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Cardenosine - Liquid Product For R&D

Discussion in 'IdeaLabs' started by haidut, Feb 9, 2018.

  1. OP
    haidut

    haidut Member

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    Interesting, thanks. Please keep us posted.
     
  2. OP
    haidut

    haidut Member

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    Great, thanks for the feedback Dan!
     
  3. OP
    haidut

    haidut Member

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    Yes, and it seems to work rather well. Look at the studied in the "Reproductive/menopause" section in the original thread.
     
  4. DCLOSE

    DCLOSE Member

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    How would one know if there ETC is not working properly?
     
  5. OP
    haidut

    haidut Member

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    Most people with malfunctioning ETC have high lactate, and symptoms of MELAS.
    MELAS syndrome - Wikipedia

    I don't know if there is a specific easily obtainable test to see if just ETC is working properly. Maybe @Travis / @Koveras / @Kyle M would know.
     
  6. Travis

    Travis Member

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    Perhaps indirectly through lactic acid would be the best bet, but it is actually possible to measure the mitochondrial membrane potential (ψ) which is probably the most direct measure of mitochondrial activity. Determining the activity of the electron transport chain in this way is tantamount to measuring the electrons themselves; the value for ψ is generally around −180‧mV. Obviously, this is not a routine clinical test but this has been done.
     
  7. Ron J

    Ron J Member

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    Hello haidut
    Along 1g of inosine, what topical dose of cardenosine would I need for a muscle imbalance? And does it mix with other SFA esters-ethanol products?
     
  8. DCLOSE

    DCLOSE Member

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    This product would definitely be a benefit to people with MELAS syndrome!
     
  9. Kyle M

    Kyle M Member

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    The problem is in isolating someone's biopsied mitochondria, lots of variables. A crude test off the top of my head would be disappearance time of methylene blue, using the assumption that problem respiration is linked to a well-oxidized cell potential.
     
  10. OP
    haidut

    haidut Member

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    Did anybody ever ask Peat about his opinion on using oral methylene blue as a health test? I wonder if he thinks it's reliable and what doses would indicate good health. What do you think?
     
  11. Kyle M

    Kyle M Member

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    What would be the outcome you look for? I've only read him about the disappearance of MB color on skin is indicative of the oxidative potential of cells. That would only be at the skin though, and there may be many confounders such as extracellular reducing agents and extracellular oxidants competing with the MB.

    My gut feeling is that it's worth trying if someone has MB and doesn't mind a bit of blue on their skin for a while, but it would be more qualitative than quantitative.
     
  12. OP
    haidut

    haidut Member

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    Yeah, the skin test is nice but it can be skewed by local conditions not indicative of systemic health. I was thinking that maybe ingesting up to a certain amount of MB and checking for urine discoloration would be more indicative of systemic health as it has to pass through the GI, liver and then kidneys. Human studies with oral MB show that the bioavailability is pretty stable and does not vary much. I think it was around 70%. I have seen very young children get blue pee from 1mg oral MB doses and I am inclined to think it signifies their high oxidative state, while I have seen adults not get any change in urine color from even 15mg doses. This can't be a coincidence and as such could be developed into a more robust test with "normal" ranges where say a person ingests increasing MB doses once daily for several days until the pee turns blue. The lowest dose at which this happens can be compared to the results of a large number of other adults and this could gauge redox status. I suppose the same can be achieved with a simple blood test for pyruvate and lactate and then the pyruvate/lactate ratio can be checked against known pathological ranges for which data already exists. But the MB test would be better since it would be non-invasive and everybody can do at home without doctors getting involved.
     
  13. dand

    dand Member

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    Wow. Love this ❤️
     
  14. Regina

    Regina Member

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    Hey, interestingly enough, I got blue pee a few days ago. And it corresponded with feeling much better overall.
    I have been taking MB for many months now. 3 drops oxidal on the back of my tongue in the am and another dose at night. Maybe totalling 8 - 10 drops per day.
     
  15. dand

    dand Member

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    Goes to buy more oxidal :).
     
  16. OP
    haidut

    haidut Member

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    Interesting, thanks for sharing. So, this means about 5mg MB daily right?
     
  17. Kyle M

    Kyle M Member

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    Yes that would be better, but for any kind of rigor you would need a spectrophotometer to measure differences in "blueness" outside of eye perception. The other hues of urine, which vary by what you're consuming and your metabolism, would obfuscate small to moderate blues. At best this could be a safe and easy qualitative test, but I still don't see potential for quantitative results.
     
  18. Regina

    Regina Member

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    Yes. I think so.
     
  19. OP
    haidut

    haidut Member

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    Yes, and that's why I was thinking of switching the test into trying different doses until ANY hint of blue is seen, not trying to determine how blue it is. In my experience, a person who sees any change in urine color from say 5mg is healthier than somebody who has no change from 5mg but very deep blue from 10mg. It's almost like a threshold test, since any amount of unused MB is enough to indicate sufficiently oxidative state. Checking the blue saturation would be better but would probably only become necessary when a large amount of people fall into a specific group where say 1,000 of them see urine changes form 5mg and these people need to be segregated further. However, even that group can be subtested with 4mg, 4.5mg, etc in order to get an even finer breakdown. But I think that much of granularity may not be needed since we are only looking for a few categories like "unhealthy", "borderline/OK", "healthy". And the dose would need to be on a mg/kg basis, not set to 5mg since a massive person like a NLF linebacker will probably not react much to 5mg while a baby would get oversaturated with the same dose.
    Anyways, I will ask Peat and see what he says.
     
  20. Travis

    Travis Member

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    Well, inspired O₂ cannot be reduced (+4e⁻) to water without flux through the electron transport chain. Of course you'd expect some O₂ to be consumed in the body during enzymatic reactions (i.e. cyclooxygenase, glycine oxidase), become a hapless bystander of incidental non-energy-yielding reductions (i.e. NADH, vitamin C), and participate in spontaneous peroxides with polyunsaturated lipids—all of which are probably negligible; I think it would be safe to say that over 90% of inhaled oxygen not expired becomes converted to H₂O and trapped within the body. If you could accurately estimate the total amount of mitochondrial heme groups within the body, then you could perhaps divide oxygen consumption by that to yield an efficiency ratio rate—or mol·O₂ per mitochondrial heme group per second. Of course this neglects the O₂ transport efficiency in the blood, so wouldn't be 'perfect,' but there should be enough data on this to quickly find out its applicability. Since O₂ is directly coupled to the electron transport chain, I think it would be provide a better indicator than expired CO₂—which can be produced from non-respirative glycolysis. But expired CO₂ is also a useful thing to know, as that would allow the calculation of The Meyerhof–Warburg quotient (the cancer quotient):

    ➞ Otto Warburg & Dean Burk: "On respiratory impairment in cancer cells." Science (1956)

    'the higher the malignancy, the greater the fermentation and the smaller the respiration...' ―Warburg

    'The more cancer cells a tumor contained, the higher was the fermentation and the lower was the respiration.' ―Warburg

    'If there is a disturbance in respiration that leads to an accumulation of lactic acid, it can occur only at or beyond the pyruvic acid stage and. must be due either to some aberration in carbon transport through the citric acid cycle or to some "bottleneck" in electron transport.' ―Weinhouse

    'When, in more extensive experimentation, ¹⁴C-marked substrates were tested (glucose, lactate, acetate, butyrate, octanoate, palmitate, and 2,4-acetoacetate), there was in general a relatively much greater aerobic production of ¹⁴CO₂ by the normal tissue groups than by the tumor groups employed.' ―Burk

    'On the basis of impairment type i, and as a confirmatory qualitative demonstration thereof, the following simple manometric test has been devised that permits investigators to distinguish cancer cells from virtually all normal body cells, growing or nongrowing. The cells under test are placed in a manometric vessel of any convenient size. The vessel is filled to one-third to one-half of its volume with physiological serum or other equivalent body fluid. The volume of cells is of the order of ¹⁄₃₀₀ the volume of serum. Cancer cells cause the manometer to register a steady and notable increase in pressure with time, whereas normal body cells cause a negative (or zero) change in pressure with time. The few-if any exceptions extant are only apparent, or are readily ruled out on other bases; thus, use of nonphysiological media (for example, unfortified saline ) may vitiate the test for normal cells, and omission of the carbohydrate glucose certainly will for cancer cells. [...] Thus, the sign and magnitude of the pressure change can be expressed as an exact mathematical function of the ratio of the absolute magnitude of aerobic glycolysis to the absolute magnitude of respiration for any given conditions of experimental arrangement. ―Burk

    'The impaired respiration may involve any combination-usually at least three-of the following experimental quantities readily measurable under appropriate conditions: (i) a high ratio of glycolysis to respiration; (ii) a low absolute value for oxygen consumption (QO₂); (iii) an inefficient or uncoupled respiration; or (iv) a low paraphenylenediamine (succinate) oxidative response (3). This list could be expanded.' ―Burk
     
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