Changes in regional cerebral blood flow associated with a 45 day course of the ketogenic agent, caprylidene, in patients with mild to moderate Alzheimer's disease: Results of a randomized, double-blinded, pilot study

Torosyan, Nare; Sethanandha, Chakmeedaj; Grill, Joshua D.; Dilley, Michelle; Lee, Jooyeon; Cummings, Jeffrey L.; Ossinalde, Celine; Silverman, Daniel

doi:10.1016/j.exger.2018.07.009

Cited by 53 publications

(44 citation statements)

References 22 publications

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“…Five studies used the Mini-Mental Status Examination [28,31,32,34,38], and four of them utilized the Alzheimer Disease Assessment Scale (ADAS-cog) [31,35,37,38]. Two studies used a neuroimaging (PET) endpoint: regional cerebral blood flow [30] or [11C]-acetoacetate tracer [28].…”

Section: Discussionmentioning

confidence: 99%

“…One can notice that the use of Aβ or tau biomarkers, highly recommended for increasing diagnostic accuracy, was not mentioned in these studies. APOE genotyping was performed in four studies only [28,30,37,38].…”

Section: Effects Of Kd/ks On Weightmentioning

confidence: 99%

“…The number of individuals included varied among studies from 6 to 152 (mean 31.3 ± 38.2). Likewise, the follow-up durations were rather short and heterogeneous, from 0 to 26 weeks (mean 11.2 ± 9) including three studies examining the immediate effect, the same day as the clinical and cognitive examination of KS [28,30,37,38].…”

Section: Clinical Studiesmentioning

confidence: 99%

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Are ketogenic diets promising for Alzheimer’s disease? A translational review

et al. 2020

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Background: Brain amyloid deposition and neurofibrillary tangles in Alzheimer's disease (AD) are associated with complex neuroinflammatory reactions such as microglial activation and cytokine production. Glucose metabolism is closely related to neuroinflammation. Ketogenic diets (KDs) include a high amount of fat, low carbohydrate and medium-chain triglyceride (MCT) intake. KDs lead to the production of ketone bodies to fuel the brain, in the absence of glucose. These nutritional interventions are validated treatments of pharmacoresistant epilepsy, consequently leading to a better intellectual development in epileptic children. In neurodegenerative diseases and cognitive decline, potential benefits of KD were previously pointed out, but the published evidence remains scarce. The main objective of this review was to critically examine the evidence regarding KD or MCT intake effects both in AD and ageing animal models and in humans. Main body: We conducted a review based on a systematic search of interventional trials published from January 2000 to March 2019 found on MEDLINE and Cochrane databases. Overall, 11 animal and 11 human studies were included in the present review. In preclinical studies, this review revealed an improvement of cognition and motor function in AD mouse model and ageing animals. However, the KD and ketone supplementation were also associated with significant weight loss. In human studies, most of the published articles showed a significant improvement of cognitive outcomes (global cognition, memory and executive functions) with ketone supplementation or KD, regardless of the severity of cognitive impairments previously detected. Both interventions seemed acceptable and efficient to achieve ketosis. Conclusion: The KD or MCT intake might be promising ways to alter cognitive symptoms in AD, especially at the prodromal stage of the disease. The need for efficient disease-modifying strategies suggests to pursue further KD interventional studies to assess the efficacy, the adherence to this diet and the potential adverse effects of these nutritional approaches.

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Section: Discussionmentioning

confidence: 99%

Section: Effects Of Kd/ks On Weightmentioning

confidence: 99%

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Are ketogenic diets promising for Alzheimer’s disease? A translational review

et al. 2020

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“…It was recently demonstrated that mice treated with a ketogenic diet experienced a significant increase in CBF, and this may have been mediated via the mechanistic target of rapamycin (mTOR) and endothelial nitric oxide synthase (eNOS) pathway paralleling beneficial changes to the gut microbiota . Supplementation with medium chain triglycerides (known to increase blood levels of ketones) has been shown to enhance regional CBF in humans with Alzheimer's disease . Ketone‐mediated improvements in CBF have significant potential to alleviate the metabolic supply and demand mismatch seen after mTBI.…”

Section: Mtbi Pathophysiology and Potential Therapeutic Role For Ketosismentioning

confidence: 99%

“…The efficacy of this practice has been well‐validated and is still commonly used . The ketogenic diet has also demonstrated promise in research with other neurological diseases such as Alzheimer's disease and Parkinson's disease …”

Section: Introductionmentioning

confidence: 99%

Therapeutic ketosis for mild traumatic brain injury

Crownover

Holland

2019

Transl Sports Med

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Traumatic brain injuries (TBIs) are common in the United States, especially in the athlete and pediatric populations. Treatment options to expedite the recovery process are limited. The immediate disruption of cellular metabolism in the brain contributes to the pathophysiological cascade that occurs after a TBI. Recent studies show that providing ketone bodies via supplementation, a very-low-carbohydrate diet, or fasting improves cellular metabolism and reduces the pathophysiological features of a TBI. The current review presents the damaging physiological processes that occur after a mild TBI and illustrates the potential therapeutic nature of ketosis as it relates to each occurrence including ionic imbalance, mitochondrial dysfunction, metabolic deficiencies, oxidative stress, cerebral blood flow, and neuroinflammation. K E Y W O R D Sbeta-hydroxybutyrate, cerebral metabolism, concussion, ketogenic diet, traumatic brain injury How to cite this article: Emery Joseph Crownover J, Holland AM. Therapeutic ketosis for mild traumatic brain injury. Transl Sports Med. 2019;2:279-286.

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Safety and target engagement profile of two oxaloacetate doses in Alzheimer's patients

Vidoni

Choi

Lee

et al. 2020

Alzheimer's & Dementia

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Introduction: Brain bioenergetics are defective in Alzheimer's disease (AD). Preclinical studies find oxaloacetate (OAA) enhances bioenergetics, but human safety and target engagement data are lacking. Methods: We orally administered 500 or 1000 mg OAA, twice daily for 1 month, to AD participants (n = 15 each group) and monitored safety and tolerability. To assess brain metabolism engagement, we performed fluorodeoxyglucose positron emission tomography (FDG PET) and magnetic resonance spectroscopy before and after the intervention. We also assessed pharmacokinetics and cognitive performance. Results: Both doses were safe and tolerated. Compared to the lower dose, the higher dose benefited FDG PET glucose uptake across multiple brain regions (P < .05), and the higher dose increased parietal and frontoparietal glutathione (P < .05). We did not demonstrate consistent blood level changes and cognitive scores did not improve. Conclusions: 1000 mg OAA, taken twice daily for 1 month, is safe in AD patients and engages brain energy metabolism.

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Changes in regional cerebral blood flow associated with a 45 day course of the ketogenic agent, caprylidene, in patients with mild to moderate Alzheimer's disease: Results of a randomized, double-blinded, pilot study

Cited by 53 publications

References 22 publications

Are ketogenic diets promising for Alzheimer’s disease? A translational review

Are ketogenic diets promising for Alzheimer’s disease? A translational review

Therapeutic ketosis for mild traumatic brain injury

Safety and target engagement profile of two oxaloacetate doses in Alzheimer's patients

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Changes in regional cerebral blood flow associated with a 45 day course of the ketogenic agent, caprylidene, in patients with mild to moderate Alzheimer's disease: Results of a randomized, double-blinded, pilot study

Cited by 53 publications

References 22 publications

Are ketogenic diets promising for Alzheimer’s disease? A translational review

Are ketogenic diets promising for Alzheimer’s disease? A translational review

Therapeutic ketosis for mild traumatic brain injury

Safety and target engagement profile of two oxaloacetate doses in Alzheimer's patients

Contact Info

Product

Resources

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Changes in regional cerebral blood flow associated with a 45 day course of the ketogenic agent, caprylidene, in patients with mild to moderate Alzheimer's disease: Results of a randomized, double-blinded, pilot study