Ketone Supplement Fundamentals # 2 | Yasser Kashef

Ketone Supplement Fundamentals # 2

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

Ketone Salts

Benefits of Ketone Salts: What Does the Research Say?

Disadvantages of Ketone Salts: What Does the Research Show?

Ketone Esters

D-BHB Monoester (HVMN Ketone Ester)

Ketone Salts

They’re not something you sprinkle on top of your roasted vegetables or use to season your stew. 

Rather, ketone salts are a supplement that comes in powder form, to be mixed (traditionally) in some type of liquid for consumption. Ketone salts contain a ketone (usually BHB) bound to a mineral salt; usually sodium, potassium, calcium, or magnesium or an amino acid-like lysine or arginine. 

Ketone salts are one way to raise blood ketone levels. Studies have shown that ketone salt ingestion can elevate blood BHB levels to around 0.6 – 0.8mM (i.e. ketosis).9,10

Benefits of Ketone Salts: What Does the Research Say?

Ketone salts aren’t a new “invention.” They’ve been around for quite some time, and early studies of these ketone supplements were conducted in children with metabolic disorders, where they showed efficacy in inducing ketosis and an improvement of symptoms like better cardiac performance and cognitive function due to better ability to oxidize fatty acids.11,12 

Similar levels of ketosis around 0.5mM have been observed in rats given BHB ketone salts. Health benefits such as improved blood glucose, beneficial changes in lipid biomarkers and fat mass, and reduced anxiety-like behavior were noted in multiple different studies.13,14,15

Disadvantages of Ketone Salts: What Does the Research Show?

Compared to other ketone supplements, ketone salts might not deliver as much “ketogenic power”—meaning they don’t elevate blood BHB to levels as high as other products. 

For example, one study showed that blood BHB was raised to around 1mM following ketone salt ingestion, while the same amount of BHB provided from a ketone ester raised blood ketone levels to 2.8mM.16 The salt also provided a greater amount of the L-isomer of BHB as opposed to the D-isomer. While not going into the deep end of structural chemistry, L-BHB is like a mirror image of D-BHB (like your left and right hand). They are what is known as optical isomers. While structurally similar, L-BHB may not have the same pattern of metabolism nor the benefits that D-BHB has. 

Another disadvantage with ketone salts has less to do with the ketone element, and more to do with the salt. 

Typically, you’ll need about 50g of BHB in a ketone salt to mimic nutritional ketosis. Given the formulation of many salts, this would require an intake of about 5,800mg magnesium, 9,600mg of calcium, 11,000mg of sodium, and 18,800mg of potassium. Needless to say, these values are above and beyond any recommended daily allowance for humans.

Excessive salt intake may come with health concerns such as high blood pressure and cardiovascular disease in some individuals.17 Regardless, the high dosage of minerals that would accompany the ketone dose consumed with salt makes this form of supplementation less than practical.

And finally, ketone salts may have no benefit for athletic performance and, in the worst cases, actually, impair it.18 

In one study, oral BHB salt ingestion prior to exercise actually led to a 7% decrease in high-intensity cycling performance.10 Even though the participants were in ketosis and oxidizing fat for fuel, they reported massive GI side effects which inhibited optimal performance. This isn’t uncommon; two more studies (one in athletes) reported gastrointestinal side effects in 68% and 50% of participants.18 

So, should anyone use ketone salts? And, if so, who?

These supplements might be best for those already on a ketogenic or very-low-carbohydrate diet and looking to further increase ketone levels—since this would require a lower dose of ketone salts and prevent many of the side effects seen with higher doses.

One final point. Many ketone salts on the market aren’t FDA approved as a “generally recognized as safe” (GRAS) food ingredient. Make sure to do your research before buying any supplement. 

Ketone Esters

While ketone salts are solids, ketone esters come in liquid form and usually contain one of two ketones; BHB or AcAc bound to a ketone precursor such as butanediol or glycerol. 

The word “ester” refers to the specific chemical bond (an ester bond) which attaches the two molecules. The two most popular formulations of ketone esters are the D-BHBmonoester and the AcAc ketone diester. Each of these has its own effects. 

D-BHB Monoester (HVMN Ketone Ester)

The BHB ketone monoester (R-1,3-butanediol-R-3-hydroxybutyrate; BD-BHB) was first invented through a DARPA program called “Metabolic Dominance, with the intent of being used primarily to enhance the endurance and performance of US Soldiers. Through years of research with Oxford University, and the NIH, this ketone supplement can now be purchased and consumed by anyone as HVMN Ketone Ester

In contrast to the BHB salts, the BHB in the ketone monoester is all of the D-isoform. When the ester bond is metabolized, D-BHB is released into the blood along with the ketone precursor butanediol, which is eventually metabolized into D-BHB in the liver. 

The ketone monoester provides the highest levels of blood BHB (around 3 – 6mM) which is achieved rapidly (usually within 30 minutes of ingestion).

And levels stay elevated. Blood BHB following BHB monoester ingestion is ~1.1mM after 4 hours and ~.7mM after 8 hours.16 

 It’s also salt-free, permitted by the world anti-doping agency (WADA), and to date has been shown to be relatively side-effect free at normal doses (meaning no stomach aches!).19,20

Research on HVMN Ketone

To date, many studies have been done (with more in the works) on the BHB monoester in HVMN Ketone Ester. Several of these studies have looked at the effect of ketone ingestion on athletic and physical performance. 

Consumption of HVMN Ketone Ester has been shown to improve endurance exercise performance by 2% – 3% when taken before exercise with carbohydrates.19 In addition to boosting performance directly, HVMN Ketone Ester enhances recovery by boosting post-exercise muscle glycogen replenishment20 and raising post-exercise activation of genes involved in muscle protein synthesis.21 In each case, HVMN Ketone Ester was consumed with either a source of carbohydrates or carbs and protein.

In the most recent study of HVMN Ketone Ester, chronic intake of ketone ester during a period of endurance training overload blunted many symptoms of overtraining, revealing a heretofore unseen potential for this supplement in athletes.22 Athletes were able to go harder in training because they recovered more effectively. 

BHB monoester might also have some metabolic benefits. 

Exogenous BHB lowers blood glucose levels23 and has also been shown to have an appetite-suppressant effect, lowering the desire to eat—this may be related to the reduction in ghrelin (the hunger hormone) after BHB ingestion.24 Many people claim that a ketogenic diet also has many similar effects on satiety. 

Scientific Citations

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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.
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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.
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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.
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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.
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