Ketone Salts: Ketosis with a Cost

Authored by Nate Martins • 
October 19, 2018
ketosisresearchexogenous-ketones

With the snowballing excitement and scientific research surrounding keto, more and more people are trying out the high-fat, low-carb diet for body composition and exercise performance. Maybe you’re one of them. Maybe you’ve also found that maintaining ketosis can be extremely difficult, especially with the Western diet’s love affair with carbohydrates.

You want to optimize the keto diet based on your needs–supplements are a great tool, and can provide a deep state of ketosis faster than through dieting or fasting alone.

The most widely-available on the market are ketone salts, formed when the ketones are bound to a mineral ion (salt), like sodium or potassium. Let’s assess some of the nuances around ketone salt supplements and other types of exogenous ketones to help you make the best decision to optimize ketosis.

Ketones 101

Before launching right into ketosis, it’s important to understand the science behind ketones themselves.

Ketones are a fundamentally different fuel source than the carbohydrates, fat and protein our bodies typically rely on for energy. A highly efficient energy source, the body produces ketones when pushed to its limits; either during extreme carb restriction1 or after heavy exercise.2

Achieving Ketosis

Ketosis is generally defined as elevated blood ketone levels greater than 0.5mM.1 There are two types of blood ketones: endogenous and exogenous ketones. Both ultimately give you a state of ketosis, albeit through very different methods.

Endogenous ketones are produced by the liver, usually spurred by fasting or following a ketogenic diet. A body producing its own ketones naturally could be described as ketogenic.3 The production of endogenous ketones can take weeks or months of strict dieting.1 But there’s a payoff to that patience–the body can become fat-adapted, learning to use fat as fuel when carbohydrate intake is depleted. This process is sometimes referred to as nutritional ketosis.

Taking exogenous ketones can deliver a fast-acting, deep state of ketosis almost immediately.

However, the body isn’t producing its own ketones, so blood levels of ketone don’t remain high many hours after ketone supplementation.

Exogenous ketones are consumed through a supplement or food. They can provide a state of ketosis,4 but the body isn’t ketogenic because the ketones were delivered from an external source (meaning, the body didn’t produce from fat them itself). Exogenous ketones don’t trigger natural ketone production, but they still lead to a elevated blood ketone levels.

Different Types of Ketone Bodies

There are three ketone bodies: beta hydroxybutyrate (BHB), acetone, and acetoacetate (AcAc). Most exogenous ketones close to deliver BHB rather than AcAc because BHB is more stable and easier to make into a sellable product.

Acetoacetate is created in the liver from the breakdown of fatty acids, and is then mostly converted into BHB for transport in the blood. Any AcAc in the blood can be either taken up into the cells or spontaneously broken down to produce acetone–which cannot be used for energy production. Acetone is removed from the body through waste product like urine, or through the breath.

BHB is the ketone body present in the blood at the highest level when produced naturally.5 This is because it doesn’t spontaneously degrade like AcAc . Once taken up into the cells from the blood BHB offers the advantage of being more reduced than AcAc. This means that when BHB is converted into AcAc inside the cell’s mitochondria, it generates NADH–a coenzyme needed for ATP production. AcAc whiffs on the energy-providing power of NADH. Plus, when an AcAc-based supplement is consumed, the body will reverse-convert some of to BHB, which actually uses up those NADH, maybe even compromise ATP production.

Generally, the body selects BHB as its ketone of choice for transporting throughout the blood, likely because BHB is better for cell production energy and is a more stable ketone molecule.

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Exogenous Ketones: Salts, MCT and Esters

Let’s first explore ketone salts before analyzing some potentially more effective alternatives.

Ketone Salts

Ketone salts typically come as a powder containing BHB bound to a mineral salt (commonly sodium, potassium or calcium) or an amino acid (like lysine or arginine); these powdered BHB salts are dissolved in liquid to be consumed.

Despite the lack of published work analyzing the effects on biomarkers or performance measures in humans, ketone salts are a growing market. The FDA doesn’t even recognize ketone salts as GRAS (Generally Regarded as Safe) food ingredient.

Many studies have been conducted in rats,6,7,8 resulting in relatively low levels of BHB in the blood. Human studies showed similar results; clinical trials reported blood BHB levels of 0.6 - 1 mM after ketone salt drinks.9,10,4

One recent study in young adults illustrated the differences between salts and esters (more on these later) acutely: ketone salts provided a peak D-BHB of 1 mM whereas the same amount of BHB in a ketone ester raised blood BHB levels to 2.8 mM.4

For performance, data has been mixed at best. Four studies investigated the effects of ketone salts in athletes (total n = 22), with none of the studies finding improvement in performance.9,10,11,12 In one study, performance actually decreased by 7%, and GI distress (ranging from nausea to diarrhoea to vomiting) was reported in a high percentage of athletes.11,13

While ketone salts are relatively inexpensive, and may be a nice co-deliverer of other nutrients, BHB levels are only raised slightly–to 1 mM.9,10 ,4 There are also some health concerns with consuming enough salt to raise BHB significantly.

Excessive salt consumption may have long-term health implications.

High salt intake is linked to hypertension, cardiovascular disease and even stomach cancer.14 The 2015 - 2020 Dietary Guidelines for Americans recommends 2,300mg of salt consumption a day; but most Americans consume 3,400mg daily. Some ketone salt products contain nearly 70% of the recommended daily allowance of sodium in a single serving.

A perceived benefit of ketone salt consumption is linked to the replacement of electrolytes–they’re usually excreted in the urine, a common problem in the early weeks of the keto diet. However, electrolyte imbalances usually don’t persist after keto-adaptation period of about 28 days,15 and so then excessive salt consumption may still be harmful.

Let’s review: ketone salts provide sub-optimal BHB, have no effect on performance and cause significant GI issues. That could be why some makers of ketone salts have cited studies conducted on ketone esters.

If not salts, then what other options do you have to increase ketones exogenously? Here are two, with varying degrees of success.

MCT Oil

OK–you caught us. MCT oils don’t actually contain ketones. They’re medium-chain triglycerides (MCT) fat molecules made of glycerol joined to three medium-length fatty acids and end up being 6-12 carbons in fatty acid chain length.

You’re probably wondering where the ketones come from. The ketones result from the breakdown of MCT fat molecules by the body. They’re processed differently than long-chain fats, which are absorbed and released into the blood via the lymphatic system, bypassing the liver (where ketones are produced). MCTs are transported straight to the liver in the blood, where they’re either used directly for energy or turned into ketones.

MCT sources exist naturally in some food. For example, coconut oil and dairy products contain MCTs. But a high amount are required to increase blood BHB. Studies of MCT supplements report that blood ketone levels reached while using MCT were relatively low (0.5 - 1mM).16 This means you need to consume large amounts to get high ketones, and this can cause gastrointestinal side effects.16,17 Even worse, people who are trying to lose weight should watch out for MCTs. Often, sources of MCTs are highly caloric.

While MCTs aren’t exactly exogenous ketones, they do provide a supplemental approach to potentially increasing blood ketone levels.

Ketone Esters

Ketone esters are salt-free liquids that contain BHB without any extras. Instead of being bound to a mineral like BHB salts, they’re bound to a ketone precursor (like butanediol or glycerol) via an ester bond. You can tell how many ester bonds there are from the name: monoester (one), diester (two), or triester (three).

They aren’t a new discovery–the first ketone ester was developed in the late 70s, and other types were developed in the mid-90s.18,19

There are a couple types of ketone esters being developed and sold right now, and each affects the body differently: D-BHB ketone monoester (HVMN Ketone) and an AcAc diester. It’s important to distinguish the differences, because the physical characteristics and metabolic effects differ.

The AcAc diester was developed at the University of South Florida. In rodents, it rose blood D-BHB to 1 - 4mM, and blood AcAC up to 5mM.20 Animal studies have shown that it might help with seizures,20 weight loss,21 and cancer.22 The published study in humans resulted in a 2% decrease in a 31km cycling time trial performance, possibly due to: side effects, low levels of BHB (less than 2mM), the short high-intensity nature of the time trial, or the use of AcAc vs. BHB.23,24

The D-BHB monoester in HVMN Ketone raises blood ketones to exceptional levels: 3 - 6 mM within 30 minutes of consumption.4,25,26,27 This means a faster, deeper ketosis than all other products currently on the market. It was developed over the course of 15+ years by DARPA, the NIH, and University of Oxford.

And it’s salt free–so it won’t impact water retention or pose any health risks that are often associated with high salt levels. Side effects of the ester itself are also minimal. A single does of D-BHB mixed with a meal replacement formula reported very little gastrointestinal issues at typical doses, and only caused mild symptoms when taken at 4x the recommended amount.25

HVMN Ketone has proved supreme for endurance performance.28,27 Studies of athletes using HVMN Ketone before a workout reported no side effects hindering performance. This is key, as ketone salts and the acetoacetate diester have reported side effects (GI issues) hampering athletic performance.24 There have been published clinical trials in humans demonstrating the efficacy of HVMN Ketone for performance, recovery and several health outcomes such as appetite control,4 blood glucose management29 and even neurodegenerative disease.30

The list of benefits of HVMN Ketone’s BHB monoester runs long. Taste is not on that list. We’ve heard it “tastes like it works,” which is a polite way of saying that the taste is distinct and strong. But for athletes, a single bitter sip is worth the performance benefits. HVMN Ketone has FDA GRAS (generally regarded as safe) status as a food, is cleared for use in athletes by the World Anti Doping Agency (WADA), and is batch tested as part of the NSF Safe for Sport program.

For performance and recovery, human studies of HVMN Ketone have demonstrated extremely positive results.

When consumed before exercise, D-BHB from HVMN Ketone helps muscle to work 28% more efficiently than carbs alone–meaning, the body does more work with the same amount of oxygen.31 In a 30-minute time trial test, in which cyclists consumed the D-BHB ester before exercise with carbohydrates, riders’ performance improved by 2-3% (400m).27 When taken after exercise with glucose, the D-BHB ketone ester improved the resynthesis of glycogen and muscle protein synthesis.28,32

There’s also some exciting research emerging around the health benefits and cognitive benefits of ketone bodies (because ketones can cross the blood-brain barrier), with HVMN Ketone helping mice solve maze puzzles 38% faster than normal33 and helping to keep players cognitive performance high in a study that mimicked soccer.11

Are Ketone Salts Right For You?

It depends on what you want in an exogenous ketone supplement. And that depends on what type of person you are, and what your goals are for introducing exogenous ketones in the first place.

Ketone salts are less expensive than ketone esters, and do provide a mild boost in ketone levels. They have a milder taste that is easier to mask with artificial sweeteners. However, the science behind ketone salts is still lacking, with no clear evidence for weight loss, cognitive ability or better performance; in fact, in some cases, performance decreased, quite possibly due to the overwhelming side effects.

While the taste of esters leaves something to be desired, the data for increased performance in human studies is stronger.

If you’re an athlete or dieter considering an exogenous BHB supplement for physical performance or nutritional support, analyze the data. Science-backed, evidence-based results are best for understanding how exogenous ketones might affect you based on personal need.

Have you used BHB salts? Have you tried esters? Let us know your experience in the comments.

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Scientific Citations

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