Topics created by DavidPS

Inhibition of gut-derived serotonin synthesis: a potential bone anabolic treatment

Abstract

Osteoporosis is a low bone mass disease most often caused by an increase in bone resorption not compensated by a similar hike in bone formation1. Since gut–derived serotonin (GDS) inhibits bone formation2, we asked whether hampering its biosynthesis could treat osteoporosis through an anabolic mechanism. To that end we synthesized and used LP533401, a small molecule inhibitor of Tph1, the initial enzyme in GDS biosynthesis. Oral administration once daily for up to 6 weeks of this small molecule prevents the development of and fully rescues, in a dose–dependent manner, osteoporosis in ovariectomized rodents because of an isolated increase in bone formation. These results provide a proof of principle that inhibiting GDS biosynthesis could become a novel anabolic treatment for osteoporosis.

Or for the non-pharmaceutical approach:

Peatbot: To lower gut serotonin, you can consider the following strategies based on the provided context:

Avoid Foods Containing Fermentable Fibers and Starches: These include grains, beans, and other seeds that resist quick digestion and can promote intestinal irritation, leading to increased serotonin production.

Consume Fibrous Foods with Antibacterial Properties: Foods such as bamboo shoots and raw carrots contain antibacterial chemicals that help reduce endotoxin and serotonin levels in the gut.

Use Activated Charcoal: Activated charcoal can absorb many toxins, including bacterial endotoxin, which is likely to reduce serotonin absorption from the intestine. However, it should be used intermittently as it can also bind or destroy vitamins.

Consider Theanine Supplementation: Theanine, an amino acid found in tea, has been reported to decrease the amount of serotonin in the brain by decreasing its synthesis and increasing its degradation.

Supplement with Progesterone, Thyroid, and Niacinamide: These substances can help reduce serotonin formation and/or accelerate its elimination. Niacinamide, in particular, seems to increase serotonin uptake.

Address Hypothyroidism: Since hypothyroidism is a common cause of increased serotonin, supplementing thyroid hormone until symptoms are resolved can help normalize serotonin levels.

By implementing these strategies, you may be able to lower gut serotonin and mitigate its associated effects.

@Sugarnotsnow will do, thanks!

@DavidPS

Your argument is well noted. I don't diminish the causality involved with those factors. But I fail to see why those factors mentioned are made at the exclusion of others. Except that the authors want to frame PD as predominantly environmental. I take exception to their mix of omission of other factors and their concentration of focus on the factors they call environmental. I also can't be sure of your reassurance that these folks won't frame CO² as part of the pollutants in their study. Their kind has for decades been blaming CO² with nary a mention of CO (carbon monoxide), and would obfuscate the distinction by simply calling us to lower our "carbon footprint." These are the same people who banned the use of carbogen in hospitals, and excoriate progesterone while praising estrogen.

I also want to add that I don't see the increases in PD as being unmistakably caused by the rise in incidences of wild fires. It is probably, not possibly, rooted in iatrogenic causes, particularly with the penchant for doctors to prescribe neurotoxin antibiotics of the fluroquinolone classes, and their m.o. is to tell patients that it is the only oralantibiotic that the dominant pathogen in a culture (urine or sputum) is sensitive to. There are alternatives such as essential oils that will do as good a job, but of course that is woo to the medical priestly class. I am living proof of that.

Exercise is an old family of senoytics.

Senolytic effects of exercise in human muscles require acute inflammation 2024

We provide the first evidence demonstrating an attenuated senolytic effect of HIIE in human skeletal muscle under ibuprofen treatments, suggesting the necessity of inflammation for the exercise-induced senolytic outcomes.

@yerrag said in The role of cerebral blood flow in the pathogenesis of Alzheimer's Disease Dementia:

@mostlylurking said in The role of cerebral blood flow in the pathogenesis of Alzheimer's Disease Dementia:

@yerrag said in The role of cerebral blood flow in the pathogenesis of Alzheimer's Disease Dementia:

@mostlylurking

I got to read the article on efferocytosis. It is a good read, though like most of these articles we get, they're a hard read as it's hard to keep up the different names of enzymes and proteins and what not involved. They get too detailed beyond what is practical for us to use. I get to wonder often if doctors actually read to such detail as they hardly find them to read and rather go to Hawaiian resorts for all+expenses paid symposiums. And they get a nice spiel and summary from their med reps. I would prefer they present these things in a black box way, without too much detail. Honestly, I just brush thru these articles because I feel the law of diminishing returns at work when I have to be thorough finishing such articles. Still, I'm disappointed the article leaves out mention of hemolyzed red blood cells and how they are disposed.

You noticed. I agree with you. But once in a while I stumble upon a gem of an article that is actually insightful and helpful. This happens mainly in articles written for veterinary research, including for the fishing industry. Here's an example: Fatty acid signatures connect thiamine deficiency with the diet of the Atlantic salmon (Salmo salar) feeding in the Baltic Sea Go down to the Conclusions: "As Keinänen et al. (2017) suggested, fatty young sprat specimens, when abundantly preyed on by salmon, easily overload them, particularly with highly unsaturated DHA, thereby predisposing them to oxidative stress, which results in the depletion of thiamine." That right there made it worth it to me to slog through the article. The fisheries solved the die off problem by adding thiamine to the water for the salmon hatchlings.

Yes! I think, with the exception of false rabies shots, vets have been better care of animals than doctors have been taking care of humans.

I've found that vets (at least the ones I've gotten to know) are decent people who like animals. Modern day doctors, on the other hand, seem to consider people to be something like a commodity to extract money from.

Research for humans is really horrible. I get sent notifications for new papers released about hypothyroidism; about 99% of them are bought and paid for papers that try to shore up the American Thyroid Association's position that T3 isn't needed (except for very rare occasions) and synthetic T4 alone is the "proper" treatment. The ATA should be RICOed.

It is really a racket. But racketeers are our overlords, so such evident rackets become accepted as the norm.

But once you see it, you cannot unsee it. If you see it, you can take steps to defend yourself via learning (for free on the internet).

One nit I have with such publications is that they talk too much unnecessary detail that they lose the forest for the trees. They are heavy on the ABC's and light on the why's and wherefore's that forms a cause and effect narrative on disease. It is mainly useless circumlocution that gets the reader no nowhere. Perhaps that is the intent- to make us go around in an endless circle of meaningless twiddling and twaddling.

I've noticed that they also consistently make erroneous assumptions and then base the rest of the paper on those assumptions. It's really terrible. Also why in the world do they insist on using thousands of initials for thousands of technical words/things? It makes reading the paper impossible. But I think that's the point.

To keep us second-guessing and paralyzed in such a way we become so reliant on their "experts" to save us.

Once you see the game and "get it" then the wise saying comes into play: "Fool me once, shame on you; fool me twice, shame on me."

Perhaps I have been spoiled by Peat, as he cuts through that wasteland and skims it of its gems and summarizes the studies for us. And I still find it more rewarding to read the articles and books that I have not read. And there's a lot of material left of his I have to read up on.

Peat's papers were a godsend for me. Although they aren't easy to read, multiple readings made for better understanding. Peat actually had things to say, truths you can sink your teeth into. I'm much better able to discern if someone else's paper is worth struggling through now after studying Ray Peat's work.

I feel as guided as you are by having read and understood his writing. I am not as blind and less given to be led by the pied pipers.

Knowledge is power.

Thanks for the effort compiling the supplements you take, though I have to admit I have moved on from taking a lot of supplements as it was my intent to seek nutrients from food when I go back to my country. As the nice thing about backward countries is the diversity of the food supply chain which still allows me to get nutrients from food that is typically missing in the US.

That's good about your country's food supply; I hope you can return to it so that you may benefit from it.

I have been back to my country for 16 years already. The control of pharma is much much less even if the Philippines is a total tributary state of the Evil Empire. It is much poorer but being poorer makes it less a fertile ground to be fleeced by the racketeers.

I misunderstood you before; I thought you had traveled out of the Philippines.

The B-vitamins and Vitamin E and C are the only exceptions.

And I have benefited from this strategy. Like you, my eyesight has improved within a 5-yr span from starting to eat beef liver weekly. The retinol it provides is what I consider real vitamin A as opposed to the beta-carotene almost always pushed by supplement companies. A sister of mine who sells and also uses supplements for a well-known supplement marketing company, Shaklee, has been faithfully using its products yet her eyesight is no better that in fact her eye doctor is telling her she would be due for cataract surgery in the near future. No wonder, Shaklee considers beta-carotene to be the only vitamin A in their supplements.

I was overloaded with beta-carotene when I found Peat's work in 2014. I'm very sensitive to it, not in a good way.

But me, I am no longer required to wear glasses to drive and I still easily read the small type from my cellphone. And this is coming from where I had been prescribed bifocals 15 years back.

My vision history is very similar. I no longer have to wear glasses to drive. but I do need to grab my readers to read small print; I'm 74, after all.

It may be that you are sufficient in retinol, but need more endogenous CO2 production. Just a guess.

As CO2 abundance is needed for good vision as well. With optimal sugar metabolism, CO2 abundance is assured.

Yes about the need for CO2. If you are deficient in thiamine you cannot make CO2 via sugar metabolism; the end product is lactic acid instead of CO2. Thiamine acts as an enzyme cofactor in the process. Supplementing with thiamine hcl has corrected my inefficient oxidative metabolism and thus has restored my level of CO2.

Two proxies I use to ensure I am optimal metabolically is acid-base balance and good blood sugar requisition. IMHO, all other testing is just superfluous.

Testing for those two can be done at home, at a miniscule fraction of the cost.

Which is why I consider the medical system a Rube Goldberg system that I always seek to find an alternate and simpler for. In many ways, health forums such as ours are unavoidably thus infected with the creep from our games medical system. This makes me decide to limit digging to deep into the medical literature wasteland, as it is designed to make us go in circles for a solution.

To me, a Rube Goldberg system implies a lack of sinister purpose and more a cobbling things together in ignorant bliss. The business of still filling people's teeth with mercury in this day and age is inexcusable. Likewise the intentional destruction of treatment for hypothyroidism with desiccated thyroid while banishing food sources of thyroid. Likewise the promotion of PUFA as "heart healthy". I could go on, but I'm sure you get the point. We're not witnessing innocent stupidity.

Rackets sprockets.

I'm more focused on connecting the dots from reading and benefiting from disinterested medical tomes from Peat, Long, St Gyorgi et all than from commercially vetted and supported research works that form a larger part of the wasteland.

I agree; it's a much better way to use your time.

I sigh with dismay when we continue to talk of cell membranes, and accept the use of HbA1c as a valid marker for blood sugar health when Ray has pointed out how poorly it represent our blood sugar health. And we are so close-minded that we are tribal in the sense that this forum has never wanted to consider the use of urine pH and saliva pH as a proxy marker for metabolic health, still following the beat of the pied piper of mainstream medicine. Just because the pied piper says so.

I'm hoping that we will get to witness the destruction of Rockefeller medicine, the medical industrial complex, and most especially the pharmaceutical industry. Sooner rather than later would be good. Before the total decimation of the human race is an accomplished fact. Here's a video about our medical complex's problem; set to start at the Rockefeller chapter.

That will only happen when the US military is swallowed by the Red Sea.

I suspect the situation is on a positive tract; we just are not told all the details. It's a war, after all. An unconventional war with no news coverage. This week should prove interesting.

S2099 Persistent Damage to the Gut Microbiome Following Messenger RNA SARS-CoV-2 Vaccine

We longitudinally recorded the relative abundance of genus Bifidobacteria in 4 subjects before receiving mRNA vaccine (Pfizer or Moderna), approximately one month after vaccine, and 6 to 9 months later. Additional SARS-CoV-2 vaccines were given during that period, totaling 2 to 3 doses. Samples were collected at the timepoints mentioned. There were no diet changes or new medication’s during the entire period and subjects were told to stay on the same regimen throughout the 6 months. Metagenomic next generation sequencing-based methods were applied to samples obtained from fecal collection. DNA was extracted, and the library prepped, enriched and sequenced on an Illumina Nextseq 550 system. Relative abundance of Bifidobacteria decreased after 1 month to in 3 of 4 subjects to: 38%, 258%, 49% and 90% of pre-vaccine levels. After 6-9 months, all Bifidobacteria relative abundance decreased to: 15%, 0%, 35%, and 60% of pre-vaccine levels.

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@DavidPS it also solves heart disease in the Linus Pauling protocol

it's an interesting substance

@jgs130

Tell me, if you are such a stickler for evidence, what constitutes evidence for you? Do you need a trial to be made by the FDA, in the way that they asked for evidence for Ivermectin?

Or do you need 10 people in this forum saying so?

You give examples of Ray correcting Kate, yet because you say so that Ray corrected Kate on the matter of progesterone, without yourself giving us an actual example, but you just say so, and even saying he corrected her many times, stretching your point, isn't even enough evidence. Without proof, you give the appearance you know what you're talking about.

The reason this world is so fucked up is because there are so many know nothings like you is because you depend on experts to give you evidence while evidence is not necessarily the first thing to look for.

The first thing is to establish ground for why you believe such is such. Then you a hypothesis. It becomes a theory. Then becomes a law as more evidence is gathered to bolster that hypothesis.

But evidence is not always necessary, as people have worked off theories.

Why do people use TCM, herbs, and aromatherapy despite the FDA or some meddling agency came to act as judge and jury for evidence?

You are a programmed scientism evidence-based zealot raised to depend on titles and degrees to establish credibility, with no iota of training in logic and reason. But the greatest healers in history have not depended solely on the "scientific method' to heal people.

Tell me, what does progesterone do, and why is it safe for anyone to use? Do you know what a hormone does? If it's so safe as you would say it is, why don't you try to OD on it?

You simply have no idea, do you? You don't even understand the way the body works. It is not an entity that runs off magical bullets that the medical industry tends to rely on to alleviate symptoms without fixing the root cause of a problem. Yet you are such a fool for thinking of progesterone as one such substance.

Without the kind of thinking that the body runs in a complex web of interrelationships that would be called cycles. If you are on a virtuous cycle, you are in good balance and health. But when you are in a vicious cycle, you are in poor health, and will likely stay so unless you break that cycle. But this has no meaning for a dolt like you.

Now off you go in your search for an Elysium device to entertain your medical fantasies!

@Ecstatic_Hamster - I have been playing with slowing my breathing in accordance with this video linked below.
30 Second Exercise to Build Up Your CO2 Tolerance | Part 1

This one's a goodie, have only listened to half of it but have already learned a few new things. Thank you David, this will soon be passed on to my own circles.

@DavidPS Nice summary!

@cremes Yes. Anti-cortisol. I thought I would try 1 pill. 🤷 just to see.
thx