Ketosis in an evolutionary context
Humans are unique in their remarkable ability to enter ketosis. They’re also situated near the top of the food chain. Coincidence?

During starvation, humans rapidly enter ketosis; they do this better than king penguins, and bears don’t do it at all.

Starvation ketosis

Humans maintain a high level of functionality during starvation. We can still hunt & plan; some would even argue it’s a more finely tuned state, cognitively. And that’s important, because if we became progressively weaker and slower, chances of acquiring food would rapidly decline.

Perhaps this is why fasting bears just sleep most of the time: no ketones = no bueno..?

Observation: chronic ketosis is relatively rare in nature. This doen't mean animals evolved a protective mechanism against ketosis.

Animals with a low brain/carcass weight ratio (ie, small brain) don’t need it. Babies and children have a higher brain/carcass weight ratio, so they  develop ketosis more rapidly than adults. Is this a harmful process?  No, more likely an evolutionary adaptation which supports the brain.

The brain of newborn babies consumes a huge amount of total daily  energy, and nearly half comes from ketones. A week or so later, even after the carbohydrate content of breast milk increases, they still don’t get “kicked out of ketosis” (Bourneres et al., 1986). If this were a harmful state, why would Nature have done this? …and all those anecdotes, like babies learn at incredibly rapid rates… coincidence? Maybe they’re myths.  Maybe not.

Ketosis in the animal kingdom

Imagine a hibernating bear: huge adipose tissue but small brain fuel  requirement relative to body size and total energy expenditure. No  ketosis, because brain accounts for less than 5% of total metabolism. In adult humans, this is around 19-23%, and babies are much higher (eg,  Cahill and Veech, 2003Hayes et al., 2012).

A possible exception to this is ruminant ketosis, but that’s for a different reason. They become ketotic because: 1) their gut turns much of what they eat into a ketogenic diet; and 2) this frequently happens during lactation, which combines very high energy expenditure and an enhanced draw on the OAA pool to make lactose.

Whales? Nope. Despite eating for like, 1 month out of the year, they don’t develop ketosis.

Snakes will enter ketosis, not due to high brain needs per se, but likely because even though small brain, total energy expenditure is so low that brain metabolism easily surpasses the [theoretical] 5%  threshold (McCue 2006):

Fasting baby elephant seals get ketotic, because they’re babies (Castellini and Costa, 1990):

Carnivores (eg, cats) don’t develop ketosis even on very low carb diets, like humans would, which seems to be due to their inability to down regulate protein catabolism (urea cycle takes care of the nitrogen;  gluconeogenesis the carbon)… but they will do so readily during  starvation because of relatively big brains (Blanchard et al., 2002):

Similar to cats, dolphins are carnivorous and also exhibit what appears to be a pathological inability to reduce protein catabolism when necessary.  However, unlike cats, dolphins fail to develop ketosis of any sort, whether it’s on their typical low carb diet of fatty fish, or even complete starvation!

Dolphins are the exception to a lot of rules. I don’t know why. 

Most animals with big brains have the ability to enter ketosis, but none do it as well as humans.

Historically, while intermittent or cyclical ketosis may have been more common than nutritional [chronic] ketosis in humans, this doesn’t mean  one form is better than another. Common =/= optimal.

Starvation ketosis isn’t nutritional ketosis, but much of what we know about the latter stems from our understanding of the former… this is getting better, with more and more studies of longer and longer durations being published regularly. And hint: chronic ketosis doesn’t dissolve bones, deteriorate cognitive function, or break your metabolism. It also doesn't make you superhuman. It's just a different way of eating.

Are ketones the brain’s preferred fuel?

Well, let’s just say this: when there are more ketones than glucose, brain uses more ketones than glucose. This happens in both starvation and nutritional ketosis. Disclaimer: I don't think this can define a "preferred fuel."

Ketosis proportionately spares glucose utilization in the brain (Zhang et al., 2013)

If ketones were harmful, Nature would’ve surely devised a way to protect the brain!

Disclosure: Tbh, I’m not pro-or anti-keto.

Most of the time, I advocate a Hunger-Free Diet for health; LC if obese insulin resistant. Keto for therapeutic, eg, epilepsy. High[ish] protein for  all (ymmv). Seasonal when possible.

Impact of ketones on cognition

Would our ability to plan and set traps to acquire food, or quickly  devise a strategy to escape predation have been negatively impacted  during periods of intermittent or cyclical ketosis?  I think not; more  likely the opposite.  And while I [still] believe the physical feats  required to do these is not hindered after ketoadaptation,  I also [still] believe it’s because we *out-smarted* them, not out-ran  them.  Compared to many other species, humans suck at speed.

Some evidence:

1. acute: in patients with moderate cognitive impairment or Alzheimer’s disease, given 40 mL MCTs to bolster ketones: cognitive performance improved roughly in parallel with increasing ketones (Reger et al., 2004).

2. chronic: 20 grams of Axona (purified MCTs) daily for 90 days improved cognition in people with age-associated memory impairment (Constantini et al., 2008).

3. cruel and unusual: expose a group of type 1 diabetic patients to experimental hypoglycemia and give half 40 grams of coconut oil (which is like a longer-chained version of MCTs) (Page et al., 2009).   Result?  Hypoglycemia impairs cognition; however, this is largely  offset by increasing ketones with coconut oil.  This group experienced  improved: 1) verbal memory; 2) delayed verbal memory; and 3) verbal  memory recognition.

4. nutritional ketosis: 6 weeks of a bona fide  ketogenic diet in patients with mild cognitive impairment = improved  verbal memory performance, and this positively correlated with ketones (Krikorian et al., 2012).

Optimal, harmful, or somewhere in between?  You decide (but if you choose harmful, please provide a link! or at least explain why, very clearly…)

Hint: nutritional ketosis isn’t harmful.  FOR. FIVE. YEARS…  1) that’s not cyclical or intermittent ketosis; and 2) five years is probably much longer than the diet you’re following has been tested for “safety.”

Ketones in evolution

Without our ability to rapidly enter a robust state of ketosis, we wouldn’t be here, or we’d be some weaker subhuman species.  But ketones have been around for a while… some bacteria store energy in the form of poly-beta-hydroxybutyrate.  Some prokaryotes use ketones instead  of triacylglycerols. Archaea also use ketones; and they’ve been around  for billions of years…  it’s estimated that we’ve been doing it for quite a long time, too (from evidence on when our brain would’ve surpassed the [theoretical] threshold). I’d cite a study by George Cahill here, and maybe you’d read it. But you should really read all of the studies by George Cahill (it’s not a-whole-lot). Sorry, I know that sounds ‘preachy.’

Would ketosis have hindered our ability to hunt prey and avoid  predation? My thoughts on our ability to perform high intensity physical activity after ketoadaptation have been thoroughly expressed in the past.  And ketosis clearly doesn’t hinder cognitive functioning.

So, from both a mental and physical perspective, ketosis, chronic or  otherwise, probably didn't hinder us from becoming who we are. It may have contributed to how we did so by delaying death by starvation. 

And seafood.

That's all for now!

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