Ketone Supplement Fundamentals # 3 | Yasser Kashef

Ketone Supplement Fundamentals # 3

Ketone Supplement
Ketone Supplement

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

Acetoacetate Diester 

Research on Acetoacetate Diester

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? 

Acetoacetate Diester 

The second type of ketone ester is the acetoacetate (AcAc) diester (1,3-butanediol acetoacetate diester)—a sodium-free precursor to the ketone acetoacetate. Compared to the BHB monoester, AcAc diester results in lower blood BHB levels (about 1mM) and may result in a few more side effects. Most common among these are gastrointestinal related issues.25 

Research on Acetoacetate Diester

The AcAc diester has much fewer data to support or refute its use when compared to other ketone supplements. 

In terms of athletic performance, results are inconclusive or non-existent. One study showed that ingestion of a 1,3 butanediol AcAc diester before a 31 kilometer cycling time trial actually impaired performance around 2%. However, this wasn’t likely due to the athletes being in ketosis, but rather the side effects. Several of the study’s participants complained of gut discomfort that likely put a hamper on their ability to perform.25 

More research has been done in the area of neurological health. Studies have shown that ketosis achieved with an AcAc diester is able to delay the onset of seizures from central nervous system toxicity in rats26 and lead to lower seizure activity and improved brain plasticity in a mouse model of neurological disease.27 

The research is pretty convincing in favor of the use of AcAc diester to treat neurological conditions and benefit cognition, while less supportive of its use for exercise performance.

General Benefits of Exogenous Ketones: How do They Compare to Nutritional Ketosis?

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. 

Choosing the Best Ketone Supplement

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.

Considerations for Athletes

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.

Consideration for General Health

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. 

Are Exogenous Ketones for You? 

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

1.Cahill, G.F., Jr. (2006). Fuel metabolism in starvation. Annu Rev Nutr 26, 1-22.
2.St-onge MP, Mayrsohn B, O’keeffe M, Kissileff HR, Choudhury AR, Laferrère B. Impact of medium and long chain triglycerides consumption on appetite and food intake in overweight men. Eur J Clin Nutr. 2014;68(10):1134-40.
3.Kinsella R, Maher T, Clegg ME. Coconut oil has less satiating properties than medium chain triglyceride oil. Physiol Behav. 2017;179:422-426.
4.St-onge MP, Jones PJ. Greater rise in fat oxidation with medium-chain triglyceride consumption relative to long-chain triglyceride is associated with lower initial body weight and greater loss of subcutaneous adipose tissue. Int J Obes Relat Metab Disord. 2003;27(12):1565-71.
5.Baba N, Bracco EF, Hashim SA. Enhanced thermogenesis and diminished deposition of fat in response to overfeeding with diet containing medium chain triglyceride. Am J Clin Nutr. 1982;35(4):678-82.
6.St-onge MP, Lamarche B, Mauger JF, Jones PJ. Consumption of a functional oil rich in phytosterols and medium-chain triglyceride oil improves plasma lipid profiles in men. J Nutr. 2003;133(6):1815-20.
7.Henderson, S.T., Vogel, J.L., Barr, L.J., Garvin, F., Jones, J.J., and Costantini, L.C. (2009). Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond) 6, 31.
8.Ivy JL, Costill DL, Fink WJ, Maglischo E. Contribution of Medium and Long Chain Triglyceride Intake to Energy Metabolism During Prolonged Exercise. Int J Sports Med. 1980;01(01):15-20.
9.Rodger, S., Plews, D., Laursen, P., and Driller, M. (2017). The effects of an oral β-hydroxybutyrate supplement on exercise metabolism and cycling performance.
10.O’Malley, T., Myette-Cote, E., Durrer, C., and Little, J.P. (2017). Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males. Applied Physiology, Nutrition, and Metabolism, 1-5.
11.Plecko, B., Stoeckler-Ipsiroglu, S., Schober, E., Harrer, G., Mlynarik, V., and Gruber, S. (2002). Oral beta-hydroxybutyrate supplementation in two patients with hyperinsulinemic hypoglycemia: monitoring of beta-hydroxybutyrate levels in blood and cerebrospinal fluid, and in the brain by in vivo magnetic resonance spectroscopy. Pediatr Res 52.
12.Van Hove, J.L.K., Grunewald, S., Jaeken, J., Demaerel, P., Declercq, P.E., Bourdoux, P., Niezen-Koning, K., Deanfeld, J.E., and Leonard, J.V. (2003). D,L-3-hydroxybutyrate treatment of multiple acyl-CoA dehydrogenase deficiency (MADD). Lancet 361, 1433-1435.
13.Kesl, S.L., Poff, A.M., Ward, N.P., Fiorelli, T.N., Ari, C., Van Putten, A.J., Sherwood, J.W., Arnold, P., and D’Agostino, D.P. (2016). Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague–Dawley rats. Nutr. Metab. 13, 9.
14.Ari, C., Kovács, Z., Juhasz, G., Murdun, C., Goldhagen, C.R., Koutnik, A.P., Poff, A.M., Kesl, S.L., and D’Agostino, D.P. (2016). Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats. Front. Mol. Neurosci. 9, 137.
15.Caminhotto, R.d.O., Komino, A.C.M., de Fatima Silva, F., Andreotti, S., Sertié, R.A.L., Boltes Reis, G., and Lima, F.B. (2017). Oral β-hydroxybutyrate increases ketonemia, decreases visceral adipocyte volume and improves serum lipid profile in Wistar rats. Nutr. Metab. 14, 31.
16.Stubbs, B.Cox, P.; Evans, R.; Santer, P.; Miller, J.; Faull, O.; Magor-Elliott, S.; Hiyama, S.; Stirling, M.; Clarke, K. (2017). On the metabolism of exogenous ketones in humans. Front. Physiol.
17.Strazzullo, P., D’Elia, L., Kandala, N.B., and Cappuccio, F.P. (2009). Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies. BMJ 339, b4567.
18.Evans M, Patchett E, Nally R, Kearns R, Larney M, Egan B. Effect of acute ingestion of β-hydroxybutyrate salts on the response to graded exercise in trained cyclists. Eur J Sport Sci. 2018:1-11.
19.Cox, P.J., Kirk, T., Ashmore, T., Willerton, K., Evans, R., Smith, A., Murray, Andrew J., Stubbs, B., West, J., McLure, Stewart W., et al. (2016). Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metabolism 24, 1-13.
20.Holdsworth, D.A., Cox, P.J., Kirk, T., Stradling, H., Impey, S.G., and Clarke, K. (2017). A Ketone Ester Drink Increases Postexercise Muscle Glycogen Synthesis in Humans. Med Sci Sports Exerc.
21.Vandoorne, T., De Smet, S., Ramaekers, M., Van Thienen, R., De Bock, K., Clarke, K., and Hespel, P. (2017). Intake of a Ketone Ester Drink during Recovery from Exercise Promotes mTORC1 Signaling but Not Glycogen Resynthesis in Human Muscle. Front. Physiol. 8, 310.
22.Poffé C, Ramaekers M, Van thienen R, Hespel P. Ketone ester supplementation blunts overreaching symptoms during endurance training overload. J Physiol (Lond). 2019;597(12):3009-3027.
23.Myette-Cote E, Neudorf H, Rafiei H, Clarke K, Little JP. Prior ingestion of exogenous ketone monoester attenuates the glycaemic response to an oral glucose tolerance test in healthy young individuals. LID – 10.1113/JP275709 [doi]. 2018(1469-7793 (Electronic)).
24.Stubbs BJ, Cox PJ, Evans RD, Cyranka M, Clarke K, De wet H. A Ketone Ester Drink Lowers Human Ghrelin and Appetite. Obesity (Silver Spring). 2018;26(2):269-273.
25.Leckey, J.J., Ross, M.L., Quod, M., Hawley, J.A., and Burke, L.M. (2017). Ketone Diester Ingestion Impairs Time-Trial Performance in Professional Cyclists. Front. Physiol. 8, 806.
26.D’Agostino, D.P., Pilla, R., Held, H.E., Landon, C.S., Puchowicz, M., Brunengraber, H., Ari, C., Arnold, P., and Dean, J.B. (2013). Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 304, R829-836.
27.Ciarlone SL, Grieco JC, D’agostino DP, Weeber EJ. Ketone ester supplementation attenuates seizure activity, and improves behavior and hippocampal synaptic plasticity in an Angelman syndrome mouse model. Neurobiol Dis. 2016;96:38-46.
28.Nosaka N, Suzuki Y, Nagatoishi A, Kasai M, Wu J, Taguchi M. Effect of ingestion of medium-chain triacylglycerols on moderate- and high-intensity exercise in recreational athletes. J Nutr Sci Vitaminol. 2009;55(2):120-5.
29.Wang Y, Liu Z, Han Y, Xu J, Huang W, Li Z. Medium Chain Triglycerides enhances exercise endurance through the increased mitochondrial biogenesis and metabolism. PLoS ONE. 2018;13(2):e0191182.


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