Please explore a collection of articles and videos related to MiDR1V3. We will update these as the science evolves.
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RESOURCE HUB
Please explore a collection of articles and videos related to MiDR1V3. We will update these as the science evolves.
Participant totals: R-1,3-butanediol exposures (pure + esters) = 113; all modern human trials on this page = 307.
| Category | Title | Authors | Journal | Summary |
|---|---|---|---|---|
| Core Human Trials | Open-Label Trial of (R)-1,3-Butanediol (Avela) | Lowder et al. (2023) | Frontiers in Physiology | Open-label; n=24 healthy adults. Safe, rapid nutritional ketosis; mild GI events only. Implication: Direct human safety/tolerability for pure R-1,3-butanediol. |
| Core Human Trials | Tolerability and Safety of Bis-Hexanoyl (R)-1,3-Butanediol (BH-BD): Randomized Controlled Trial | Mah, Chen, Blonquist, et al. (2021) | Nutrients | Double-blind RCT; n=59 (30 BH-BD, 29 placebo). Daily up to 25 g BH-BD raised BHB with no safety signal. Implication: Even as a di-ester matrix, R-1,3-BD shows strong tolerability. |
| Core Human Trials | Daily Bis-Octanoyl (R)-1,3-Butanediol (BO-BD) in Older Adults: Randomized Controlled Trial | Stubbs, Stephens, et al. (2024) | medRxiv / PubMed | 12-week double-blind RCT; n=30 randomized (23 completed) aged ≥65. Safe and well tolerated; expected BHB rise. Implication: Supports R-1,3-BD safety in aging populations, despite ester complexity. |
| Core Human Trials | Safety and Tolerability of Orally Administered Free D-β-Hydroxybutyrate | Pimentel-Suárez et al. (2024) | BMJ Nutrition, Prevention & Health | Open-label crossover; n=12. Salt-free BHB induced nutritional ketosis safely with minimal GI effects. Implication: Oral ketone precursors show favorable safety, supporting the BD platform. |
| Core Human Trials | Ketogenic MCT Drink Improves Brain Energy and Cognition in Mild Cognitive Impairment | Fortier et al. (2019) | Alzheimer’s & Dementia | Double-blind trial; n=122 MCI. MCTs raised brain ketones and improved memory outcomes. Implication: Clinical support for ketone-based strategies in neurodegeneration. |
| Core Human Trials | Medium-Chain Triglycerides Improve Cognition in Frail Elderly | Abe et al. (2020) | Journal of Nutrition | 3-month intervention; n=60 older adults. Improved memory and attention with 6 g/day MCTs. Implication: Reinforces translational relevance of ketone availability to cognition. |
| Brain Metabolism & Aging | Brain Metabolism in Health, Aging, and Neurodegeneration | Camandola & Mattson (2017) | The EMBO Journal | Fasting, exercise, and ketosis as adaptive metabolic stressors supporting neuronal resilience. |
| Brain Metabolism & Aging | Energy Metabolic Pathways in Neuronal Development and Function | Rumpf et al. (2023) | Oxford Open Neuroscience | How glycolysis and oxidative phosphorylation shape neuronal development and plasticity. |
| Brain Metabolism & Aging | Mitochondrial Health and Fitness | San-Millán (2023) | Antioxidants | Defines “mitochondrial fitness” and links it to healthspan and disease risk. |
| Brain Metabolism & Aging | Oxidative Stress, Dysfunctional Glucose Metabolism, and Alzheimer Disease | Butterfield & Halliwell (2019) | Nature Reviews Neuroscience | AD framed as bioenergetic/oxidative disorder; supports metabolic interventions. |
| Brain Networks & Connectivity | Diet Modulates Brain Network Stability | Mujica-Parodi et al. (2020) | PNAS | Ketone availability increases network stability versus glucose-dominant metabolism. |
| Brain Trauma / Concussion | Post-Concussion Syndrome Trial | Rippee et al. (2020) | Frontiers in Nutrition | Two-month ketogenic diet reduced symptoms and improved visual memory. |
| Brain Trauma / TBI | Ketogenic Diet Feasibility in Adult TBI (Phase I) | Arora et al. (2022) | Clinical Nutrition ESPEN | Enteral KD achieved safe, sustained ketosis in ICU TBI patients. |
| Brain Trauma / TBI (Preclinical) | Ketone Monoester Reduces Lesion Volume and Neuroinflammation | Almeida-Suhett et al. (2022) | Nutritional Neuroscience | Post-injury ketone ester lowered lesion size and inflammatory biomarkers (mouse CCI model). |
| Core Metabolic Foundations | Glucose-Sparing Action of Ketones Boosts Functions Exclusive to Glucose in the Brain | Zilberter & Zilberter (2020) | eNeuro | Ketones provide ATP while sparing glucose for neurotransmission and plasticity. |
| Core Metabolic Foundations | Multi-Dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics | Puchalska & Crawford (2017) | Cell Metabolism | Defines ketone bodies as fuels and signaling molecules regulating inflammation and epigenetics. |
| Core Metabolic Foundations | The Energy Homeostasis Principle | Vergara et al. (2019) | Frontiers in Computational Neuroscience | Energy balance as a driver of network dynamics and behavior. |
| Core Metabolic Foundations | The Therapeutic Implications of Ketone Bodies | Veech (2004) | Prostaglandins, Leukotrienes & Essential Fatty Acids | Foundational biochemistry: redox, energetic efficiency, therapeutic logic of ketosis. |
| Epilepsy & Seizures | Infant Epilepsy RCT: Ketogenic Diet vs Additional Anticonvulsants | Schoeler et al. (2023) | Lancet Neurology | KD comparable or superior to add-on ASM in seizure reduction and tolerability. |
| Epilepsy & Seizures | Ketogenic Diets for Drug-Resistant Epilepsy (Systematic Review) | Martin-McGill et al. (2020) | Cochrane Database of Systematic Reviews | Confirms KD effectiveness for seizure reduction across ages. |
| Ketone Mechanisms | Ketones Inhibit Mitochondrial Production of Reactive Oxygen Species | Maalouf et al. (2009) | Neurobiology of Aging | BHB decreases ROS production and neuronal injury in oxidative models. |
| Mechanistic Neuroprotection | Ketones Inhibit Mitochondrial ROS After Excitotoxicity | Maalouf et al. (2007) | Neuroscience | BHB reduces oxidative stress and cell death via enhanced NADH oxidation. |
| Mechanisms of Action | Mechanisms of Ketogenic Diet Action | Masino & Rho (2012) | Jasper’s Mechanisms of the Epilepsies | Adenosine/KATP, mitochondrial effects, inflammatory pathways, network stability. |
| Mitochondrial Health & Disease | The Key Role of Mitochondrial Function in Health and Disease | Horan et al. (2023) | Antioxidants | Overview of mitochondrial dysfunction, oxidative stress, and exercise-based therapy. |
| Mitochondrial Health & Longevity | NADPARK Trial: Nicotinamide Riboside in Parkinson’s Disease | Brakedal et al. (2022) | Cell Metabolism | NR raises brain NAD+ and improves mitochondrial gene signatures in PD. |
| PD & Neurodegeneration | Impact of a Ketogenic Diet on PD Symptoms and Quality of Life | Tidman et al. (2024) | Neurodegenerative Disease Management | Longitudinal KD improved biomarkers, mood, and quality of life in PD. |
| PD & TBI Overlap | Biological Links Between Traumatic Brain Injury and Parkinson’s Disease | Delic et al. (2020) | Acta Neuropathologica Communications | Shared mitochondrial and inflammatory mechanisms between TBI and PD. |
| Psychiatry & Cognition | Adjunct Ketogenic Diet for Major Depression (Pilot) | Decker et al. (2025) | Translational Psychiatry | Adjunct KD reduced depressive symptoms; improved energy metabolism markers. |
| Psychiatry & Cognition | Brain and Body Energy Metabolism and Treatment of Psychiatric Disorders | Andreazza et al. (2025) | Nature Mental Health | Bioenergetic dysfunction as a unifying mechanism in psychiatric illness. |
| Psychiatry & Cognition | Ketogenic Diet in Serious Mental Illness (BD + SCZ Pilot) | Sethi et al. (2024) | Psychiatry Research | Four-month KD improved psychiatric severity and metabolic parameters. |
| Psychiatry & Cognition | Ketogenic Diet Pilot in Bipolar Disorder | Needham et al. (2023) | BJPsych Open | Eight-week KD improved mood stability and metabolic health. |
| Psychiatry & Cognition | Remission of Psychotic Symptoms on Ketogenic Diet (Case Series) | Palmer et al. (2019) | Schizophrenia Research | Reports symptom remission associated with sustained nutritional ketosis. |
| Psychiatry Mechanisms | Brain and Body Energy Metabolism and Potential for Treatment of Psychiatric Disorders | Roberts et al. (2024) | Nature Reviews Neuroscience | Mitochondrial–glial coupling and metabolic stress in psychiatric illness. |
| Systems Biology | Why We Focus on Disease More Than Health | Picard (2020) | Preprint | Reframing health around systems energy regulation and adaptation. |
| Theoretical Neuroenergetics | Brain and Body Energy Metabolism | Raichle et al. (2023) | Nature Reviews Neuroscience | Integration of metabolic demands, glucose/lactate use, mitochondrial efficiency. |
| Women’s Brain Health | Menopause Impacts Brain Energy and Connectivity | Mosconi et al. (2021) | Scientific Reports | Menopause-related declines in cerebral glucose metabolism and connectivity. |
| Women’s Brain Health | Perimenopause and Alzheimer-Like Bioenergetic Shift | Mosconi et al. (2017) | PLOS ONE | Early mitochondrial/metabolic transitions linking estrogen decline to Alzheimer’s risk. |
Note: R-1,3-butanediol human exposure across trials = 113 participants (Avela 24; BH-BD 59; BO-BD 30). Total participants across all modern human trials = 307.
