Exogenous Ketones: To Ketone or Not To Ketone

My thoughts on Exogenous Ketones

After being contacted (following the Youtube Q&A) by several folks – both members of Ketogains and Internet strangers, I felt compelled to write as fair and even-handed a write-up on exogenous ketone supplementation as I feel can be mustered. I condition my response by saying this – I want to deal only in evidence and hypotheses grounded in biochemistry.

I admit up front that this will probably become something of a treatise on what constitutes a well-formulated ketogenic diet. I don’t have the time (or the energy) to put together a document that covers all facets of the use of exogenous ketones in sufficient depth, so what I want to do is to address the folks that I see asking me about them most often – those who have excess body fat, and are looking to lose weight. They have been told about the potential benefits to fat loss via exogenous ketones, and they want to know if the hype is real. Those of you who know me (or read my previous post here) know that I like to respond with “it depends.” So…when the question is raised, “Should I supplement with exogenous ketones?” what do you think my answer will be? Probably not! (HA, I tricked you!)…but let’s explore why.

As I’m sure this is going to be hotly debated enough (as the topic is raging in numerous ketogenic groups) there isn’t any value in dealing with speculation that doesn’t have a basis in science, nor in anecdotes. The challenge in dealing with exogenous ketone supplementation is two-fold:

  1. One side of the debate has a product to sell. Anytime someone’s livelihood is tied to your purchase of their product, bias and subjective interpretation of the evidence should be considered.
  2. The evidence (either for or against) their supplemental use by average schleps like us is extremely limited. This is largely due to the newness of the synthesis of exogenous ketones and a heavy focus of research funding on their medicinal, not ergogenic supplementation.
So let’s start with what we can say…what are the areas where exogenous ketone use has the most promise?
  • Medical Treatment – The bulk of the research into the supplementation of exogenous ketone has had its origins in the treatment of conditions such as cancer, epilepsy, and Alzheimer’s/dementia.
  • Top-Level Performance – For those who are putting in the efforts (and possess the superior genetics for) high-level performance in a sport of their choosing, who want to remain ketogenic, the use of exogenous ketones could provide additional fuel source for the body.

If you notice, not one of the promising uses of exogenous ketones has to do with the loss of fat. Nor was one about “getting into ketosis faster!” Let’s take a look at what nutritional ketosis is.

Ketosis happens, in otherwise healthy individuals, when the levels of glycogen in the liver are diminished. When this occurs, the body (without the presence of carbohydrate) increases glucagon, which shifts the I/G ratio, and since glucagon is the “liberating hormone” (as opposed to insulin as the “storage hormone”) fatty acids (stored as triglyceride in adipocytes) are released into the blood stream, find their way to the liver where “the magic happens” and they are converted to ketone bodies. Ketone bodies’ primary purpose is as an alternative fuel source to spare glucose for the tissues of the body that can be fueled ONLY by glucose. They work in symbiosis with gluconeogenesis to ensure that even during times of true fasting or modified fasting (which is the essence of what a low carb diet is for those seeking to lose fat) so that the body can spare muscle mass and sustain itself for long periods of time without food.

The question is begged, then, how difficult a metabolic state ketosis is to enter into and sustain. The longer answer has been touched on by Dustin Sikstrom in a previous article, but in short – in the absence of significant amounts of carbohydrate, the avoidance of substantial excesses of protein, and the consumption of a contextually appropriate amount of fat, pretty darn easy.
Now let’s consider what exogenous ketone supplementation is.

An individual (who may or may not otherwise be in ketosis depending on their diet) consumes a drink that is comprised of some amount of beta-hydroxybutyrate mixed in with some flavoring, some other “stuff” like MCT oil, and voila…magic ketosis right? Well…no. Remember the requirements for someone to be in nutritional ketosis. Without a depleted liver glycogen level, altered I/G ratio, and the liberation of fats from the adipocytes – the person is NOT in a state of ketosis. So what happens when they drink the juice? Stand back, here comes the science (Apologies to Ben Affleck!): when you consume a drink chock-full of beta-hydroxybutyrate (BOHB), the BOHB is oxidized via beta-hydroxybutyrate dehydrogenase into Acetoacetic Acid (ACAC). The bulk of the ACAC is decarboxylated via acetoacetate decarboxylase into acetone. Some trace amounts remain as ACAC, and because of this, reagent test strips (the ketostix that you purchased) test positive. The process seems to occur fairly quickly, with the maximum time that one is “in ketosis” via this method being about 3-6 hours, depending on a number of factors. Given the cost and marketing methods of the supplementation of exogenous ketones, I’m reminded of a drug dealer telling someone, “the first hit’s always free!”

Moving on, let’s consider the marketing methods and cost of the supplementation of exogenous ketones. Depending upon your source, whether through the use of one of the ever-increasing number of multi-level marketing firms or from a non-MLM source, the price per month can range from around $100 to over $300 per month. Much of this is also dependent up on the number of servings per day that someone consumes. If we ignore the egregious cost of the supplementation, we have to move into the discussion of the aggressive marketing of these products by a number of their VIP Platinum Original Gangsta Triple-Dipped Double-Secret Ambassadors has floored me. Not only is their lack of understanding of the basic biochemistry of ketosis astounding (I’ve watched the YouTube videos and discussed at length with several of them), the truly scary part is that they are convinced that the product that they have purchased is well-researched for fat loss and all sorts of amazing unicorn tears of medical wonderment. And unless they are epileptic, cancer-stricken, or suffering from Alzheimer’s – there is NO current peer-reviewed study which can substantiate those claims.

The last topic I want to tackle may be the most controversial topic in this article. That of whether ketone supplementation can, by itself, cause fat mobilization…that is, can I drink my way to fat loss? In a word, no. In the presence of dietary carbohydrate (assuming that someone isn’t drinking fructose syrup), in a carbohydrate-fed state (this is especially true of highly insulin resistant folks) insulin levels will be high enough to prevent the mobilization of stored body fat from adipocytes. The next question, then, is, “If I am eating a ketogenic diet and supplement with exogenous ketones, will I lose MORE fat?” Again, in a word, no. In fact, given the body’s natural response to significantly elevated blood ketones is to increase insulin secretion (this the current thinking as to what the feedback mechanism is for the restriction of ketone production to prevent ketoacidosis), supplementing ketone, plus eating to generate ketone bodies would potentially be counterproductive to the mobilization of stored body fat.
So we are left asking the question – when it comes to “the rest of us,” who could benefit from the supplementation of exogenous ketones? After considering the evidence, I’m left with the answer that, “If you are a lean, individual with a favorable set of genes, who is not metabolically damaged, who has been training and performing at a very high level, who wants to supplement additional fuel without the consequences of a carb load, who has a substantial bank account, and who wants to test the boundaries of human performance” then probably you. If you’re an individual who wants an energy pick-me-up or an elixir to help you focus, might I suggest coffee…or (insert shocked facial expression here) simply eat a well-formulated ketogenic diet, become ketoadapted, and enjoy the myriad health benefits.

At present, the jury is still out. What we know is that exogenous ketones are:
  • Likely beneficial for cancer patients, epileptics, and Alzheimer’s patients.
  • Are very expensive.
  • Have likely NO benefit to those who are not also eating a well-formulated ketogenic diet, and only marginal benefits to those who are ketoadapted.
  • Have no currently-published research into their efficacy in fat loss in the obese, and have only recently begun being studied by the University of Tampa Human Performance Lab (shout out to Jacob Wilson, Ryan Lowery, and the rest of the muscle nerds down there!)

And because of the cost, the marginal benefit, and the potential for reduced fat loss for those who need it most…the last question I’ll ask is, why?



A quick Add up by Luis Villaseñor (aka, Darthluiggi) in regards to some “Exogenous Ketones” being sold now as a MLM product:

“I regularly get questions about this or that MLM product, whether it be Advocare, Herbalife, Visalus, Isagenix, or Whateverthehell. I am yet to come across a health/nutrition-related MLM company that doesn’t economize production costs with sub-par nutritional formulations, especially the protein-containing products (for example, MLMs love to use soy as the first ingredient or fructose as the second ingredient). Adding insult to injury, these protein-based products cost at least double that of the leading non-MLM brands that actually use higher-quality protein formulations. To top it all off, these mediocre MLM products are hyped as the best things on the market, and of course they rely on the emotional triggers of zealous testimonials rather than the weight of the scientific evidence. So yeah, my opinion of MLM-based nutritional products is LOL (yes, let the hurt flow through your butt over that)” Alan Aragon on this Facebook Post.

I personally asked Alan about the brand in question…. his reply:

And this is what Dom D’Agostino has to say regarding Exogenous Ketones for Fat Loss: