Ketones, The Ketogenic Sate and Weight Loss
Ketones are compounds our liver produces during conditions such as starvation or a diet that is very low in carbs. In these states the body shifts from using glucose – which comes from carbohydrates – to fats for energy. The liver produces three main ketones: acetoacetate, acetone and β-hydroxybutyrate (BHB).
A ketogenic diet is a low-carbohydrate diet. The basis behind the diet is that the low glucose (or blood sugar) causes a change in hormones (from insulin to glucagon) so the body can burn fat for fuel. There are many versions of this diet and one of the most clinically studied consists of 20-50 g/day of carbs – a.k.a. the very-low-carbohydrate ketogenic diet. Although 200 g/day of carbs is considered a low-carb diet, most experts do not consider this low enough to cause the metabolic shift to fat for fuel. Some argue that 50-150 g/day of carbs is above the level of generating urinary ketones for most people.
When in a ketogenic state, as the level of ketones in the blood rises the body’s rate of producing ketones slows down. The liver’s production of ketones matches requirements for the brain to use them. This suggests that there is a threshold for muscles to use ketones. Basically, the body prioritizes ketone production for the brain, not working muscle. This boils down to survival, and ultimately your brain is #1 when it comes to survival.
Individuals Vary in Response
Given the massive amount of marketing behind ketones and ketogenic diets, keep in mind that there is a lot of variation among individual responses to the diet and ketone supplementation.
First, the most successful low-carb ketogenic diet studies have found that the greatest weight loss was experienced by people who had a lot of dietary and behavioral support (i.e. all their food was tracked and prepared; nutrition and other types of counseling was regularly available). Even in those studies, not everyone experienced the same level of weight loss.
Second, recent genetic studies show that depending on your genes your body may respond differently to a low-fat diet than a high-fat diet. Thus, the ketogenic diet isn’t necessarily the most effective weight loss strategy for everyone. Studies on exogenous ketones – as the commercially available ketone salts – have even shown variation in blood ketones among people when the dosage is standardized per kg of body mass. How this affects muscle and fat loss responses has yet to be discovered.
Another interesting point is that your body’s ability to use ketone bodies is higher in exercise-trained muscle than non-exercise-trained muscle. This reflects the body’s general adaptations to exercise, which include enhanced respiratory capacity, strength ability, and improved ability to use and deliver various nutrients.
Moreover, type I fibers – your slow twitch muscle fibers that support you in endurance activities, are most responsive to exogenous ketones. Type II fibers – your fast twitch “sprint” muscle fibers – are less responsive to exogenous ketones. Depending on your sport, the supplementation or a ketogenic diet may not enhance your performance. As one study summarized: Therefore, the uptake and utilization of ketones in skeletal muscle is likely to be greatest in those individuals that are highly trained with a high proportion of type I muscle fibers and a high oxidative capacity in skeletal muscle. Currently, “the most important determinant of [ketone body] metabolism during exercise is the degree of ketonaemia, and the method by which [it] is achieved, i.e. of endogenous or exogenous origin.”
With so many terms that include “keto” getting tossed around, there are several key things to clarify when it comes to exogenous ketone supplements. “Exogenous ketones” should not be confused with raspberry ketones. They are simply very different substances and do different things!
Another thing to point out is that when taking exogenous ketones, it is not the same thing as being in a ketogenic state. This was best stated by Dr. Brendan Egan of Dublin City University:
I see [exogenous ketones] as a way to enhance or speed that process rather than try to have it happen in the presence of non-fasting stimuli. In other words, I don’t see how a [Standard American Diet] can be ‘overcome’ by ketones, nor how ketones could be effective in the presence of high glucose levels.
Also, the ability of ketones to suppress appetite is questionable. All the talk about appetite suppression is likely confused with the spontaneous reduction in food that occurs on a ketogenic diet. A review on low-carb diets showed that the decrease in calorie intake is a result of appetite and hunger reduction. It goes along with the increase in the percentage of calories from fat and protein. Since it takes your body a longer time to digest and absorb fat and protein, it would make sense that the nutrient shift would make you feel fuller for longer and ultimately lead to a perceived suppressed appetite. The evidence, as it stands now, indicates that exogenous ketones alone do not cause appetite suppression.
Furthermore, high ketone bodies in the blood reduce the breakdown of fat. In other words, they have an antilipolytic effect. One of the benefits of exercise is that you promote the use of fat for energy. As Dr. Egan stated in a recent podcast by Sigma Nutrition, “… I think it’s a mistake to say that … exogenous ketones are going to help burn fat. I think that’s completely erroneous. But I think it’s also probably not true to say that if you take them, you won’t burn any fat… [it just doesn’t work] like that.”
Types of Exogenous Ketone Supplements
There are various exogenous ketone supplements emerging in the market. The commercially available forms are typically sold as ketone sodium/potassium/calcium salts. This is cheaper than ketone bodies in their free acid form. However, both the free acid form and the ketone salt form are ineffective at producing ketosis. The amount of BHB delivered per serving of the standard commercially available exogenous ketone supplement is low. That doesn’t mean more is better either. Taking in extra ketone salt servings often results in GI issues and can potentially lead to cation overload or acidosis.
The type of exogenous ketones used in research come in the form of ketone esters, which are not commercially available yet. Ingestion of the esters can result in short-term (30 minutes – 6 hours) nutritional ketosis without the impracticality – for an athlete – of prolonged fasting or a strict ketogenic diet. The potential benefit of exogenous ketone supplementation for an endurance athlete – or one dominant in type I muscle fibers – is the ability to replenish muscle glycogen and spare protein and carb stores during post exercise ketosis or during low carb availability.
There is some argument regarding the optimal range of ketones, such as BHB, for sport performance. For the most part it is argued that 1-3 mM of ketone concentration in the blood after ketone ester ingestion is best. The rise in blood ketone levels usually occurs within about 10 minutes. In contrast, the ingestion of ketone salts typically results in a maximal peak around 0.5 – 0.7 mM of ketones within about 60 minutes after ingestion. Basically, this means that the way our bodies process different forms of exogenous ketones varies and scientists are still trying to figure out what is the best form and how it works.
Buying Into It
A lot of the research done on ketogenic diets include dietary restriction and changes. There is limited quality research on exogenous ketones as a weight loss supplement. The research that exists also includes controlled diets on study participants or participants that are athletes. Therefore, if you’re health/fitness goal is weight loss, exogenous ketones alone aren’t the answer. Consider working with a personal trainer to adopt an exercise routine and a nutritionist for a personalized diet program, maybe one based on your genetics. Perhaps just try a whole foods ketogenic diet with regular exercise. If you are an endurance athlete, exogenous ketones are something worth keeping your eye on as the science develops.
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- Egan B. Sigma Nutrition Podcast. http://sigmanutrition.com/episode195/.
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- Vandoorne T, De Smet S, Ramaekers M, et al. Intake of a ketone ester drink during recovery from exercise promotes mTORC1 signaling but not glycogen resynthesis in human muscle. Front Physiol. 2017;8(MAY):1-12. doi:10.3389/fphys.2017.00310.
- O’Malley T, Myette-Cote E, Little JP. Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males. Appl Physiol Nutr Metab. 2017;(42):1031-1035. https://doi.org/10.1139/apnm-2016-0641.
- Brendan Egan, PhD Exogenous Ketone Supplementation Podcast – Sigma Nutrition
- Dr. Egan Exogenous Ketone Supplementation Podcast Transcript – Sigma Nutrition