Exogenous ketones have become a popular nutritional supplement since their introduction in 2014. Unfortunately there is a lot of inaccurate information and marketing you have to read through to find the truth about them. This article does the hard work for you. It gets right to the true benefits and drawbacks of exogenous ketones supported by research studies.
Ketogenic diets have been successfully used to treat diseases that have an underlying metabolic component, effectively decreasing seizures in recalcitrant pediatric epilepsy (Kossoff et al., 2003), lowering blood glucose concentrations in type 2 diabetes mellitus (Feinman et al., 2015) and aiding weight-loss (Bueno et al., 2013). Emerging evidence supports several clinical uses of ketogenic diets, for example in neurodegenerative diseases (Vanitallie et al., 2005), specific genetic disorders of metabolism (Veech, 2004) and as an adjunct to cancer therapy (Nebeling et al., 1995). Ketone bodies themselves may underlie the efficacy of the ketogenic diet, either through their role as a respiratory fuel, by altering the use of carbohydrate, protein and lipids (Thompson and Wu, 1991; Cox et al., 2016), or through other extra- and intracellular signaling effects (Newman and Verdin, 2014). Furthermore, ketone metabolism may offer a strategy to improve endurance performance and recovery from exercise (Cox et al., 2016; Evans et al., 2017; Holdsworth et al., 2017; Vandoorne et al., 2017). However, achieving compliance to a ketogenic diet can be difficult for both patients and athletes and may have undesirable side effects, such as gastro-intestinal upset (Cai et al., 2017), dyslipidemia (Kwiterovich et al., 2003) or decreased exercise “efficiency” (Edwards et al., 2011; Burke et al., 2016). Hence, alternative methods to raise blood ketone concentrations have been sought to provide the benefits of a ketogenic diet with no other dietary changes.
The effects of ketone drinks on endogenous insulin secretion are unclear. Whilst the small increase in plasma insulin after KE and KS drinks may have been due to the small quantity of dextrose in the diluent, it has been proposed that ketones could potentiate or even stimulate insulin secretion. Isolated pancreatic islets secreted insulin when stimulated by ketones at glucose concentrations of >5 mM (Biden and Taylor, 1983), and small amounts of insulin are secreted in vivo following exposure to exogenous ketones in animals (Madison et al., 1964; Miles et al., 1981). In response to an intra-venous 10 mM glucose clamp, ketone ester drinks increased glucose uptake and plasma insulin (Holdsworth et al., 2017). The increases in insulin with ketone drinks taken whilst fasted were small compared to the increases seen when the ketone ester drink was consumed with a meal and with consumption of a dextrose drink. Furthermore, the lack of difference in peak plasma insulin between the two latter conditions indicates that nutritional ketosis did not inhibit or increase normal carbohydrate induced insulin production.
Why is this desirable? Think about energy production in your body much like macro energy consumption on a planetary level. Coal is gross and dirty and messes tons of different things up. You need to continue to burn it to get energy. Solar power is free, clean and pretty much limitless. This is pretty much the same story when you are burning carbs (coal) versus fats (solar) for energy.
Background and aims: Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate “ketogenic” diet, but adherence to such diets can be difficult. An alternative way to increase blood D-β-hydroxybutyrate (D-βHB) concentrations is ketone drinks, but the metabolic effects of exogenous ketones are relatively unknown. Here, healthy human volunteers took part in three randomized metabolic studies of drinks containing a ketone ester (KE); (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, or ketone salts (KS); sodium plus potassium βHB.
The metabolic phenotype of endogenous ketosis is characterized by lowered blood glucose and elevated FFA concentrations, whereas both blood glucose and FFA are lowered in exogenous ketosis. During endogenous ketosis, low insulin and elevated cortisol increase adipose tissue lipolysis, with hepatic FFA supply being a key determinant of ketogenesis. Ketone bodies exert negative feedback on their own production by reducing hepatic FFA supply through βHB-mediated agonism of the PUMA-G receptor in adipose tissue, which suppresses lipolysis (Taggart et al., 2005). Exogenous ketones from either intravenous infusions (Balasse and Ooms, 1968; Mikkelsen et al., 2015) or ketone drinks, as studied here, inhibit adipose tissue lipolysis by the same mechanism, making the co-existence of low FFA and high βHB unique to exogenous ketosis.
Because of how effectively exogenous ketones can reduce hunger for those in ketosis, pay attention to the cues your body gives you. It’s possible to extend your fasts longer than necessary because of a decreased appetite cue. While those who have some weight to lose might be tempted to think this is a favorable side effect, there is a difference between fasting and starving for nutrients. Make sure to get enough food to support your activities and maintain your muscle mass.
Some general side effects of your body producing beta hydroxybutyrate is essentially the lull in time it takes to switch from carbohydrate metabolism to fat metabolism, which can take 3-4 days. This can lead to mood swings, fatigue, and general low energy. If you want to skip that step, we recommend taking exogenous BHBs to switch your body over effortlessly.
Compared to our other cellular gasoline (carbs), we can store an unlimited supply of energy from ketones in our body within our fat. When you’re reliant on carbohydrates, you’re forced to keep your tank partly full as we can only store just over 2,000 calories of glycogen from carbs. An empty carb tank results in carb-withdrawal symptoms from not being able to switch into a ketone or fat burning metabolism.
I’m getting an increasing number of questions about exogenous ketones. Are they good? Do they work for performance? Is there a dose-response curve? If I’m fasting, can I consume them without “breaking” the fast? Am I in ketosis if my liver isn’t producing ketones, but my BOHB is 1.5 mmol/L after ingesting ketones? Can they “ramp-up” ketogenesis? Are they a “smart drug?” What happens if someone has high levels of both glucose and ketones? Are some products better than others? Salts vs esters? BHB vs AcAc? Can taking exogenous ketones reduce endogenous production on a ketogenic diet? What’s the difference between racemic mixtures, D-form, and L-form? What’s your experience with MCTs and C8?
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