Surgery for obesity & metabolic diseases
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Originally published on HVMN by Brady Holmer.
Evolution is likely the reason for ketosis.
This process evolved to enable humans to survive long periods of time without food. Ketosis was a necessity, since without an external source of energy in the form of food, humans would have eventually starved. An evolutionary “work-around” maintained energy stores in the face of deprivation by producing molecules called ketones from the body’s own internal fat stores.
These molecules are now known to have more benefits than just survival.
Table of Contents
What is Ketosis?
Endogenous vs. Exogenous Ketosis
Why Use Exogenous Ketones?
Medium-Chain Triglycerides (MCTs)
Benefits of MCTs: What Does the Research Say?
Disadvantages of MCTs: What Does the Research Say?
General Benefits of Exogenous Ketones: How do They Compare to Nutritional Ketosis?
Choosing the Best Ketone Supplement
Considerations for Athletes
Consideration for General Health
Are Exogenous Ketones for You?
But today, we rarely encounter anything close to nutrient deprivation. Our food-plenty society and high-carb food options ensure many of us are well-fed. We never force our bodies to become “ketogenic”—meaning that it’s actively producing ketones. What a shame, since ketones have a variety of beneficial effects for cell signaling and metabolism.
How then, can we gain the benefits of ketosis? One way is to eat a low-carbohydrate ketogenic diet, a.k.a the “keto diet”, or to fast.
Other avenues into ketosis exist, ways to “hack” evolution and enter ketosis without having to eat a low-carb diet or fast for days on end.
This method involves the use of exogenous ketones (“exo” meaning “from outside”) in the form of supplements. Furthermore, these exogenous ketones and keto supplements can be used to deepen levels of ketosis and provide a fuel source under certain metabolic conditions like fasting.
First, let’s talk about ketones.
Ketones are the products of the breakdown of fats in the body. Under a state of carbohydrate depletion, blood sugar is reduced, insulin levels fall, glucagon and cortisol rise, and fatty acids (FFAs) are liberated into the blood through a process called lipolysis. The increase in blood levels of FFAs is then sensed by the body, and FFAs are then transported to the liver and used in the production of ketone bodies. Three ketones exist: Acetoacetate (AcAc), Beta-hydroxybutyrate (BHB), and Acetone.
Being in ketosis simply means that you have elevated levels of ketones in your blood, usually agreed upon at 0.5mM. Typically, this means elevated AcAc or, more commonly and in greater amounts, BHB.
BHB and AcAc are the ketones mostly referred to when talking about ketosis and, as we will see later on, ketone supplements.
BHB is the ketone present at the highest levels in the blood of a body in ketosis.1 This is significant for two reasons. For one, BHB is more stable than AcAc, and can be transported through the blood to other organs and tissues much more effectively. AcAc can be spontaneously broken down when it’s in the blood, where it forms acetone—a metabolic “waste product” that we excrete in the breath. We can’t use much acetone for energy.
But this doesn’t make AcAc any less important.
In fact, AcAc is the “parent” ketone body—it’s what the body produces first, when the body is entering ketosis, and serves as the precursor for BHB. AcAc produced in the liver is converted to BHB, and then shuttled out and delivered elsewhere. A small amount of AcAc does travel through the circulation to be used as a fuel source, just to a lesser extent than BHB.
The science of ketones can be confusing
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“Am I in ketosis?” This question has a straightforward answer. As mentioned, typically a blood ketone level >0.5mM signifies that the body is producing ketones (or is in ketosis, depending on the route taken).
Route taken? Correct. There are two ways to achieve ketosis—endogenously or exogenously.
Endogenous ketosis (“endo” meaning within”) is achieved through a low-carb high-fat diet (i.e. ketogenic diet) or fasting, in which the body produces its own ketones. The stimulus is dietary carbohydrate restriction, and the response is that we start to burn fat, leading to (eventually) an outflow of ketones from the liver. Since diverse signaling pathways are activated in order to activate endogenous ketosis and in response to it, diverse physiological benefits also occur.
In contrast, exogenous ketosis (“exo” meaning outside) is achieved through the use of dietary ketone supplements and/or intake of certain types of dietary fats. These supplements can boost ketone levels either directly (ketone supplements) or indirectly (MCTs) but either way, elevate levels of blood ketones. Ketosis achieved exogenously can occur even in the absence of a ketogenic diet or prolonged fast. Sounds too good to be true.
Ketosis might be ketosis, but the profiles used to achieve endogenous and exogenous ketosis vary drastically, and therefore have different benefits. There is something to be said about triggering the body to naturally produce ketones vs. “artificial” induction of ketosis. In the former, you’re forcing the body to be “ketogenic” whereas in the latter, you’re in ketosis, but not “ketogenic.” There are benefits to both.
Exogenous ketones are an alternative to physiological ketosis, and can be used in diverse ways to achieve certain mind and body states, almost like ketosis on cue.
While supplements are only chemically synthesized versions of ketones, the structure and function are essentially the same.
But, structural similarities aside, exogenous and endogenous ketosis have varying effects on the body. For instance — exogenous ketone supplementation is likely best for those trying to meet the needs of a ketogenic diet, improve sport performance, or further increase ketone levels on a ketogenic diet or a fast. However, the health benefits of ketosis like increased fat metabolism, weight loss, and some of the other metabolic benefits might only come from lifestyle changes like fasting or a ketogenic diet.
Before diving into the specific forms of exogenous ketones and the nuances of each, let’s discuss some of the general reasons one might choose to use exogenous ketone supplements in the first place.
One of the primary reasons to use exogenous ketones may be to enhance the effects of your low-carb ketogenic diet or intermittent fasting regimen. These practices will likely have you in a ketogenic state already. To further enhance the benefits many people claim to feel when ketogenic/fasting— like mental clarity, sharpness, lower fatigue—exogenous ketones can be superimposed, which essentially means going “deeper” into ketosis.
Exogenous ketones might also be a helpful aid to transition into ketosis when starting out on a ketogenic diet.
Many cite the “keto flu” as a badge of honor one must experience when entering into ketosis. When the body is first adapting to a diet very low in carbohydrates, and not yet fully adapted to burning fat/utilizing ketones, you may experience symptoms like nausea, headache, weakness, irritability, muscle soreness, difficulty sleeping, and irritability. Using an exogenous ketone supplement during your transition into keto may mitigate some of these symptoms by ramping up the level of ketones in your blood to use as an energy source for brain and body. It may also improve energy levels early on in ketosis before adaptation occurs.
And finally, whether endogenously produced or not, ketones have diverse signaling roles in the body that could benefit mental and physical health, metabolism, and longevity, as well as serving as a cellular energy source.
MCTs aren’t ketones, but rather a type of fat molecule comprised of a glycerol bonded to three medium-length fatty acids (FAs) that are 6 - 12 carbons in length.
Why are we talking about these then, if they aren’t ketones?
Well, MCTs are actually pretty good sources for the body to breakdown and turn into ketones. When it comes to ketone production, not all fats are created equal, and longer isn’t always better. Size matters.
The source of fat in MCT oil and other MCT containing fats (like coconut oil) is the most efficient type for producing ketone bodies. The medium chain fats go right to the liver, where they require less work to break down compared to long- and short-chain fatty acids.
You can get your MCTs in two ways: through an MCT oil or powder, or by consuming a rich (and tasty) source of MCTs such as coconut oil.
The MCTs include caproic acid (C6), caprylic acid (C8), capric acid (C10), and lauric acid (C12). Of these, caprylic acid (C8) is preferred for ketone production, and optimally what you should look for when purchasing an MCT oil supplement. Lauric acid is the MCT found most abundantly in coconut oil (about 50% of the total MCTs).
Because of its efficacy, we selected pure C8 a part of the base (along with prebiotic acacia fiber) of HVMN’s MCT Oil Powder. It’s 100% natural, real food, harvested sustainably and carefully purified into pure C8. No additives, no artificial ingredients, zero net-carbs. It’s a great source of MCT without all the other junk you might find in inferior products.
Though marketed as a supplement, one benefit of MCTs is that they’re derived from all natural food sources. For those who are “anti-synthetic,” you have nothing to fear from MCTs.
A powerful benefit of MCT ingestion, like ketone supplements, might be appetite suppression.
MCTs might help blunt hunger and help with calorie and portion control, thereby indirectly helping you adhere to a diet and thus meet your body composition goals.
One study demonstrated that acute intake of MCTs led to reduced food consumption at lunch while also reducing the blood glucose and triglyceride response to the meal.2Interestingly, MCT oil also has a “satiating” effect that is not observed with coconut oil.3
MCTs might directly aid in weight loss as well, outside of general satiety.
This action might be due to the fact that MCT oil supplementation can increase energy expenditure, fat oxidation, metabolism, and thermogenesis (body heat production) which leads to a lower body weight and more fat loss over time.4,5 Furthermore, MCT supplementation might have metabolic benefits like lowering LDL cholesterol and increasing lipoprotein particle size.6
Large amount of MCTs, like any supplement, have been reported to cause gastrointestinal side effects.7,8
This might be an issue, since in order to raise blood BHB to adequate levels to reach ketosis, a high amount of MCTs (and even more coconut oil) must be consumed. Remember, MCTs must be metabolized first before they become ketones—they don’t directly elevate blood ketone levels. Most studies show that MCT consumption elevates blood BHB to levels around 0.5 - 1mM.
Let’s not forget about calories. One downside to coconut oil and MCTs is that they’re fairly calorie-dense, so it’s important to keep track of your macros and calories when using supplements. Compared to ketone salts and ketone esters, MCTs result in much lower levels of ketosis, but they may be a more cost-effective and approachable option for new keto dieters.
The blood levels of BHB that can be achieved through nutritional ketosis (ketogenic diet or fasting) are likely similar to those you can achieve using certain exogenous ketone supplements: about 1 - 3mM. In this regard, your “level” of ketosis might be the same.
However, achieving endogenous ketosis has unique benefits that aren’t achieved with exogenous ketone supplements. One of these is in regards to “fat burning.”
When you achieve endogenous ketosis, you’re using your own body fat as a fuel, and this has several metabolic and health-related benefits.
But, with exogenous ketones, you actually decrease adipose tissue lipolysis (breakdown) and FFA availability—essentially the opposite of what happens when you’re in a ketogenic state.
Thus, exogenous ketones likely have little to no benefit in terms of fat burning and weight loss.
Most exogenous ketone supplement protocols involve taking one “large” bolus of ketones. While this raises blood ketone levels rapidly, it’s not really what happens “naturally” when the body is in a ketogenic state, where blood ketone levels rise more gradually.
It’s unclear what this might mean in terms of metabolic signaling, but there exists a difference in the two ways to achieve ketosis.
While several different ketone supplements are on the market, what you choose may depend on your individual goals. Let’s take a look at which types of supplements might benefit specific groups of people.
If you’re not ready to commit to a ketogenic diet for your training regimen, but are curious about how ketosis might impact your performance, exogenous ketones might be your go-to experiment. Several athletes and sports teams are now using exogenous ketones as a way to fuel performance.
The main thing to consider is the proper time, situation, and adaptations required for exogenous ketone use. How you strategically employ exogenous ketones might make all the difference.
Since BHB monoester (HVMN Ketone Ester) is cleared by WADA (meaning it’s not a “performance enhancing drug”), athletes can rest easy in this regard.
A majority of the positive research for exogenous ketones lends support to HVMN Ketone Ester, where benefits have been shown for endurance performance, enhanced adaptations to training, and in the prevention of overreaching syndrome. Another aspect is cognitive performance; we’ve heard many anecdotal responses that athletes who use HVMN Ketone Ester for training experience a feeling of being “locked in” mentally, too.
Some smaller studies on MCTs suggest they might benefit endurance exercise performance28 and enhance gene expression and mitochondrial biogenesis.29
Data on other supplements such as ketone salts and AcAc diesters is less compelling and in most cases, negative.
The support for exogenous ketones in non-disease states is more in the anecdotal stage right now.
Anecdotal reports include claims of enhanced mental clarity, alertness, energy, and productivity.
None of these claims has been scientifically tested yet. While the theoretical basis might be sound, you’ll have to wait for some trials—until then, experiment for yourself.
A huge role for exogenous ketones might be in dietary adherence, whether that means eating less, eating better, or sticking to a low-carb or ketogenic diet.
Exogenous ketones suppress appetite,24 and might help reduce certain food craving or obliterate those “hangry” feelings. If you’re into fasting and not opposed to consuming ketones on a fast, ketone supplements might help you get through an extended no-food period. Even better, they might deepen your fasting-induced state of ketosis.
Whether you are an athlete looking to boost performance through exogenous ketones, or simply out to harness to power of ketones for better mental or physical performance, there are several questions you should ask before buying and using a ketone supplement.
First, what is your goal? And what level of ketosis do you need to achieve to accomplish those goals? Consider if you want constant low levels of ketones in your blood, or a larger level for a shorter amount of time (for a competition, for example).
Are you looking for something inexpensive? Something palatable? Maybe something that can be integrated into meals and/or other supplements? Or perhaps, even a post-workout smoothie? What about the side effects? If you have had stomach issues with other kinds of supplements in the past, this should be taken into consideration.
Maybe you want to achieve the benefits of ketosis without making a change in your lifestyle, like adopting a low-carb ketogenic diet or becoming a regular intermittent-faster. That’s fine, too—these practices aren’t for everyone, but ketosis can be.
All it takes is a well-formulated exogenous ketone supplement and obviously, a bit of attention paid to maintaining a generally healthy diet and exercise regimen. Your nutrition strategy is an investment in your life.
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Scientific Citations
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Cahill, G.F., Jr. (2006). Fuel metabolism in starvation. Annu Rev Nutr 26, 1-22.
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