If you’ve ever wondered “what is butanediol and why does it matter?", 1,3-butanediol is a ketone supplement that increases blood beta-hydroxybutyrate (BHB) levels—the main ketone responsible for inducing ketosis.
Ketones are a natural energy source your body produces during fasting or when carbs and/or calories run low enough to prompt fat to be broken down into ketones, putting the body in a state of ketosis. Ketones are energy molecules that can cross the blood–brain barrier and provide a clean, efficient energy source for the brain.
Ketosis has been shown to have many positive effects on the brain, including improving energy metabolism, reducing inflammation, and even enhancing cognitive performance(*).
Research shows that 1,3-butanediol (Ketone Diol) effectively raises and sustains blood ketone levels, prompting researchers to investigate its impact on brain health and function.
The Study: Testing Ketone Diol for Brain Health
Researchers aimed to understand:
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Whether Ketone Diol, the ketone found in Ketone-IQ, can be an alternative strategy to fasting and calorie restriction for brain protection?
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The impact of Ketone Diol on the hippocampus, an area of the brain critical for memory and learning, and particularly vulnerable to inflammation.
Check the full publication here.
Why study Ketone Diol for the brain?
To understand what Ketone Diol is and why it’s being studied for brain health, it helps to first look at how ketosis supports the brain.
Fasting and calorie restriction (CR) are two of the most studied interventions for promoting brain health and longevity(*). While these strategies trigger multiple protective pathways, researchers increasingly believe that ketosis itself may be one of the key mechanisms behind their neuroprotective effects(*).
During fasting and reduced-calorie (or carb) intake, the body naturally shifts into ketosis, producing ketone bodies like beta-hydroxybutyrate (BHB) that serve as both an efficient fuel and a potent signaling molecule. This metabolic shift can support the brain in several ways:
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Improved energy metabolism: Ketones provide a clean and efficient fuel source for the brain(*).
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Reduced oxidative stress and inflammation: BHB helps modulate key stress-response and antioxidant pathways(*).
- Enhanced synaptic and cognitive function: Ketosis may elevate neurotrophic factors, such as BDNF, which support learning, memory, and neuroplasticity(*).
Because Ketone Diol has been shown to naturally reduce calorie intake and raise and sustain ketone levels(*), it offers a way to test whether these same protective mechanisms of fasting and calorie restriction can be achieved with a Ketone Diol supplement alone.
What did the new study find?
This study investigated the effects of Ketone Diol (KD) in healthy rats, focusing on the hippocampus—a brain region critical for learning and memory, and highly susceptible to oxidative stress and inflammation.
To determine how KD compared to calorie restriction and whether KD’s effects were simply due to reduced energy intake, researchers compared rats given Ketone Diol to both control animals and those on a calorie-restricted diet designed to match the same energy intake as the KD group.
Key findings included:
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Reduced stress responses: Ketone Diol lowered stress within cells and improved how they manage autophagy, effects not observed with calorie restriction alone.
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Improved inflammatory balance: Both Ketone Diol and calorie restriction reduced oxidative stress and inflammation, but KD-treated animals showed stronger activation of antioxidant defenses.
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Increases in critical brain proteins: Only the Ketone Diol group showed increases in BDNF and key brain proteins involved in learning and communication between neurons.
In summary, this study found that Ketone Diol may not only mimic the neuroprotective effects of fasting and calorie restriction, but potentially exceed them, activating similar pathways while offering additional benefits.
What does this mean for human health?
Although this study was conducted in rats, it builds on a growing body of human evidence showing that ketosis supports both brain and metabolic health, and that ketone supplements can effectively elevate circulating ketone levels.
Several human trials have specifically investigated R-1,3-butanediol, demonstrating that it safely elevates blood D-BHB levels for several hours while causing minimal side effects. Reported benefits of Ketone Diol supplementation in research include:
Together, these findings suggest that Ketone Diol can raise and sustain blood ketone levels, providing an accessible way to tap into many of the same brain-protective pathways triggered by fasting and calorie restriction. It may also deliver additional benefits not achieved through diet alone.
Who benefits most?
The neuroprotective findings of this preclinical study have the most potential for individuals aiming to support brain health and function or experiencing stress and high cognitive demand, including:
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Professionals or students seeking enhanced focus and supporting mental performance.
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Athletes and tactical operators under both physical and psychological stress.
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Individuals interested in longevity and metabolic health, where reducing inflammation and cellular stress is key.
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Individuals interested in optimizing their brain metabolism and supporting their brain health.
Suggested protocol based on the study’s implications
While the preclinical study doesn’t provide a direct dosing protocol for humans, its mechanisms suggest benefits from maintaining steady, moderate ketone levels, similar to the state achieved through fasting and calorie restriction.
A practical approach could include:
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Supplementation: One serving of Ketone-IQ® (Ketone Diol) to elevate ketones >0.5 mmol/L for several hours.
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Timing: Consuming before cognitively demanding work, during fasting, or in recovery periods to support brain energy and resilience.
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Combination with fasting: Fasting naturally elevates ketones; pairing it with Ketone Diol may help sustain optimal ketone levels longer and reinforce protective pathways.
Butanediol vs. Ketone Esters: What’s the Difference?
Through our work on a $6 million contract with the United States Department of Defense Special Operations Command (US DOD SOCOM) investigating ketone supplements, Ketone-IQ identified that Ketone Diol has the ideal pharmacokinetic curve for physically and cognitively demanding tasks. This curve describes the speed, magnitude, and duration of blood ketone elevation, what we call the “ketone curve.”
The Optimal Ketone Curve
The optimal range for supporting physical and mental performance sits between 1.0–2.5 mmol/L of blood ketones:
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Below 1.0 mmol/L, benefits may be minimal(*).
- Above 2.5 mmol/L, higher spikes may offer little extra benefit and can induce GI distress, acidosis, oxidative stress(*), and performance drawbacks(*)
Why Ketone Diol Hits the Sweet Spot
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No large spike: Ketone Diol is a D-BHB precursor—not free D-BHB. It raises ketones smoothly without exceeding 2.5 mmol/L, avoiding the sharp peaks that can impair performance.
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Naturally long-lasting: Because it’s the closest molecular precursor to D-BHB, it converts efficiently and steadily, maintaining elevated ketones (>1.0 mmol/L) for several hours.
- Optimal energy regulation: This stable curve may support sustained energy for both physical and cognitive output.
Comparing Ketone Supplements: Ester vs. Diol vs. Salts
Understanding the difference between ester vs diol forms of ketones helps explain why their pharmacokinetic curves differ. With esters, the ester to ketone conversion happens directly and spikes BHB rapidly, while diols (like 1-3 butanediol) are converted more gradually, supporting sustained performance over time.
Here’s a full breakdown comparing Ketone Diol, ketone esters, and ketone salts, showing the key differences between ester vs diol vs salt formulations and how effective each delivers ketosis:
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Ketone Esters |
R-1,3-Butanediol (Ketone Diol) |
Ketone Salts |
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Delivers D-BHB directly, causing rapid spikes >2.5 mmol/L |
Gradual rise and sustained range (1.0–2.5 mmol/L) |
Immediate but limited BHB rise (<1.0 mmol/L) |
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Often induces GI distress and acidity |
Smoother tolerance and stable energy |
High salt content can lead to GI discomfort and potential electrolyte imbalance |
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Partial hydrolysis leads to wasted ketone absorption |
Nearly 100% conversion to D-BHB |
Difficult to consume enough to significantly elevate ketone levels without upset stomach |
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Bitter taste and poor palatability |
Improved taste profile in Ketone-IQ® |
Often poorly formulated; includes both active (D-) and inactive (L-) BHB isomers |
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~3× higher cost per gram of ketone |
1/3 the cost per gram compared to esters |
Usually cheaper but significantly less effective |
In short, Ketone Diol provides a steady, efficient, and cost-effective way to elevate ketones—ideal for endurance, cognition, and recovery, without the drawbacks often associated with other ketone products.
Key Takeaways
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Ketone Diol can increase blood BHB levels.
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In rats, Ketone Diol supplementation reduced cellular stress and inflammation and boosted neurotrophic factors in the hippocampus.
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Ketone Diol may engage some of the same pathways activated by fasting and calorie restriction, while also offering distinct benefits of its own, presenting a novel way to support brain health.
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More human studies are needed, but these findings highlight that Ketone Diol supplements have broad potential, from fuel to signaling molecules, in shaping brain health, longevity, and performance.
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
