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Study · Measured the body's own peptide · 2017

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Ketone-Based Metabolic Therapy: Is Increased NAD+ a Primary Mechanism?

Elamin M, Ruskin DN, Masino SA, Sacchetti P

Frontiers in molecular neuroscience14 Nov 2017Cited by 80 (Europe PMC)

PMID29184484 (opens in a new tab)PMCIDPMC5694488 (opens in a new tab)DOI10.3389/fnmol.2017.00377 (opens in a new tab)PepBankPUB-29184484
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Summary

The ketogenic diet's (KD) anticonvulsant effects have been well-documented for nearly a century, including in randomized controlled trials. Some patients become seizure-free and some remain so after diet cessation. Many recent studies have explored its expanded therapeutic potential in diverse neurological disorders, yet no mechanism(s) of action have been established. The diet's high fat, low carbohydrate composition reduces glucose utilization and promotes the production of ketone bodies. Ketone bodies are a more efficient energy source than glucose and improve mitochondrial function and biogenesis. Cellular energy production depends on the metabolic coenzyme nicotinamide adenine dinucleotide (NAD), a marker for mitochondrial and cellular health. Furthermore, NAD activates downstream signaling pathways (such as the sirtuin enzymes) associated with major benefits such as longevity and reduced inflammation; thus, increasing NAD is a coveted therapeutic endpoint. Based on differential NAD+ utilization during glucose- vs. ketone body-based acetyl-CoA generation for entry into the tricarboxylic cycle, we propose that a KD will increase the NAD+/NADH ratio. When rats were fed ad libitum KD, significant increases in hippocampal NAD+/NADH ratio and blood ketone bodies were detected already at 2 days and remained elevated at 3 weeks, indicating an early and persistent metabolic shift. Based on diverse published literature and these initial data we suggest that increased NAD during ketolytic metabolism may be a primary mechanism behind the beneficial effects of this metabolic therapy in a variety of brain disorders and in promoting health and longevity.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study1

No result from this study comes from a test of the peptide.

Natural levels measured1

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

  1. 01AnimalEndogenous levelAnimal study (in vivo)Other

    In rats fed a ketogenic diet, hippocampal NAD+/NADH ratio increased at 2 days and remained elevated at 3 weeks.

    In plain wordsIn rats, a ketogenic diet increased the natural NAD+/NADH ratio in the hippocampus.

    Peptide
    NAD+ (nicotinamide adenine dinucleotide)
    Outcome
    IncreaseHippocampal NAD+/NADH ratio
    Study

    ratn: not reported in source

    hippocampus
    Outcome group
    Mitochondrial function · Nervous system and cognition

    Source sentences

    Summary
    When rats were fed ad libitum KD, significant increases in hippocampal NAD+/NADH ratio and blood ketone bodies were detected already at 2 days and remained elevated at 3 weeks, indicating an early and persistent metabolic shift.

    This result measures the body's own NAD+ (nicotinamide adenine dinucleotide). Nobody was given the peptide. It is not evidence about taking it.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    14 Oct 2026, 05:02 UTC

    Study results updated

  2. Version 1

    14 Oct 2026, 01:46 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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