Low salt diet and water restriction
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@izkrov said in Low salt diet and water restriction:
Low salt raises aldosterone and I think prolactin too. Aldosterone helps you retain sodium by disposing potassium and magnesium, I don't think you want that.
In a kidney cell:
MR expression is tightly regulated by osmotic stress. Hypertonic conditions induce expression of tonicity-responsive enhancer binding protein, an osmoregulatory transcription factor capable of binding tonicity-responsive enhancer response elements located in MR regulatory sequences. Surprisingly, hypertonicity leads to a severe reduction in MR transcript and protein levels. [...] In sharp contrast, hypotonicity causes a strong increase in MR transcript and protein levels.
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@NNight I don't really understand what MR gene expression is. Could you explain?
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Aldosterone effects are mediated by the mineralocorticoid receptor (MR), a transcription factor highly expressed in the distal nephron. Given that MR expression level constitutes a key element controlling hormone responsiveness, there is much interest in elucidating the molecular mechanisms governing MR expression.
This means that the mineralocorticoid receptor (which mediates the effects of aldosterone) expression might be reduced in conditions of water restriction ("osmotic stress").
Thus, you might (this is an in vitro study) want to restrict water consumption when you limit your salt intake, and vice versa.
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My latest fad is molybdenum (that's not my first time).
It could be helpful to increase uric acid which seems to be needed during "dehydration" (or dry fasting at least):
Also, it is thought to be able to chelate unbound copper while copper could be impairing transcription factors:
Nevertheless, what is the link between a selective LXR activation and copper homeostasis?
First, copper may bind with high affinity to the DNA‐binding domain of several nuclear receptors, including LXRs, inducing a conformational change that prevents DNA binding and, in turn, their transcriptional activity.
Liver X receptors and copper metabolism: New frontiers for the oxysterol receptorsPs:
Another theory, first proposed in the 1950s, suggests that uric acid is structural homolog of caffeine (which in turn is a structural homolog of adenosine), and that high uric acid levels promoted mental alertness for primates and contributed to the development of human intelligence [8]. This hypothesis has been increasingly supported by experimental observations, although its role in evolution remains to be confirmed.
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Caffeine inhibits hypothalamic A1R to excite oxytocin neuron and ameliorate dietary obesity in mice
We also show that caffeine excites oxytocin expressing neurons, and blockade of the action of oxytocin significantly attenuates the effect of caffeine on energy balance.
Was Ray Peat "against" oxytocin?
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@NNight said in Low salt diet and water restriction:
Caffeine inhibits hypothalamic A1R to excite oxytocin neuron and ameliorate dietary obesity in mice
Was Ray Peat "against" oxytocin?
I thought this was an interesting question.
User: was ray Peat against oxytocin
Peatbot: I don't know.
My second attempt at finding an answer:
User: is oxytocin healthy?
Peatbot: Oxytocin is a hormone that plays various roles in the body, including in social bonding, sexual reproduction, childbirth, and the period after childbirth. It is often referred to as the "love hormone" or "cuddle hormone" because it is released when people snuggle up or bond socially. However, its effects are not universally positive.
According to the context provided, oxytocin is described as one of the adaptive hormones that can have stress-related responses. It is not solely a "happiness and euphoria hormone" because it can also increase under stress, and its effects are not always beneficial. This suggests that while oxytocin has important functions, it is not inherently "healthy" or "unhealthy" but rather has complex roles that can vary depending on the situation.
I hope this helps.
““Effective health care depends on self-care” - Ivan Illich, 👀
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@NNight Inosine could also help with the uric acid. During a low water diet, I feel thirst decreased when taking that.
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@Razvan
Also adding P5P and zinc to this low water intake cleared more weight out. Lost much more weight overnight, prolactin? -
@DavidPS thanks!
This Peatbot is quite good for an AI.
That's the impression I've got from reading articles about oxytocin too (and what I've read from Haidut was less "balanced" than these conclusions, but he can have differing opinions from Ray Peat). However, the interpretation of oxytocin effects might be "biased" by how research is done, e.g. supplementing oxytocin with a nasal spray, when oxytocin levels are associated with vasopressin levels, potential other hormones (like secretin) or physiological parameters, and "side effects" could happen if you "de-correlate" them (for example hypo-osmolarity).@Razvan
Interesting, I've never tried inosine nor P5P.
Last time I took zinc, I had a very strong metallic/strange taste (it was a sort of colloidal solution) and had to spit it out. Made me wondered if I had too much zinc (while I was not even supplementing chronically at the time). -
Could oxytocin be helpful as it can bind free copper ions in the cells?
Copper and silver ions seem to impair LXR and FXR activation. This is not necessarily a good thing and could be a cause of symptoms seen in copper overload situations (e.g. Wilson's disease):
Together, these data demonstrate that copper-mediated nuclear receptor dysfunction disrupts liver function in WD and potentially in other disorders associated with increased hepatic copper levels.
Elevated copper impairs hepatic nuclear receptor function in Wilson’s diseaseIs this still true when copper is bound to oxytocin?
In this work, we focus on characterizing copper and zinc bound forms of oxytocin and related analogs through far-UV circular dichroism. We report that Cu(II) and Zn(II) bind uniquely to oxytocin and all analogs investigated. Furthermore, we investigate how these metal bound forms may affect downstream signaling of MAPK activation upon receptor binding. We find that both Cu(II) and Zn(II) bound oxytocin attenuates the activation of the MAPK pathway upon receptor binding relative to oxytocin alone.
Metal-induced structural changes to a peptide hormone may have a number of effects on storage, secretion, stability, and/or signaling. In this case, it is possible that both Zn(II) and Cu(II) lend different structural integrities to oxOT at different points in oxOT lifetime. Physiologically, it is possible that Cu(II) is bound to oxOT in serum but, because the concentrations of metal ions surrounding specific tissues are believed to fluctuate, Zn(II) may be able to displace Cu(II) under specific concentrations. It still remains to be seen how Cu(II) would affect oxOT in serum, however, metal binding may be a key player in prevention of degradation; further studies in our lab are underway to test this hypothesis. The binding of metal ions to peptide hormones, particularly oxOT, may provide an additional source for regulation, and this study provides the foundation for future studies.
Investigation of metal modulation of oxytocin structure receptor-mediated signaling
It would be interesting to determine if such an effect (oxytocin binding to copper thus avoiding free copper to disturb FXR and LXR, or other nuclear receptors, activation) could be "significant" in terms of the number of moles of oxytocin with respect to the quantity of copper ions in a cell.
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Travis told me several times that the process of making oxytocin creates one molecule of vasopressin in addition to the oxytocin, so you have both.
I believe that animals secrete oxytocin and vasopressin when they are thirsty. It serves the purpose of raising trust, so that an animal can face potential carnivore enemies, despite the normal fear. Otherwise the animal would never have the courage to get to the water hole, and would die from thirst.
An other word for vasopressin is antidiuretic hormone, and when we are low in water, it shuts down our kidneys so we don’t sludge/thicken our blood too much by drawing out too much water.
It is secreted when we sleep, to avoid the same fate (blood getting too thick) and to help us sleep without waking up to pee.
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@Ecstatic_Hamster said in Low salt diet and water restriction:
Travis told me several times that the process of making oxytocin creates one molecule of vasopressin in addition to the oxytocin, so you have both.
I didn't know their production was necessarily simultaneous, interesting! I believe their degradation might not be though.
I've made a rapid comparison of oxytocin and copper quantities (with help of ChatGPT @sharko ) and they don't match. Copper seems to outnumber oxytocin by a 10^6 factor so this hypothesis seems completely wrong at first sight (except if you consider that it's possible that oxytocin and copper concentrations could be vastly different a the cell's compartment where copper disturbs nuclear receptors activation).
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@NNight Manganese could be key in this. And feeling very dopaminergic and androgenic. Better libido, less lethargy and weakness. Almost high feeling.
I tried zinc before with dehydratation, made things worse, more weakness, numbness and lethargy. -
@Razvan
Manganese is interesting as it's part of the SOD2 enzyme which is particularly needed in case of "dehydration".Empirically, I've also found it to gave me what (the energy) you described. But I don't believe it stayed that way very long, I don't remember well.
Also, manganese is interesting as it seems to do positive things regarding the AQP4 aquaporin, which is involved in the glymphatic system (cleansing system of the brain).
In brain, astrocytes predominantly take up and accumulate manganese and are thus vulnerable to its toxicity. Manganese was shown to induce cell swelling in cultured astrocytes, and oxidative/nitrosative stress (ONS) mediates such swelling. As aquaporin-4 (AQP4) is important in the mechanism of astrocyte swelling, we examined the effect of manganese on AQP4 protein levels in cultured astrocytes. Treatment of cultures with manganese increased AQP4 protein in the plasma membrane (PM), whereas total cellular AQP4 protein and mRNA levels were unchanged, suggesting that increased AQP4 levels is due to its increased stability and/or increased trafficking to the PM and not to its neosynthesis.
Aquaporin-4 in manganese-treated cultured astrocytes
They talk about AQP4 in negative terms here but it really seems to be fundamental for the glymphatic system, for example:
CSF transport is facilitated by the expression of aquaporin-4 (AQP4) water channels on the perivascular endfeet of astrocytes. Mice with genetic deletion of AQP4 (AQP4 KO) exhibit abnormalities in the brain structure and molecular water transport.
