Newsletter #57: 💃 Creatine: an unlock for women's health, fertility, and metabolism?

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I’ve been wanting to do a deep dive on creatine for a long time. Despite all the buzz, it’s not something I ever learned about in medical training (I don’t even mention it in Good Energy! 🤦‍♀️). But as someone endlessly curious about the human body and metabolism, I knew I had to go down the rabbit hole—and bring you with me. So here it is! Spoiler alert: creatine is a FASCINATING molecule, and perhaps the most misunderstood compound in health. 🤯 Read on! 👇️

When most people think of creatine, they picture bodybuilders and gym supplements—but at its core, creatine is a molecule of profound biological importance for cellular energy production and metabolism. Made naturally by the body, creatine acts as an energy buffer and reserve, especially in tissues with high and fluctuating energy demands — like the brain, muscles, heart, and reproductive organs — all of which use tons of cellular energy (ATP) and need varying amount of energy based on what “work” the organs are doing.

Creatine works by rapidly regenerating adenosine triphosphate (ATP)—the body’s cellular “energy currency”—through a phosphate donation from its stored form, phosphocreatine. The enzyme creatine kinase lets this donation happen. This process allows cells to sustain performance and function under stress and high energy demand (i.e., sprinting, thinking, pregnancy, healing). Basically, when you (or, more specifically, your brain, muscles, ovaries, etc) need extra energy quickly, phosphcreatine is there to donate phosphate to make ATP.

Creatine is an energy buffer: it takes on a phosphate to make creatine phosphate, then can donate that phosphate back quickly to make ATP when energy demands rise in the cell. It’s a key player in metabolism in the body.

Creatine plays many other vital roles in the body beyond ATP turnover, including maintaining acid–base balance, supporting mitochondrial function, stabilizing cell membranes, and acting as an antioxidant, vasodilator, and anti-excitotoxic agent (aka, helping protect brain cells from damage caused by excessive neural stimulation). Far beyond its athletic associations, creatine is emerging as a critical nutrient for metabolic health, fertility, cognitive function, hormone regulation, and longevity—especially for women.

Today, I’m diving deep into what creatine is and why it might be important on our health journeys—not just because it increases muscle mass and strength, but because it is core aspect of metabolic functioning.

“Via the creatine kinase circuit, creatine derived from our diet or synthesized in the body provides spatial and temporal maintenance of intracellular adenosine triphosphate (ATP) production; this is particularly important for cells with high or fluctuating energy demands.”

From Creatine Metabolism in Female Reproduction, Pregnancy and Newborn Health, 2021

🤔 What is creatine?

Creatine is NOT just a body builder supplement! FAR FROM IT! Creatine is a naturally occurring compound synthesized in the liver, kidneys, and pancreas from three amino acids: arginine, glycine, and methionine. It is stored primarily in skeletal muscle (about 95%), but it’s also found in the brain, ovaries, uterus, and heart. Its primary function, as mentioned above, is regenerating ATP (adenosine triphosphate)—the body’s energy currency—especially during short bursts of high-demand activity.

How creatine is made in the body from arginine, glycine, and methionine, three amino acids we get from eating protein.

How creatine is made in the body from arginine, glycine, and methionine, three amino acids we get from eating protein.

Creatine Deficiency Disorders (CDDs) are rare genetic conditions affecting creatine synthesis or transport, and all of them commonly lead to developmental delays, intellectual disability, epilepsy, low muscle tone, and/or movement disorders. These conditions highlight how important creatine is to baseline brain and muscle functioning. Creatine is not a “nice-to-have;” it’s required for functional life. Treatment of these conditions typically involves oral creatine supplementation—with specific amino acid management depending on the subtype.

Creatine is present in many animal-based foods (notably red meat, pork, fish, chicken, and dairy), and not found in non-animal based foods. Supplemental forms of creatine are also widely available, with creatine monohydrate being the most common. Creatine monohydrate is synthesized in the lab via a chemical reaction between sarcosine and cyanamide, then crystallized with a water molecule to create the monohydrate form.

We get about half our daily creatine from an omnivorous diet that includes animal products, and the other half is made by the body from amino acids.

🚺 Sex-specific difference in creatine dynamics

According to “Creatine for Women: A Review of the Relationship Between Creatine and the Reproductive Cycle and Female-Specific Benefits of Creatine Therapy,” women tend to produce 70–80% lower amounts of creatine than males in the body. Women also consume significantly less dietary creatine (about 25% less meat than men) and have significantly less skeletal muscle mass—the primary storage site for creatine.

A study by Mihic et al. (2000) found that while creatine loading (20 grams per day for 5 days) increased total and fat-free body mass in both sexes, the effects are significantly greater in men. So, while supplementing with creatine has benefits for both sexes, the results and magnitude of the impact are sex-specific.

However, most of these studies have not accounted for menstrual cycle phases or hormone levels, which have profound effects on skeletal muscle metabolism and energy dynamics in women. Estrogen and progesterone are known to modulate creatine kinase activity and influence the enzymes involved in creatine synthesis. The review concludes:

“In terms of the effectiveness of dietary creatine supplementation either for athletic performance or for other therapeutic purposes, the implications of the possible changes in creatine metabolism in line with reproductive status of women has not been thoroughly investigated.”

From Creatine for Women: A Review of the Relationship Between Creatine and the Reproductive Cycle and Female-Specific Benefits of Creatine Therapy

Interestingly, as you can see above, creatine kinase activity shifts a lot throughout the menstrual cycle, further suggesting a dynamic relationship between creatine metabolism and female hormones. Therefore, it would not really make any sense to design a creatine study in women that doesn’t take into account hormonal status and phase of menstrual cycle.

🔮 Creatine and hormonal health

“Women who consumed greater than or equal to 13 mg of food-derived creatine per kilogram body mass per day exhibited a notably reduced risk of irregular menstrual periods, obstetric conditions, and pelvic pathology.”

From Association between dietary intake of creatine and female reproductive health: Evidence from NHANES 2017–2020

In the study “Association Between Dietary Intake of Creatine and Female Reproductive Health: Evidence from NHANES 2017–2020,” which included over 4,500 U.S. women aged 12 and older, researchers found that consuming ≥13 mg of creatine per kg of body weight daily was associated with a 25% lower risk of irregular periods (OR 0.75). 🤯

Conversely, those consuming less than this amount had significantly higher risks of reproductive challenges, including:

• Fetal macrosomia — unusually large baby at birth, increasing delivery risks (Odds ratio 1.26, p = .04)

• Pelvic infection — infection in reproductive organs that can affect fertility (Odds ratio 1.68, p = .01)

• Hysterectomy — surgical removal of the uterus, resulting in infertility (Odds ratio 1.42, p < .001)

• Oophorectomy — removal of one or both ovaries (Odds ratio 1.54, p < .001)

• Hormone replacement therapy — treatment for menopause symptoms or after ovary removal (Odds ratio 1.26, p = .02)

Lower dietary creatine levels from food (supplements were not included in this study) was associated with more reproductive challenges.

These findings suggest that higher creatine intake may be protective against a range of gynecologic and obstetric issues. Why might this be? 👇️

“1. Female reproductive health is highly dependent on the successful regulation of cellular bioenergetics, utilizing various fuel sources to support the divergent needs of oocytes and neighboring tissues.

2. The ovary and other reproductive organs (including the placenta) have a high expression of creatine-specific enzymes/transporters and total creatine content, highlighting the role of this compound for reproductive health.

3. Adequate dietary creatine perhaps upholds cellular energy circuits in critical organs during specific stages of a female's reproductive life, including pregnancy and menopause.

4. Moreover, dietary creatine could aid in preserving cell hydration during the luteal phase of menstruation, which has been associated with positive effects on reducing menstrual discomfort.

5. By acting as an antioxidant, creatine could also alleviate oxidative stress and modulate ovarian and oviductal function to enhance reproductive performance.”

From Association between dietary intake of creatine and female reproductive health: Evidence from NHANES 2017–2020

🤰 Pregnancy & postpartum

Though research is still emerging around creatine and pregnancy, it's compelling: creatine may be both neuroprotective for the fetus and supportive for maternal and placental health.

Animal studies show that creatine protects fetal brains during hypoxic stress (low oxygen), such as that experienced during labor, along with other benefits. Preliminary data suggests:

“1. Maternal creatine supplementation during pregnancy in pre-clinical animal studies has demonstrated a protective effect against fetal death and organ damage associated with intrapartum hypoxia.

2. Reduced creatine levels in late pregnancy have also been associated with low fetal growth.

3. There is additional data that metabolic demand from the placenta during gestation further lowers the creatine pool of the mother, which may be associated with low birth weight and pre-term birth.

4. Creatine supplementation during pregnancy has been shown to enhance neuronal cell uptake of creatine and support mitochondrial integrity in animal offspring, thereby reducing brain injury induced by intrapartum asphyxia.

5. Although there are no human studies evaluating the effects of creatine supplementation during pregnancy, creatine could provide a safe, low-cost nutritional intervention for reducing intra- and post-partum complications associated with cellular energy depletion.”

From Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?

So, to summarize: 

• Animal studies show creatine in pregnancy may protect against fetal death and organ damage. (This would make sense in theory, because creatine can donate phosphate to make cellular energy even in a low oxygen state where oxidative phosphorylation - aka making ATP with oxygen - is impaired).

• Low maternal creatine is linked to reduced fetal growth and lower birth weight.

• Pregnancy increases metabolic demand, depleting the mother's creatine stores. (This may then lead to adaptive upregulation of creatine synthesis in the placenta through several mechanisms).

• Supplementation supports fetal brain development and protects against birth-related brain injury, in animals.

• Though not yet studied in humans, creatine may offer a safe, affordable way to reduce birth complications and postpartum complications related to cellular energy depletion. (This would require much further study in humans to fully prove-out, but is promising!)

In “Creatine Metabolism in Female Reproduction, Pregnancy and Newborn Health,” researchers explain that inadequate placental perfusion and metabolic compromise—hallmarks of common conditions like preeclampsia (PE), fetal growth restriction (FGR), and gestational diabetes—are linked to oxygen and energy deficiency, prompting increased reliance on the creatine kinase circuit to maintain ATP.

Studies show that in compromised pregnancies:

• The placenta adapts by increasing creatine content and transporter expression, especially in the third trimester when energy demands peak.

• These changes occur without changes in maternal or fetal serum creatine, suggesting local metabolic adaptation in the placenta.

• These adaptations suggest that placental creatine metabolism plays a compensatory, protective role during pregnancy-related metabolic stress, with maternally imprinted genes like GATM - a gene which codes for a protein that helps make creatine - potentially regulating energy allocation between mother and fetus.

Long story short: if there are pregnancy complication, the placenta seems to adapt to increase creatine content to help with metabolic activity and function.

The “Creatine for Women” review also notes:

“Creatine is actively transported from the mother to the placenta, where it builds up and then moves into the fetal circulation... The placenta itself appears to increasingly rely on creatine as pregnancy progresses, especially in the third trimester when its energy demands rise.”

Creatine from mom goes to the baby!

Research has shown that muscle creatine content increases a lot in pregnancy — from 200 mmol per kilogram of alkali-soluble protein (ASP) before pregnancy to 223 mmol/kg ASP at 18 weeks and 233 mmol/kg ASP at 36 weeks gestation, possibly to meet the high energy demands of labor's ultra-intense uterine contractions. Though human data are limited, creatine supplementation in late pregnancy may help prevent uterine fatigue (dystonia) by supporting energy metabolism.

“Given that uterine activity in late gestation can be uncoordinated and labour sometimes ‘fail to progress’, a creatine supplementation program in pregnant women might also decrease the C-section rate.”

From: Creatine supplementation during pregnancy: summary of experimental studies suggesting a treatment to improve fetal and neonatal morbidity and reduce mortality in high-risk human pregnancy

🔬 Other promising areas of creatine research and study

• 🧠 BRAIN: Creatine supports brain energy metabolism by increasing brain energy levels, especially under stress or sleep deprivation. Genetic creatine disorders can be characterized by severe mental issues, highlighting the importance of creatine for brain health. 

  • Read more about creatine and brain health in this article from my dear friend Louisa Nicola, here: Creatine and Brain Development

• 💪 MUSCLE: The most well know aspect of creatine: increasing muscle mass. Supplementation improves strength, power, and lean body mass when combined with resistance training in women.

Relative effects of creatine supplementation on strength performance demonstrate a consistent improvement in performance compared to placebo.

• 😥 DEPRESSION: Creatine may lower depression risk in women, with “dietary creatine intake inversely proportional with depression occurrence; with a 31% greater incidence of depression in adults in the lowest quartile of creatine intake.” 

  • This makes sense, since more research is showing that mental illness may have a common root cause of impaired brain energy production and utilization. Women taking antidepressants plus creatine have been show to have significantly better improvements in depression. This is especially relevant to women because women have depression rates twice as high as men. 

  • 📚️ Read more: Brain Energy by Chris Palmer, MD

  • 🎙️ Listen: Creatine and Brain Health, Chris Palmer, MD and Andrew Huberman, PhD (I link to section on creatine and mental health)

• OTHER, including Menopause: Overall, creatine is showing promise as a safe intervention for a range of conditions, including neurodegenerative diseases like Huntington’s and Parkinson’s, traumatic brain injury, cognitive decline, and sleep deprivation-related impairments. It may also support metabolic health and aging by improving glucose tolerance, muscle performance in elderly men and post-menopausal women, and bone health—suggesting potential benefits for type 2 diabetes, metabolic syndrome, sarcopenia, osteopenia, osteoporosis, and menopause-related decline.

💡 The thesis of my book, Good Energy, is that metabolic dysfunction is at the core of nearly every chronic disease we face right now. Therefore, it makes sense that a molecule in our body that has a key effect on support cellular energy dynamics - creatine - would help a wide range of chronic illnesses.

✅ How to get enough creatine in your diet

🥩 Top natural sources (animal-based foods):

• Beef and game meats: ~1–2 g per 8 oz cooked

• Fish (herring, salmon, tuna): up to ~2.5 g per 8 oz

• Pork & chicken: ~0.4–1 g per 8 oz

🥛 Dairy sources:

• Parmesan: ~0.3–0.4 g per 3.5 oz (highest among cheeses)

• Milk, cheddar, yogurt: ~0.1 g per serving

• Eggs: 0.1 g per egg

🥗 Plant-based diets contain almost no creatine, but you can support your body’s internal production of creatine with:

• Pumpkin seeds – rich in arginine and contain methionine

• Soybeans (and tofu/tempeh) – good source of glycine, arginine, and some methionine

• Hemp seeds – contain all three amino acids required for creatine, including relatively high methionine for a plant source

• Sunflower seeds – good for glycine and arginine

• Chickpeas – high in arginine and provide some glycine

• Lentils – rich in arginine and support glycine intake

• Spinach – contains glycine and supports overall amino acid diversity

• Almonds – decent arginine content, plus some methionine

• Brazil nuts – contain methionine and small amounts of arginine

• Quinoa – a complete protein with modest amounts of methionine and other amino acids

💊 Should you supplement?

• Research suggests that creatine supplementation is very, very safe. You can read more about safety here.

• Optimal dosages for women at various life states have not been established, unfortunately.

• A standard dose 3–5 g/day of creatine monohydrate has been research is known safe, effective, and well-studied, although doses in research vary widely.

• Some studies include a short loading phase (20 g/day split over 5–7 days) for faster saturation, but this would be something to definitely talk to your healthcare or fitness practitioner about first.

Ok, off to eat some grass-fed beef and make my creatine-matcha latte and then lift! 😆🏋️

With good energy 💓

Dr. Casey

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Heading into my forties, and knowing that muscle mass declines every year after age 35, I take a scoop of creatine every single day—and having the travel-size option is so handy in making sure I stick to it! After doing this deep dive, I’m also excited to take it for hormone health and, potentially, pregnancy.

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