Beyond the Gym: Why Your Brain Craves Creatine

 What does your doctor think? Or doesn't your doctor think at all as proven by knowing nothing EXACT about stroke recovery! Exact is stroke protocols, doesn't have any does s/he?

And how long has your doctor been incompetent in not informing you of this?

• creatine (10 posts to February 2015)

Beyond the Gym: Why Your Brain Craves Creatine

Summary: Creatine is far more than a “gym supplement”; it is a naturally occurring compound essential for cellular energy. Produced in the liver, kidneys, and pancreas, approximately 95% of the body’s creatine is stored in skeletal muscle, with the remainder supporting the brain and heart.

In a comprehensive analysis, researchers clarify that creatine acts as a high-speed energy regenerator, not a steroid, and holds growing promise for clinical and cognitive health.

Key Scientific Insights

• Energy Regeneration (ATP): Inside cells, creatine converts to phosphocreatine (PCR) to rapidly regenerate adenosine triphosphate (ATP), the body’s primary energy source. This process is critical for high-intensity activity and tissues with high energy demands like the brain.
• Cognitive Benefits: Beyond physical performance, creatine may improve memory, processing speed, and mood, particularly in older adults or those with lower baseline levels.
• Clinical Potential: Emerging research explores its anti-inflammatory and antioxidant properties for conditions such as Parkinson’s disease, depression, and menopause-related bone loss.
• Safety Profile: Concerns regarding kidney damage have been largely debunked for healthy individuals, though those with pre-existing renal conditions should seek medical advice.
• Saturation Limits: The body has a finite capacity to store creatine. Excess intake does not provide additional benefits and is simply excreted as the waste product creatinine.

Source: Taylor and Francis Group

Creatine, a compound often associated with gym-goers and athletes, has long been touted as a performance-enhancing supplement. But beyond the hype, what does science actually reveal about its effects on the body and mind?

From its role in energy metabolism to its potential therapeutic applications, creatine is a molecule that continues to intrigue researchers.

Dr Mehdi Boroujerdi, pharmaceutical researcher and former professor, has carried out a thorough and extensive analysis of the compound in the Handbook of Creatine and Creatinine In Vivo Kinetics. Here’s a closer look at the science behind creatine supplementation.

The science of creatine

Your body naturally makes creatine, produced in the liver, kidneys and pancreas from amino acids like glycine, arginine and methionine.

It travels through the bloodstream to different tissues, like muscles, where it’s used for energy. Approximately 95% of the body’s creatine is stored in skeletal muscle, with the remainder distributed across the brain, heart and other tissues.

Once inside cells, creatine is converted into phosphocreatine (PCR), a high-energy molecule that plays a critical role in regenerating adenosine triphosphate (ATP), the body’s primary energy converter.

The ability to quickly regenerate ATP is crucial for maintaining energy supply, especially in tissues with high energy demands, such as skeletal muscle, cardiac muscle and the brain. This ensures that cells can sustain their functions during periods of intense activity or stress, which is why it has come to the attention of athletes.

After creatine has done its job, it gets broken down into a waste product called creatinine, which is then removed from the body by the kidneys and excreted in urine.

But there are several factors that impact how creatine is stored and used in the body, for example tissue can only hold a certain amount of creatine and everyone’s individual levels are different.

Crucially, despite concerns oft levied on social media, it is not a steroid. “Creatine’s role in muscle development is solely to provide energy for contraction and respiration, it is certainly not a substitute for steroids,” Dr Boroujerdi explains.

Creatine as a dietary supplement: what we know

Creatine monohydrate is the most widely studied and used form of creatine supplement.

As evidenced in the book, it has been shown to increase muscle creatine and phosphocreatine levels, enhancing ATP regeneration during high-intensity, short-duration activities. This translates to improved power output, sprint performance and training volume.

Beyond physical performance, creatine has demonstrated some potential benefits for cognitive function, including memory, mood and processing speed, particularly in populations with lower baseline creatine levels, such as in older adults.

Emerging evidence also explored in the book positions creatine as more than a sports supplement. It has sparked interest in its potential applications for conditions like Parkinson’s disease, depression and even menopause-related muscle and bone loss – but more research is needed before any claims can be made.

“Creatine’s anti-inflammatory and antioxidant properties further underscore its promise in clinical settings, though more robust trials are needed to confirm these benefits,” he explains.“With sufficient justification, appropriate dosage form, and dosing regimen, creatine may eventually be recognised as an over-the-counter therapeutic agent rather than merely a dietary supplement.”

Dosing regimens and bioavailability

The standard dosing protocol for creatine involves a loading phase of 20 grams per day (split into four doses) for 5-7 days, followed by a maintenance dose of 3-5 grams per day.

“This approach rapidly saturates muscle creatine stores, but a lower daily dose of 3-5 grams can achieve similar saturation over a longer period (approximately 28 days),” Dr Boroujerdi says.

Bioavailability, however, is not absolute. Contrary to popular belief, not all orally ingested creatine is absorbed. Factors such as gastrointestinal stability and individual muscle capacity influence how much creatine is retained. Co-ingestion with carbohydrates has been shown to enhance creatine uptake by stimulating insulin-mediated transport.

Factors influencing creatine’s effects

Research suggests that men and women may respond differently to creatine supplementation due to variations in muscle mass and baseline creatine levels. There are limits to our current understanding, however, and Dr Borouherdi would like to see these areas explored further.

For example, women, who typically have lower muscle creatine stores, may experience greater relative benefits. Similarly, older adults may benefit from creatine’s ability to counteract age-related declines in muscle mass, bone density and cognitive function.

Vegetarians and vegans, who may obtain little to no creatine from their diets, often exhibit lower baseline creatine levels and may experience more pronounced effects from supplementation compared to omnivores – although not all vegetarian and vegan diets are the same, so impacts would differ in different individuals.

“There is a pressing need for well-designed research projects in humans, utilising labelled creatine to generate relevant data and illuminate the grey areas of our knowledge about these compounds,” Dr Boroujerdi explains.

Creatine is often combined with other compounds to enhance its effects, like the amino acid beta-alanine. However, Dr Boroujerdi warns the efficacy of such combinations varies, and more research is needed to establish optimal protocols.

The verdict

Creatine remains one of the most researched and effective dietary supplements available, with a strong safety profile and a growing list of potential applications. But it does have limitations.

“Despite its many benefits, creatine is not a magic bullet. It does not directly build muscle or replace the need for proper training and nutrition. Additionally, the belief that larger doses yield greater benefits is unfounded, as muscle creatine stores have a saturation limit. Excess creatine is simply excreted as creatinine, offering no additional advantage,” Dr Boroujerdi says.

Concerns about side effects, such as kidney damage, have largely been debunked in healthy individuals. However, those with pre-existing renal conditions should consult a healthcare provider before supplementation.However, its benefits are not universal and depend on factors like baseline creatine levels, dosing strategies, and individual physiology.

“For now, creatine is best viewed as a supplement with significant potential, but not a panacea” Dr Boroujerdi says. “Whether you’re an athlete, a student, or simply someone looking to support your health, understanding the science behind creatine is key to making informed decisions.”

Key Questions Answered:

Q: Is creatine actually a steroid?

A: No. Creatine’s role is strictly to provide energy for muscle contraction and respiration. It does not mimic the hormonal effects of steroids or directly build muscle tissue without training.

Q: What is the best way to take it for maximum absorption?

A: Taking creatine with carbohydrates can enhance uptake by stimulating insulin-mediated transport. While a “loading phase” (20g/day for 5-7 days) saturates muscles quickly, a consistent dose of 3-5g/day achieves the same result over 28 days.

Q: Can it really make me smarter?

A: It won’t raise your IQ, but it supports the “bioenergetics” of the brain. By ensuring the brain has a steady supply of ATP, it can improve processing speed and memory, especially during periods of stress or in populations where baseline levels are naturally low.

Editorial Notes:

• This article was edited by a Neuroscience News editor.
• Journal paper reviewed in full.
• Additional context added by our staff.About this creatine and neuroscience research news

Author: Becky Parker-Ellis
Source: Taylor & Francis Group
Contact: Becky Parker-Ellis – Taylor & Francis Group
Image: The image is credited to Neuroscience News

Original Research: Handbook of Creatine and Creatinine In Vivo Kinetics is available to purchase online.

Disproving Dogma: How the Brain Uses Fat as Fuel

 How can your competent? doctor use this to power your brain during a stroke and save neurons?

Disproving Dogma: How the Brain Uses Fat as Fuel

Timothy Ryan, PhD, runs a lab at Weill Cornell Medicine in New York City, where the team focuses on studying synapses and adenosine triphosphate (ATP). Like most teams, they kick around lots of what-ifs. One day, a postdoctoral researcher, Mukesh Kumar, PhD, asked Ryan if fat could serve as a fuel to run a synapse.

Other parts of the body break down fat to make ATP, so why doesn’t the brain? After all, the brain is nearly 60% fat.

“My immediate reaction, honestly, was just that I had a bias because every review article says it doesn’t look like it does that,” Ryan said.Well, guess what.In their new studyNature Metabolism, Ryan and his team showed that a triglyceride-filled lipid droplet in the synapse of a mouse is broken down by neurons into fatty acids, which are sent to mitochondria to produce ATP. The process is similar to how muscle in other parts of the body uses fat to make ATP. It’s a somewhat hidden process because it does not occur when at rest (lipid droplets are present before exercise but not afterward). Like most discoveries, it began with the question. But the path to the discovery meant delving into decades of dogma. Ryan initially told Kumar it’s going to be a pretty high bar to prove the brain uses fat as fuel. “But then I started reading the background literature of where it came from,” said Ryan. “And it really started in 1933.” Nearly 100 Years of Dogma On the Line Back then, the foundational research demonstrated respiration in muscle tissue when given fat for fuel, but the same wasn’t apparent when the researchers tried brain tissue.“The problem is that when you chop up brain, you make a really nonfunctional tissue. The cells can’t do anything anymore. I’m not blaming them. In 1933, we didn’t have that level of sophistication,” Ryan said. But decades of subsequent laboratory approaches also used brain tissue and increasingly sophisticated techniques — looking for fat-fueled brain tissue to produce radioactive CO2 or examining processes at the cellular level. Another reason it seemed unlikely that the brain metabolizes fat is because electron microscopy of brain cells has never shown lipid droplets. Combined with metabolism experiments, the case seemed settled — other parts of the body metabolize fat but the brain didn’t seem to do it in lab experiments, and lipid droplets didn’t appear on high resolution images. Neurologist John K. Fink, MD, said he wasn’t shocked by Ryan’s findings “because I don’t tightly hold to the dogma that neurons cannot utilize triglycerides as a source of energy. Are other people shocked? Only to the degree that they hold tightly to dogma.” “This exposes not so much new areas of neurology but how cautious we have to be about overzealous acceptance,” said Fink, a professor at the University of Michigan Medical School, Ann Arbor, Michigan, who also practices in the area of spastic paraplegia. These latest findings, Fink said, offer an important basis for further exploring brain function in low-glucose conditions. “Now that we know that it can happen, we need to know to what extent does it happen,” he said. What Does It Mean to Not See Something? The question of does the brain use fat persisted in Ryan’s lab, which is well-known for its 2014 work demonstrating that synapses don’t store ATP and it’s produced on demand. The on-demand nature is important — when ATP can’t be made on demand, things start to go wrong. “Keeping synapses working is the most important thing in the brain. I say that as a person who studies synapses for a living, but I don’t think anyone would argue that that’s the business end of the brain. It’s synaptic communication,” said Ryan. “That was our motivation — to learn all the rules we can about what controls how well we do this job.” A primary question that needed to be answered in that exploration was: What fuel is used to make ATP? Glucose is the standard, Ryan acknowledged, but “the brain doesn’t tolerate not having enough fuel because it needs to use it all the time. And so that brought up the question: What other things might you use?” Ketones were something they considered, partly driven by the fact that a severe ketogenic diet is sometimes effective as a last recourse for treating children with epilepsy. The link between ketones and the brain is unclear. “Ketones are made probably in the liver and get shipped to the brain, and neurons use the ketones. So we have studied this, but we don’t quite understand why that ends up resetting things well,” Ryan said. Another fuel the brain may use is fat, the team hypothesized. Muscle also needs on-demand fuel and uses glucose. “But muscle famously is also well-known to use fat,” Ryan said, noting that it’s a very now-you-see-it, now-you-don’t process. “Actually, if you look at resting muscle in a biopsy, you discover that resting muscle has lipid droplets,” he said. “So if you look at fat cells, which we all have — and we all have more and more of as we age — those cells are full of big lipid droplets. They’re giant. That’s how fat is stored, in lipid droplets.” The lipid droplets are perfect spheres. But after exercise, most lipid droplets are gone because they were used as fuel to make ATP. “So what does it mean to not see lipid droplets in the brain? It could well mean that part of the brain is resting,” Ryan said. Ryan and the team also leveraged understanding of genetic susceptibilities for diseases like Parkinson’s disease and spastic paraplegia using existing research about how mutations affect enzymes involved in lipid metabolism. A DDHD2 mutation — which is linked to hereditary spastic paraplegia type 54 — can drive a huge buildup of lipid droplets in the brain, as shown in previous work by Benjamin Cravatt, PhD, of Scripps Research in La Jolla, California. “We knew that the neurons were accumulating lipid droplets, but that’s where we left it,” said Cravatt, a chemical biologist. The implication, Ryan said, is that if the brain doesn’t have the enzyme made by DDHD2, it can’t take apart lipid droplets to make fatty acids, which can’t then be given to mitochondria to make ATP. “Luckily for us, Cravatt also made — he’s a chemist — a small molecule inhibitor, so we didn’t just have to rely on knockout mice. We could do really fast experiments, where we could block this enzyme with a drug that he made…in 10 hours, you could see a huge buildup of lipid droplets in the neurons.” Turns out the inhibitor Cravatt made was reversible. “That allowed us to pull all the tricks my lab is good at and to show that now you could run a synapse with absolutely no glucose whatsoever,” Ryan said. “If you would build up lipid droplets, you could skate by as if nothing was wrong without any fuel — like if you did that, you would be insulin resistant because it wouldn’t matter if your glucose drops because for a little while, you could run a synapse without any fuel whatsoever because it had its fuel depot.” It’s a possibility, Ryan said, that as we age, we become more reliant on this backup fuel source for the brain, posing potential areas of future research that intersect with dementia and other neurologic diseases. “What we’re seeing in the DDHD2-disrupted humans that get spasmodic hyperplasia is obviously an extreme nonphysiologic outcome of losing the enzyme,” Cravatt said. “But what does the enzyme normally do? And is it normally relevant? Is a triglyceride hydrolase activity relevant for brain energetics, brain signaling? This paper really speaks to that quite well — there appears to be an intriguing role for lipid metabolism as a source of energy and fuel in neurons normally as part of their signaling.”

Key Enzyme Found to Drive Inflammation in Aging Cells

 Can your competent? doctor be trusted to get this research going in humans? NO? So you don't have a functioning stroke doctor, do you?

Key Enzyme Found to Drive Inflammation in Aging Cells

Summary: Researchers have discovered that the enzyme ATP-citrate lyase (ACLY) plays a critical role in driving the inflammatory process linked to aging, known as the senescence-associated secretory phenotype (SASP). The study shows that blocking ACLY can reduce the expression of inflammation-related genes in aging cells, opening the door for potential therapies to combat age-related diseases like dementia and atherosclerosis.

By inhibiting ACLY, researchers were able to suppress chronic inflammation in aged mice, offering a promising new strategy for extending healthy lifespans. This breakthrough could lead to treatments that specifically target the damaging aspects of aging without eliminating aging cells.

Key Facts:

• ACLY enzyme drives inflammation in aging cells by activating inflammatory genes.
• Inhibiting ACLY reduced inflammation-related gene expression in aged mice.
• Targeting the ACLY-BRD4 pathway may promote healthy aging by controlling inflammation.

Source: Kumamoto University

A team at Kumamoto University has made a groundbreaking discovery in the field of aging and inflammation. Japan’s aging population is growing at an unprecedented rate, making it crucial to extend healthy lifespans rather than just lifespans.

The research focuses on “cellular senescence,” a process where cells stop dividing and enter a state associated with chronic inflammation and aging.

Furthermore, the study revealed that ACLY-derived acetyl-CoA modifies histones, proteins that DNA wraps around, allowing the chromatin reader BRD4 to activate inflammatory genes. Credit: Neuroscience News

This cellular state, known as the senescence-associated secretory phenotype (SASP), involves the secretion of inflammatory proteins that accelerate aging and disease, such as dementia, diabetes, and atherosclerosis.

The researchers found that ATP-citrate lyase (ACLY), an enzyme involved in converting citrate to acetyl-CoA, plays a critical role in activating SASP. This discovery was made using advanced sequencing and bioinformatics analyses on human fibroblasts, a type of cell found throughout the body.

They demonstrated that blocking ACLY activity, either genetically or with inhibitors, significantly reduced the expression of inflammation-related genes in aging cells. This suggests that ACLY is a crucial factor in maintaining the pro-inflammatory environment in aged tissues.

Furthermore, the study revealed that ACLY-derived acetyl-CoA modifies histones, proteins that DNA wraps around, allowing the chromatin reader BRD4 to activate inflammatory genes.

By targeting the ACLY-BRD4 pathway, the researchers were able to suppress inflammation responses in aged mice, highlighting the potential of ACLY inhibitors in controlling chronic inflammation while maintaining healthy aging.

This discovery opens new avenues for developing treatments that specifically target the harmful aspects of aging cells without removing them, offering a promising strategy for managing aging and age-related diseases.

The research provides a stepping stone toward therapies that can control cellular aging, promoting longer, healthier lives.

About this inflammation and aging research news

Author: Nuo LI
Source: Kumamoto University
Contact: Nuo LI – Kumamoto University
Image: The image is credited to Neuroscience News

Original Research: Open access.
“Citrate metabolism controls the senescent microenvironment via the remodeling of pro-inflammatory enhancers” by Kan Etoh et al. Cell Reports

Tired? 4 simple ways to boost energy

Has your doctor validated that these ideas from Harvard Medical school help stroke fatigue? 

Tired? 4 simple ways to boost energy

Posted September 07, 2018, 6:30 am

Matthew Solan
Executive Editor, Harvard Men's Health Watch

When I’m dragging and feeling tired during the occasional low-energy day, my go-to elixir is an extra cup (or two or three) of black French press coffee. It gives my body and brain a needed jolt, but it may not help where I need it the most: my cells.

The cellular basis of being tired

What we call “energy” is actually a molecule called adenosine triphosphate (ATP), produced by tiny cellular structures called mitochondria. ATP’s job is to store energy and then deliver that energy to cells in other parts of the body. However, as you grow older, your body has fewer mitochondria. “If you feel you don’t have enough energy, it can be because your body has problems producing enough ATP and thus providing cells with enough energy,” says Dr. Anthony Komaroff, professor of medicine at Harvard Medical School. You may not be able to overcome all aspects of age-related energy loss, but there are ways to help your body produce more ATP and replenish dwindling energy levels. The most common strategies revolve around three basic concepts: diet, exercise, and sleep.
Diet. Boost your ATP with fatty acids and protein from lean meats like chicken and turkey, fatty fish like salmon and tuna, and nuts. While eating large amounts can feed your body more material for ATP, it also increases your risk for weight gain, which can lower energy levels. “The excess pounds mean your body has to work harder to move, so you use up more ATP,” says Dr. Komaroff. When lack of energy is an issue, it’s better to eat small meals and snacks every few hours than three large meals a day, according to Dr. Komaroff. “Your brain has very few energy reserves of its own and needs a steady supply of nutrients,” he says. “Also, large meals cause insulin levels to spike, which then drops your blood sugar rapidly, causing the sensation of fatigue.”
Drink enough water. If your body is short on fluids, one of the first signs is a feeling of fatigue. Although individual needs vary, the Institute of Medicine recommends men should aim for about 15 cups (3.7 liters) of fluids per day, and women about 12 cups (2.7 liters). Besides water and beverages like coffee, tea, and juices, you can also get your fluids from liquid-heavy fruits and vegetables that are up to 90% water, such as cucumbers, zucchini, squash, strawberries, citrus fruit, and melons.
Get plenty of sleep. Research suggests that healthy sleep can increase ATP levels. ATP levels surge in the initial hours of sleep, especially in key brain regions that are active during waking hours. Talk with your doctor if you have problems sleeping through the night.
Stick to an exercise routine. Exercise can boost energy levels by raising energy-promoting neurotransmitters in the brain, such as dopamine, norepinephrine, and serotonin, which is why you feel so good after a workout. Exercise also makes muscles stronger and more efficient, so they need less energy, and therefore conserve ATP. It doesn’t really matter what kind of exercise you do, but consistency is key. Some research has suggested that as little as 20 minutes of low-to-moderate aerobic activity, three days a week, can help sedentary people feel more energized.

When being tired warrants a visit to your doctor

You should see your doctor if you experience a prolonged bout of low energy, as it can be an early warning of a serious illness. “Unusual fatigue is often the first major red flag that something is wrong,” says Dr. Komaroff. Lack of energy is a typical symptom for most major diseases, like heart disease, many types of cancer, autoimmune diseases such as lupus and multiple sclerosis, and anemia (too few red blood cells). Fatigue also is a common sign of depression and anxiety. And fatigue is a side effect of some medications.

Related Information: Boosting Your Energy

Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits

Seems to be quite useful to our recovery if only we had a stroke leader to push answers to these simple questions. 

Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits

1. Bing Zhou,1
2. Panpan Yu,2
3. Mei-Yao Lin,1
4. Tao Sun,1
5. Yanmin Chen,1 and
6. Zu-Hang Sheng1

+ Author Affiliations

1. ¹Synaptic Functions Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892
2. ²Guangdong–Hong Kong–Macau Institute of CNS Regeneration, Ministry of Education Joint International Research Laboratory of CNS Regeneration, Jinan University, Guangzhou 510632, China

1. Correspondence to Zu-Hang Sheng: shengz@ninds.nih.gov

Abstract

Although neuronal regeneration is a highly energy-demanding process, axonal mitochondrial transport progressively declines with maturation. Mature neurons typically fail to regenerate after injury, thus raising a fundamental question as to whether mitochondrial transport is necessary to meet enhanced metabolic requirements during regeneration. Here, we reveal that reduced mitochondrial motility and energy deficits in injured axons are intrinsic mechanisms controlling regrowth in mature neurons. Axotomy induces acute mitochondrial depolarization and ATP depletion in injured axons. Thus, mature neuron-associated increases in mitochondria-anchoring protein syntaphilin (SNPH) and decreases in mitochondrial transport cause local energy deficits. Strikingly, enhancing mitochondrial transport via genetic manipulation facilitates regenerative capacity by replenishing healthy mitochondria in injured axons, thereby rescuing energy deficits. An in vivo sciatic nerve crush study further shows that enhanced mitochondrial transport in snph knockout mice accelerates axon regeneration. Understanding deficits in mitochondrial trafficking and energy supply in injured axons of mature neurons benefits development of new strategies to stimulate axon regeneration.

• Submitted: 26 May 2016
• Accepted: 31 May 2016

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).