Not Getting into Ketosis? Try Plain Old Caffeine to Double Your AM Ketone Levels Regardless of High CHO Breakfast

Neither a ketogenic breakfast nor buttered coffee were necessary to double the subjects' ketone production.
Ok, I have to admit that the breakfast that was served in the latest study from the Research Center on Aging, Sherbrooke, CIUSSS de l’Estrie – CHUS and the Department of Pharmacology & Physiology, Universit√© de Sherbrooke in Canada (Vandenberghe. 2016) is not exactly what anyone would recommend to people who are trying to get into full ketosis. This, however, does not make the scientists' observation that the addition of 3mg/kg and 5mg/kg of caffeine in form of cheap caffeine pills from the pharmacy will almost (moderate dose) and more than (high dose) double the subjects' ketone production, does not make the latest study from Camille Vandenberghe's lab less interesting.
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But, let's tackle things one by one: With ketogenic diets getting more and more attention in mainstream dietary research, it is not exactly surprising to see a study that uses the potential therapeutic effects of ketones on aging-induced cognitive impairments in Alzheimer’s disease as a point of departure for their investigation of caffeine "as a potential ketogenic agent" (Vandenberghe. 2016) - or I guess whe should say "ketogenic facilitator".

Owing to its actions on  lipolysis/ lipid oxidation, the scientists expected that caffeine co-ingestion with breakfast would be ketogenic in healthy adult subjects. To test this hypothesis, the authors recruited a group of healthy adults (BMI 24kg/m² | previous daily caffeine intake < 300mg/day!) to evaluate their individual and average response to the acute ingestion of...
  • 2.5 mg/kg caffeine (equiv. to ca. 1.5-3 cups of coffee w/ ~95 mg/cup)
  • 5.0 mg/kg caffeine (equiv. to ca. 3-5 cups of coffee w/ ~95 mg/cup)
alongside the afore-hinted-at standardized breakfast that consisted of  two pieces of toast with raspberry jam, a piece of cheese, applesauce and 100 ml of juice - a breakfast that is, with its 85 grams of carbohydrate, only 9.5 g of fat and 14 g of protein, not exactly "ketogenic".
Figure 1: Ketone production and FFA levels in the control and caffeine 2.5 ad 5.0 mg/kg trials (Vandenberghe. 2016).
As you can see in Figure 1, the bolus of caffeine still elevated both, the concentrations of ketone bodies and free fatty acids in the subjects' blood. And what's even more exciting, the ketone advantage became significantly more (not less) pronounced over time (see Figure 2)
Yes, you remember that correctly: High FFA = lower insulin sensitivity - So eventually, you have to be careful with the caffeine for ketones approach if you consume high amounts of carbohydrates and/or are already having issues with glucose management. If that's not you, I'd like to remind you of the beneficial effects of caffeine on glycogen repletion, I discussed in "Post-Workout Coffee Boosts Glycogen Repletion by Up to 30% and May Even Have Sign. Glucose Partitioning Effects" | more.
This is an observation which would suggest that the breakfast coffee could be even more useful for ketogenic dieters who are intermittently fasting, as it would give them a headstart into full-blown ketosis in the time between breakfast and dinner.
Figure 2: Time course of the ketone response in the study subjects according to treatment (Vandenberghe. 2016).
The observation that caffeine enhances lipolysis and increases blood FFA levels, which in turn provide substrates for ketogenesis ad thus stimulate safe and mild ketonemia in healthy adults to a ketone level twice that seen after an overnight fast, has the authors speculate that regular caffeine consumption may be linked to the decreased risk of developing late-life cognitive decline, as it was observed by Panza, et al. only recently in what is one of the latest reviews on this topic, if not primarily, then at least also because of its effect on ketogenesis.

Eventually, we do yet still need evidence that the "trick" works with a ketogenic diet, as well. After all, the relative increase in the study at hand may be huge, the absolute levels of ketones in the blood, on the other hand, are small (compared to eating a 100% ketogenic diet (=nutritional ketosis), where levels will go up to 0.5 - 3.0 mmol/L), but still impressive in view of the fact that the caffeine was consumed with a high carbohydrate (high GI) breakfast.
Bulletproof coffee is a fad, but is it also bad for your blood lipids? Studies suggest that it's at least not the butter that elevates cholesterol | Learn more!
Bottom line: Yes, it's too early to get all-too-excited, but whence we have (a) the studies to evaluate caffeine’s long-term effect on ketonemia and the corresponding impact on brain function during aging, the authors ask for, as well as (b) insights into potential interactions with the composition of the meal it is co-ingested with, and all that confirms what the study at hand suggests, i.e. that caffeine can double the ketone production in healthy individuals, ketogenic dieters would have all-the-more reasons to cherish their large AM pot of coffee (not necessarily with butter, though; after all the trick works without sign. amounts MCTs and even in the presence of ~90g of carbohydrates) | Leave a comment on the SuppVersity Facebook Page!
  • Panza, Francesco, et al. "Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: a systematic review." The journal of nutrition, health & aging 19.3 (2015): 313-328.
  • Vandenberghe, Camille, et al. "Caffeine intake increases plasma ketones: an acute metabolic study in humans." Canadian Journal of Physiology and Pharmacology (2016) [ahead of print].
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