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The 'Japanese Paradox'

Discussion in 'Diet' started by Travis, Jan 23, 2018.

  1. Travis

    Travis Member

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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.

    '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:

    esophagus.pngstomach.pngliver.png
    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⁾

    polyamine.pngpolyamine2.png

    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⁾

    tea44.png

    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⁾

    cox.pngodc.pnggt.png

    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:

    distribution.png

    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. OP
    Travis

    Travis Member

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    'The highest concentration of EGC was found in the bladder, whereas the highest concentration of EGCG was found in the large intestine. In the kidney, prostate, and lung, substantial concentrations of EGC and EGCG were found; the concentration of EGCG was much lower than that of EGC, similar to the situation in plasma. In the liver, spleen, heart, and thyroid, tea catechins were present in low levels.' ―Sungbin Kim

    distribution.png

    'As the Japanese life-style and diet continue to become more “westernized,” the rates of malignancies of the breast, ovary, corpus uteri, prostate, pancreas, and colon also continue to rise. Nevertheless, the mortality patterns of certain malignancies, viz., laryngeal, esophageal, and urinary bladder cancer, are discrepant with their established risk factor associations, suggesting the existence of other differences in risk factor exposure between the two countries.' ―Ernst L. Wynder, MD


    colon.pngprostate7.pngbladder.pnglung.png
     
  3. raypeatclips

    raypeatclips Member

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    Very infesting thank you for the post. Do you think green tea can do anything coffee can't?
     
  4. Wagner83

    Wagner83 Member

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    That's not nice.
    I benefited from pycnogenol, it is rich in polyphonies and has been show' to have very interesting properties on veins, collagen and even asthma. When I asked Ray about it he said the benefits likely resulted from the flavonoids. It seems he dislikes polypheonols, green tea has been shown to be anti Thyroid as well (I have a thread on this). Do you think polyphenols can actually be beneficial, even without cancer? The polyphonols from green tea are anti dht but the tea itself isn't. It sounds like there should be a strong anti androgenic effect in the prostate if polyphonols are concentrated there. Is there a link between ornithine decarboxylase, cellular proliferation and Dht ?
    Edit: I decided to keep some of the auto correct errors for the fun. Polyphonys would have been a nice one too.
     
  5. OP
    Travis

    Travis Member

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    The thing is: these polyphenols have been tested on so many isolated enzymes. They have been shown to inhibit aromatase, 5α-reductase, histidine decarboyxlase, thyroid peroxidase, and catechol‐O‐methyltransferase. But if you look at the distribution in rats, you will see that these polyphenols don't partition to the thyroid. You will also know, if you find the study, that daily supplementation with epigallocatechin gallate did absolutely nothing to T₃ and T₄ levels in humans. Think whatever you want about it's effects on androgens, or whether it inhibits aromatase or 5α-reductase more in vitro, but it cannot be argued that they do prevent cancer in rats and have no effect on thyroid hormone in people.
     
  6. Wagner83

    Wagner83 Member

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  7. OP
    Travis

    Travis Member

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    I am getting the feeling that it's most likely the F⁻ ions in tea, which are present around 3‧ppm—or about three times higher than fluoridated tapwater. Rats are particularly sensitive to thyroid changes since they lack thyroxine binding globulin, and I don't think you'll be able to find a study showing changes with the polyphenols in humans. The only study I had found showed no change in T₄ or T₃, and only an insignificant 4% change in free T₃ (at 50‧mg polyphenols). But since there was no change in total thyroid levels—reflecting synthesis rates—you might think this has something to do with thyroxine binding globulin, which it has been shown to bind to:

    Miyata, Masanori. "The crystal structure of the green tea polyphenol (−)-epigallocatechin gallate–transthyretin complex reveals a novel binding site distinct from the thyroxine binding site." Biochemistry (2010)

    Now I don't particularly care for tea, but the polyphenols found within inhibit cancer and don't significantly affect the thyroid in humans (fluoride is a different story).
     
  8. BenPatrick

    BenPatrick Member

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    Well, would you look at that.. I have been eating steamed rice daily for many years, and every time I try reintroducing tamari— as in, used as a condiment on the rice for flavor— I always end up with excess peeling on my lips for a day or two after consuming the soy sauce. It’s very annoying, and I do not get this reaction from my rice meals without the soy sauce. I thought maybe the sodium was drying out my lips..

    However, this makes me wonder if this effect is caused by dramatically increased skin cell turnover due to the high polyamine content of the soy sauce? It’s bizarre, but I have thrown out many bottles, halfway used, because I get sick of the lip peeling before I run out of the soy sauce.
     
  9. tca300

    tca300 Member

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    " Studies in which animals were fed popular Japanese foods--“salted cuttlefish guts, broiled, salted, dried sardines, pickled radish, and soy sauce”--besides a chemical carcinogen, showed that the Japanese foods increased the number of tumors. But another study, adding only soy sauce (with a salt content of about 18%) to the diet did not increase the incidence of cancer, in another it was protective against stomach cancer (Benjamin, et al., 1991). Several studies show that dried fish and pickled vegetables are carcinogenic, probably because of the oxidized fats, and other chemical changes, and fungal contamination, which are likely to be worse without the salt. Animals fed dried fish were found to have mutagenic urine, apparently as a result of toxic materials occurring in various preserved foods (Fong, et al., 1979). " Salt, energy, metabolic rate, and longevity

    Also might the high calcium content of Tofu be protective of certain things?
     
  10. OP
    Travis

    Travis Member

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    Interesting. Polyamines will increase the growth of cells in culture, but mycotoxins are also carcinogenic. In the Balkans, where mycotoxicity is endemic, the cancer usually occurs in the bladder and kindneys—places where the Japanese have low tumor rates. I suppose it could be a different mycotoxin than the carcinogenic ochratoxins responsible for Balkan mycotoxic nephropathy, but the high polyamine content of Japanese foods still makes me suspicious.

    Whatever it is, I refuse to believe that Na⁺ is responsible for these high stomach cancer rates.
     
  11. OP
    Travis

    Travis Member

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    I think their polyphenols can inhibit cancer, and green tea has a high level of polyphenols in general compared to fruits. I am worried a bit about the high F⁻ content, and might read a little more about boron pretty soon here. I know that F⁻ will complex with boron (B) in solution forming fluoroborates—such as trifluoroborate (BF₃). Tea also has quite a bit of threanine, which is an amino acid similar to glutamate and could perhaps interfere with that to some degree. I like coffee more, but I think tea would be a better think to drink in certain types of cancers.

    There is nothing stopping people from drinking both. The last few days I switched from coffee to green tea around 7‧pm, but I think I am going to lay off the tea from now on. This stuff is starting to make me feel weird—yet I really don't think it's the polyphenols; I think it's the massive concentrations of F⁻ and/or threanine.

    The polyphenols could have slightly estrogenic effects, but I haven't seen a very good study on this yet. Even if this were true, this wouldn't negate the cancer‐protective effects of the main polyphenol; this would only strengthen them by providing a plausible mechanism (in the case of prostate cancer).
     
  12. HDD

    HDD Member

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    “Japanese women's relative freedom from breast cancer is independent of soy products: traditional soy foods aren't the same as those so widely used in the US, for example, soy sauce doesn't contain the so-called soy estrogens, and tea is used much more commonly in Japan than in the US, and contains health protective ingredients. The “estrogenic” and “antioxidant” polyphenolic compounds of tea are not the protective agents (they raise the level of estrogen), but tea's caffeine is a very powerful and general anti-cancer protectant. The influential article in Lancet (D. Ingram, Lancet 1997;350:990-994. “Phytoestrogens and their role in breast cancer,” Breast NEWS: Newsletter of the NHMRC National Breast Cancer Centre, Vol. 3, No. 2, Winter 1997) used a method known to produce false results, namely, comparing the phytoestrogens (found in large amounts in soybeans) in the urine of women with or without breast cancer. For over fifty years, it has been known that the liver excretes estrogens and other toxins from the body, and that when (because of liver inertia) estrogen isn't excreted by the liver and kidneys, it is retained in the body. This process was observed in both animals and humans decades ago, and it is also well established that estrogen itself suppresses the detoxifying systems, causing fewer carcinogens to be excreted in the urine. Ingram's evidence logically would suggest that the women who have cancer are failing to eliminate estrogens, including phytoestrogens, at a normal rate, and so are retaining a higher percentage of the chemicals consumed in their diets. Flavonoids and polyphenols, like our own estrogens, suppress the detoxifying systems of the body. “

    Natural Estrogens
     
  13. HDD

    HDD Member

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    The following were references from one (or more) of Ray Peat’s articles.


    Proc Soc Exp Biol Med 1999 Apr;220(4):244-8. The prevention of lung cancer induced by a tobacco-specific carcinogen in rodents by green and black Tea. Chung FL “The oxidation products found in black tea, thearubigins and theaflavins, also possess antioxidant activity, suggesting that black tea may also inhibit NNK-induced lung tumorigenesis. Indeed, bioassays in A/J mice have shown that black tea given as drinking water retarded the development of lung cancer caused by NNK.” “We conducted a 2-year lifetime bioassay in F344 rats to determine whether black tea and caffeine are protective against lung tumorigenesis induced by NNK. Our studies in both mice and rats have generated important new data that support green and black tea and caffeine as potential preventive agents against lung cancer, suggesting that a closer examination of the roles of tea and caffeine on lung cancer in smokers may be warranted.”


    Cancer Res 1998 Sep 15;58(18):4096-101. Inhibition of lung carcinogenesis by black tea in Fischer rats treated with a tobacco-specific carcinogen: caffeine as an important constituent. Chung FL, Wang M, Rivenson A, Iatropoulos MJ, Reinhardt JC, Pittman B, Ho CT, Amin SG. “The NNK-treated group, given 2% black tea, showed a significant reduction of the total lung tumor (adenomas, adenocarcinomas, and adenosquamous carcinomas) incidence from 47% to 19%, whereas the group given 1% and 0.5% black tea showed no change. The 2% tea also reduced liver tumor incidence induced by NNK from 34% in the group given only deionized water to 12%.” “The most unexpected finding was the remarkable reduction of the lung tumor incidence, from 47% to 10%, in the group treated with 680 ppm caffeine, a concentration equivalent to that found in the 2% tea. This incidence is comparable to background levels seen in the control group. This study demonstrated for the first time in a 2-year lifetime bioassay that black tea protects against lung tumorigenesis in F344 rats, and this effect appears to be attributed, to a significant extent, to caffeine as an active ingredient of tea.”


    Nutr Cancer 1998;30(1):21-4. Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese women. Nagata C, Kabuto M, Shimizu H. “Although the effect of caffeine cannot be distinguished from effects of coffee and green tea, consumption of caffeine-containing beverages appeared to favorably alter hormone levels associated with the risk of developing breast cancer.”
     
  14. OP
    Travis

    Travis Member

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    Nice. I had read a few articles on prostate cancer and coffee a few months ago; it is protective, but not as much as green tea. Most of the authors had attributed this to the usual 'general antioxidant' properties, due mostly to its caffeic acid content.

    But we do eat polyphenols everyday, and only some of them are estrogenic. To give an idea, I'll hunt down some binding data:

    First of all: polyphenols can be further subdivided into flavones, flavonones, and isoflavones. Some of the tea polyphenols are 'epi'‐polyphenols and not included in the binding assay below.

    polyphenole.png

    The leftmost line (below) of course represents estradiol displacing itself—or a radioactive version of itself to be specific. The most estrogenic flavone is kaempferol—found in strawberries—and the least estrogenic is rutin, found in apples (the glycosylated form of quercetin.)

    flavone.png

    The flavonones (below) don't really have common names except naringenin, found in grapefruit.

    flavonone.png

    And of course the soy isoflavones are the most powerful at binding the estrogen receptor, binding strongly in high nanomolar and low micromolar range. The soy isoflavones bind around 100× to 1000× stronger than your average fruit polyphenol.

    isoflavone.png

    Quotes:

    'More recently, neonatal exposure to genistein has been shown to induce both uterine [...] abnormalities similar to those caused by the potent estrogen, ethinyl estradiol.' ―Branham

    'The purpose of this study was to assess the ER binding of several groups of compounds of plant (flavones, isoflavones, flavanones, coumarins, chalcones) or fungal origin (zearalanone derivatives).' ―Branham

    'We used a competitive binding assay for the rat uterine ER, in which receptor and ligand concentrations were optimized for chemical throughput.' ―Branham

    'Recent crystal structure analysis of four ligand-receptor complexes has indicated that the phenolic ring, normally the A-ring in steroids or phytoestrogens, is crucial for binding because it forms three hydrogen bonds with ER amino acids and water. However, a recent crystal structure for ER-β and genistein showed that the phenolic C-ring served to form the hydrogen bonds. This suggests that a chemical may bind in two orientations that differ by 180°. Our data showing that 3′-hydroxyflavanone and 4′-hydroxyflavanone have a phenolic C-ring important in binding suggests the possibility that “flipping” of these chemicals may occur in a manner similar to the situation for genistein binding to ER-β.' ―Branham

    'The mycoestrogens examined here exhibited the greatest binding to ER of all chemical classes examined. The affinity of α-zearalanol to ER is ∼30% lower than that for E₂, which is in agreement with previous assays. Using the yeast cell estrogen screening assay, Coldham et al. showed that α-zearalanol induces an estrogen-responsive reporter gene at a level that is only 1.3% of that induced by E₂.' ―Branham

    Branham, William S. "Phytoestrogens and mycoestrogens bind to the rat uterine estrogen receptor." The Journal of nutrition (2002)
     
  15. HDD

    HDD Member

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    Effects of tea polyphenols and flavonoids on liver microsomal glucuronidation of estradiol and estrone. - PubMed - NCBI
    Abstract
    Administration of 0.5 or 1% lyophilized green tea (5 or 10 mg tea solids per ml, respectively) as the sole source of drinking fluid to female Long-Evans rats for 18 days stimulated liver microsomal glucuronidation of estrone, estradiol and 4-nitrophenol by 30-37%, 15-27% and 26-60%, respectively. Oral administration of 0.5% lyophilized green tea to female CD-1 mice for 18 days stimulated liver microsomal glucuronidation of estrone, estradiol and 4-nitrophenol by 33-37%, 12-22% and 172-191%, respectively. The in vitro addition of a green tea polyphenol mixture, a black tea polyphenol mixture or (-)-epigallocatechin gallate inhibited rat liver microsomal glucuronidation of estrone and estradiol in a concentration-dependent manner and their IC50 values for inhibition of estrogen metabolism were approximately 12.5, 50 and 10 microg/ml, respectively. Enzyme kinetic analysis indicates that the inhibition of estrone glucuronidation by 10 microM (-)-epigallocatechin gallate was competitive while inhibition by 50 microM (-)-epigallocatechin gallate was noncompetitive. Similarly, several flavonoids (naringenin, hesperetin, kaempferol, quercetin, rutin, flavone, alpha-naphthoflavone and beta-naphthoflavone) also inhibited rat liver microsomal glucuronidation of estrone and estradiol to varying degrees. Naringenin and hesperetin displayed the strongest inhibitory effects (IC50 value of approximately 25 microM). These two hydroxylated flavonoids had a competitive mechanism of enzyme inhibition for estrone glucuronidation at a 10 microM inhibitor concentration and a predominantly noncompetitive mechanism of inhibition at a 50 microM inhibitor concentration.
     
  16. OP
    Travis

    Travis Member

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    Those IC₅₀ values are approximately 500× the concentrations found in the rat liver after chronic green tea feeding, which are expressed in nanograms per gram (ng/g; see chart above); these values are equivalent to micrograms per kilogram (μg/kg), or essentially one microgram per liter (because the density of the liver approaches the density of water: one kilogram per liter). The concentrations in the above abstract are on the order of micrograms per milliliter (μg/ml), which become milligram per liter concentrations after multiplying by unity—or one‐thousand over one‐thousand (μg/ml × 10³/10³ = mg/L). Expressing the IC₅₀ of (−)‐epigallocatechin gallate for estradiol glucoronidation inhibition in the equivalent units of milligrams per liter allow easy juxtaposition against the liver tissue concentration found in the rat after routine administration; those values are 10‧mg/L vs ~20‧μg/L.

    ...or 10,000‧μg/L vs ~20‧μg/L.
     
  17. HDD

    HDD Member

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    Lol, now in layman’s terms please? I vaguely understand. The abstract is flawed?
     
  18. OP
    Travis

    Travis Member

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    No, just pointing out the dose was a bit high. I've been paying more attention to the doses used lately, and am starting to look into tissue distribution and pharmacokinetics. I think the food molecules which reach the liver tend to a be a bit more oil‐soluble; the polyphenols are absorbed to a large degree in the small intestine. Sure, the liver will filter the blood and get those polyphenols but for some reason more are found in the lungs and the prostate [?]. I am not sure why; nor do I know whether polyphenols in general follow the same distribution pattern.
     
  19. Philjay

    Philjay Member

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  20. OP
    Travis

    Travis Member

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    Yes. We need to look into caffeine because both coffee and tea have this, and both coffee and tea are protective against cancer of the prostate. It would be quite embarrassing to everybody if it were found that it is caffeine alone which is responsible for these effects (lol).