Well Being: Creatine Supplements- Emerging Benefits

Creatine is a compound that your body naturally makes, and you also get it from protein-rich foods. It supplies energy to your muscles and may also promote brain health. Many people take creatine supplements to enhance strength, improve performance, and support cognitive (brain) function. There has been extensive high-quality research on creatine, and creatine supplements are generally considered safe for most people to take.

What is Creatine?

Creatine is an organic compound that is naturally produced in the human body from the amino acids glycine and arginine, with an additional requirement for S-adenosyl methionine (a derivative of methionine) to catalyze the transformation of guanidinoacetate to creatine. The body produces creatine primarily in the kidneys and completed in the liver, by three amino acids: glycine, arginine, and methionine.

For inquiring minds who want or need to know, here is a brief video focusing on the biochemical synthesis of creatine. For most, this is way more than you really need. Bottom line, this is a natural product that your body, and many other living things, produces all the time.

<Organic, in this context, refers to the chemical composition. “Organic” compounds are generally based on carbon atoms, and also include hydrogen (H), nitrogen (N), Oxygen (O), Phosphorus (P), and Sulphur (S).>

So, with that background, it is no surprise that in addition to being synthesized internally, creatine can also be obtained from dietary sources, particularly protein-rich foods such as red meat, seafood, and animal milk. For instance, fish, cows, pigs, and chickens store over 90% of their creatine in muscle tissue, with some fish like herring containing up to 5 grams of creatine per pound.

Creatine can also be supplemented externally, with creatine monohydrate being a common form. This supplement is manufactured outside the body from sarcosine and cyanamide, which are combined in a reactor with other catalyst compounds to form creatine crystals. This is the “nutraceutical” form that you can purchase from your local health food store or on-line from Amazon.

As always when purchasing nutraceuticals, be careful to look for evidence of independent laboratory testing and certification for purity and identity (is it what is claimed on the label). Creatine supplements can be purchased as: powders, tablets, capsules, liquids, and energy bars.

Why should you care?

Creatine helps maintain a continuous energy supply to your muscles during intense lifting or exercise.

When you take supplemental creatine, most of it goes to your skeletal muscles, which convert creatine into a compound composed of of creatine and phosphoric acid (phosphocreatine or creatine phosphate). Phosphocreatine then helps create adenosine triphosphate (ATP). ATP is a source of energy that your cells use when you exercise.

Creatine also helps to:

1. Speed up muscle recovery. When you exercise, you create micro-tears in your muscle fibers. As you recover, the micro-tears in your muscle fibers heal, and your muscles get stronger. Creatine helps activate satellite cells in your muscles, which help the micro-tears heal.

2. Increase anabolic hormones. Anabolic hormones contribute to growth and tissue repair. They include insulin, human growth hormone (hGH), estrogen and testosterone.

3. Boost water content in muscle cells. Better cell hydration may increase muscle growth and reduce dehydration and muscle cramps.

4. Creatine can also increase the amount of phosphocreatine in your brain, which may help with your memory.

Benefits and Risks of taking supplemental Creatine

What are the Benefits?

For people who work out regularly, studies show that taking creatine supplements may provide the following:

1. Improve their exercise performance.

2. Help their recovery after intense exercise.

3. Increase their muscle mass.

4. Prevent severe muscle injuries or reduce the severity of muscle injuries.

5. Help athletes tolerate more intense activity.

6. Reduce dehydration and cramping.

7. Minimize muscle tightness, including muscle strains and pulls.

If you’re a vegetarian or vegan, you may see more significant muscle gains by taking creatine supplements because you don’t get creatine through animal-based sources. However, building up creatine levels in your muscles may take longer.

In addition to its athletic benefits, creatine supplements may benefit people who have:

1. Neurodegenerative diseases, such as muscular dystrophy, Parkinson’s disease and Huntington’s disease.

2. Diabetes.

3. Osteoarthritis.

4. Fibromyalgia.

5. Conditions that affect creatine metabolism.

6. Conditions that affect how creatine transports through your body.

7. Insufficient blood flow to your heart muscle (myocardial ischemia).

Although creatine has long been recognized as a way to build muscle, and studies have shown benefits of creatine supplementation in helping older adults maintain their strength, the benefits of using creatine to improve memory and learning in adults are less widely known. Nonetheless, there is substantial clinical trial evidence supporting its use for this purpose.

A 2022 systematic review and meta-analysis of randomized controlled trials published in Nutrition Reviews documented that creatine supplementation improved memory performance, particularly in older adults aged 66 to 76.

In this meta-analysis, numerous peer-reviewed papers summarized studies that show that creatine supplementation can have a positive impact on almost all cognitive tasks (except for backward number recall). The bottom line is that creatine is very useful in supporting cognitive health in older people. At least one of these studies goes back to 2007, so it’s natural to wonder why more doctors haven’t been recommending creatine to their older patients. Also, why hasn’t NIH done more to fund and share these important findings? Skeptics might infer that this is because there is little profit to be made for the big pharmaceutical companies from producing and marketing creatine supplements.

What are the risks?

Creatine is a relatively safe supplement. However, side effects may include:

• Weight gain because of water retention.

• Dizziness.

• Nausea and vomiting.

• Diarrhea.

• Excessive sweating (hyperhidrosis).

If you develop any of these side effects after taking creatine, divide the amount you take each day into smaller doses. Take these smaller doses throughout the day instead of all at once.

Dosage

The most widely recommended dose of creatine for healthy adults is 3–5 grams per day of creatine monohydrate. A loading phase be used, with the recommended amount being 20–25 grams per day (split into 4–5 doses) for 5–7 days, followed by the maintenance dose. These doses are based on muscle saturation, but most of the cognitive studies followed similar dosing regimes, with 5 grams per day being the most common dose.

A recent pilot study using Creatine monohydrate for Alzheimer’s used a much higher dose (20 grams per day). The study enrolled a total of 20 patients, resulting in a very small sample size. At this dose, creatine monohydrate was associated with increased brain total creatine and improvements in cognition in individuals with Alzheimer’s disease. That said, Stomach discomfort and gastrointestinal issues are very possible at this high of dose. Taking large single doses (e.g., 10 grams or more at once) can cause stomach pain, diarrhea, nausea, and belching, muscle cramps and weight gain. There are also kidney and liver concerns at much higher doses.

It is a good idea to talk to your healthcare provider before you start taking creatine, particularly at higher dosing regimes. Key questions they may consider include:

1. Do you currently have any conditions, including diabetes, kidney disease or liver disease?

2. Are you taking any medications, vitamins or other supplements that may interact with creatine?

3. Why do you want to take creatine?

4. What are your goals?

5. Are you pregnant or planning to get pregnant?

6. Are you currently breastfeeding?

For these or other conditions, your health care provider may recommend a specific creatine supplement and dosage for you. It’s also a good idea to talk to a healthcare provider if you have side effects after taking creatine.

What about using Creatine to treat Post-Viral Fatigue Syndrome?

Long COVID is one example of a recognized diagnosis known as “Post-Viral Fatigue Syndrome” (PVFS). Fortunately, an updated review article has recently been published which focuses on the use of creatine to treat this relatively common but poorly understood syndrome.

Post-viral fatigue syndrome, classified as a neurological condition by the WHO (ICD-11 code: 8E49), manifests as persistent fatigue, cognitive difficulties, bioenergetic disruptions and post-exertional malaise following viral infections. It shares commonalities with chronic fatigue syndrome and myalgic encephalomyelitis but is distinct due to its association with preceding viral events. Emerging research identifies bioenergetic disruptions, particularly mitochondrial dysfunction and impaired creatine metabolism, as key contributors. Recent studies suggest creatine supplementation may alleviate symptoms and improve energy metabolism.

Despite recent advancements, challenges persist in understanding its pathophysiology, identifying precise diagnostic markers, and developing effective therapies.

Emerging evidence highlights the role of mitochondrial dysfunction and creatine metabolism in PVFS, positioning creatine as a promising therapeutic candidate. While initial studies suggest its efficacy in alleviating fatigue and improving bioenergetics, further large-scale, rigorous trials are essential. Addressing these gaps will pave the way for optimized care and improved patient outcomes.

As many readers may be aware, “long COVID” (originally called “long hauler syndrome”) is virtually indistinguishable from the post-vaccination syndrome associated with receipt of various mRNA COVID-19 genetic therapy products (mRNA COVID “vaccines”).

Both the natural infection with SARS-CoV-2 and all of these products cause your body to manufacture Spike protein, which is itself associated with a variety of toxicities and may play a key role in the development of both long COVID and post-vaccination syndrome. A recently published peer-reviewed analysis of post COVID-19 vaccination syndrome (PCVS) summarizes the cluster of symptoms and proposed pathophysiology of PCVS, and the role of Spike protein in promoting key aspects of the disease.

Disease definition for post covid-19 vaccination syndrome (PCVS) has been challenging, owing to different clinical presentations. The terminology ‘acute covid-19 vaccination syndrome’ (ACVS) is adopted to refer to adverse events which occur soon (immediately after up to days) after vaccination. The terminology ‘post-acute covid-19 vaccination syndrome’ (PACVS) refers to a different clinical presentation than PCVS, and refers to lingering symptoms which last typically longer than one month and may last for years.

Clinically, PACVS presents as similar to another disease cluster, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Other overlaps with existing syndromes include postural orthostatic syndrome (POTS), mast cell activation syndrome (MCAS) and small fibre neuropathy (SFN). PACVS is characterized by dysautonomia (disorders that affect the autonomic nervous system (ANS) –POTS as an example), post-exertional malaise, fatigue, and often accompanying neuropathic pain and cognitive disturbances, such as brain fog. In a cohort of 191 PACVS-affected persons, common symptoms are included in Table 1, with their associations with one of the above listed syndromes included.

Table 1. Common symptoms of PACVS and their overlap with existing syndromes. Symptoms are self-reported and/or determined by general practitioner. ME/CFS, myalgic encephalomyelitis/chronic fatigue syndrome; POTS, postural orthostatic syndrome; MCAS, mast cell activation syndrome; SFN, small fiber neuropathy. Potential molecular mechanisms involving spike protein are included in the rightmost column.

Fig. 1. Pathophysiology related to spike protein.

The question is, if creatine can be used to successfully treat Post-Viral Fatigue Syndrome, is there a role for the use of creating in treating Post COVID-19 Vaccination Syndrome (PCVS)?

Given the excellent safety profile of creatine supplementation, it seems reasonable to suggest that physicians managing challenging PCVS cases might consider reviewing the data concerning use of creatine to treat PVFS.

I look forward to learning from their experience and observations!