How a recent scientific paper demonstrates the importance of logical consistency in nutrition research
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The Seductive Appeal of “More is Better”
A new research paper has been making waves in the supplement world with a compelling headline: “Creatine Supplementation: More Is Likely Better for Brain Bioenergetics, Health and Function.” At first glance, this sounds like the kind of breakthrough we all want to hear – a simple solution where taking more of a well-researched supplement could boost our brain power.
But when we dig deeper using principles of logical analysis, this paper reveals a fascinating case study in how even well-intentioned scientific communication can go astray. The issues aren’t with the individual studies cited, but with how the conclusions are drawn and presented.
Let me walk you through what happens when we apply rigorous logical analysis to scientific claims – and why it matters for anyone trying to make sense of nutrition research.
The Logical House of Cards
Paradox #1: Fighting a Biological Speed Limit
The paper presents what I call the “Homeostatic Resistance Paradox,” but there’s a concrete mechanism behind it. The brain’s creatine transporter (SLC6A8) at the blood-brain barrier has a low Vmax – meaning it reaches saturation quickly and can’t be pushed much harder.
Here’s the logic chain:
- Established fact: The brain actively regulates creatine entry via a saturable transporter
- Observed reality: Even with massive dose increases, brain creatine only rises ~10% vs. ~20% in muscle
- Proposed solution: Use even higher doses to overcome this biological speed limit
But this isn’t a design flaw – it’s a feature. The brain carefully controls creatine entry because too much can disrupt cellular osmotic balance. It’s like your car’s fuel injection system limiting gas flow to prevent engine flooding, and the response being: “Let’s use a bigger pump to force more gas in!”
Paradox #2: The Self-Defeating Strategy (With Numbers)
Here’s where it gets really interesting. The paper acknowledges that prolonged creatine supplementation actually reduces the brain’s ability to transport creatine. But this isn’t theoretical – rodent studies show 15-40% reductions in CT1 mRNA after chronic loading.
Let me break this down:
- Paper’s recommendation: Take higher doses for longer periods
- Paper’s own evidence: Longer supplementation reduces transport capacity by 15-40%
- Logical conclusion: The strategy becomes progressively less effective over time
This is like recommending people honk their car horns more to get attention, while simultaneously noting that prolonged honking makes people tune out horn sounds by 15-40%.
Paradox #3: The Evidence Switcheroo
The most compelling evidence for high-dose creatine comes from people under severe metabolic stress:
- Alzheimer’s patients
- Sleep-deprived individuals
- Children with traumatic brain injuries
- People with depression
But the paper then leaps to recommending higher doses for general “brain health” in healthy people. This is like studying how extra oxygen helps people with pneumonia breathe better, then recommending oxygen tanks for everyone who wants to “optimize their breathing.”
The Numbers Don’t Add Up
Let’s look at actual data the paper presents but misinterprets:
Depression Study Results:
- 2 grams daily → 4.6% brain creatine increase
- 4 grams daily → 4.1% brain creatine increase
- 10 grams daily → 9.1% brain creatine increase
The paper uses this to support “more is better,” but look closely: doubling from 2g to 4g actually decreased the effect slightly! Only at 10g did we see a big jump. This suggests a threshold effect around 8-10g, not a linear “more is better” relationship.
Picture this as a graph: a nearly flat line from 2-4g, then a steep jump at 10g. That’s not “more is better” – that’s “there might be a specific threshold, but we need more data to understand it.”
The Safety Shell Game
Here’s perhaps the most concerning logical flaw: the paper recommends doses of 20-25g daily based on the safety profile of 3-5g daily, with zero long-term renal or GI monitoring in the cited trials.
Let’s put this in regulatory context:
- EFSA: 3g daily for chronic use
- Health Canada: 5g daily maximum
- Study doses: 20-25g daily (4-8x regulatory limits)
This creates what I call the “Safety-Efficacy Gap”:
- Low doses: Safe (regulatory approval) but ineffective for brain benefits (according to the paper)
- High doses: Needed for brain benefits but no long-term safety data
- Recommendation: Take the high doses anyway
It’s like saying “aspirin is safe at 100mg, so 800mg must be fine too” – which is definitely not how pharmacology works.
This Pattern Has Failed Before
The “more is better” logic has backfired spectacularly with other nutrients:
| Nutrient | “More is Better” Backfire | Evidence |
|---|---|---|
| Vitamin D (>1,000 IU) | No fracture benefit; doses above 1,000 IU trended toward more fractures | Meta-analysis: 32 RCTs, 104k participants |
| β-Carotene (20-30 mg) | 22-31% increase in lung cancer among male smokers | ATBC trial: 29,133 smokers |
| Selenium (200 μg) | 55% increase in type-2 diabetes after 7.7 years | Nutritional Prevention of Cancer trial |
| High-dose EPA(≥4g) | 50% relative increase in bleeding events | 2024 meta-analysis: 62 RCTs |
These weren’t obscure megadoses – they were modest increases that seemed logical until tested rigorously. The selenium case is particularly striking: just 2.5x the RDA increased diabetes risk by 55%.
What This Means for You
If You’re Healthy:
The evidence for high-dose creatine in healthy people is weak. The standard 3-5g daily dose has regulatory approval(EFSA: 3g daily for chronic use) and proven benefits for physical performance. There’s no compelling reason to venture into uncharted high-dose territory.
If You Have Specific Conditions:
The evidence is actually quite good for higher doses in specific situations:
- Alzheimer’s disease
- Depression (as an adjunct to treatment)
- Recovery from brain injury
- Acute sleep deprivation
But these should be medical decisions made with healthcare providers, not general wellness recommendations.
The Bigger Picture:
This paper illustrates why we need to be skeptical of “more is better” logic in nutrition. Biology rarely works that way. Most nutrients and supplements follow U-shaped curves – too little is bad, but too much can also be harmful.
The Real Lesson: Mechanisms + Numbers Matter
This analysis isn’t meant to bash creatine research or the researchers involved. Creatine is one of the most well-studied supplements we have, with excellent safety data at regulatory-approved doses.
Instead, this is about the importance of combining logical consistency with mechanistic understanding. When papers ignore biological speed limits (like transporter saturation), dismiss their own contradictory data (like 15-40% transporter downregulation), or extrapolate beyond their evidence base, it can mislead both healthcare providers and consumers.
The principles I used here – checking transporter mechanisms, quantifying downregulation effects, examining regulatory limits – can be applied to any health claim you encounter. Whether it’s the latest superfood, a new supplement protocol, or a revolutionary diet, asking these mechanistic questions can help you separate solid science from compelling-but-flawed reasoning.
The Bottom Line
For most people: Stick with the regulatory-approved 3-5g daily creatine dose if you’re using it for physical performance. This has both efficacy evidence and long-term safety monitoring.
For brain health: Focus on the fundamentals – sleep, exercise, nutrition, stress management, and social connection. These have far stronger evidence for brain health than any supplement protocol.
For critical thinking: When you see “more is better” claims, ask yourself: What are the biological mechanisms? Are there natural regulatory systems being ignored? Do the doses exceed regulatory safety limits? Is the evidence actually from the population being recommended to?
Science works best when we combine rigorous research with rigorous thinking. This paper reminds us that even good research can lead to questionable conclusions when logical analysis and mechanistic understanding take a back seat to compelling narratives.
What do you think? Have you encountered other examples where “more is better” logic doesn’t hold up to mechanistic scrutiny? Share your thoughts in the comments below.
System D 