Bill W. Brazil Blog: What Are Exogenous Ketones and Who Should Take Them?

Interest in the ketogenic diet is at an all-time high, and for good reason. It’s a great way to lose body fat, gain steady energy throughout the day, increase fat-burning capacity at rest and during exercise, reduce inflammation, and improve cognitive function. Keto also has a number of promising medical applications, including seizure control, enhanced efficacy of chemotherapy, and abatement of age-related cognitive impairment.

But going keto takes work. You have to overhaul your diet, restrict certain classes of foods, and pay close attention to what you eat. People prefer to avoid work if they can. They like shortcuts. Exogenous ketone supplements promise a shortcut—swallow this pill or mix this powder into your water and see your ketones skyrocket without changing the rest of your diet.

Although I’ve discussed exogenous ketones in the past, I’ve had many readers ask for a straightforward primer and takeaway recommendations for exogenous ketones. Here it is. Before I evaluate the proper role of ketone supplements, let’s dig into some basic questions.

What Are Exogenous Ketones?

There are two main types: ketone esters and ketone salts.

Ketone esters are ketone bodies bonded to an alcohol molecule. They taste terrible but are more potent than ketone salts. The rise in ketones after ketone ester supplementation is more pronounced but doesn’t last as long.

Ketone salts are ketone bodies bonded to a salt, such as sodium, magnesium, or potassium. They taste better (but not good) but are less potent than esters. The rise in ketones after ketone salt supplementation doesn’t get as high but lasts longer.

Do They Work?

Exogenous ketones increase blood, urine, and breath levels of ketone bodies. In that sense, they “work.”

Are they an effective substitute for actually following a ketogenic diet? Probably not.

First, there’s something unnatural about having elevated levels of ketones and glucose together. It’s really hard to make that happen using traditional whole foods. The closest natural approximation you could get to it would be the traditional coconut-rich diets of the Kitava people in the South Pacific, where the medium chain triglycerides (MCT) in the coconut fat increased ketone production alongside the carbs in the fruit and tubers they ate. They had excellent metabolic health, but they weren’t anywhere close to a ketogenic diet. Coconut fat isn’t as ketogenic as purified MCT oil, let alone exogenous ketones.

That alone gives me pause. The evolutionary novelty raises my hackles.

Second, there are inherent metabolic differences between boosting ketones via diet and boosting ketones via supplements. On a ketogenic diet, ketones go up because you’re converting body and dietary fat into ketone bodies. A rise in endogenous ketones means you’re burning fat and building the requisite machinery to metabolize the new energy source. On exogenous ketones, ketones go up because you ate some ketones; conversion of body and dietary fat into ketone bodies goes down if anything.

Take this study where human volunteers drank either ketone ester or ketone salt beverages alongside their normal diet. It worked. They got into ketosis, showed elevated levels of ketone bodies, and did this without changing their diet. Their conclusion says it all: “exogenous ketone drinks are a practical, efficacious way to achieve ketosis.”

Another effect of the ketone drinks was to lower blood glucose, free fatty acids, and triglyceride levels. This sounds great. Elevated levels of all those markers are harbingers of disease, particularly if they remain chronically elevated. But think about what this means. If free fatty acids go down, that means adipose tissue isn’t being liberated for burning.

That’s exactly what ketones do: inhibit lipolysis, the breakdown of body fat into triglycerides and free fatty acids for burning. In normal conditions where ketones are produced endogenously, this is expected and beneficial. If homemade ketones increased lipolysis, you’d end up with ketoacidosis. You’d make ketones which released more body fat which got turned into more ketones which released more body fat which became more ketones. And on and on. It simply wouldn’t stop.

But if you’re taking exogenous ketones to lose weight, you’re going to be disappointed.

Although they aren’t officially classified as a macronutrient, they are a source of energy. If you’re consuming exogenous ketones, you’re burning less of another energy source. And you’re making less ketones.

That’s not to suggest that exogenous ketones are useless. They have many potential uses, as I’ll explain. They just aren’t the same as getting into ketosis using diet or fasting.

What Are Their Practical Benefits?

Exogenous ketones can lower appetite during a fast. After an overnight fast, normal weight human subjects either drank a ketone ester supplement or a calorie-matched glucose drink. Compared to the glucose drinkers, the ketone drinkers had lower insulin, lower ghrelin, greater satiety, and less hunger. This can be useful for people trying to extend their fast who don’t want to or can’t yet deal with the hunger. You’re still taking in energy, but the metabolic profile remains similar to that of a fasted person.

Exogenous ketones can acutely improve the glucose response. After an overnight fast, healthy, normal weight humans drank a ketone ester supplement which spiked their ketone levels up to 3.2 and remained elevated throughout the oral glucose tolerance test. This reduced their blood glucose response and increased their insulin sensitivity.

Exogenous ketones can suppress expression of an inflammatory pathway linked to several disease states, including arthritis.

As it stands now, there are two areas where exogenous ketones show great potential.

Where Do Exogenous Ketones Make the Most Difference?

Medical Applications

For whatever reason, many patients won’t attempt a ketogenic diet—even if the evidence is clear that it could help. Doctors are often hesitant to recommend dramatic dietary shifts—even if they believe in their efficacy—to patients who are already dealing with difficult health issues. If you’ve got a picky kid with epilepsy, a pickier adult with Alzheimer’s, or a cancer patient who refuses to give up the familiar-yet-non-ketogenic foods that give him some small manner of comfort in this trying ordeal, exogenous ketones could make a big difference.

The human studies aren’t quite there yet, but it seems likely that they’d help. A recent human case study found that ketone esters added to the regular diet improved Alzheimer’s symptoms. Animal studies indicate that adding exogenous ketones to a regular lab (read: not ketogenic) diet can reduce seizure activity and improve overall symptoms in epilepsy animal models, reverse early neuronal hyperactivity in Alzheimer’s animal models, and reduce anxiety in rats.

High Performance Endurance Athletics

Alongside a normal high-carb athlete’s diet, the provision of exogenous ketones before a race increased performance over carbohydrate alone. It increased fat utilization and preserved glycogen reserves until the later part of the race—just like fat-adapted training, only with carbs in the diet.

Exogenous ketones don’t seem to improve high-intensity, glucose-intensive exercise, increasing fat burning during steady state exercise but dropping top-end high-intensity performance. Another study found that ketone dieters reduced 50-minute time trial performance in cyclists, though another group of researchers have criticized the methods. Even when a ketone ester didn’t improve performance in the shuttle run to exhaustion and 15 meter sprint repeats, it did reduce the drop in brain function following the exercise.

There’s a lot more research coming down the pike in this area, but there’s clearly some efficacy in endurance athletics, and maybe athletics in general.

Suggestions for Purchasing Exogenous Ketone Supplements

Ketone supplement choices include a variety of products with beta-hydroxybutyrate or those containing medium-chain triglycerides (liquid or powder), which will help boost liver ketone production if you’re already following a keto dietary approach. Products with beta-hydroxybutyrate often include additional agents like amino acids or minerals.

As for MCT oil (and oil powders), powder formulations tend to cause less digestive distress (e.g. probiotics), but some folks object to the additional ingredients like sunflower lecithin or soluble corn fiber). Even if you’d like to eventually settle on an oil, I’d recommend starting with a powder to see how you respond and to give your body the chance to adapt over time.

Over the past couple years, I’ve tried a number of ketone supplements, generally to enhance a longer fast or to offer an edge before one of my Ultimate Frisbee evenings. This Kegenix variety is one I’d recommend. I’ve also used Quest Nutrition MCT oil powder with good results as well, but there are plenty of other solid formulations to choose from.

Are There Side Effects?

The most common side effect is GI distress. In my experience, it’s urgent GI distress. If you decide to try an exogenous ketone supplement, do so slowly. Space out your doses. Remain close to a trusted bathroom.

They also taste terrible, although that’s improving. If you don’t think “tastes bad” is a side effect worth mentioning, you haven’t take a shot of ketone esters.

If you take exogenous ketones, use them for something of substantial benefit:

Seizure cessation.
Cognitive improvement in dementia.
Increased fasting tolerance.
High-end performance, especially endurance training.

But don’t sit around and take ketone esters or salts because you want to “bump your ketones up” for some vague reason. Or because you think they’ll be a miracle weight loss supplement (they won’t be). Have a purpose. Give those ketones something to do. Have a specific, appropriate, research-affirmed job for them.

Finally, don’t expect them to be a replacement for regularly spending time in an endogenously-ketogenic state. Living keto is considerably more effective than trying to supplement your way to it.

Thanks for stopping in, everybody. I’d love to hear your thoughts and questions. As I mentioned, I intended this as a basic primer for beginners and visitors to the site. (Welcome, by the way!) If questions warrant, I’ll do a follow-up post that gets more granular.