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Aging is Not a Disease, Damn It!

Discussion in 'The Cave' started by Dennis Clark, Sep 27, 2020.

  1. JanSz

    JanSz Gold

    454 mEq/d is 17706 mg potassium per day
    and it is about 15x larger than the 1200mg/day dose
    (1200mg=1teaspoon potassium bicarbonate)

    ==============================================
    It would help figure out the daily potassium intake of someone who would strictly be on the Epi-Paleo diet. (And where it would come from).
    @Jack Kruse

    ===============================================
    @DrEttinger
    You are taking a lot of potassium (comparing to average discussions about it).
    Thank you for sharing this information with me (with us).
    But with all this (supposedly) high dose,
    I suspect that it may possibly not be big enough.

    And we could possibly benefit from even larger doses.
    Potassium is highly correlated with many common problems (see table #2 that I copied in my post above).
    Low stomach acid
    high blood pressure
    low Growth Hormone
    many many others
    That reference (from your website) is rather convincing.
    Add to that possibility that lots of kidney problems may really be due to low potassium consumption.
    Which would be rather opposite to what MD's are telling us.


    I got on this topic because I have two peoples (women) in my circle that have kidney problems.
    One of them has insane muscle cramps, is highly disabled. Her daughter, caring for her is on the last legs herself, because of it.
    Any time I mention: give her some potassium I am getting:
    the doctor said, weak kidneys, no potassium, in return.

    It looks like potassium is a good subject to review again.
    ................................................................

    Given the fundamental physiologic and metabolic importance of potassium, such a large magnitude of change in potassium intake invites the question of whether in human beings the quantitative values of potassium-influenced physiologic phenomena (eg, blood pressure, insulin, and aldosterone secretion rates, and intracellular pH) that currently are viewed as normal in fact are in disaccord with genetically conditioned norms.

    https://www.advancedhealing.com/wp-content/uploads/Potassium-BEST.pdf
    upload_2021-2-2_17-38-47.png
     
    Last edited: Feb 2, 2021
  2. JanSz

    JanSz Gold

    Understanding potassium – How I Recovered

    https://howirecovered.com/understanding-potassium/#:~:text=Note that one teaspoon of potassium bicarbonate contains,help balance pH (if urine pH becomes acidic).

    ...
    there’s a risk of creating a potassium deficiency which is potentially lethal. It’s called hypokalemia. Muscle cramping is one of the warning signs and I’ve experienced some of those cramps.
    ...
    Note that one teaspoon of potassium bicarbonate contains roughly 2000 mg of potassium.

    ...
    upload_2021-2-3_8-23-27.png
     
  3. DrEttinger

    DrEttinger Choice, the only thing we control

    RBC and serum potassium blood test. Also, comp metabolic panel to make sure kidneys and other electrolytes are good, and to measure anion gap.
     
    JanSz and John Schumacher like this.
  4. JanSz

    JanSz Gold


    Na
    K
    Cl
    (Anion Gap)

    upload_2021-2-6_7-57-4.png

    (229) Are Neurons Just Electric Circuits? - YouTube

    I have posted this comment there:
    At time 7:25 there is a comment that ATP is energy derived from food.
    That would mean that our body runs on about 2000 calories/day or more if one eats more.
    We are also exposed to sunlight, that is additional energy, let assume naked person at noon at equator.
    All that energy is a small number, behind decimal point, if what Dr Boros is saying is correct.
    We live mostly on energy released by water synthesis that happens mostly in mitochondrial matrix and some in perixosomes. That is the water that eventually helps in production of ATP by nanomotors. That ATP daily production nears total body weight of individual.
    The matrix water is a fourth phase water, have nothing to do with the water we consume. Those waters newer mix in mitochondria.
    When at rest we produce 7437 liters of matrix water. 7437 kilograms.
    When working hard we may make up to 3x that much.
    The amount of that water is about the same as if blood going thru the heart was always made of fresh water.
    That water is synthesizing from hydrogen that comes from food, with oxygen from the breath.
    H2 + 1/2O2=H2O
    2kg + 16kg=18kg
    7437/9=826.33 kg hydrogen is burned over 24hr (at rest)
    When one kg of hydrogen is burned it releases 33920kcal/kg
    Body at rest uses 1358 kWh over a day (to stay alive).
    That is the same amount of energy as 1358 sodium street lamps use in medium size city.
    Three times that much when running marathon.
    Energy from food and sunlight at equator, are minute fraction (of rounding numbers in above analysis).
    Dr Boros is a professor at UCLA.
    If interested see him describing the amount of matrix water we produce here:
    Facebook
    https://www.facebook.com/photo.php?fbid=727069880999039&set=a.233328083706557&type=3&theater
    I am not professional in this field, sincerely looking for clear professional comments on the topic of how much energy (in kwh per day) our body uses to continue on living.
    My email
    xxxxxxxxxxxxxxxx
    .
     

    Attached Files:

    Last edited: Feb 6, 2021
    Dan2 likes this.
  5. JanSz

    JanSz Gold

    @DrEttinger
    @John Schumacher
    I would appreciate your guesses in regards to my melatonin.
    In a week or so, I will get DUTCH test results.
    I will know then my melatonin status.
    So far, I do not see any specific outstanding impact of the 30mg/night melatonin that I am consuming.
    If the DUTCH says that my melatonin is still deficient, I may want to increase the dose; that would be an easy conclusion.
    But if it says that melatonin is very high, what that may mean?
    I am already doing my best in regards to what Jack is suggesting (below).
    That would be about sunlight.
    But since melatonin is made in mitochondria, what kind of tweaks could be profitable in boosting its melatonin production?

    upload_2021-2-8_7-23-14.png

    https://twitter.com/DrJackKruse/status/1358499461278937088

    https://twitter.com/DrJackKruse/status/1358499461278937088/photo/1

    upload_2021-2-8_6-23-20.png
     
    Last edited: Feb 8, 2021
  6. DrEttinger

    DrEttinger Choice, the only thing we control

    Jan,

    Overanalyzing again. Everything can be plotted on a bell curve. Just because one is on the far right or left quantile in relation to a specific marker does not make it abnormal, it's just their normal. How much melatonin you make may be exactly what you need.
     
    JanSz likes this.
  7. JanSz

    JanSz Gold

    Thank you doctor.
    Someplace on another thread, I already admitted that some here, especially me, are likely somewhat paranoid.
    When I do not know much about some markers, I like to think that an acceptable laboratory level will likely be someplace within the laboratory range, between maximum and minimum.
    The last time I checked my melatonin was below minimum laboratory level.
    A year earlier it was already low, but still within laboratory range.
    So, at the minimum, I know that my melatonin is falling.
    .
     
  8. Dan2

    Dan2 Pedantic schlub

    edit:
    "From my observations, my leg cramps are strongly correlated to low potassium.
    I still get cramps sometimes.
    When I do, I get additional 1/2 tsp of potassium bicarbonate and go back to sleep, cramps go away immediately."
    (https://forum.jackkruse.com/index.p...on-gap-thiamine-deficiency.25474/#post-294736)
    Okay, i don't know, maybe most of this post isn't useful. But still maybe less of some supplement (other than potassium) would be a better adjustment than supplementing more melatonin.

    https://www.ncbi.nlm.nih.gov/books/NBK550972/
    Skimming the article I found this:
    "Pathological or traumatic sympathetic denervation of the pineal gland or administration of β-adrenergic antagonists abolishes the rhythmic synthesis of melatonin and the light-dark control of its production."

    "beta-adrenergic antagonist
    A type of drug that blocks the action of substances, such as adrenaline, on nerve cells and causes blood vessels to relax and dilate (widen). This allows blood to flow more easily and lowers blood pressure and the heart rate. Beta-adrenergic antagonists are used to treat high blood pressure, chest pain (angina), abnormal heart rate (arrhythmia), congestive heart failure, and several other conditions. They may also shrink certain types of vascular tumors, such as hemangiomas. Also called beta-adrenergic blocking agent and beta-blocker."
    (https://www.cancer.gov/publications/dictionaries/cancer-terms/def/beta-adrenergic-antagonist)

    So are there beta blockers in common foods and herbal supplements?
    https://www.healthline.com/health/natural-beta-blockers
    Okay, generally, yes.
    But how much would it need to be to affect pineal/melatonin function?
    Normal doses of herbs that have beta blockers shouldn't be enough to interfere with that.
    Then what if normal amounts of beta blocker chemicals in context of an excess of something else that they interact with could?

    https://en.wikipedia.org/wiki/Hyperkalemia
    "Beta2-adrenergic agonists act on beta-2 receptors to drive potassium into the cells. Therefore, beta blockers can raise potassium levels by blocking beta-2 receptors. However, the rise in potassium levels is not marked unless there are other co-morbidities present."

    Maybe if you're regularly supplementing with both lots of potassium and a variety of herbal medicines that have beta blocker chemicals in them, maybe there are other chemicals in the herb/food that help make the beta blocker chemicals not cause hyperkalemia when there's enough potassium in the blood, and when there's an excess of potassium then the chemicals other than beta blockers need to make the beta blockers affect potassium even less, and so there's a short-term-beneficial tradeoff of the beta blocker chemicals doing something else that's a less acutely risky longer-term problem from an excess of beta blocker chemical effects somewhere else, like the beta-blocker chemicals are diverted by other chemicals in the herb to another reaction that'll be less acutely risky. And maybe affecting the pineal (affecting the amount of melatonin made, and maybe also the way supplemented melatonin is used) is a less acutely risky effect?

    And similar to that...

    "Medications that interferes with urinary excretion by inhibiting the renin–angiotensin system is one of the most common causes of hyperkalemia. Examples of medications that can cause hyperkalemia include ACE inhibitors, angiotensin receptor blockers,[13] beta blockers, and calcineurin inhibitor immunosuppressants such as ciclosporin and tacrolimus.[15]"
    (https://en.wikipedia.org/wiki/Hyperkalemia)

    ... if there are chemicals in herbal supplements or foods that do the same as the ACE inhibitors, angiotensin receptor blockers, and calcineurin inhibitor immunosuppressants, and you're regularly supplementing with those, maybe a similar situation of an interaction of those chemicals with lots of potassium so the change in pineal function/melatonin function being a tradeoff for less acute problem?

    And back to that paper about the Yanomamo, potassium in the diet, and potassium supplements...

    https://www.advancedhealing.com/wp-content/uploads/Potassium-BEST.pdf

    And about the mixture of chemicals in a herbal supplement or plant food having a different effect on metabolism with nutrients in the herb or food than with isolated chemical(s) or mineral(s), like the large amounts of potassium as an isolated supplement compared to in context of the other chemicals in vegetables...

    https://forum.jackkruse.com/index.php?threads/napping-in-the-sun.25075/#post-290502

    There's a lot there that probably isn't useful, but I think something relevant is this:

    "In Table 4, under 'How Diet K Was Increased', the only one that wasn't a supplement was 'Grain-free vegetarian diet', increasing the K in the diet from 98 to 341 mEq/day, and they're the only group whose serum K mEq/L decreased from the baseline before the K increase in the diet. Maybe a different combination of vegetables in the diet and/or prepared differently could get the results the authors were looking for, but if the supplements worked better than the diet with lots of vegetables I think that's a sign of inaccurate assumption(s) about or ignorance of how something other than potassium in the metabolic context of eating lots of potassium-rich vegetables affects potassium's role."

    K table.png

    (Before reading my speculation, maybe this is better:
    ---->>> Is it simply that the serum potassium is less with the vegetable diet because the chemicals in the vegetables help the potassium get into cells and the isolated potassium supplements can't so stay in the blood?
    But would that still mean though that supplemented isolated potassium and chemicals in other herbal supplements that aren't the chemicals in the vegetables (and so are mismatched with the amount of potassium being ingested (because normally the potassum (and other minerals and nutrients) in the plant/herb would be more proportional with the chemicals in it than when mixing and matching the interactions of various isolated or standardized-active-ingredient supplements)) could be interacting making the less acutely risky tradeoff situation of the plant chemicals (the ones mismatched with the isolated or standardized supplemented nutrients and so not useful-in-proportional-context ones) having excessive effects somewhere else like if an excessive amount of the plant/herb were eaten?)

    So about the paper...
    If all the isolated potassium supplements increased serum potassium but the diet of vegetables with lots of potassium didn't, does that mean people really being adapted to higher levels of potassium in the blood because we used to eat a lot more potassium isn't accurate, considering the people eating the diet like the Yanomamo actually had less potassium in their blood after eating that way? And so if the metabolisms of the people in the study aren't adapted to use the high-potassium vegetable diet to increase serum potassium (edit: maybe this is wrong because of the thing about how much cells can use making there be less in the blood), then what's the reasoning that someone should supplement isolated potassium so it'll increase serum potassium? Because adapting to potassium supplements can be useful? But then does adapting to potassium supplements conflict with adaptations of how the metabolism uses mixtures of chemicals and nutrients in foods that affect the metabolism of each other; like the way the other things in the high-K vegetable diet reduced serum potassium, but the reverse -- how the supplemental isolated potassium affects the metabolism of chemicals in the herbal supplements or plant foods; and so there are long term less acutely risky tradeoffs in reaction to that (like pineal melatonin use changes?) until an unnecessary supplement isn't affecting the metabolism?

    Let me try to organize better my guesses about why the vegetable group has lower serum K and supplement groups higher...
    - maybe #1 plant chemicals help the lots of potassium get into the cells, so less in blood
    - maybe #2 plant chemicals don't help the lots of potassium get into cells, but do help it get out through the kidneys, so (about) the same in cells as before high potassium diet and also not more in blood
    - so either way, 1 or 2, supplement groups' lack of matched plant chemicals (matched from being in the foods high in potassium) means lack of help getting potassium into cells, so more in blood, or lack of help getting potassium out through kidneys, so more in blood
    - other possibility is matched plant chemicals in high-K foods helping potassium get into cells isn't important (and so supplements should be as good as the high-K vegetables), and higher levels of potassium in blood (like supplement groups) are good because that's a sign of more potassium available to cells
    - but then why, if that's good, is the high vegetable diet the only group with lower serum potassium? The study's saying what we're adapted to do is like the Yanomamo, and higher serum potassium is good so we should use potassium supplements because they raise the serum K?, even though the Yanomamo didn't have potassium supplements and what the Yanomamo did have made the serum K lower in the group who did that? (And potassium in the vegetables the Yanomamo ate compared to what the high-veg diet group ate shouldn't be much of a difference because of potassium being a common fertilizer for modern crops, right?) Am I misunderstanding something about the study? That data table seems to contradict the recommendation.

    So maybe less of some supplement(s) (herbal and/or potassium) would allow the melatonin production to increase, or the supplemented melatonin to be more usable?

    I don't know if my idea that beta blocker chemicals and lots of supplemented potassium together affecting pineal function makes sense, or if it could be just chemicals in herbal supplements affecting pineal function (and maybe interacting with some supplement other than potassium?) and the potassium supplements aren't involved in the melatonin thing. Even if the potassium supplements aren't involved with the melatonin thing, what about that Yanomamo paper in relation to other potassium things? Is what I focused on about the vegetable diet versus supplements serum potassium levels not very relevant compared to other things about the potassium bicarbonate supplementation I'm not considering? Or is there something about the availability of the potassium in the serum to the cells and what the kidneys do that affect the serum level that makes that data table make sense?
     
    Last edited: Feb 9, 2021
  9. DrEttinger

    DrEttinger Choice, the only thing we control

    My personal gauge is: do I fall asleep within 5-10 minutes of going to bed and do I wake up w/o an alarm at the same time every day. When I'm on vacation, no matter what time zone, do I calibrate to the local time zone within 24-48 hours. I do. I believe my melatonin is good. If you are not like this then maybe your's is off. This is merely my logical thought process, not from a text book.
     
  10. JanSz

    JanSz Gold

    Your thought process seems ok.
    Your melatonin seems ok.
    My melatonin is off.
    .
     
  11. JanSz

    JanSz Gold

    Thank you @Dan2 for the above compilation. Lots of good guesses.
    Indeed, I am taking so much stuff that cutting some off from my long list should be helpful.
    On my coming consult with @DrEttinger that will be priority #1.
    The melatonin vs octopus ink is new stuff that I plan on adding in, but still not sure how. (have already one suggestion from @Sue-UK )
    I plan on studying supplementation with (K + Mg +salt) vs its results which I think should be in the form of (Anion Gap).
    Overall my (Anion Gap) seems to be off.
    First
    wonder if there are (easy ways) of testing it.
    That may be as quick as the testing PH of a drop of blood.
    Are there any (worthwhile) (not too expensive) tools to test PH in a drop of blood (that I could buy)?
    Something similar to testing blood glucose.

    Second
    are there any useful tests that I could buy for testing at LabCorp, bought here (but other than (Panel-14) this I already know about):

    https://www.mcssl.com/store/bltsystem/comp-metabolic-panel-14
    The Comp Metabolic 14 Panel includes testing of these lab items:
    A/G Ratio
    ALT (SGPT)
    AST (SGOT)
    Albumin, Serum
    Alkaline Phosphatase, S
    BUN
    BUN/Creatinine
    Bilirubin, Total
    Calcium, Serum
    Carbon Dioxide, Total
    Chloride, Serum

    Creatinine, Serum
    Globulin, Total
    Glom Filt Rate, Est
    Glucose, Serum
    Potassium, Serum
    Protein, Total, Serum
    Sodium, Serum
    =========================================================
    https://selfhacked.com/blog/anion-gap/#What_Is_the_Anion_Gap

    Other than the above 4 highlighted items, Anion Gasp is influenced by many things.
    Measuring PH directly could be of some help.

    upload_2021-2-9_11-7-51.png
     
    Last edited: Feb 9, 2021
  12. Dan2

    Dan2 Pedantic schlub

    "The melatonin vs octopus ink is new stuff that I plan on adding in"

    I searched for "melanin melatonin" posted by Sue.

    https://forum.jackkruse.com/index.p...ournal-articles-ever.22932/page-2#post-282218

    "IIRC Dr Herrera said in an interview that melatonin is a natural inhibitor of human photosynthesis."

    https://forum.jackkruse.com/index.php?threads/dan2s-journal.25288/page-2#post-293604

    "...Herrera's human photosynthesis book and his work using melanin or its precursors as a treatment for AD, and its relevance to the substantia nigra in PD."

    "Melatonin controls pigmentation changes by aggregation of melanin into the melanocytes within the skin, causing the skin to change color. This interaction is also responsible for the paler skin color of elderly people and those with insomnia."

    So is the reasoning that eating the melanin in squid ink helps the pineal gland prepare for melatonin release at night, with the melatonin's inhibition of the human photosynthesis being the complement to the melanin's functions? And also supplemented melanin for the pineal similar to for the substantia nigra?

    And the italicized quote -- if melatonin controls pigmentation changes by melanin, and JanSz you put something on your skin to darken it, right?, a synthetic melanin? Then maybe there's feedback from the effect of the stuff put on your skin going to the melatonin regulation. If some step(s) of what the melanin and melanoctye activity would normally be without the stuff you put on your skin isn't happening because of that stuff shortcutting the melanin production system, maybe the steps that stuff skips are important feedback for melatonin regulation?
    Maybe eating the squid ink would make the synthetic melanin directly on your skin redundant, or maybe even putting the diluted squid ink on your skin would do the same as the synthetic melanin but with some difference from small amounts of other things in the ink that make it not mess up the skin melanin--melatonin feedback system.
     
    Last edited: Feb 9, 2021
  13. JanSz

    JanSz Gold

    if melatonin controls pigmentation changes by melanin, and JanSz you put something on your skin to darken it, right?, a synthetic melanin? Then maybe there's feedback

    I use Melanotan (MT-II) injections.
    When I am standing daily for 16 minutes, in front of the Red Sperti lamp, those injections help in getting the skin darker.

    ...........
     
  14. Dan2

    Dan2 Pedantic schlub

    Part 1 -- Why I'm Probably Wrong And You Probably Shouldn't Read Part 2

    Is melatonin used up in the melanocytes, so the amount the skin needs makes more needed from the pineal, or does it get recycled?

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3688757/
    "...pathways of skin melatonin metabolism were monitored ... in human keratinocytes, melanocytes, dermal fibroblasts, and melanoma cells... The major metabolites, 6(OH)M and AFMK, were produced in all cells... Melanocytes, keratinocytes, and fibroblasts transformed melatonin primarily into 6(OH)M and AFMK."

    Are those recylced into more melatonin?
    I don't think so; I didn't find something about that.


    Can the skin make melatonin too? And how much melatonin is made outside the pineal?

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583885/
    "Since in 2002 Slominski et al.32 reported that skin cells of multiple types (normal and immortalized skin keratinocytes, hair follicle keratinocytes, fibroblasts from dermis and hair follicle dermal papilla, melanocytes, melanoma cells and squamous cell carcinoma cell lines) and cutaneous tissue samples from benign as well as malignant skin phenotypes (skin of basal cell carcinoma) express the essential enzymes for melatonin synthesis such as TPH, AANAT and HIOMT, it seemed very likely that melatonin can be produced in the skin as an extrapineal site of melatonin synthesis...

    For decades, investigations concerning occurrence of melatonin in different body compartments revealed that significantly high concentrations are found in the bile fluid,20 bone marrow,21 cerebrospinal fluid,22 ovary,23 eye,24 lymphocytes5 or skin25 and is differentially distributed in subcellular organelles.21,26-28 It was reported that melatonin levels in organs mentioned above may be 10- to 1000-fold higher than in the plasma.27,28 High concentrations of melatonin across different organs suggest an ubiquitous, biologically highly relevant existence of tissue-specific, local melatoninergic systems which have the biological role of counteracting specific tissue-related regional stressors exactly at the place where they occur."


    https://sci-hub.do/10.1016/j.tem.2007.10.007
    "Recent research has revealed that mammalian skin also harbors a complex melatoninergic system, whose role in the maintenance of cutaneous homeostasis is explored here...

    Extrapineal melatonin synthesis has, to date, been identified in the brain, retina, Harderian gland, ciliary body, lens, thymus, airway epithelium, bone marrow, immune cells, gonads, placenta, GI tract and skin [7,9,5,18,19] and there might well be additional, as yet unrecognized, sites of peripheral melatonin synthesis.

    Melatonin synthesis in the skin

    Mammalian skin contains the entire molecular and biochemical machinery necessary to transform L-tryptophan to melatonin, through serotonin and N-acetylserotonin (NAS) intermediates... [details about melatonin production pathways]... Thus, mammalian skin has the capability to transform serotonin to melatonin through both classical (AANAT-dependent) and alternative (AANAT-independent) pathways...

    It deserves to be emphasized that important, melatonin effects in skin and elsewhere can also be exerted indirectly through its metabolites. For example, UV stimulates melatonin metabolism, which generates hydroxyl derivatives and AFMK (metabolites that are stronger antioxidants than melatonin itself) [7–9,36]. Important as they are, these receptor-independent protective actions of melatonin and its metabolites nevertheless require high intracellular levels of the molecules. This requirement can only be met by melatonin production in situ in the relevant target tissue because cellular melatonin uptake is limited (only 0.1% of external melatonin enters the cell) [36]. Thus, melatonin produced intracellularly could have direct access to nuclear receptors in an intracrine manner."


    https://sci-hub.do/10.1152/physrev.00044.2003
    "...melatonin was also identified in extrapineal tissues including the retina, Harderian gland, gut mucosa, cerebellum, airway epithelium, liver, kidney, adrenals, thymus, thyroid, pancreas, ovary, carotid body, placenta, endometrium, mast cells, natural killer cells, eosinophilic leukocytes, platelets, and endothelial cells [14, 67]; indeed, melatonin has been detected in all organs which have been examined, where often high concentrations of this indoleamine have been measured. The physico-chemical properties of melatonin support its amphiphilic nature, which allows its passage across all morphophysiological barriers including cell membranes and the blood–brain barrier [15, 68, 69]. Although extrapineal melatonin generally does not gain access to the systemic circulation, there are several exceptions to this assumption, mainly in lower vertebrates such as chicks but also in rats...
     
    JanSz likes this.
  15. Dan2

    Dan2 Pedantic schlub

    Part 2 - What I Guessed Might Happen But I'm Probably Wrong About


    "Melanotan II is an analogue of alpha-melanocyte stimulating hormone (α-MSH).
    Alpha MSH Ac-Nle4 c[Asp5, D-Phe7, Lys10]
    It acts as an antagonist of melanocortin-3 and -4 recpetors."
    (https://echelon-inc.com/product/melanotan-ii-cyclic-α-msh/)

    "Human α-MSH is produced in sites other than the pituitary, such as the skin itself and its systemic action promotes melanin production by the human skin in response to UV light [19]."
    (https://www.hindawi.com/journals/bmri/2014/654710/)

    __________

    "Melanocyte-stimulating hormone secretion from the pituitary is increased by exposure to UV light. Unlike most hormones, melanocyte-stimulating hormone release is not thought to be controlled by a direct feedback mechanism."
    (https://www.yourhormones.info/hormones/melanocyte-stimulating-hormone/)

    So supplementing MSH doesn't feedback to the pituitary (which produces it) to make the pituitary make less.


    https://sci-hub.do/10.1016/0149-7634(80)90034-2
    "...the skin lightening effect of melatonin might be due to its direct effect on melanophores or due to its effect exerted through the hypothalamus and the pituitary causing an inhibition of pituitary MSH. Subsequently the latter explanation has also been demonstrated to be correct by Kastin and associates [37, 38, 40]... the auto regulation of melatonin secretion from the pineal and MSH secretion from the pituitary has been suggested by Kastin and associates [40,41], in maintaining a balance of the lightening and darkening of skin respectively."

    Again, supplemented MSH doesn't make the pituitary make less MSH. Then to lighten the skin the melatonin is used. Because MSH and melatonin are antagonistic there needs to be enough melatonin to balance the MSH the pituitary would normally make plus the supplemented MSH, so supplementing MSH makes more melatonin needed just for the skin color regulation?


    https://sci-hub.do/10.1016/0149-7634(80)90034-2
    "...it has been demonstrated that melatonin affects the release of MSH [melanocyte-stimulating hormone] from the rat pituitary and MIF-I [melanoctye-inhibiting factor] from the hypothalamus and that conversely melatonin release is also affected by circulating MSH and MIF-I... Melatonin and MSH seem to have antagonistic effects on various physiological and behavioral functions... the action of melatonin is thought to be inseparable from the actions of other neuropeptides (e.g., MSH, MIF-I or AVT) and central neurotransmitters (e.g., 5-HT, GABA, and NE)."

    And if "melatonin and MSH seem to have antagonistic effects on various physiological functions", would too much MSH mean the pineal can't make enough melatonin to balance the effects of the MSH? So maybe your pineal is able to make a normal amount of melatonin, but the supplemented MSH is making more melatonin needed to lighten the skin, and because there are other needs for melatonin too, then there isn't enough melatonin when there's extra MSH?


    From the same article:
    "melatonin release is also affected by circulating MSH and MIF-I".

    How does MIF-1 affect melatonin secretion?

    "Melanocyte-inhibiting factor... [inhibits] release of other neuropeptides such as alpha-MSH,[18][19][20] and [potentiates] melatonin activity.[21]"
    (https://en.wikipedia.org/wiki/Melanocyte-inhibiting_factor)

    MIF-Induced Augmentation of Melatonin Functions: Possible Relevance to Mechanisms of Action of MIF-1 in Movement Disorders.
    https://sci-hub.do/10.3109/00207459008994244
    "MIF-1 has been reported to potentiate the melanocyte-lightening effect of melatonin in rats and its effects in patients with Parkinson’s disease and Tardive dyskinesia are associated with marked mood elevation. It is, therefore, possible that the effects of MIF-I in movement disorders are associated with increased melatonin secretion."

    "Several studies have suggested reciprocal interactions between the release of melatonin from the pineal gland and the regulation of hypothalamic-pituitary MSH release (Kastin et al., 1967; Kastin et al., 1972; Datta & King, 1980). Studies in rats have suggested that MSH released by the pituitary inhibits the secretion of melatonin from the pineal gland and also inhibits the release of MIF (Kastin et al., 1972; Datta & King, 1980). Conversely, there is evidence to suggest that melatonin inhibits MSH secretion by suppressing the release of MIF (Datta & King, 1980). Such modulatory feedback interactions between melatonin and MSH regulation appear to be crucial to the maintenance of skin pigmentation and other behavioral effects mediated by both hormones (i.e., aggressive behavior) (O’Donohue & Dorsa, 1982). In addition, there is evidence to suggest that the activity of melatonin may be potentiated by MIF-I. Kastin et al. (1972) have reported that small doses of MIF-1 potentiated the melanocyte-lightening activity of melatonin in rats."

    - MSH inhibits secretion of Melanocyte Inhibiting Factor (from hypothalamus).
    - But when melatonin inhibits MIF instead -> then less MSH (secreted from pituitary).
    - Less MSH secreted -> then less inhibition of melatonin secretion (from pineal).
    - So like "melatonin and MSH seem to have antagonistic effects on various physiological functions" -- they're each other's negative feedback.

    "...there is evidence to suggest that the activity of melatonin may be potentiated by MIF-I. Kastin et al. (1972) have reported that small doses of MIF-1 potentiated the melanocyte-lightening activity of melatonin in rats."

    Does injected MSH inhibit what MIF-1 does to potentiate melatonin's skin lightening effect? Meaning injected MSH would make more melatonin needed to lighten skin because of less help for melatonin lightening skin by the MIF-1's potentiation of melatonin?

    - MSH inhibits secretion of MIF-1 from hypothalamus.
    - Supplemented MSH doesn't feedback to the pituitary to decrease MSH secretion.
    - So if supplemented MSH also inhibits secretion of MIF-1 (like MSH secreted from the pituitary does), then the extra supplemented MSH reduces how much MIF-1 gets from the pituitary to the skin.
    - And then less MIF-1 getting to the skin means less available in the skin to help potentiate melatonin's skin lightening effect.
    - So more melatonin is needed to lighten skin if supplemented MSH inhibits MIF-1 secretion.

    >>>>>But I think the idea of how much MIF-1 is available to the skin from the pituitary might not make sense because of the stuff (in Part 1) about the skin melanocytes making MSH, melatonin, melanin itself, and so probably also MIF-1 itself.
    >>>>>So then the question is -- does supplemented MSH disrupt the steps in the skin's production of melatonin and does that unusual condition somehow make more melatonin from the pineal able to enter the skin than the 0.1%?
    (https://sci-hub.do/10.1016/j.tem.2007.10.007
    "...melatonin effects in skin and elsewhere can also be exerted indirectly through its metabolites... these receptor-independent protective actions of melatonin and its metabolites nevertheless require high intracellular levels of the molecules. This requirement can only be met by melatonin production in situ in the relevant target tissue because cellular melatonin uptake is limited (only 0.1% of external melatonin enters the cell).")
    >>>>>If there isn't an exception to the 0.1% melatonin from the pineal entering the skin cells, then supplemented MSH shouldn't make much difference of how much melatonin from the pineal is used in the skin cells?
     
    Last edited: Feb 10, 2021
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    JanSz Gold

  17. Sue-UK

    Sue-UK New Member

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  18. Got Alzheimer's or Parkinson's -> try Icariin

    Icariin improves brain function decline in aging rats by enhancing neuronal autophagy through the AMPK/mTOR/ULK1 pathway - https://www.tandfonline.com/doi/full/10.1080/13880209.2021.1878238

    • Icariin can improve the cognitive dysfunction through increased cholinergic function of the hippocampus.
    • Icariin can attenuate glial cells-mediated neuroinflammation and exert dopamine neuroprotection via an Nrf2-dependent manner.
    • Icariin can significantly improve dopaminergic neuronal loss and neuroinflammation
    Several studies found that AMPK activation can improve energy metabolism and protein clearance from the brain.

    Icariin Reverses the Elevated Expression of the Hepatic Transporters Oatp1a1, Oatp1a4, Oatp1a5, Oatp1b2 and Mrp2 in Spontaneously Hypertensive - http://wap.hillpublisher.com/ArticleDetails.aspx?cid=343

    Icariin alleviates hypoxia-induced damage in MC3T3-E1 cells by downregulating TALNEC2. - https://www.x-mol.com/paper/6013815 - Icariin relieved hypoxia‐stimulated damage by restraining TALNEC2 through blocking SPAK/JNK and triggering PI3K/AKT/mTOR in the MC3T3‐E1 cell.
    upload_2021-3-1_10-42-27.png
    [​IMG]

    Icariin attenuates neuroinflammation and exerts dopamine neuroprotection via an Nrf2-dependent manner - https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-019-1472-x

    Oxidative stress and neuroinflammation are considered as the major central events in the process of Parkinson’s disease

    Activation of Nrf2 signaling has been linked to anti-inflammatory activities. The role of Nrf2 signaling on Icariin -affected functions of glial cells. After Icariin treatment for 10 days, the protein levels of pro-inflammatory mediators, such as TNF-α and iNOS (a), and the production of neurotrophic factors, such as GDNF and BDNF (b), in the midbrain of WT and Nrf2.

    Icariin attenuates glial cells-mediated neuroinflammation and evoked dopamine neuroprotection via an Nrf2-dependent manner.

    Icariin Prevents IL-1β-Induced Apoptosis in Human Nucleus Pulposus via the PI3K/AKT Pathway - https://www.hindawi.com/journals/ecam/2017/2198323/

    Icariin had a strong protective effect on IL-1β pretreated human NP cells. This anti-inflammatory effect was detected by the stabilization of mitochondrial membrane potential, apoptosis rate, apoptosis relative proteins, intracellular ROS rate, and imaging cells in an electron microscope.


    How about bone health ->

    Effects of icariin on the proliferation and osteogenic differentiation of human amniotic mesenchymal stem cells https://josr-online.biomedcentral.com/articles/10.1186/s13018-020-02076-9

    Human amniotic mesenchymal stem cells (hAMSCs), derived from ditched amniotic membrane (AM), are a center of attention in mesenchymal stem cells (MSCs) for bone stem cell-based tissue engineering and regenerative medicine (TE&RM) use owing to their superior properties. HAMSCs have unique advantages for bone regeneration in a noninvasive way and have immunomodulatory properties with weak anti-inflammatory characteristics, high differentiation, and without ethical controversy


    So Icariin improve other "bone" health ->

    https://www.unboundmedicine.com/med...e_testosterone_mimetic_properties_of_icariin_ - increased the circulating levels of testosterone.

    Icariin Improves Age-Related Testicular Dysfunction by Alleviating Sertoli Cell Injury via Upregulation of the ERα/Nrf2-Signaling Pathway - https://www.frontiersin.org/articles/10.3389/fphar.2020.00677/full - Icariin activates Nrf2 signaling in Sertoli cells by upregulating the mRNA expression of key enzymes involved in the conversion of cholesterol to testosterone, such as StAR, Cyp17a1, and PBR (Chen et al., 2014). Consequently, intratesticular testosterone can bind with androgen receptor in Sertoli cells and peritubular myoid cells to control secretion of proteins from Sertoli cells—eventually support development of pachytene spermatocytes and germ cells through stage VII.

    https://www.medchemexpress.com/Icariin.html - 50 and 100 mg/kg Icariin significantly increase testosterone levels


    Protective effect of N-acetylcysteine on changes in serum levels of Pituitary–Gonadal axis hormones and testicular tissue - https://www.aihbonline.com/article....=10;issue=1;spage=16;epage=21;aulast=Shahrzad

    So far this is the strongest version I could find at the "best price" ->


    Pure Science GH-2 - Horny Goat Weed (Epimedium) Extract - Contains 20% Icariins - https://www.amazon.com/gp/product/B00AMBMHMQ

     
    Last edited: Mar 1, 2021
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