Heat and Light as Medicine: What Research Shows About Infrared Therapy, Cardiometabolic Health, and Longevity
If you’re still skeptical about incorporating creatine into your clinical practice, or even into your own supplement stack, this second part of our blog series may help you make that final decision. I understand the hesitation. The internet is saturated with both legitimate concerns and anecdotal horror stories about creatine use (and misuse). Extreme water retention, hair loss, and gastrointestinal distress are frequent talking points. But what does the peer-reviewed evidence actually show? That’s not to dismiss N-of-1 experiences. In Functional Medicine, they matter. If anything, they remind us how profoundly bioindividuality shapes response. I’ve had a patient discontinue creatine after developing marked urinary frequency (“I’m peeing all the time!”), with complete resolution upon stopping the supplement. For some individuals, mild side effects are tolerable; for others, the impact could be a lot more significant. In this article, we’ll examine what the research tells us about safety, side effects, and practical clinical considerations so you can weigh the data alongside real-world experience and make an informed call. Let’s dive in. ~DrKF
Article written by Miranda Kusi, MS CNS FMCP
Creatine plays a central role in human bioenergetics, serving as a critical buffer in cellular energy metabolism. Through its reversible conversion to phosphocreatine, it supports rapid ATP regeneration in tissues with high and fluctuating energy demands, including skeletal muscle, brain, heart, and the gastrointestinal tract. While traditionally associated with athletic performance, emerging evidence highlights creatine’s broader therapeutic potential across the lifespan.
In this second part of our blog series, we continue to explore creatine’s potential uses in clinical settings, including a review of who may benefit most from supplementation, where caution is warranted, how different formulations compare, and what clinicians should know about dosing, safety, and real-world application. If you’ve missed the first part, you can catch up here.
Who May Benefit Most from Creatine Supplementation
In addition to individuals with cognitive decline, cardiometabolic disease, sarcopenia, and those seeking to optimize performance and longevity, creatine may be particularly beneficial for:
- Those with low dietary creatine intake (older adults, vegetarians, vegans): Plant-based diets provide minimal creatine, and older adults* typically consume less creatine overall, contributing to lower tissue stores.
- Individuals needing methylation support who do not tolerate B vitamins: Endogenous creatine synthesis consumes a large proportion of methyl donors. Creatine supplementation may spare methyl groups, rebalance methylation, and potentially reduce reliance on methylated B vitamins (and potentially lower homocysteine).
- Perimenopausal and menopausal women: When paired with resistance training, creatine may help preserve muscle mass and strength, support bone health, and reduce fatigue in peri- and post-menopausal women,* although creatine supplementation alone does not offer the same benefits. It may also improve cognition and emotional wellbeing,* potentially helping address common symptoms such as brain fog, poor sleep, and rapid mood shifts.
- Pregnancy and postpartum: Animal studies suggest creatine may enhance neuronal maturation in offspring by increasing dendritic growth and modulating ion channel function. Human data on creatine supplementation (200mg per kg body weight) in premature babies shows no side effects. A study in healthy Australian pregnant women found that maternal creatine metabolism shifts across pregnancy, with higher urinary GAA concentrations in early pregnancy associated with a very small reduction in newborn head circumference. While the clinical significance of this finding appears minimal, it adds to growing evidence that endogenous creatine metabolism may play a role in fetal brain development. Although definitive safety and outcome data are still limited, high-quality creatine used as directed has not been associated with adverse effects in women of reproductive age or preterm infants,* suggesting a reassuring safety profile overall.
- Conditions involving high energy demand: Including gastrointestinal disorders (gut barrier integrity, IBD), proinflammatory conditions,* chronic fatigue syndrome, neurodegenerative disease, traumatic brain injury, heart failure, and metabolic syndrome.
When Creatine Use Requires Caution
On the flip side, there are conditions where creatine may be contraindicated, including:
- Endometriosis (preclinical evidence): In vitro studies suggest creatine may inhibit ferroptosis of abnormal endometrial cells and promote angiogenesis and lesion progression.
- Cancer (conflicting evidence): Preclinical data suggests both antitumor and protumor effects, including enhanced immunity on one hand and possible facilitation of tumor growth on the other. Causality is unclear, and current findings support caution and the need for further high-quality human research.
- Kidney disease (limited evidence): Case reports describe adverse events in individuals with pre-existing renal dysfunction, such as recurrent renal failure and diabetic nephropathy. To date no prospective trials have evaluated safety in this population.
- Bipolar disorder (limited evidence): A small number of participants in clinical trials on depression and creatine supplementation experienced mania/hypomania, though causality is uncertain.
Creatine Formulations Explained: What the Evidence Shows
As the evidence base for creatine continues to expand, so does the supplement industry’s effort to capitalize on its popularity, often through unsubstantiated or misleading claims. A 2021 analysis of 167 creatine-containing supplements sold in Europe found that only 25% of commercial health claims complied with legal standards, with many products making unauthorized or unsupported statements.
Data on alternative forms of creatine beyond creatine monohydrate, is limited. A 2022 literature review found only a handful of high quality human studies on Cr citrate (n = 9 studies), Cr ethyl ester (CEE) (n = 1), magnesium-creatine chelate (n = 2), Cr malate (n = 2), Cr nitrate (n = 2), and Cr pyruvate (n = 2).
Below is an evidence-based summary on different creatine formulations:
| Type of Creatine | Research dosing strategies | Level of Evidence | Key Benefits & Clinical Applications / Notes |
| Creatine Monohydrate (CrM) | Loading: ~0.3 g/kg/day for 5-7 days
Maintenance: ~0.03 g/kg/day (≈3-5 g/day) for 4-6 weeks (loading optional) |
Strong | ● Gold standard form; high bioavailability, low cost, strong safety profile in healthy adults.
● Increases muscle creatine stores, athletic performance, cellular hydration. ● May cause transient water retention. Use caution with renal/hepatic disease and high dosing. |
| Creatine Hydrochloride (CrHCl) | 1.5-5g/day for 28 days
|
Emerging (limited human evidence) | ● This creatine salt has better solubility, but there is no evidence that it is absorbed better than or has physiological advantage over creatine monohydrate.
● Small scale study suggests CrHcl increased muscle mass with less water retention compared to CrM. ● No consistent evidence that CrHCl improves performance, nor does it outperform CrM. ● Research has not found superior increases in muscle creatine or effectiveness at lower doses. |
| Creatine Nitrate (CrN) | 1-6g/day for 28 days | Promising but early | ● Nitrate may potentially work synergistically with creatine to improve aerobic performance.
● Short-term supplementation (6–28 days) shows modest improvements in strength and anaerobic power, particularly at higher doses (≈6 g/day). ● Like monohydrate, CrN increases fat-free mass over 28 days, with no significant changes in total body weight or fat mass. ● CrN (5 g/day) in combination with caffeine (400 mg/day) may enhance cognitive performance. ● CrN appears comparable but not clearly superior to CrM. |
| Creatine Ethyl Ester (CEE) | Not standardized | Some Evidence | ● Creatine + esterified ethanol.
● Designed to cross membranes independently of the creatine transporter; reduced conversion to creatinine. ● Less effective at increasing muscle creatine* content compared to CrM. ● Not recommended for pregnant / lactating women, children, or those with liver/kidney disease due to ethanol content. ● Limited human safety data. |
| Creatine Gluconate | ~7.5 g/day provides ~3 g creatine | Limited Evidence | ● Creatine + glucose molecule. May enhance absorption via glucose-mediated insulin response.
● Based on data that shows pairing creatine with carbohydrates improves uptake. High carb loads may cause GI discomfort in some individuals. Clinical superiority over CrM not established. |
| Creatine Citrate | Varies by ratio (1:1, 2:1, 3:1) | Some Evidence | ● Improved solubility; similar bioavailability to CrM.
● Some evidence it can increase blood creatine levels and exercise performance. ● Dicreatine citrate (2:1) may reduce GI discomfort thanks to increased solubility. ● Has not been assessed on brain and muscle creatine content. No data of clear performance advantage over CrM. |
| Creatine Magnesium Chelate | Not standardized | Some Evidence | ● May improve stability, uptake, and reduce water retention.
● Potential synergy for muscle performance and energy metabolism. ● Limited long-term safety and comparative data. Limited evidence shows it may improve performance as effectively as CrM. |
Clinical takeaway: Creatine monohydrate remains the most evidence-based, cost-effective, and clinically supported form for both therapeutic and performance use. Other forms may offer theoretical advantages, but currently lack strong evidence of superiority.
Building the Body’s Creatine Reserves. Data estimates that it takes approximately 28 days to saturate muscle creatine stores with a daily dose of ~3 g. Earlier research commonly used a two-phase protocol consisting of a loading phase (≈20 g/day for 5–7 days) followed by a maintenance phase (≈5 g/day for several weeks). More recent studies indicate that a loading phase is not necessary to achieve intramuscular creatine saturation, it simply accelerates the process. What about creatine “cycling”? Early speculation suggested that alternating periods on and off creatine was necessary to avoid tolerance. This concept has since been disproven, as creatine works independently of receptors. Regular intake helps maintain stable tissue stores, particularly given that the body requires 2-3 g per day.
Creatine Safety and Common Side Effects
Creatine is one of the most extensively studied dietary supplements and has a strong safety profile when high-quality, pure products are used. However, product quality remains an important clinical consideration: a 2022 analysis found that only 8% of creatine supplements sold online were third-party tested.* Beyond quality and potential contamination issues, the most commonly reported side effects include water retention, gastrointestinal upset, muscle cramping, and dehydration.
Creatine and Water Retention: What the Research Shows
Among these, water retention is the most frequently cited concern. While creatine increases intracellular water, this does not always translate to increased total body water* and is typically transient, resolving within the first few days of supplementation. Interestingly, small randomized trials evaluating creatine supplementation across the menstrual cycle found that creatine loading increased total, extracellular, and intracellular water during the luteal phase* without increasing body weight. In addition, creatine may improve phase angle, a marker of cellular hydration and integrity. Collectively, these findings suggest that creatine may support cellular hydration and fluid balance in women, particularly during the luteal phase when extracellular fluid tends to accumulate and contribute to bloating.
Gastrointestinal Side Effects and Absorption Factors
Gastrointestinal symptoms represent another commonly discussed side effect. Reported complaints include mild diarrhea, nausea, bloating, heartburn, and abdominal discomfort. While some small studies* have documented these effects, most high-quality randomized trials show no greater incidence than placebo.* In practice, undissolved creatine powder and concurrent use with caffeine may increase the likelihood of GI distress. Emerging evidence also suggests a possible interaction between the gut microbiome and creatine metabolism, with certain beneficial bacterial strains potentially enhancing creatine absorption and availability.
Creatine and Kidney Health: Addressing a Persistent Concern
Kidney health is another common concern. Although creatine supplementation can cause acute increases in urine and serum creatine and creatinine, this reflects increased creatine turnover rather than impaired renal function. Creatinine and eGFR are influenced by muscle mass and dietary protein intake; therefore, muscle-independent markers such as cystatin C may provide a more accurate assessment. In contrast to early concerns, clinical trials and population studies demonstrate that creatine does not impair kidney function in healthy adults, even with long-term use of up to five years.
Creatine, testosterone and hair loss. Concerns linking creatine to hair loss stem largely from a single study reporting a modest increase in serum dihydrotestosterone (DHT) in male rugby players. Importantly, DHT levels remained within normal clinical ranges, and the findings have not been replicated. The apparent “increase” was influenced by lower baseline DHT in the creatine group and small declines in the placebo group. To date, no study has reported actual hair loss associated with creatine use, and recent trials* show no link between creatine, androgen changes, and alopecia.
Rare or Unconfirmed Adverse Effects
Less common side effects reported include anxiety, irritability, depressed mood, aggression, nervousness, sleepiness, headache, and syncope. Isolated case reports of rare events, such as atrial fibrillation, skin rash, venous thrombosis, hepatic injury, rhabdomyolysis, interstitial nephritis, and renal insufficiency, have not been confirmed in controlled clinical trials. Many reports failed to account for confounding factors such as supplement contamination, concurrent medication use, or pre-existing health conditions.
Creatine as a Foundational Molecule for Energy and Healthy Aging
Creatine has evolved from a niche sports supplement into one of the most well-researched and clinically relevant bioenergetic compounds in human physiology. Once viewed primarily through the lens of athletic performance, creatine is now recognized as a central regulator of cellular energy metabolism, with pleiotropic effects across multiple organ systems. Its central role in ATP regeneration and mitochondrial efficiency underpins benefits in muscle performance, cognitive function, cardiometabolic health, and conditions characterized by high energy demand – functions that become increasingly important with aging and chronic disease.
Current evidence consistently supports creatine monohydrate as the gold-standard formulation, with alternative salts offering theoretical but not clinically proven advantages. When high-quality products are used and individual risk factors are considered, creatine demonstrates a reassuring safety profile in healthy populations. While caution is warranted in select clinical groups (e.g., pre-existing kidney disease, bipolar disorder, active malignancy), for most healthy individuals, creatine represents a low-risk, potentially high-reward intervention.
As research continues to expand beyond sport into therapeutic domains, creatine should be viewed not merely as a performance enhancer, but as a foundational metabolic support molecule. When used judiciously and combined with exercise and other lifestyle interventions, it holds meaningful potential to support health and functional capacity across the lifespan.
Want a deeper, evidence-based understanding of creatine for clinical practice? Download our comprehensive Clinician’s Guide to Creatine, covering the history and mechanisms of action, therapeutic applications beyond sport, key populations who may benefit, clinical contexts requiring caution, evidence-based data on formulations and dosing strategies, and a clear review of safety and side effects. Equip yourself with the science you need to make confident, informed recommendations.
*Disclaimer: One or more authors of the asterisked citation have affiliations with supplement companies, including those that manufacture or sell creatine. For more details, check the citation’s “Conflicts of Interest” or “Ethics Declaration” section typically found at the bottom of the research paper.
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