The neuroprotective properties of ketone bodies.
There is some overlap between the metabolic effects of calorie restriction (CR) and ketogenic diets (Maalouf et al., 2009). A lot of the underlying mechanisms are related to mitochondrial quality and quantity, anti-apoptotic factors, and neurotrophic factors (eg, BDNF induced by ketosis).

Further, ketone bodies have a direct protective effect against multiple types of neuronal insults in vitro.

The Maalouf review article was basically about the ketogenic diet but they kept mentioning the unpalatability of it ... seriously, they said it like, 3 times ... started to irk me -- HAVE YOU EVER HEARD OF KETODIETAPP and RULEDME. But yeah, in these neurocognitive and psychiatric populations adherence to a ketogenic diet is poor and gets worse with increasing disease severity. So in this #context, I can get behind MCT-supplemented LC and ketone supps.

Obesity* is associated with an increased risk of dementia. Calorie restriction has been shown to improve outcomes in various models of Alzheimer's and Parkinson's disease. It also lowers fasting insulin and has been shown to improve mood.

*Obesity, not carbs. Please don't conflate the two!

Also note some of the animal studies are all over the board. Like, calorie restricted rats who lived longer but had worse cognitive function which was reversed by glucose administration! lol

The main mechanism of keto and CR have to do with improved mitochondrial function which leads to decreased reactive oxygen species (ROS). Increased UCP expression takes the pressure off the mitochondrial proton pump and we also see less ROS coming from complex I. So less brain degradation. And ketone-induced BDNF upregulations so more brain-building.

One weird thing: the authors said the mild hunger experienced when your in an energy deficit activates certain neurons which contributes to the cognitive effects. So if you're losing weight but NOT hungry...?

I like the ROS-attenuating effect of improved mitochondria because ROS can be nasty, messing up protein, lipids, and DNA which all may manifest as neurological disease. A lot of the neurological deficits seen following stroke, head trauma, or even Alzheimer's has been attributed to mitochondrial dysfunction. Those UCPs are quite helpful here and have been associated with longevity and neuronal resistance to ischemic, toxic, traumatic, and epileptic injury.

CR also activates Sirt1 which has shown anti-aging properties in a variety of animal models (remember all the resveratrol hype? yeah, that was thought to be due at least in part, to Sirt1).

BDNF is like Miracle Gro for your brain.

CR per se is anti-inflammatory.

The authors noted that a ketogenic diet OR the energy deficit it facilitates is neuroprotective... so a growing child may not experience these benefits, or an adult in weight-maintenance may not either. It's unclear at this point. In the former #context, I'd be happy being seizure-free. In the latter #context, you should still be getting some BDNF because that's a direct effect of ketones.

Mitochondria are an important target of ketogenic diet action.

Interestingly, the longer you're in ketosis, the better your brain gets at taking up ketones.

Eat seafood :-)

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