Travis
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The 'Japanese Paradox' is a term usually used to describe the low risk of lung cancer in Japan despite higher smoking rates. The same term is sometimes even used by followers of Ancel Keys to express confoundment over the inverse relationship between cardiovascular disease and serum cholesterol, between 1965–1990, in the same country. And the exact same term again is used by others sects to highlight the fact that the Japanese have had traditionally a much lower incidence of prostate cancer; although this isn't accompanied by a greater assumed risk the term 'paradox' is still used.
Readers of Ray Peat and Linus Pauling of course see no 'paradox'—a term which is basically an admission of ignorance, lack of comprehensive data, or the failure of a paradigm. Discerning readers probably realize by now that cardiovascular disease has very little to do with cholesterol and everything to do with ascorbate and lipoprotein(a), and that the differential cancer rates in the Japanese can probably best be explained by thee things: the ω−6/ω−3 ratio, the high polyamine content of soy and soy sauce, and green tea (don't laugh; just keep reading).
The ω−6/ω−3 ratio: This is self‐explanatory on a Ray Peat website, and I'll just post a few interesting quotes. Besides the 'Japanese Paradox,' there is an 'Israeli Paradox' which states that the Israelis should have lower cardiovascular disease due to high polyunsaturated fatty acid consumption—but they don't. Going along with average cardiovascular disease—which is essentially vitamin C dependent⁽¹⁾—rates are high cancer and diabetes rates, as you'd expect from a ω−6/ω−3 ratio of 24:1. It's worth noting that the Japanese have one of the lowest ω−6/ω−3 ratios of any country, a fact which is useful for explaining their low cancer rates of certain organs.
Polyamine content of soy and soy sauce: Despite having a lower ω−6/ω−3 ratio, the Japanese have higher prevalence of certain cancers, namely: those of the esophagus, the stomach, and the liver:
Above: Incidence of cancers of the esophagus, stomach, and liver—respectively; United States vs Japan
These are essentially the only ones, except for near‐equal rates of pancreatic cancer. Upper‐GI tract oncologists could almost rightly propose yet another 'Japanese Paradox' to describe this since the Japanese do drink less alcohol. You'd be almost temped to explain esophageal cancer by higher smoking rates yet this fails to account for the stomach cancer rates, saying nothing about the lower rates in lung cancer among the Japanese. The only logical explanation might them seem to be something they are consuming, but neither alcohol nor tobacco smoke.
Soy has an unusually‐high level of polyamines. These are small molecule polymers which reliably increase cellular proliferation. The enzyme which produces them, ornithine decarboxylase, is temporally expressed in a manner which mirrors the cell cycle; this same enzyme is also very commonly found elevated in cancer, and represents a pharmacological target of new drugs. Polyamines are capable of interacting with DNA directly, forming the final downstream process of cellular proliferation. In the cell nucleus, polyamines have been shown to induce the left‐handed Z‐configuration of DNA; and polyamines have also been shown to increase DNA replication rates during polymerase chain reaction. Studies have also shown them capable of binding microtubules, structures indispensable to cell signalling and stabilization. These molecules finally 'take the ghost out of the machine,' reduce complexity down to transcription rates, and link cellular biology to physical chemistry—explaining how growth can be created through fundamental, physical means. Polyamines are also found in soy in unusually high levels:⁽⁴⁾
The polyamine content of soy sauce, oolong tea, and soybeans completely overshadow essentially all other foods. These three foods are characteristically Japanese, and you wouldn't expect to consume such high levels anywhere else. These are small molecules, so they diffuse into tissues and don't reach the lower GI tract whole—but they can play a role there: colon cancer risk can be increased through high intakes of red meat, preferable with dairy to slow transit time. Meat makes for the best substrate of polyamine formation due to its high methionine and arginine content, and especially if transit time is comprimised by exorphins in wheat and dairy.
Green Tea: Since the Japanese have a lower ω−6/ω−3 ratio, it's not really necessary to invoke other protective factors—but this must play a role. Perhaps the best evidence is statistical: extremely high risk ratio reductions have been found in relation to green tea consumption:⁽⁵⁾
This is too strong to deny, and the in vitro data does not disappoint. Green tea polyphenols have been shown to inhibit cyclooxygenase‐2⁽⁶⁾ and ornithine decarboxylase,⁽⁷⁾ two enzymes highly associated with cancer; the first one creates prostaglandin E₂ and the second creates polyamines. And studies on rats show green tea polyphenols capable of greatly reducing cancer incidence and tumor size. Every way you look at it, these polyphenols seem highly protective; they have even been shown to reduce prostate cancer in people directly:⁽⁸⁾
So where do these tea polyphenols end‐up? Well: in rats, they end‐up in the same areas corresponding to low cancer incidence in Japan: the colon, the prostate, the bladder, and the lung:
But not the liver, where the Japanese have high cancer rates. The high levels found in the esophagus simply cannot compete with soy sauce polyamines—the stomach concentrations weren't measured—but green tea polyphenols can reduce cancer in organs further removed, especially in people having a low ω−6/ω−3 ratio to begin with.
Readers of Ray Peat and Linus Pauling of course see no 'paradox'—a term which is basically an admission of ignorance, lack of comprehensive data, or the failure of a paradigm. Discerning readers probably realize by now that cardiovascular disease has very little to do with cholesterol and everything to do with ascorbate and lipoprotein(a), and that the differential cancer rates in the Japanese can probably best be explained by thee things: the ω−6/ω−3 ratio, the high polyamine content of soy and soy sauce, and green tea (don't laugh; just keep reading).
The ω−6/ω−3 ratio: This is self‐explanatory on a Ray Peat website, and I'll just post a few interesting quotes. Besides the 'Japanese Paradox,' there is an 'Israeli Paradox' which states that the Israelis should have lower cardiovascular disease due to high polyunsaturated fatty acid consumption—but they don't. Going along with average cardiovascular disease—which is essentially vitamin C dependent⁽¹⁾—rates are high cancer and diabetes rates, as you'd expect from a ω−6/ω−3 ratio of 24:1. It's worth noting that the Japanese have one of the lowest ω−6/ω−3 ratios of any country, a fact which is useful for explaining their low cancer rates of certain organs.
'Israel has one of the highest dietary polyunsaturated/saturated fat ratios in the world; the consumption of omega-6 polyunsaturated fatty acids is about 8% higher than in the USA, and 10-12% higher than in most European countries. In fact, Israeli Jews may be regarded as a population-based dietary experiment of the effect of a high omega-6 PUFA diet, a diet that until recently was widely recommended. Despite such national habits, there is paradoxically a high prevalence of cardiovascular diseases, hypertension, non-insulin-dependent diabetes mellitus and obesity-all diseases that are associated with hyperinsulinemia and insulin resistance, and grouped together as the insulin resistance syndrome or syndrome X. There is also an increased cancer incidence and mortality rate, especially in women, compared with western countries. Studies suggest that high omega-6 linoleic acid consumption might aggravate hyperinsulinemia and insulin resistance, in addition to being a substrate for lipid peroxidation and free radical formation. Thus, rather than being beneficial, high omega-6 PUFA diets may have some long-term side effects, within the cluster of hyperinsulinemia, atherosclerosis and tumorigenesis.' ―Daniel Yam⁽²⁾
'In Japan, this ratio approximates 4:1, due to both a low fat diet and a relatively high consumption of fish and ALA-containing vegetable oils. In contrast to these regions of the world, Israelis are estimated to consume a much higher dietary omega–6/omega–3 ratio – about 22–26:1. Yet all these figures are far from a recommendation of 2:1 suggested by Okuyama et al. for industrialized countries. This ratio is based on the observed increase in cancer, allergy and atherosclerotic disease in Japan, related, at least in part, to an increase in the omega–6/omega–3 ratio from 2.8:1 to 4:1 in the past 40 years.' ―Gal Dubnov⁽³⁾
Polyamine content of soy and soy sauce: Despite having a lower ω−6/ω−3 ratio, the Japanese have higher prevalence of certain cancers, namely: those of the esophagus, the stomach, and the liver:
Above: Incidence of cancers of the esophagus, stomach, and liver—respectively; United States vs Japan
These are essentially the only ones, except for near‐equal rates of pancreatic cancer. Upper‐GI tract oncologists could almost rightly propose yet another 'Japanese Paradox' to describe this since the Japanese do drink less alcohol. You'd be almost temped to explain esophageal cancer by higher smoking rates yet this fails to account for the stomach cancer rates, saying nothing about the lower rates in lung cancer among the Japanese. The only logical explanation might them seem to be something they are consuming, but neither alcohol nor tobacco smoke.
Soy has an unusually‐high level of polyamines. These are small molecule polymers which reliably increase cellular proliferation. The enzyme which produces them, ornithine decarboxylase, is temporally expressed in a manner which mirrors the cell cycle; this same enzyme is also very commonly found elevated in cancer, and represents a pharmacological target of new drugs. Polyamines are capable of interacting with DNA directly, forming the final downstream process of cellular proliferation. In the cell nucleus, polyamines have been shown to induce the left‐handed Z‐configuration of DNA; and polyamines have also been shown to increase DNA replication rates during polymerase chain reaction. Studies have also shown them capable of binding microtubules, structures indispensable to cell signalling and stabilization. These molecules finally 'take the ghost out of the machine,' reduce complexity down to transcription rates, and link cellular biology to physical chemistry—explaining how growth can be created through fundamental, physical means. Polyamines are also found in soy in unusually high levels:⁽⁴⁾
The polyamine content of soy sauce, oolong tea, and soybeans completely overshadow essentially all other foods. These three foods are characteristically Japanese, and you wouldn't expect to consume such high levels anywhere else. These are small molecules, so they diffuse into tissues and don't reach the lower GI tract whole—but they can play a role there: colon cancer risk can be increased through high intakes of red meat, preferable with dairy to slow transit time. Meat makes for the best substrate of polyamine formation due to its high methionine and arginine content, and especially if transit time is comprimised by exorphins in wheat and dairy.
Green Tea: Since the Japanese have a lower ω−6/ω−3 ratio, it's not really necessary to invoke other protective factors—but this must play a role. Perhaps the best evidence is statistical: extremely high risk ratio reductions have been found in relation to green tea consumption:⁽⁵⁾
This is too strong to deny, and the in vitro data does not disappoint. Green tea polyphenols have been shown to inhibit cyclooxygenase‐2⁽⁶⁾ and ornithine decarboxylase,⁽⁷⁾ two enzymes highly associated with cancer; the first one creates prostaglandin E₂ and the second creates polyamines. And studies on rats show green tea polyphenols capable of greatly reducing cancer incidence and tumor size. Every way you look at it, these polyphenols seem highly protective; they have even been shown to reduce prostate cancer in people directly:⁽⁸⁾
So where do these tea polyphenols end‐up? Well: in rats, they end‐up in the same areas corresponding to low cancer incidence in Japan: the colon, the prostate, the bladder, and the lung:
But not the liver, where the Japanese have high cancer rates. The high levels found in the esophagus simply cannot compete with soy sauce polyamines—the stomach concentrations weren't measured—but green tea polyphenols can reduce cancer in organs further removed, especially in people having a low ω−6/ω−3 ratio to begin with.
[1] Pauling, L. "Solution to the Puzzle of Human Cardiovascular Disease: Its Primary Cause is Ascorbate defiency, leading to the deposition of Lp(a)." Journal of Orthomolecular Medicine (1991)
[2] Yam, Daniel. "Diet and disease—the Israeli paradox: possible dangers of a high omega-6 polyunsaturated fatty acid diet." Israel journal of medical sciences (1996)
[3] Dubnov, Gal. "Omega-6/omega-3 fatty acid ratio: the Israeli paradox." Omega-6/Omega-3 Essential Fatty Acid Ratio: The Scientific Evidence. Vol. 92. Karger Publishers (2003)
[4] Okamoto, Akiko "Polyamine content of ordinary foodstuffs and various fermented foods." Bioscience, biotechnology, and biochemistry (1997)
[5] Jian, Le. "Protective effect of green tea against prostate cancer: a case‐control study in southeast China." International journal of cancer (2004)
[6] Hussain, Tajamul. "Green tea constituent epigallocatechin‐3‐gallate selectively inhibits COX‐2 without affecting COX‐1 expression in human prostate carcinoma cells." International Journal of Cancer (2005)
[7] Gupta, Sanjay "Prostate cancer chemoprevention by green tea." Cancer research (1999)
[8] Brausi, Maurizio. "Chemoprevention of human prostate cancer by green tea catechins: two years later. A follow-up update." European urology (2008)
[2] Yam, Daniel. "Diet and disease—the Israeli paradox: possible dangers of a high omega-6 polyunsaturated fatty acid diet." Israel journal of medical sciences (1996)
[3] Dubnov, Gal. "Omega-6/omega-3 fatty acid ratio: the Israeli paradox." Omega-6/Omega-3 Essential Fatty Acid Ratio: The Scientific Evidence. Vol. 92. Karger Publishers (2003)
[4] Okamoto, Akiko "Polyamine content of ordinary foodstuffs and various fermented foods." Bioscience, biotechnology, and biochemistry (1997)
[5] Jian, Le. "Protective effect of green tea against prostate cancer: a case‐control study in southeast China." International journal of cancer (2004)
[6] Hussain, Tajamul. "Green tea constituent epigallocatechin‐3‐gallate selectively inhibits COX‐2 without affecting COX‐1 expression in human prostate carcinoma cells." International Journal of Cancer (2005)
[7] Gupta, Sanjay "Prostate cancer chemoprevention by green tea." Cancer research (1999)
[8] Brausi, Maurizio. "Chemoprevention of human prostate cancer by green tea catechins: two years later. A follow-up update." European urology (2008)
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