TL;DR: I have been taking 5g/day creatine for 3 years now and am now thinking to increase the per day dosage. After digging into 1000+ studies, I found some wild stuff about high-dose creatine for cognitive function. Single doses of ~20g can increase processing speed by 24.5% and the effects last 9 hours. Also, vegetarians respond ~2x better than meat-eaters. Full breakdown below with sources.

Why write this?: I have been taking 5g/day creatine for 3 years now. Like most people, I took the standard "5g per day" advice and never questioned it. It worked fine for my training, but I kept seeing conflicting claims about creatine for brain function. So I started reading actual papers to figure out if I should increase my dosage. 3 months and 1000+ studies later, here are the findings that genuinely surprised me:

1. The "5g for everyone" dose is based on old muscle research, not brain optimization

Most dosing recommendations come from 1990s studies measuring muscle saturation. But your brain is different.

A 2024 study (Gordji-Nejad et al., Nature Scientific Reports) found that a single high dose of ~0.35g/kg (~24.5g for a

70kg person) during 21-hour sleep deprivation:

• Improved processing speed by 24.5%

• Increased brain creatine by4.2%

• Effects peaked at 4 hours and lasted up to 9 hours

• Prevented the brain pH drop that normally happens during fatigue

Even more interesting: A 2025 review (Fabiano & Candow) analyzed dose-response data and found:

• 2-5g/day = 4-6% brain creatine increase

• 8-10g/day = 7-8% increase

• 15-20g/day = 9-11% increase

For cognitive purposes, higher doses appear significantly more effective. This is exactly why I am now thinking to increase my per day dosage.

2. Vegetarians get nearly 2x the cognitive benefit

Multiple studies (Rae 2003, Benton 2011) show vegetarians have much lower baseline brain creatine and see dramatic improvements in working memory and reasoning after supplementation. One study found p < 0.0001 for intelligence improvements in vegetarians, basically unheard of in nutrition research.

Meat-eaters already get ~1-2g/day from food, so their brains are partially saturated.

3. Creatine does NOT cause kidney damage, dehydration, or cramping, but the myths persist

This one genuinely angered me. I found the original studies that started these myths and they're either:

• Misinterpreted (one case study of someone with pre-existing kidney disease)

• Actually showed the opposite (Greenwood 2003 found LESS cramping in NCAA football players taking creatine vs placebo

The ISSN Position Stand (2017) reviewed 1000+ studies and concluded: zero evidence of adverse effects in healthy individuals at recommended doses. Long-term studies go up to 21 months with no kidney function changes.

After 3 years at 5g/day, my bloodwork is perfect. The safety data is rock solid.

4. Women have been underserved by creatine research, but that is changing

For decades, most creatine studies excluded women or had tiny female sample sizes. Recent research (Smith-Ryan 2021) confirms creatine works for women without the "bloating" fears, benefits across the lifespan without marked body weight changes.

New 2025 studies are specifically examining menstrual cycle effects and menopause benefits.

5. The mechanism for brain benefits is fascinating

Your brain is 2% of your body weight but uses 20% of your energy. During high cognitive demand or sleep deprivation, ATP in your prefrontal cortex gets depleted.

Creatine acts as a rapid-response energy buffer, literally regenerating ATP in milliseconds. A 2015 study found 20g/day for 7 days increased corticomotor excitability by 70% during hypoxia (low oxygen).

6. Meta-analysis data is stronger than most people realize

I compiled the major meta-analyses:

• Chilibeck et al. (2017): +1.37kg lean mass in older adults, n=721

• Zhang et al. (2025): SMD 0.43 for strength gains across populations

• Xu et al. (2024): SMD 0.31 for memory improvement, more beneficial for females

Effect sizes this consistent are rare in nutrition science.

7. Most "advanced" creatine forms are marketing

Creatine monohydrate has the most research, is the cheapest, and has 95%+ bioavailability. Buffered creatine, creatine

HCL, liquid creatine, none show superior absorption in head-to-head studies. The "better absorption" claims are mostly unproven.

What I am doing differently now:

After 3 years at 5g/day, I am now experimenting with:

• For training: 5g/day consistently (works fine for muscle)

• For cognitive demands: 15-20g single dose before intense mental work or when sleep-deprived

• Timing: Post-workout with carbs when possible, but consistency matters most

I am planning to try a month at 10g/day split into two doses to see if I notice cognitive differences, then potentially experiment with 15-20g on heavy work days.

Sources and Interactive Database:

I organized all the major studies into a searchable database because I got tired of PDF hunting:

https://creatine-sandy.vercel.app

Includes:

• 50+ major studies with effect sizes, sample sizes, and direct links to papers

• Interactive myth-busting (click myths to reveal the actual research)

• Dose-response visualizations for both muscle and brain benefits

• Safety timeline from 1832 to 2025

• Filterable by category: muscle, cognitive, safety, high-dose protocols

Everything is cited with PubMed links if you want to read the full papers.

Questions I still have:

1. Why has not the high-dose cognitive research filtered into mainstream recommendations yet? The 2024 Nature study is groundbreaking.
2. Are there long-term (5+ year) studies on 10g+ daily dosing for cognitive purposes?
3. What is the optimal cycling protocol for high-dose cognitive use vs continuous low-dose?
4. For those who have increased from 5g to 10g+ long-term, what subjective differences did you notice?

Would love to hear if anyone else has gone deep on this research or experimented with higher doses. What did I miss? Has anyone here gone from 5g to 10-20g daily? What was your experience?

this is a repost

Ive tried all sorts of nootropics. I guess everyone gets different benefits or lack thereof from different things. Most of those things didn't really work that well for me.

What I am finding effective is reading books.

I'm a few weeks into reading a few pages or a chapter a day, and my mind just feels calmer and more focused. Reading really trains concentration more than I thought, especially when you read challenging books.

Before that, I was really into meditation and in a way, reading has become my current form of meditation. I find it more beneficial than the traditional, seated concentration on my breath (repost)

Abstract: Histamine was the first canonical monoamine identified in the mammalian brain, yet arguably remains the least understood in its mechanistic contributions to human behaviour. Using a first-in-class causal probe (H3R inverse agonist pitolisant), we show how elevating histamine shapes offline and online temporal–hippocampal dynamics — sustaining episodic learning-related activity and polarising retrieval computations. Beyond this, histamine adaptively shifts neurocomputational strategy under high working memory load, while stabilising value updates during aversive reinforcement learning. These findings uncover a mechanistically grounded influence of this underexplored system on human neurocomputation, supporting its therapeutic potential in psychiatry.

Article: Just a day ago, the brain was in a living person. Now, hours after its owner died, it sits on a cart draped in tubes that quiver as they pump liters of blood substitute and other fluids through the organ, supplying oxygen and removing waste. With most of its key functions intact but its electrical activity quenched by anesthesia, the brain hovers between life and death. As it metabolizes experimental drugs, sensors record its reactions, capturing hundreds of data points on its cells, proteins, and physiology. Then, after 24 hours in this state, it will be sliced into hundreds of pieces for more detailed study.

The brain is one of more than 700 that the 5-year-old biotech startup Bexorg has nurtured and studied using a set of proprietary brain-sustaining machines it calls BrainEx. The platform grants researchers an intimate look into how potential therapies might work inside brains with neurodegenerative diseases such as Parkinson’s, Alzheimer’s, or amyotrophic lateral sclerosis. Bexorg can biopsy the brains and discover how long a drug stays in cells, whether it hits its molecular target, and any hints of side effects.

The system promises far more realistic conditions for testing drugs than lab animals or cells in a dish, its developers say. Whole brains come with decades of environmental exposures, histories of drug treatments, and unique genetics that can affect responses to experimental medicines, says physician Zvonimir Vrselja, one of Bexorg’s founders and CEO. “You get cells that have been there for 60 to 80 years.”

https://www.science.org/content/article/not-alive-not-dead-disembodied-human-brains-used-drug-testing (Full link here)

The brains are already almost devoid of the coordinated neural firing necessary even for minimal consciousness, says Brendan Parent, a bioethicist at New York University Langone Health and one of six ethicists on Bexorg’s advisory board. But the company also forestalls any electrical activity with the anesthetic propofol, among other measures. Bexorg obtains brains in partnership with organizations that procure donated organs for transplantation, and Vrselja says once families understand the company’s process and goals, their response is overwhelmingly positive.

Animal models have clear shortcomings, especially when it comes to testing drugs in the brain. There’s no guarantee that a drug that passes easily into a mouse’s brain will do the same in a human’s, and a harmful overdose or ineffective underdose can stop a promising therapy in its tracks. “This is threading a needle at the best of times,” Car says. “Sometimes you get it right from your [animal model] and sometimes you miss entirely.”

Recent efforts by the U.S. government to push researchers and drugmakers away from animal testing in favor of human-based systems or computer models also represent “a huge tailwind for us,” Vrselja says.

The approach is especially well-suited for studying neurodegenerative disorders because these don’t generally involve brain electrical activity, Vrselja says, and because donors’ brains often have more than one such condition—a phenomenon that’s been difficult to re-create and study in the lab.

Car’s team at Biohaven has used about 130 of Bexorg’s brains to test several drugs, including one intended to prevent toxic proteins from building up in the brain in diseases like Parkinson’s. The drug didn’t interact with its target in a mouse, but Car says it worked in human brains at a dose 20 times lower than the company had initially calculated—saving the company a year of development and potentially preventing the risk of serious side effects.

Biohaven is also developing a compound called BHV-8100, which interacts with metabolic enzymes to increase the brain’s energy and allows neurons to use glucose more efficiently. These metabolic pathways are damaged in many neurodegenerative conditions. The U.S. Food and Drug Administration has approved Biohaven’s application to begin clinical trials with BHV-8100 supported by data from the Bexorg brains; later this month the company will announce which disease it is targeting.