versus other inbred, hybrid, and outbred strains. However, we find that up-regulation of ornithine decarboxylase can override this genetically based resistance to induced tumorigenesis.' ―O'Brien
​

This is just one such study on polyamines, which are so essential to cell proliferation as to be nearly synonymous with it. To be fair: soy is higher in polyamines, on a per gram basis, than the other foods in the aforementioned study partially due to its unusually high protein content; but since people generally eat a constant amount of protein per day, the results should probably be given per gram protein (or even per calorie). But not all high protein foods have high polyamines: Cheese, for instance, was found to have very little—despite its being fermented. I think perhaps polyamines could as much a result of the precise strain of bacteria or fungi used to ferment the food than the lysine, ornithine, and arginine conctent.

'The tumors produced by a two-stage protocol constitutively overexpress ODC and have extremely high polyamine levels.' ―O'Brien​

Diverse bacteria genera can produce polyamines. This has been proven in the case of Enterococcus faecalis, Corynebacterium glutamicum, and Escherichia coli—all three even capable of producing polyamines from glucose. What is remarkable, but perhaps not surpising, is that inhibiting ornithine decarboxylase has been shown to inhibit cancer.

'It is worth noting that one recent polyamine based chemoprevention trial in human skin has yielded positive results: the ornithine decarboxylase inhibitor DFMO applied topically caused a highly significant reduction in the number of forearm actinic keratoses and total polyamine content.' ―O'Brien​

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'What is not known at present is how elevated polyamine levels could exert such a strong influence on susceptibility to cancer. By virtue of their ability to bind tightly to nucleic acids, these cations could regulate gene expression at several levels.' ―O'Brien​

Steenland, Kyle. "Lead and cancer in humans: where are we now?." American journal of industrial medicine (2000)
O'Brien, Thomas G. "Ornithine decarboxylase overexpression is a sufficient condition for tumor promotion in mouse skin." Cancer Research (1997)
Schneider, Jens. "Biotechnological production of polyamines by bacteria: recent achievements and future perspectives." Applied microbiology and biotechnology (2011)

They eat a lot of fish.

"Worldwide, stomach cancer is more common in Japan, China, Southern and Eastern Europe, and South and Central America."

Not much soy consumption in those other areas.

Fish is high in lysine, and as such could can create polyamines when fermented. I wonder if there isn't any fish sauce production going on in the South American endemic areas, or fermented meat?

 

[Travis]

Interesting, I never tried yams but checking their nutritional contents, carbs, fibers etc.. I will definitely try them, they have less interesting minerals and proteins than potatoes though, so if the bad effects of potatoes are only short lived and not serious then I may give them a try again. What do you mean by "I don't think that solanine is especially damaging if you know what's going on"? Do you have some special tricks to annihilate or reduce their deleterious effects (besides peeling)? Short-lived damage twice a day sounds like it could be an issue, I have seen quite a few people online claim nightshades were no-no for them.

Like the structurally similar oubain and digoxin, solanine appears to disrupt the the homeostasis of sodium and potassium. But as previously mentioned, this compound is excreted fairly quickly. Instances of rapid heartbeat and sweating from potatoes should be transient, and would only be expected to last a few hours. All of the fatal cases were likely instances of children ingesting the peal of very high solanine potatoes; and even then, the few that had actually died probably had an unbalanced Na⁺/K⁺ ratio to begin with.

About enriched grains, I live in Europe and I'm not sure they can enrich grains without saying so on the package. I get jasmine rice from Thailand as I said it seems ok in its effects, I'm not sure about the iron content but at the end of the day I need to eat something!

So many varieties of rice for sale; only a minority or brands actually appear to be adulterated, but these same adulterated brands are also the cheapest and occupy the most shelf space at large supermarkets. As long as people read labels, they can easily avoid all supplemental inorganic metals in foods (i.e. iron, aluminum).

 

[Travis]

Do you think supplementing with ornithine is risky re:polyamines?

I wouldn't use it if one has cancer, but it could be good for someone trying to gain mass. Androgens and growth hormone increase polyamines by upregualting ornithine decarboxylase and will increase growth in cells which have their receptors, but these hormones shouldn't be considered generally harmful. Growth factors are necessary at times and even sought by certain types of people. Without polyamines, the cell cannot divide—it dies.

So no reason to avoid them completely; only realize that putting high concentrations on a certain organ—such as in the case of the mice, and perhaps the Japanese, above—could lead to cancer at that location.

Just a small increase of methionine caused a massive increase in weight gain in this classic study:

Richie, John P. "Methionine restriction increases blood glutathione and longevity in F344 rats." The FASEB Journal (1994)
​

Glutathione is also a prerequisite for cell division, and can also be formed from methionine through another pathway: transsulfuration.

 

[Wagner83]

Like the structurally similar oubain and digoxin, solanine appears to disrupt the the homeostasis of sodium and potassium. But as previously mentioned, this compound is excreted fairly quickly. Instances of rapid heartbeat and sweating from potatoes should be transient, and would only be expected to last a few hours. All of the fatal cases were likely instances of children ingesting the peal of very high solanine potatoes; and even then, the few that had actually died probably had an unbalanced Na⁺/K⁺ ratio to begin with.

Ok! A last quick question. Now that death from potatoes is mostly history I'd like to know your opinion on this: could repeated exposure to those few hours of solanine/chacocine be more and detrimental enough over weeks so as to interfere with mood, energy etc..? So far it does seem like yams and white rice (void of added iron) are a decent choice for carbs calories.