72-hour fast changed hormones, not creatine guidance

Key Takeaways

• In five healthy adults, a 72-hour water-only fast significantly changed total cholesterol, C-reactive protein, thyroid-stimulating hormone, and free triiodothyronine.
• Insulin and glucose fell during fasting and rose after refeeding, but those changes were not statistically significant in this very small sample.
• The authors say the fasting state looked compatible with autophagy, but autophagy was not measured directly.
• The study did not test creatine supplementation, muscle creatine stores, exercise performance, or body composition.
• For most people using creatine monohydrate, standard evidence-based intake remains the same: daily consistency matters more than fasting-related speculation.

What the fasting study actually found

A pilot study in the Croatian Medical Journal tracked what happened when five healthy adults completed a 72-hour water-only fast. The headline finding was not about weight loss or performance. It was that several blood markers shifted during the fast, including total cholesterol, C-reactive protein, thyroid-stimulating hormone, and free triiodothyronine, and then tended to move back toward baseline after 11 days of refeeding.

The researchers also reported broad changes in plasma, IgG, and IgA N-glycosylation profiles. That matters because glycosylation reflects how the body is modifying proteins involved in metabolism and immune function. In plain English, the body appeared to be adjusting system-wide to the stress of several days without food.

Some expected fasting markers moved in the anticipated direction. Insulin and glucose declined during fasting and increased after refeeding. But in this sample, those changes did not reach statistical significance. The authors also noted only minor, reversible changes in liver enzymes, electrolytes, and most lipid fractions.

The paper concludes that this 72-hour fast created a metabolic and hormonal environment consistent with autophagy. That wording is important. The study did not measure autophagy directly. So the findings support the idea that prolonged fasting triggers broad adaptation, but they do not prove that a specific amount of cellular “clean-up” occurred, nor do they tell us anything direct about creatine requirements.

How the study was designed and why the sample size matters

This was a single-arm longitudinal intervention, meaning everyone in the study did the same thing and the researchers compared each participant with their own baseline. There was no control group, no placebo condition, and no comparison with shorter fasts, calorie restriction, or a normal eating pattern.

Only five healthy adults were enrolled. Blood was collected at three time points: before fasting, immediately after the 72-hour water-only fast, and after 11 days of refeeding. The team then assessed a broad set of biochemical, hormonal, inflammatory, and glycomic markers, using the Friedman test to evaluate time-dependent changes.

That design is useful for generating hypotheses, but it sharply limits what we can conclude. With just five participants, random variation can look meaningful, and real effects can be missed. The sample was also healthy adults only, so the findings may not apply to athletes in heavy training, older adults, people with metabolic disease, or anyone dieting aggressively while trying to maintain performance.

There is another key limitation for readers interested in supplements: creatine was not part of the intervention. The study did not measure muscle creatine, phosphocreatine, exercise output, hydration performance, lean mass retention, or recovery. So while the paper is interesting as a snapshot of human fasting physiology, it is not evidence that fasting changes how everyone should use creatine.

What this means if you take creatine during fasting

For creatine users, the practical takeaway is straightforward: this study does not change standard creatine guidance. Creatine monohydrate remains the most studied form, and for most adults the evidence-based approach is still a daily maintenance intake of about 3-5 g per day. If someone wants to saturate stores faster, a common loading approach is about 20 g per day split into 4 doses for 5-7 days, followed by maintenance.

If you are doing a time-restricted eating plan or an occasional fast, the main question is usually adherence, not some special fasting-specific creatine protocol. Since creatine works by gradually increasing muscle creatine stores, consistency over time matters more than the exact minute you take it. Our creatine dosage calculator can help estimate a practical daily amount, and our creatine guides cover how to use it without overcomplicating the process.

For people attempting a prolonged water-only fast, the bigger concerns are training quality, energy intake, and medical appropriateness. This study suggests short-term biomarker shifts are feasible and reversible in a tiny healthy sample, but it says nothing about whether fasting helps preserve performance or muscle. Creatine can support high-intensity training capacity, but it cannot fully offset the limitations of not eating for three days.

If your goal is strength, lean mass, or sprint performance, the existing creatine evidence base is still the better guide than extrapolating from a five-person fasting trial.

Where this fits in the wider evidence on creatine and metabolism

This paper is best viewed as fasting physiology research, not creatine research. It adds to the idea that several days without food can alter endocrine, inflammatory, and glycomic signals in coordinated ways. But it does not overturn the much larger evidence base on creatine supplementation.

That larger body of work consistently supports creatine monohydrate as the best-studied form for improving high-intensity exercise capacity and helping increase strength and lean mass when paired with training. The International Society of Sports Nutrition position stand remains one of the most useful summaries of safety and efficacy, and it continues to support creatine as a well-researched supplement when used appropriately. See Kreider et al. (2017) and the practical myth-busting review by Antonio et al. (2021).

Could fasting alter the context in which creatine is used? Possibly in narrow, indirect ways. If someone is fasting, training less, or consuming less carbohydrate and total energy, their day-to-day performance and body mass may change regardless of creatine. But that is not the same as showing a different creatine requirement or proving a fasting-creatine synergy.

Readers comparing products should stay focused on fundamentals: plain monohydrate, sensible dosing, and product quality. Our best creatine rankings, creatine brand reviews, and creatine product catalog can help with that. This new fasting study is intriguing, but it belongs in the context column, not the rulebook.

The practical questions athletes should ask before mixing fasting and creatine

If you train hard, the first question is not whether fasting changes a lab marker. It is whether your overall plan supports your actual goal. A 72-hour water-only fast is very different from skipping breakfast, using a feeding window, or doing a short cut before competition.

• Trying to build muscle? Prolonged fasting is generally at odds with the calorie and protein intake needed to maximise hypertrophy, even if you keep taking creatine.
• Trying to maintain strength while dieting? Creatine may still be useful, but preserving training quality, protein intake, and recovery is likely to matter more.
• Curious about cellular health claims? This study hints at adaptive changes during fasting, but it did not directly measure autophagy and was far too small to support broad health promises.
• Worried about safety? In this tiny healthy cohort the protocol appeared feasible and well tolerated, but that does not mean a 72-hour fast is appropriate for everyone.

For most recreational lifters and team-sport athletes, the evidence-backed play is boring but effective: train consistently, eat enough protein, and take creatine regularly. If you are experimenting with fasting for personal or religious reasons, keep your creatine routine simple rather than trying to engineer a special stack around a preliminary pilot study.

Bottom line

This study found that a 72-hour water-only fast in five healthy adults temporarily changed several hormonal, inflammatory, lipid-related, and glycomic markers, with many measures moving back toward baseline after refeeding. That is scientifically interesting and potentially useful for future fasting research.

What it does not show is equally important. It does not show that fasting improves performance, protects muscle, changes creatine needs, or directly triggers autophagy. It does not compare fasters with non-fasters, and it is far too small to support sweeping conclusions.

So if you take or are considering creatine, there is no reason here to abandon standard best practice. Stick with a high-quality creatine monohydrate product, use an evidence-based dose, and prioritise consistency. If prolonged fasting is part of your routine, treat this paper as an early signal about human adaptation, not as a new creatine protocol.

That is the sober read: interesting fasting biology, preliminary evidence, and no meaningful change to mainstream creatine guidance.

Fast facts from the study and creatine context

• 5 healthy adults studied — Very small pilot sample
• 72 hours water-only fast — Single intervention tested
• 11 days refeeding follow-up — Markers were checked again after normal eating resumed
• 3-5 g/day typical creatine maintenance dose — Mainstream evidence-based guidance for creatine monohydrate

Frequently Asked Questions

Sources & Further Reading

• Kreider et al. (2017), ISSN Position Stand: Safety and Efficacy of Creatine — JISSN
• Antonio et al. (2021), Common questions and misconceptions about creatine supplementation — JISSN