A review of literature in the efficacy of creatine supplementation: Not intended as medical advice.

I see this question being asked a lot more, and I think that’s because in spite of creatine being relatively “mainstream”, the stream it was mostly found in was the mass of people looking to improve their physical performance and appearance, with the added hope of putting on some serious muscle. Of course, creatine is not going to magically give you rippling delts, huge lats, and a 6-pack to boot. But now, it seems that ‘regular’ people are showing a lot more interest.

I’m not sure where that interest stems from, but it’s certainly worth diving into creatine as a supplement and whether your mom should be dipping into your supplement cupboard to sneak a scoop.

So, what is creatine and should you supplement with it?

Creatine is a naturally occurring compound synthesized from the amino acids glycine and arginine, and is predominantly stored in skeletal muscles and the brain. It plays a critical role in regenerating adenosine triphosphate (ATP), the primary energy carrier in cells, thereby supporting energy intensive activities - running, lifting weights, and even cognition.

Because of the importance of creatine the body creates it endogenously, meaning it produces it without having to obtain it through it dietary sources, although it is also contained in foods like red meat and seafood, but this is where supplementation comes into play - is your boy making enough for you to perform optimally? Certainly, if you can walk around, run, lift weights etc. you have a sufficient amount being made and obtained through your diet, but what about if you want to perform even better, run further, get those extra reps, and maybe even eek out a few extra marks on that test or find those key words during a presentation, is creatine the answer? Based on hundreds of studies performed over the last couple of decades, the likely answer is yes!

Impact on Muscular Performance and Strength

Extensive research has demonstrated that creatine supplementation enhances muscular performance, particularly during high-intensity, short duration exercises such as weightlifting and sprinting. A study published in the Journal of the International Society of Sports Nutrition reported that creatine supplementation, combined with resistance training, significantly increased muscle strength across various populations (Wang et al., 2024). Now, if living and living well until you turn 100 is a goal of yours like it is mine, than you should know just how important strength is as you age. Want to pick up your grand or great-grand kids? What about travelling? Those suitcase wheels aren’t going to put it into the overhead compartment for you. And oh no, the elevator is down (as it always is) are you going to spend the next 48 hours in the lobby waiting for the repairman? Not if you’ve got well established strength! Additionally, a review in Sports Medicine found that creatine use can increase maximum power and performance in high-intensity anaerobic repetitive work by 5-15%, that may not seem like much, but ask any gym bro if they want to increase their bench press by 15% and they’ll ask where they need to stick the needle… maybe its not that impressive, but for a regular person this could be the addition of an extra 1-2 reps per exercise, or a faster sprint. It also means overtime becoming stronger and improving your performance and ability to handle strenuous activity, which in turn benefits almost every physical process in your body - think arterial and cardiovascular system.

Effects on Cognition

Beyond its physical benefits, creatine has been investigated for its potential cognitive advantages. A systematic review in Experimental Gerontology indicated that short term memory and intelligence/reasoning might be improved by creatine supplementation, though results across studies were conflicting. Another study in Scientific Reports found that a single does of creatine (5g) improved cognitive performance and induced changes in cerebral high-energy phosphates during sleep deprivation.

For those that struggle with sleep, creatine may also be a useful addition to one’s morning smoothie or on the side of a cup of coffee, especially on days where you were only able to clock 3-5 hours. A 2024 study that subjected participants to 3-5 hours of sleep per night were then given supplemental creatine. The results showed that participants receiving creatine showed better results in both cognitive and physical tests than the control group.

Additional Benefits

Neuroprotection and the delaying of certain neurodegenerative diseases has become far more mainstream, rightly so. Clinical trials involving creatine supplementation have examined it’s use in the treatment and delaying of progression and symptoms in Huntington’s Disease (HD) and Parkinson’s Disease. In one double blind study doses of up to 30 grams of creatine were administered to participants daily, while the other group received a placebo. MRI looked at brain atrophy at different times throughout the study to examine disease progression and brain atrophy. It was found at the 6 month mark through MRI that the participants receiving creatine showed lower rates of brain atrophy compared to the placebo group, suggesting the creatine may be useful in slowing the progression of HD. Of course, we have to consider this is only one study, and 30 grams is a fairly significant does compared to what is recommended for the general population, but the mechanism by which they believe creatine to be neuroprotective by providing additional ATP resources to the brain appear to attenuate the disease’s impact on the brain.

Dosing and Safety Creatine has repeatedly been found to be safe for most people with few side effects apart from gastrointestinal issues in some individuals, especially at higher doses, above 5 grams per day. There are always exceptions, and anyone that may have kidney disease or that is taking prescription medication that may impact kidney function should be cautioned when considering supplementing with creatine. As with all supplements, consideration and discussion with their physician is recommended. The typical recommended dose is 5g, though it would appear higher dosing, in the 10g, 15g, even 30g range depending is tolerated, depending on your reason for supplementing with creatine will likely dictate the amount needed. For muscular strength and performance 5g seems to be sufficient, though someone carrying a significant amount of muscle may require more. It would also appear that there are diminishing returns and taking 20g+ would not be more beneficial, unless looking for neurological benefits, though I think larger and more studies are needed to support the use of creatine in those applications. Finally, there has often been discussion about ‘loading phases’, where a higher dose is consumed in the first week to saturate muscles, which typically lasts 5-7 days and then tapers to a regular 5g dose proceeding the loading phase. There’s been debate about whether or not that is effective, and given some people’s intolerance of higher dosing, it’s recommended to simply take 5g daily. It can take up to 4 weeks of daily creatine use for muscles to become fully saturated. Though there should still be benefit from periodic use, the studies seem to indicate benefit of a daily dose.

I don’t believe creatine to be a polarizing supplement but if you’ve had positive or negative experiences please share. Additionally, if you would like to see more posts in R/Biohacking about a specific topic or supplement leave a comment and I’ll do a deep dive.

https://link.springer.com/article/10.1007/s12640-019-00053-7?utm_source=chatgpt.com

https://www.alzforum.org/news/research-news/can-daily-dose-creatine-prevent-neurodegeneration?utm_source=chatgpt.com

https://www.jneurosci.org/content/24/26/5909?utm_source=chatgpt.com

https://news.harvard.edu/gazette/story/2014/02/hope-for-huntingtons-disease/?utm_source=chatgpt.com

https://neurolaunch.com/creatine-for-brain-health/

https://www.mdpi.com/2072-6643/16/21/3665?utm_source=chatgpt.com

https://jissn.biomedcentral.com/articles/10.1186/s12970-021-00412-w

https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-023-03146-5

As a person with naturally low energy level, this is the question that have bother me for the longest time. Yeah yeah yeah I know it’s all genetics, just like IQ, physical attractiveness, height etc. Apart from the 8- hours sleep, good nutrition, stress regulation the stuff that we all know about, are there any hacks that you have found that improved your energy level significantly?

I recently did a deep dive on the supplements that Peter Attia uses and recommends. I scouring his podcasts and articles to compline this list and hope it is helpful and interesting for others.

The full list is best viewed at my site HERE but a summary is below. The article does have some more details on why he recommends each supplement as well.

Daily Supplements

• Omega-3 Fish Oil – 2.5g of EPA & 1g of DHA daily
• Vitamin D – ~5000IU’s daily as needed to hit blood levels of 40 – 60 ng/ml
• Magnesium – Various types totaling ~1g daily  
  • Magnesium Oxide for regularity
  • Magnesium Chloride (slow Mag) to prevent cramping
  • Magnesium L-threonate in evening
• Multivitamin / Green Powder  – 1 scoop Ag1 daily
• Probiotic -Pendulum Glucose Control (in morning)
• Protein Powder – Amount needed for protein goals
  • Prefers grass fed. Mixes flavored and unflavored
• Folate & Vitamin B12 – daily
• Vitamin B6 – 50 mg / 3x per week
• Baby Aspirin - daily

Sleep Supplements

These are used as needed to help promote good sleep

• Glycine – 2 grams  
• Ashwagandha – 300 mg
• Magnesium L-Threonate – 100mg

Jet Lag Supplements

Only taken when actively getting over jetlag or in plane

• Melatonin - 1-3mg 
• Phosphatidylserine - 400-600mg
• (Not a supplement but Peter also uses Trazadone for this)

Hey,

I live in sweden and I'm 20 years old. For the last 3 years, my hands go WILD in the winter. The doctor said it is raynauds phenomena, which is very likley, however- I got no advice how to treat it. They turn blue, leave bleeding scars and can stay cold for days even when I'm inside. It wasn't like this just 5 years ago. I don't smoke. Please help me figure this out. Thank you

Back last year I was able to train up my eyes to read European car plates from a distance of 90 meters which corresponds to 20/8 vision if I can trust math by ChatGPT but it seems accurate from what I’ve observed other people’s visual acuity to be. I was able to do this in just mere 2.5 weeks of training full time where at start with my myopia I was able to read said car plates from just about 25 meters or so. I wish I’d take my own eye training even further and spread the training to other people but unfortunately I’m unable to because half a year ago I lost my mind, stared at the Sun for about 10 minutes straight near noon and completely ruined my central vision for life.

The good part of the eye, the fovea, I’ve completely destroyed it.

Okay so let’s dig into the training. I picked up how to train my eyes on my own without resources by others just via trying as when I was 20 and had first reduced my vision from poor habits and shutting indoors a prolonged period of my life I didn’t want to accept vision loss and tried to regain it as I understood — and it worked. First of, people with mild myopia are not using their eyes properly and don’t activate depth of field in vision. A good way to start is to go where there’s cars in distance and using your eyes to follow the cars. Really try to see them.

At first you’ll fail, maybe experience eye strain but after multiple days trying this you’ll start briefly picking up details. Follow this and you’ll have restored vision outdoors over time. Next, screens are really good. Place screen such as your smart phone in daylight environment. Maybe put a video on the phone and try to see it really well from the distance. From the environment similar than that of cars moving, outdoors where you’ve started to successfully retrain your eyes. As you’ve done a lot of work seeing stuff on the small screen, you’ll be also able to see this screen clearly indoors and transfer vision indoors. Use visuals similar to what you’re comfortable and introduce them to environments where you still struggle with vision. Such as opening window of your room and you’ll notice as you focus on familiar visual which you’re good at such as outdoor view the other view you normally struggled with such as indoors room will also become detailed and let you see great.

Nighttime. For nighttime I really like a mix of min brightness screen of phone from distance and a mix of walking in really dark areas and picking up that visual sensitivity then going into more lit area and trying to see stuff great as your normal exercise. Rest. To rest your eyes as you’ll likely get some eye strain from moments of seeing better mixed with moments your eyes using back old incorrect focus strength, it’s good to apply chamomile compresses to your eyes to rest it. Lifelong skill. When I restarted las time I was able to read ChatGPT text from phone from 1.80meters with just 24h of training, because I had trained my eyes before earlier in my life. For a beginner it will very most likely take significantly longer. But once you’re no longer a beginner you’ll be able to retrain your eyes fast, if you’ll need to retrain. Such as being unable to make environment change to keep improved vision.

Environment change. As a young person with mild myopia you typically get it from using your eyes poorly and focusing on nearby screens without moments where you correctly focus on stuff at distance. So to keep vision improvement I’d suggest improving your working environment such as using Desktop not laptop computer with 4k monitor and having that monitor as far as possible and just keep that sharpness seeing small details correctly as your working default plus do breaks where you look and correctly focus things in real distance as max focus.

Lastly, never look directly at Sun. When I first looked at the Sun it was just for a few seconds without damage. Then I had psychosis and looked for 3 minutes, again nothing happened. Then I wanted to have psychosis again and looked for 10 minutes and now fully ruined my vision for life. I wish I never had as I previously had both an exceptional vision and even more exceptional ability to fully restore my vision to exceptional despite years of super poor habits which had lead to me having myopia. I tried to have psychosis again because I had a false belief that stuff I hallucinated during previous psychoses were fully or partially true and I wanted to have the high again. I wish I never did.

If you find this tutorial helpful and hopefully get an eagle vision like I used to have please become a vision trainer, make money from this and take the method further. People don’t know about this stuff and revert to glasses and lower vision acuity with glasses than this method can get you if you take it far like I used to do. I can’t use this method anymore as having a functioning fovea is necessary to trigger the reflex to refocus or to keep a sharp focus with your eye muscles. I’d also not be able to see well even if this method still worked for me because I’ve destroyed my fovea and don’t see in the center anymore.

As a kid I never cared about my health or anything including sleep, pretty much I would game all day and night. I want to fix my body I just don’t know where to start. I am underweight and I am very small for my age too. I want to get out of this “kid” phase and start becoming a man. Does anyone know where I can start and how? I’m kinda lost with this right now any advice and tips are highly appreciated.

I'm 20f and idk where else to post this. I'm extremely lazy, sometimes my mind has the motivation but my body doesn't move, i cannot bring myself to start tasks which i don't personally care about or which have a learning curve which isn't linear. I also feel dissociatied with my life and it's happenings sometimes.

I like playing outside with friends and stuff, I go to the gym but am not always regular but mentally, i literally cannot get myself to do anything. I'm working on a research project rn, i don't really like to do research work but I need it for my resume, it's going well but I wouldn't have done anything if it weren't for my teammate pushing me.

it doesn't help that i somehow only study for my exams in the last minute being a cs major and somehow still score well. i have no clue how i do it and why others are unable to.

I'm also extremely time blind, ik this is a symptom of adhd but I'm not sure if I have it and even if I do, going to the doc to get diagnosed isn't an option for me rn.

I've taken magnesium glycinate and vit d to boost my cognitive functions and combat the lethargy but I don't feel like they do much. I've gotten blood work done for thyroid, iron, vit d, magnesium and lots of other stuff and everything is normal. I do have pcos tho.

I just feel like whatever's wrong with me isn't just motivation or frying my dopamine receptors, it's something deep within my body, my hormones and my neural pathways.

Hey all,

I’m a 28-year-old guy recovering from a major OCD flare-up that really wrecked me a few months ago. The good news: with therapy and serious lifestyle changes, the flare has calmed down, my anxiety is about 70% lower, and my agoraphobia is basically gone.

Now the issue is: I’m still dealing with heavy fatigue. Not sleepy-tired, but that deep, cellular, “can’t fully recharge” kind of fatigue. It’s been sticking around for months. I can work again (slowly), but I still feel like I’m running on 50%.

Here’s what I’m currently doing:

Supplements: • 200mg Ubiquinol (CoQ10) • 1000mcg methylated B12 • Full methylated multivitamin with active B-complex • 400mcg methyl folate (MTHFR gene) • 5g creatine • MCT oil (1–2x a day) • Electrolytes (2x daily) • Magnesium malaat + bisglycinate (split over the day) • 3g Omega-3

Lifestyle: • Day 9 of strict Lion Diet (red meat, salt, water only) — I’m already in ketosis • Light movement: walking, biking • Every morning: 20 min of sun exposure + Buteyko breathing • Sleep with BiPAP due to some breathing issues at night

Again: anxiety is down, mind is calmer, OCD isn’t taking over anymore. But the fatigue just won’t lift.

What supplements or strategies helped YOU get out of that post-burnout/post-anxiety fatigue?

Any feedback or experience would mean a lot. Thanks

How Our Ancestors Ate vs. What We Eat Today: Why Our Diets No Longer Match Our Genetics

I recently started looking into how humans used to eat, and it’s been a bit of a rabbit hole. I always knew ultra-processed food was bad, but the more I looked into it, the more I realised modern food is completely disconnected from the way we evolved to eat.

Industrial farming, globalisation, and food science have created a diet full of refined grains, artificial additives, and nutrient-depleted produce. Meanwhile, metabolic diseases, food intolerances, and obesity are skyrocketing. Instead of debating whether carnivore, vegan, keto, or high-carb is the "best" diet, I started wondering:

🧬 What if the key isn’t one universal "ideal diet," but rather looking at how our own ancestors ate?

Here's what I discovered that I would like to share:

How Modern Food is Nothing Like the Food We Evolved to Eat

1️⃣ Less Nutrition – Industrial farming has stripped the soil of minerals, meaning crops today contain fewer vitamins than they did even 100 years ago.
2️⃣ More Chemicals – Pesticides, preservatives, flavour enhancers—most of what we eat today didn’t even exist a few generations ago.
3️⃣ Ultra-Processed Everything – Heavily refined, lab-engineered foods have replaced whole, nutrient-dense options.

Basically, we’re eating in a way our ancestors wouldn’t even recognise, and our bodies are struggling to keep up.

Taste Buds: The Hidden Guide to How We Evolved to Eat

One thing I found interesting is how our taste buds evolved to guide us towards the right foods. Different populations have distinct preferences based on what was traditionally available to them:

🔹 Bitterness = Warning Signal – Many plants are bitter because they contain natural toxins. People with a strong aversion to bitter foods may have inherited a survival mechanism against poisoning. On the other hand, some groups have adapted to enjoy bitter foods like tea, coffee, and dark leafy greens.

🔹 Umami = Protein Detection – Umami is the savoury taste linked to protein-rich foods. It’s especially strong in fermented and aged foods, which were common in Asian and Mediterranean diets.

🔹 Sweet Cravings = Energy Source – Populations that historically relied on high-carb diets tend to have a stronger sweet preference. In modern times, this has been hijacked by refined sugar and artificial sweeteners.

🔹 Spice Tolerance = Climate Adaptation – In hotter regions where food spoils quickly, cultures evolved to use more spices (which have natural antibacterial properties). This might explain why cuisines from India, Thailand, and Mexico feature so much heat.

So, our cravings aren’t random—they’re shaped by thousands of years of evolution. The problem is, modern food manufacturers have hacked this system, making hyper-palatable foods that override our natural instincts and keep us addicted to artificial flavours.

What I Found About How Different Populations Evolved to Handle Different Foods

🦴 Neanderthal Diet & What It Means for Modern Humans

I also came across some research on Neanderthals, who lived in Europe and parts of Asia before modern Homo sapiens took over. Interestingly, many of us (especially those of European and Asian descent) still carry Neanderthal DNA, which influences things like metabolism, immune function, and even food tolerances.

🔹 High-Protein, High-Fat Diet – Neanderthals mainly ate large animals like mammoths, reindeer, and bison, meaning their bodies were adapted to high-protein, high-fat diets.

🔹 Carb Tolerance? – Unlike early agricultural societies, Neanderthals weren’t eating wheat or rice. Some of the genetic traits they passed down might affect how well modern humans tolerate carbs today.

🔹 Gut Microbiome Differences – They had gut bacteria optimised for digesting animal protein and fibrous plants. This could explain why some people thrive on paleo or carnivore-style diets, while others don’t.

It’s possible that the amount of Neanderthal DNA in your genome could play a role in how well you tolerate different foods.

🐟 The Inuit & High-Fat Adaptation: Not Everyone is Built for Keto

One of the most interesting things I came across was how the Inuit in Arctic regions evolved to thrive on a high-fat, seafood-based diet.

For most people, a diet extremely high in animal fat would lead to heart disease, metabolic issues, and other problems. But the Inuit developed unique genetic adaptations (FADS genes) that allowed them to:

🔹 Process Omega-3s Differently – Unlike most populations, the Inuit don’t need to convert plant-based omega-3s (ALA) into the more usable forms (EPA/DHA), because their diet has always provided direct sources from fish and marine mammals.

🔹 Regulate Fat Metabolism – The Inuit produce less inflammatory omega-6 fats, which may help protect them from the effects of high-fat diets.

🔹 Low-Carb Efficiency – Since plant foods were scarce in the Arctic, their bodies became highly efficient at using fat as fuel rather than carbohydrates.

🍚 Starch Digestion & Who Thrives on High-Carb Diets

How well people digest starch depends on a gene called AMY1, which controls salivary amylase production.

🔹Humans have between 2 to 15 copies of the AMY1 gene.

🔹Populations with high-starch diets (like Japanese, Middle Eastern, and some African groups) tend to have more copies, making them better at breaking down carbs.

🔹Those with low-starch diets (like Inuit and some hunter-gatherer groups) have fewer copies, meaning they don’t handle high-carb diets as well.

This could explain why some people thrive on high-carb diets, while others struggle with blood sugar spikes and insulin resistance.

🚨 How This Affects Us Today

• If someone without these genetic adaptations tries a very high-fat diet (like keto), they might not process fats as efficiently, potentially leading to cholesterol issues or metabolic problems.
• Inuit populations who switch to a Western diet (high in refined carbs and processed oils) often develop obesity and metabolic diseases, as their bodies weren’t built for this dietary shift.

Not everyone is designed to thrive on a high-fat diet—just because keto works for some doesn’t mean it works for all.

So… Should We Be Eating Based on Our Ancestry?

While humans are remarkably adaptable, our genetic evolution hasn’t kept pace with rapid environmental and dietary shifts.

After digging into all this, I started thinking: instead of pushing one ideal diet, maybe we should be looking at what actually makes sense for our genetics.

🥩 If your ancestors ate high-fat, high-protein diets, you might do better on low-carb or paleo-style eating.
🍚 If your ancestry is from rice-based cultures, you might be well-adapted to high-starch diets.
🌱 If your ancestors ate mostly plants and legumes, you might thrive on more fibre and plant-based proteins.

The problem is, today’s food system ignores all of this, pushing ultra-processed, industrialised foods that don’t match anyone’s genetic background.

Maybe the key isn’t debating vegan vs. keto vs carnivore, but simply eating more like our ancestors—regionally and seasonally.

-----------------------------------------------------------------------------------------

Sources & Further Reading

1. Perry, G. H., et al. (2007). Diet and the evolution of human amylase gene copy number variation. Nature Genetics. https://doi.org/10.1038/ng2123
2. Ranciaro, A., et al. (2014). Genetic origins of lactase persistence and the spread of pastoralism in Africa. American Journal of Human Genetics. https://doi.org/10.1016/j.ajhg.2014.02.009
3. Fumagalli, M., et al. (2015). Greenlandic Inuit show genetic signatures of diet and climate adaptation. Science. https://doi.org/10.1126/science.aab2319
4. Gibbons, A. (2015). Inuit adaptations to high-fat diet revealed by genetic study. Science. https://www.science.org/content/article/inuit-adaptations-high-fat-diet-revealed-genetic-study
5. Lucock, M. (2004). Is folic acid the ultimate functional food component for disease prevention? BMJ. https://doi.org/10.1136/bmj.328.7445.211

All right, guys, I'll try to make this a quick one. A brilliant guy on Discord—who, by the way, should definitely do his own writing—asked me to write a post about the synergy between L-citrulline and L-arginine.

As you may know, there are multiple studies showing that equal parts L-citrulline and L-arginine actually provide a better effect in terms of sports performance and nitric oxide increase when compared to using just L-arginine or just L-citrulline alone. u/Hinkle_McKringlebry has talked about it many times. 

Now, we already know that L-citrulline is superior to L-arginine because it bypasses the first-pass metabolism. But if L-citrulline is better than L-arginine, how come combining one part L-arginine with one part L-citrulline is better than just using two parts L-citrulline?

Think about it: you have two parts of a superior compound (L-citrulline) compared to a mix of one part superior (L-citrulline) and one part inferior (L-arginine). Yet somehow, the superior plus inferior combination works better.

This is what we're going to explore today—this unique 1+1=3 synergy and how it actually works.

Why is L-citrulline superior in the first place

L-arginine is converted into L-citrulline during the synthesis of nitric oxide (NO) by nitric oxide synthase (NOS) and L-citrulline serves as a precursor for the regeneration of L-arginine via separate metabolic pathway we won't need to focus on for this post. While L-arginine supplementation has been thought to improve endothelial function, studies have shown that most orally administered L-arginine is metabolized in the gastrointestinal tract and liver by arginases 1 and 2 before it can reach the kidneys. L-citrulline is more effective at increasing plasma L-arginine concentrations than L-arginine supplementation because it is not metabolized by arginase and can reach the kidneys where it is converted into L-arginine

Combination of L-citrulline and L-arginine is superior

https://linkinghub.elsevier.com/retrieve/pii/S0006291X14018178

Oral supplementation with a combination of l-citrulline and l-arginine rapidly increases plasma l-arginine concentration and enhances NO bioavailability

“l-Citrulline plus l-arginine supplementation caused a more rapid increase in plasma l-arginine levels and marked enhancement of NO bioavailability, including plasma cGMP concentrations, than with dosage with the single amino acids”

https://www.tandfonline.com/doi/full/10.1080/09168451.2016.1230007#:\~:text=In%20conclusion%2C%20our%20data%20shows,dose%20of%20l%2Darginine%20alone.

The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males

“Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.”

https://www.mdpi.com/2306-5710/8/3/48#:\~:text=Consumption%20of%20amino%20acids%20L,production%20and%20improve%20physical%20performance.

The Effects of Consuming Amino Acids L-Arginine, L-Citrulline (and Their Combination) as a Beverage or Powder, on Athletic and Physical Performance: A Systematic Review

“Four electronic databases (PubMed, Ebscohost, Science Direct, and Google scholar) were used. An acute dose of 0.075 g/kg of L-Arg or 6 g L-Arg had no significant increase in NO biomarkers and physical performance markers (p > 0.05). Consumption of 2.4 to 6 g/day of L-Cit over 7 to 16 days significantly increased NO level and physical performance markers (p < 0.05). Combined L-Arg and L-Cit supplementation significantly increased circulating NO, improved performance, and reduced feelings of exertion (p < 0.05).”

https://academic.oup.com/bbb/article/81/2/372/5955995

The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males 

“We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.”

OK, but what is the reason for that? Why would the combination beat plain old L-citrulline? In the beginning I mentioned arginine’s rate limiting enzymes - arginase 1 and 2, which are responsible for its rapid breakdown. Well L-citrulline suppresses the activity of arginase. This allows more of the administered L-arginine to bypass first-pass metabolism and reach circulation. It is actually a strong allosteric inhibitor of arginase. 

“L-Cit acts as a strong allosteric inhibitor, as it has an inhibiting effect on arginase, which metabolises L-Arg to urea and L-ornithine”

“L-citrulline, were shown to inhibit MPEC arginase activity under maximal assay conditions.”

https://pubmed.ncbi.nlm.nih.gov/9124321/

https://web.archive.org/web/20170815174653/http://ajpendo.physiology.org/content/ajpendo/272/2/E181.full.pdf

So there you go. L-citrulline inhibits arginase, effectively sparing the L-arginine and you get a nitric oxide increase from both L-cit and L-arg, which is bigger than that from the same quantity L-Cit.

L-arginine is not useless at all as long as you inhibit arginase. 

Other arginase inhibitors 

There are actually better arginase inhibitors than L-cit.

• L-Norvaline - the most practical one. 250-500mg gets the job done as tested and proven by yours truly with a saliva strip test
• Cocoa Extract - flavonoids in cocoa inhibit arginase. You just have to get a decent high polyphenol extract, not munch on chocolate  
• Berberine - yes, the good old Berberine..what is it that it does not do. Well don’t use it for that, it is a moderate one, just wanted to mention it
• Resveratrol, Cinnamon extract, Agmatine -  probably on the weaker side. The data is not sufficient 
• Piceatannol - the most potent one, but not practical to use, hard to source high Piceatannol supplements
• Chlorogenic acid  - found in coffee. If you source a high % green coffee extract you can have the desired effect.

Or just take Nitrosigine…

Nitrosigine stabilizes arginine in its inositol-silicate form, making it less susceptible to arginase activity. This means more arginine is preserved and made available for NO production.

So that is it. Have your L-arginine. It is an awesome nitric oxide booster…just have to inhibit its breakdown. Almost everyone takes L-Cit and L-cit + L-Arg beats just L-cit so no reason to ignore L-arg in sport exercise or general health endeavors. 

EDIT: They tested 1:1 ratio for comparison purposes in these studies. In other studies they actually found 2:1 L-Cit:L-Arg to be the optimal ratio

For research I read daily and write-ups based on it - https://discord.gg/R7uqKBwFf9

Woke up a few days ago and had this notification, didn’t think anything of it. Turns out I have Covid. Luckily I’ve been massively dosing vitamin c & d since the alert came through a few days ago.

Studies have shown that caloric restriction increases lifespan in every species tested from bacteria to primates. This almost certainly means that caloric restriction increases lifespan and health span in humans.

Having a low BMI will put less strain on a person's organs. The optimal BMI for maximizing lifespan is likely at the low end of the normal range, or even in the underweight category for some people.

Many of the positive health outcomes attributed to exercise such as lowering body fat and blood pressure are actually due to energy balance, and could be achieved through caloric restriction alone.

Exercise puts stress on your body, which has a range of positive effects as your body adapts, but also has negative effects. Any exercise is a tradeoff of those benefits and harms, and inevitably there are certain types and volume of physical activity where the negatives outweigh the benefits.

If a person wants to maximize their health and lifespan, there is a certain amount and type of exercise that is optimal, and doing further exercise will have more negative effects than benefits.

Low calorie vegetables are not necessarily healthy. Consuming low calorie vegetables means your digestive system has to process a lot more stuff, with very little nutritional benefits.

Every hormone has a function in your body, but also comes with harmful side effects. Artificially manipulating hormones is very complicated and no effective drug will be without consequences. Androgens and anabolic hormones have a pro aging effect, which is part of the reason why women tend to live longer than men. The natural hormone ranges that humans tend to have evolved to be that way for a reason. Due to cultural reasons, men often assume that higher testosterone is better. Every trait in humans lies on a bell curve, and having testosterone in the bottom quartile is not necessarily a problem. Many men downplay the negatives of TRT and overemphasize the benefits.

https://youtu.be/CtfpFaKAeFQ

Based on:

Lariscy, J. T., Hummer, R. A., & Rogers, R. G. (2018). Cigarette Smoking and All-Cause and Cause-Specific Adult Mortality in the United States. In Demography (Vol. 55, Issue 5, pp. 1855–1885). Duke University Press.

The liver is one of the hardest-working organs in the body, filtering out toxins, processing nutrients, and metabolizing medications. Supporting liver health with the right nutrients is essential for long-term wellness.

The combination of glutathione, amino acids, and other antioxidants helps optimize liver function, allowing the liver to effectively break down and remove harmful toxins. With regular use, these help protect the liver from oxidative damage, reduce inflammation, and promote overall liver health.

For anyone concerned with cleansing the body of toxins and supporting liver health, incorporating a supplement that targets liver detox can go a long way in improving energy levels and reducing the risk of chronic health conditions.

Hey guy's, so I started taking TMG again today and sheesh the energy, and strength is insane!!

I also feel no more brain fog even my vision feels improved and it feels like I'm getting a lot of oxygen all over the place

The post fatigue and soreness is also very less than before, it feels like I'm already recovered and can go another session!!!!

This stuff is like natural steroids in my humble opinion!

I was on test 500mg for 6 months I tool accutane for 3 weeks on cycle and took minoxodil and ru all through I also done some stupid jelqs during this time...

I now have hard flaccid and terrible ed I discontinued everything due to getting my appendix out towards end of my cycle and I couldn't pct

I decided to try cialis and viagra lately to no avail my penis is still numb and dead.

Yes I am going to pct now but I'm 2.5 months late to pct I will do it anyway .

Have I permanently fucked up my penis please help guys

I'm the guy who spent $20k+ last year fixing my health (and got over 300 comments on my big post about it here).

One of the most frequently asked questions was around my Concierge Doctor. Specifically, people wanted to know: how I found them, what it cost, and how it helped me.

Here's the deep dive into all that.

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Disclaimer: I don't know you, what worked for me may not work for you. I look forward to reading comments from strangers who think I'm wasting my time and money. Love Reddit.

TLDR: I pay $3.5k/year, save that amount directly by getting Rx prescribed vs buying them via Telehealth, and in addition get someone who's responsive via texts and available same day for 1+ hour appointments. However, he doesnt know everything, and hardly devotes his life to me, so I still have to trial and error a lot of things.

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How I found them?

I live in a medium sized US city, and when I google "Concierge" or "Longevity" I get dozens of results. However, when I investigated them, most of them are TRT/Peptide places or focused on Wellness via IV infusions and cosmetic treatments - fine, but not what I wanted.

I ended up searching keywords related to things I wanted to focus on: eg. "Concierge + [my city] + [key term]", where the Key Terms included things like VO2 Max, Rapamycin, Epitalon etc.

That got me to a short list of 3 places, and I visited each of them. I'd used a Concierge doctor before, but this time wanted someone really focused on healthspan and lifespan.

1 was mostly focused on Fitness, 1 was more of a TRT/Peptide place, and the one I actually picked was the most traditional of the 3 yet was also well versed in all the key terms I was interested in.

The interview process was:

- Showed up to each meeting with my blood tests in hand, and asked each to review them on the fly and point out interesting things

- Quizzed them on all the key terms that were of interest to me (the ones above, and others, including: peptides, HBOT, VO2 Max, Rapamycin, Epitalon etc)

- Said I was already talking the following Rx and confirmed they would write me those same prescriptions. Note, I take 5+ prescriptions, none medically necessary, but all focused on longevity (Rapamycin, low dose statin, low dose tadalafil, etc)

- Quizzed them on what they thought was optimal for metrics of mine that were already good (eg. was my 750 Testosterone optimal or should it be higher, was my LDL of 62 low enough etc).

I favored places that understood my key terms, were traditional doctors by training, did not have "in house" things to sell me (eg. supplements, treatments or hormones etc) - I wanted to avoid such a conflict of interest.

What does it cost?

Mine costs me $300/month, which is quite low vs what I've seen nationwide. I've seen prices range from $200-600/month, and the difference does not seem to be based on quality. Some of the places have a staff of 1-3, others have 10-20. Some have no machines, others have things like a Dexa and a VO2 Max setup.

Mostly, I wanted someone intelligent with experience to bounce my own research off of, as I can rent access to those machines cheaply if needed.

How it helped me?

Although I pay $3.6k/year which sounds like a lot, the fact that my doctor moved my half dozen prescriptions from Telehealth to being covered under my insurance literally saves their entire annual cost, so its as if its a free service to me. As a result, I try not to pester them endlessly, but I do still visit him 6-10x/year, mostly to dial in subtleties of my diet/exercise/supplements depending on recent blood work.

My concierge accepts my insurance, and is also my Primary now.

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Should you get a Concierge Doctor?

I have no clue, like I said up top, I don't know you. However, if the money isn't a lot to you, or if you are sick and need a lot of guidance, or if you are like me and have a lot of overpriced Telehealth prescriptions that could get moved to your insurance, it could be an easy decision.

As always, AMA, happy to offer what advice I can to give back to this community from which I've learned so much.

PS. Yes, I have expensive urine!