A newly published study in Nutrients (2026) by Dr. Bikman`s team provides important insight into how different ketone supplements affect liver metabolism, mitochondrial function, and inflammation. The findings highlight a critical point that is often overlooked in the supplement industry:
Not all ketone molecules/supplements are metabolically equivalent.
The study, titled “Disparate Hepatic Mitochondrial and Inflammatory Effects of Ketone Supplements,” examined the biological effects of three commonly used ketone sources:
- D-β-hydroxybutyrate (D-BHB)
- L-β-hydroxybutyrate (L-BHB)
- 1,3-butanediol (BD), a ketone precursor used in some formulations
The results revealed striking differences between these compounds, particularly in how they affect liver energy metabolism, oxidative stress, mitochondrial function, and inflammation.
Let’s break down what the research found.
The Two Forms of BHB: D-BHB and L-BHB
Beta-hydroxybutyrate (BHB) is the primary ketone body produced during fasting or carbohydrate restriction. It exists in two mirror-image forms, known as enantiomers:
- D-BHB – the natural form produced during ketosis
- L-BHB – a stereoisomer that the body makes in smaller amounts, also appears in racemic BHB supplements and may have unique signaling roles
The Audacious Nutrition ketone supplements contain a 50:50 mixture of these forms (D,L-BHB), while other brands mainly use only D-BHB.
D-BHB is well studied as an efficient fuel for the brain, heart, and muscles, far less research has examined the biological role of L-BHB.
This new study provides valuable insight into how both forms behave metabolically.
Key Finding #1
BHB Increased Cellular Energy, 1,3-BD caused severe ATP depletion
One of the most important outcomes measured in the study was ATP production, the cell’s primary energy currency.
Both D-BHB and L-BHB increased hepatic ATP levels, indicating improved energy availability within liver cells.
In contrast, the ketone precursor 1,3-butanediol caused severe ATP depletion, suggesting a metabolic burden on liver energy systems .
This distinction is crucial.
Direct BHB provides energy without taxing the liver, while BD must first be metabolized through pathways similar to alcohol metabolism.
Key Finding #2
BHB Reduced Oxidative Stress, 1,3-BD dramatically increased oxidative damage
The researchers also measured malondialdehyde (MDA), a biomarker of lipid peroxidation and oxidative stress.
Results showed:
- D-BHB and L-BHB lowered oxidative stress
- 1,3-butanediol dramatically increased oxidative damage
This aligns with previous research demonstrating that BHB can function as a signaling metabolite that activates antioxidant pathways and supports cellular resilience.
Key Finding #3
Mitochondrial Function Was Preserved with BHB, 1,3-BD impaired mitochondrial respiration
After eight days of supplementation, the study evaluated mitochondrial respiration, which reflects how efficiently cells generate energy.
The results were clear:
- BHB maintained normal mitochondrial function
- 1,3-butanediol impaired mitochondrial respiration and enzyme activity
Mitochondria are central to metabolic health, endurance, cognitive performance, and aging.
Maintaining mitochondrial efficiency is therefore a key factor in the long-term safety of any metabolic supplement.
Key Finding #4
1,3-Butanediol Increased Inflammation
Perhaps the most concerning finding was the effect of BD on inflammatory signaling.
The study measured several inflammatory cytokines including:
- IL-1β
- TNF-α
- C-reactive protein (CRP)
Both BHB forms maintained normal inflammatory levels, while 1,3-butanediol significantly increased inflammatory markers, including a roughly six-fold increase in TNF-α .
Chronic inflammation is closely linked to:
- metabolic disease
- insulin resistance
- cardiovascular risk
- liver disease
This finding underscores why formulation matters.
Key Finding #5
Only BD Caused Fat Accumulation in the Liver
After eight days of supplementation, researchers also evaluated hepatic triglyceride accumulation, a marker of fatty liver risk.
The results showed:
- BHB maintained normal liver fat levels
- 1,3-butanediol significantly increased triglyceride accumulation
The mechanism likely relates to BD metabolism, which resembles ethanol metabolism and shifts cellular redox balance toward fat synthesis rather than fat oxidation.
These findings support our recent study on liver histology.
Why This Matters for Ketone Supplements
Exogenous ketones are becoming increasingly popular for:
- cognitive performance
- metabolic health
- endurance and recovery
- neurological support
However, the type of ketone molecule used in a supplement matters enormously.
According to the authors:
- BHB enantiomers demonstrated favorable or neutral hepatic effects
- 1,3-butanediol induced metabolic stress in the liver
The study concludes that formulation choice is critical for long-term safety and metabolic outcomes.
The Bottom Line
This research reinforces an important principle:
Elevating ketones in the blood does not automatically mean a supplement is metabolically beneficial.
How ketones are delivered to the body matters.
Based on the data:
Direct BHB supplementation appears to be the most metabolically favorable approach, supporting cellular energy while maintaining mitochondrial function and inflammatory balance.
In contrast, certain ketone precursors may impose additional metabolic stress on the liver.
As research into ketone metabolism continues to expand, understanding these biochemical differences will be essential for developing safe and effective metabolic therapies.
Final Thoughts
The science of ketone metabolism is evolving rapidly. What we are learning is that ketones are not simply an alternative fuel — they are also powerful signaling molecules that influence metabolism, inflammation, and mitochondrial function.
Studies like this help clarify which formulations support metabolic health and which may carry unintended metabolic costs. In all Audacious Nutrition products, we use the combination of D-BHB and L-BHB for maximum benefit, none of our products contain 1,3-butanediol.
As interest in metabolic therapies continues to grow, rigorous research and responsible formulation will remain essential.
1 comment
What commercial formulations use racemic 1,3 Butanediol?
That is an inaccurate and intentionally misleading statement.