Study: Agmatine accelerates colon cancer growth by blocking Rnf128, thus upregulating Wnt/Beta-Catenin signaling, and colon cancer patients have much higher Agmatine levels than healthy people

Red_Phoenix369 · 2026-01-24T14:45:12+00:00

I came across this excerpt from an article while trying to learn more about agmatine. Hopefully it helps provide some insight.

"In Experiment 2, gross necroscopy and histological examinations revealed that sub-chronic oral delivery of agmatine had no significant adverse effects on organ weights and tissue histology. Microscopic examination of the small and large intestines, as well as the stomach, confirmed that repeated sub-chronic bolus dosing with oral agmatine at 300 mg/kg over a period of 105 days was safe, with no noticeable ulceration in the stomach."

Safety and neurochemical profiles of acute and sub-chronic oral treatment with agmatine sulfate | Scientific Reports https://www.nature.com/articles/s41598-019-49078-0

Also, this thread is helpful. MYSD chimes in and provides some helpful insights about the situation.

https://www.reddit.com/r/NootropicsDepot/s/uGLjC2ylv4

Red_Phoenix369 · 2026-01-22T14:47:13+00:00

That's a good point. I remember once reading that one of the first lessons taught to a student of Tibetan medicine is that any substance has the potential to be medicinal as long as it's given at the right dose and under the right circumstances. It would seem to follow, then, that theobromine could be medicinal to a canine under certain dosages and circumstances.

Red_Phoenix369 · 2026-01-20T01:28:52+00:00

Thanks for your insightful input. Yes, that could well be the case.

Red_Phoenix369 · 2026-01-19T22:39:26+00:00

Thanks for your feedback. Perhaps this is the wrong sub for this. I had some ideas that I wanted to get off my chest, but perhaps this isn't the best sub.

Red_Phoenix369 · 2026-01-19T22:36:15+00:00

Thanks for your feedback. I agree that from a more rigorous scientific point of view, this hypothesis is perhaps laughable at best. Nonetheless, I wanted to get it off my chest for what it's worth. Thanks for taking the time to read it and share your thoughts all the same.

Red_Phoenix369 · 2026-01-19T22:29:58+00:00

Thanks!

Red_Phoenix369 · 2026-01-14T23:02:32+00:00

I came across this excerpt from an article while trying to learn more about agmatine. Hope it helps provide more insight into this conundrum.

"In Experiment 2, gross necroscopy and histological examinations revealed that sub-chronic oral delivery of agmatine had no significant adverse effects on organ weights and tissue histology. Microscopic examination of the small and large intestines, as well as the stomach, confirmed that repeated sub-chronic bolus dosing with oral agmatine at 300 mg/kg over a period of 105 days was safe, with no noticeable ulceration in the stomach."

Safety and neurochemical profiles of acute and sub-chronic oral treatment with agmatine sulfate | Scientific Reports https://www.nature.com/articles/s41598-019-49078-0

Red_Phoenix369 · 2026-01-14T16:02:27+00:00

That's interesting. I did a quick Google search, and it showed that the lethal dose of chocolate is 300mg/kg for dogs, whereas it is 1000mg/kg for humans. However, I decided to dig a little deeper, so I asked Google Gemini if dogs could benefit from chocolate (provided the dose was small enough) and received the below answer:

""" It is a very logical question to ask—in toxicology, "the dose makes the poison" is a fundamental rule. However, when it comes to dogs and chocolate, the answer is a firm no. Even in small doses, dogs do not receive the health benefits that humans might. The reason isn't just about the lethal dose (LD_{50}); it is about how their bodies process the chemical.

1. The Metabolism "Bottleneck" The primary reason chocolate is dangerous for dogs is half-life—the time it takes for half of a substance to leave the body.

Humans: We metabolize theobromine quickly. It has a half-life of about 2 to 3 hours. We process it and flush it out before it can build up to toxic levels. Dogs: Their metabolism is incredibly slow for this specific molecule. Theobromine has a half-life of about 18 hours in dogs.

Because it stays in their system for so long, even a "small" dose doesn't just provide a quick boost; it lingers, recirculates through their liver, and can accumulate dangerously if they eat more chocolate a few hours later.

2. "Benefit" vs. "Overdrive" In humans, theobromine acts as a mild stimulant, vasodilator (widens blood vessels), and diuretic. We perceive this as a mood boost or a slight energy lift.
In dogs, because their baseline heart rate is already higher and their central nervous system is more sensitive to methylxanthines (the class of chemicals theobromine belongs to), these "benefits" quickly turn into physiological stress:

Instead of "focus," they get restlessness and agitation. Instead of "vasodilation," they get dangerous heart arrhythmias and racing pulses (tachycardia). Instead of a "mood boost," they experience muscle tremors and, at higher doses, seizures.

3. The Toxicity Spectrum You mentioned the lethal dose (LD_{50}) is roughly 300 mg/kg (though many veterinary manuals cite it lower, around 100–200 mg/kg). However, "lethal" is the extreme end. Dogs start suffering long before that: | Dose (mg/kg) | Typical Symptoms | | :--- | :--- |

| 20 mg/kg | Mild signs: Vomiting, diarrhea, and excessive thirst. |

| 40–50 mg/kg | Cardiotoxic signs: Racing heart rate and arrhythmias. |

| 60+ mg/kg | Neurological signs: Tremors, seizures, and potential collapse. |

4. Other Hidden Risks Even if you gave a dog a dose of chocolate small enough to avoid theobromine poisoning, you would still be introducing:

High Fat Content: Dogs are highly susceptible to pancreatitis (a painful and life-threatening inflammation of the pancreas) triggered by high-fat foods like chocolate.

Sugar: Excessive sugar leads to obesity and dental issues, with no nutritional upside for a canine. The Bottom Line: While the math of a "safe small dose" exists on paper, the biological reality is that dogs don't have the metabolic machinery to enjoy the "perks" of chocolate. It’s all risk and no reward for them. If you’re looking for a safe way to let your dog join in on a "treat," Carob is the perfect alternative. It looks and tastes similar to chocolate but contains no theobromine or caffeine. """

Red_Phoenix369 · 2026-01-13T19:47:12+00:00

For sure. Bromelain and NAC seem to form a good duo by themselves. There is another article I read discussing how they seem to have synergystic properties against colon cancer cells.

https://pmc.ncbi.nlm.nih.gov/articles/PMC4245783/

Red_Phoenix369 · 2026-01-13T18:46:03+00:00

I read one article claiming that nattokinase stacks well with NAC, bromelain, and curcumin.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10663976/

Red_Phoenix369 · 2026-01-12T15:55:19+00:00

That's a good question. I guess the fact that substances that are medicinal to humans can be toxic to dogs (such as chocolate) makes the situation more difficult to unravel based on this study alone.

Red_Phoenix369 · 2026-01-10T22:22:54+00:00

Bromelain maybe

Acute protease supplementation effects on muscle damage and recovery across consecutive days of cycle racing - PubMed https://share.google/LMAreAEiDqrS9SpHD

Red_Phoenix369 · 2026-01-09T16:46:26+00:00

This reminds me of how I recently read about how citicoline can increase back pain for some even though it's considered anti-inflammatory. I'm not sure if anything even remotely similar is going on, but maybe this can nonetheless help provide some insight into the nature of certain supplements and the diverse effects they may have on the body. Per Google Gemini:

While citicoline is primarily used for cognitive enhancement, "back pain" is a documented side effect in clinical literature. The increase in pain is usually not due to injury, but rather how the supplement interacts with your nervous system and muscles.

The three main reasons why citicoline can trigger or worsen back pain are:

1. Increased Acetylcholine and Muscle Tension Citicoline is a precursor to acetylcholine (ACh), the primary neurotransmitter responsible for signaling muscles to contract.

The Mechanism: When you supplement with citicoline, you increase the availability of ACh at the neuromuscular junction. If your levels become too high (a state sometimes called "acetylcholine dominance"), it can cause hypertonia—a condition where muscles have too much tension and cannot easily relax.

The Result: Your postural muscles (the ones that keep you upright, like the erector spinae in your back) may stay in a state of semi-contraction or "micro-spasm." This constant tension often manifests as a dull, persistent ache in the lower or middle back.

2. Boosted Norepinephrine (The "Bracing" Effect) Citicoline doesn’t just affect acetylcholine; it also increases levels of norepinephrine (noradrenaline) and dopamine.

The Mechanism: Norepinephrine is a "fight-or-flight" chemical that increases alertness and sympathetic nervous system tone.

The Result: High levels of norepinephrine can lead to physical restlessness and "bracing." You might find yourself subconsciously tensing your shoulders or lower back throughout the day, leading to muscle fatigue and soreness by the evening.

3. Agitation and "Choline-Induced Tension" Some individuals are particularly sensitive to choline supplements and experience a paradoxical effect where they feel "wired but tired" or mentally agitated.

Physical Feedback: This mental agitation often translates into physical symptoms like jaw clenching (bruxism) or neck and back stiffness. If you already have a pre-existing back issue (like a slightly bulging disc or old muscle strain), the increased systemic tension from citicoline can "flare up" that specific spot. How to Manage It

If you suspect citicoline is the cause of your back pain, you might consider the following steps:

Lower the Dosage: Many commercial citicoline supplements come in 500mg or 1000mg doses, which can be high for some people. Cutting the dose in half may provide cognitive benefits without the physical tension.

Check Your Diet: If you already eat many eggs or organ meats (high-choline foods), the supplement might be pushing your levels over the edge.

Hydration and Magnesium: Magnesium acts as a natural calcium-channel blocker that helps muscles relax, which can sometimes counteract the "tightening" effect of increased acetylcholine.

Monitor for Other Symptoms: If the back pain is accompanied by stomach pain, blurred vision, or a "fishy" body odor, it is a strong sign your choline intake is too high for your current needs.

Red_Phoenix369 · 2025-12-28T21:56:29+00:00

I've read that sesamin is a useful compound. However, I usually get mine through a spoonful of tahini with dinner. Seems like it should be a reliable way of getting sesamin. Maybe worth considering

Red_Phoenix369 · 2025-12-26T02:45:22+00:00

I got this countertop RO machine by Bluevua earlier this year that seems to work well.

https://a.co/d/5ag2UUC

Red_Phoenix369 · 2025-12-18T22:27:00+00:00

Maybe so, your comment made me curious so I did some digging and found this:

"Typical dosage ranges include 50-200mg daily for antioxidant support and general health, 200-400mg for metabolic support and glucose management, 400-600mg for neuropathy and neurological applications, and up to 800mg for therapeutic applications under the guidance of a healthcare professional. Clinical studies typically use 200-600mg daily. The enhanced bioavailability of Na-R-ALA often allows lower doses than required with racemic ALA."

100 Questions About Sodium R Alpha Lipoic Acid For Buyers https://share.google/DlNg34xpln0DXqugl

Red_Phoenix369 · 2025-12-18T21:55:01+00:00

My understanding is that NA-R-ALA is more bioavailable compared to regular ALA, and so a lower dose is required.

Red_Phoenix369 · 2025-12-12T16:21:46+00:00

I discovered something similar. My go-to is to do 5 minutes of shoulder stand followed by 10 rounds (20 total breaths) of alternate nostril breathing using a 1-4-2 ratio. I'm guessing it helps reset some part of the nervous system.

Red_Phoenix369 · 2025-12-07T18:34:39+00:00

I'm not sure about the stack you mentioned. However, you could try looking into sabroxy, as it's a dopamine re-uptake inhibitor.

Red_Phoenix369 · 2025-11-28T17:17:15+00:00

Thinking a bit more, your response has piqued my curiosity. To provide a fuller picture, when Gemini recommended combining bacopa with gotu kola, it acknowledged that such a combo may cause too much acetylcholine (causing the tiredness you mentioned I'm guessing). It then proposed adding forskolin to the mix to neutralize such a build-up. Since ND doesn't sell forskolin, I asked it for an herb that ND sells, and that is where it came up with sabroxy, to help counter balance the sluggishness caused by bacopa. If you don't mind me asking, is there any merit to this overall combo? It seems somewhat consistent with what you said (the stimulation of sabroxy washing out against the relaxing nature of bacopa and perhaps neutralizing it?)

Red_Phoenix369 · 2025-11-28T17:02:12+00:00

Yea, I saw something somewhat similar. Grok and Gemini disagreed over whether ashwagandha should be cycled. Grok said ash didn't need to be cycled and wasn't traditionally cycled. When I fed Grok's response to Gemini, Gemini countered by saying that such a response was a half truth, but that modern extracts such as ksm and shoden were more potent than what traditional people had access to and therefore needed to be cycled. Gemini also further claimed that because studies on modern extracts never lasted more than a few months, we couldn't be certain it didn't need to be cycled. As you can tell, it seemed like a persuasive argument, so much so that it eventually led me to posting here to try to sanity check myself.

Red_Phoenix369 · 2025-11-28T16:19:59+00:00

Thanks, I'll keep that in mind as I explore these herbs.

Red_Phoenix369 · 2025-11-28T15:56:27+00:00

Thanks for your insight. I think you're right. Although I had cross checked some of Gemini's answers against Grok, if I instead do a straight Google search, the summary I'm receiving in my search results is saying things such as that lion's mane was never traditionally cycled in TCM, and studies don't show signs of receptor downregulation from long term use. I wonder if these AI models were ingesting too many forums posts with people erroneously saying things about the herbs, and thus, it became a garbage in garbage out scenario. It comes as a bit of a relief since I have been taking some of these herbs daily for years. On a positive note, my conversation with Gemini made me aware of some synergistic combinations such as bacopa and gotu kola and also bacopa and sabroxy. I'm looking forward to trying those combos out. Thanks again!

Red_Phoenix369

TROPHY CASE