Diet modulates brain network stability, a biomarker for brain aging, in young adults

”Targeted experiments show that this biomarker for brain aging is reliably modulated with consumption of different fuel sources: Glucose decreases, and ketones increase the stability of brain networks.”

Listen to the Author Lilianne R. Mujica-Parodi talk about this paper at STEM-Talk podcast [00:59:33] into the podcast.

Diet modulates brain network stability, a biomarker for brain aging, in young adults

Lilianne R. Mujica-Parodi, Anar Amgalan, Syed Fahad Sultan, Botond Antal, Xiaofei Sun, Steven Skiena, Andrew Lithen, Noor Adra, Eva-Maria Ratai, Corey Weistuch, Sindhuja Tirumalai Govindarajan, Helmut H. Strey, Ken A. Dill, Steven M. Stufflebeam, Richard L. Veech, Kieran Clarke

Proceedings of the National Academy of Sciences Mar 2020, 117 (11) 6170-6177; DOI: 10.1073/pnas.1913042117

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Nutrients | Potential Protective Mechanisms of Ketone Bodies in Migraine Prevention | HTML

”An increasing amount of evidence suggests that migraines are a response to a cerebral energy deficiency or oxidative stress levels that exceed antioxidant capacity. The ketogenic diet (KD), a diet mimicking fasting that leads to the elevation of ketone bodies (KBs), is a therapeutic intervention targeting cerebral metabolism that has recently shown great promise in the prevention of migraines.”

Gross, E. C., Klement, R. J., Schoenen, J., D’Agostino, D. P. & Fischer, D. (2019). Potential Protective Mechanisms of Ketone Bodies in Migraine Prevention. Nutrients, 11(4), s. 811.

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Anticatabolic Effects of Ketone Bodies in Skeletal Muscle

”Anticatabolic effects of β-hydroxybutyrate have recently been demonstrated in human skeletal muscle under inflammatory insult, thereby expanding upon the wide-ranging therapeutic applications of nutritional ketosis.”

Koutnik, A. P., D’Agostino, D. P. & Egan, B. (2019). Anticatabolic Effects of Ketone Bodies in Skeletal Muscle. Trends in Endocrinology & Metabolism, 30(4), ss. 227-229. doi:

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Ketone Bodies as a Therapeutic Strategy for Heart Failure: Biophysical Journal

Taken together, we conclude that the shift to ketone body oxidation in heart failure is adaptive and that strategies to increase myocardial ketone body delivery show promise for the treatment of heart failure.


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Press-pulse: a novel therapeutic strategy for the metabolic management of cancer | Nutrition & Metabolism | Full Text


Optimization of dosing, timing, and scheduling of the press-pulse therapeutic strategy will facilitate the eradication of tumor cells with minimal patient toxicity. This therapeutic strategy can be used as a framework for the design of clinical trials for the non-toxic management of most cancers.”
Press-pulse: a novel therapeutic strategy for the metabolic management of cancerThomas N. SeyfriedEmail author, George Yu, Joseph C. Maroon and Dominic P. D’AgostinoNutrition & Metabolism201714:19  The Author(s). 2017Received: 29 September 2016Accepted: 17 February 2017Published: 23 February 2017

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Brain metabolism in health, aging, and neurodegeneration. – PubMed – NCBI

Emerging findings suggest that lifestyles that include intermittent bioenergetic challenges, most notably exercise and dietary energy restriction, can increase the likelihood that the brain will function optimally and in the absence of disease throughout life.”

EMBO J. 2017 Apr 24. pii: e201695810. doi: 10.15252/embj.201695810.

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Ketone bodies are protective against oxidative stress in neocortical neurons – Kim – 2007 – Journal of Neurochemistry – Wiley Online Library


Ketone bodies (KB) have been shown to
prevent neurodegeneration in models of Parkinson’s and Alzheimer’s diseases,
but the mechanisms underlying these effects remain unclear. One possibility is
that KB may exert antioxidant activity. In the current study, we explored the
effects of KB on rat neocortical neurons exposed to hydrogen peroxide (H
2O2) or diamide – a thiol oxidant
and activator of mitochondrial permeability transition (mPT). We found that:
(i) KB completely blocked large inward currents induced by either H
2O2 or diamide; (ii) KB
significantly decreased the number of propidium iodide-labeled cells in
neocortical slices after exposure to H
2Oor diamide; (iii) KB significantly decreased
reactive oxygen species (ROS) levels in dissociated neurons and in isolated
neocortical mitochondria; (iv) the electrophysiological effects of KB in
neurons exposed to H
2Oor diamide were mimicked by bongkrekic acid and cyclosporin A, known
inhibitors of mPT, as well as by catalase and DL
– dithiothreitol, known
antioxidants; (v) diamide alone did not significantly alter basal ROS levels in
neurons, supporting previous studies indicating that diamide-induced neuronal
injury may be mediated by mPT opening; and (vi) KB significantly increased the
threshold for calcium-induced mPT in isolated mitochondria. Taken together, our
data suggest that KB may prevent mPT and oxidative injury in neocortical
neurons, most likely by decreasing mitochondrial ROS production.”

Kim, D. Y., Davis, L. M., Sullivan, P. G., Maalouf, M., Simeone, T. A., Brederode, J. v. and Rho, J. M. (2007), Ketone bodies are protective against oxidative stress in neocortical neurons. Journal of Neurochemistry, 101: 1316–1326. doi:10.1111/j.1471-4159.2007.04483.x

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Rethinking fat as a fuel for endurance exercise. – PubMed – NCBI


…… Beyond simply providing a stable source of fuel for the brain, the major circulating ketone body, beta-hydroxybutyrate, has recently been shown to act as a signalling molecule capable of altering gene expression, eliciting complementary effects of keto-adaptation that could extend human physical and mental performance beyond current expectation ……

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