This research is a good reminder to discuss with your doctor before taking any supplements. Given the widespread use of calcium supplements, more research is required before any final conclusions can be drawn. Several ketone companies have tried to avoid the large sodium loads but instead relied on a bump in the calcium content from the BHB ketone salts, seemingly without consideration for the aforementioned results. Calcium BHB will likely absorb slower compared to sodium BHB due to digestion and absorption kinetics. For those looking to optimize brain uptake of ketones, this probably isn’t the best strategy (as uptake is directly proportional to the levels in the blood). Be cautious of supplements running from the sodium and chasing the calcium BHB instead, and make sure you factor that into your overall daily needs.
As Dr. Ryan Lowery pointed out to me, ketone supplements could play an important role in the future for elite sports performance, for example, or for people with brain injuries who cannot metabolize glucose properly. I am encouraged that scientists are working to develop these possibilities and, as long as plenty of peer-reviewed scientific research is done into the products being developed, I could feel more positive about the ketone salts in the future. For now, that scientific support is lacking.
Exogenous ketones drinks are growing in popularity as a method to elevate blood ketone concentrations and mimic a ketogenic diet without the need for dietary changes (Ari et al., 2016; Cox et al., 2016; Kesl et al., 2016; Caminhotto et al., 2017; Evans et al., 2017). The present study describes the pharmacokinetic and pharmacodynamics properties of ketone ester and salt drinks in humans at rest, and characterizes the effects of a prior meal, which is pertinent to use as a dietary supplement. The main findings were that KE drinks elevated blood d-βHB > 50% higher than KS drinks, the latter significantly increasing blood l-βHB, which was metabolized more slowly by the body. Both drinks had similar effects on FFA, TG, glucose and electrolyte concentrations, although with disparate effects on pH. A prior meal decreased total blood d-βHB appearance after a KE drink. Finally, either three KE drinks or nasogastric feeding effectively maintained nutritional ketosis over 1 mM for 9 h.
Although decreases in FFA, TG and glucose occurred, there were no significant differences between the KE and KS drinks or with intake amount. Ingestion of ketone drinks significantly decreased overall mean plasma FFA from 0.7 to 0.4 mM, TG from 1.1 to 0.9 mM and glucose from 5.7 to 4.8 mM after 1 h (all p < 0.05). Concentrations were the same as at baseline by 4 h, with FFA at 0.6 mM, TG at 0.9 mM and glucose 5.1 mM (Figures 2A–C). There was a rise in insulin concentrations 30 min following all drinks, probably due to the small amount of carbohydrate in the sweetener (Figure (Figure2D2D).
The keto-esters are more appropriate for delivering higher doses of BOHB, but with repeated dosing can push the limits of taste and GI tolerance. There has been fairly extensive research on a compound 3-hydroxybutyl 3-hydroxybutyrate that is converted via hydrolysis and liver metabolism to yield 2 molecules of ketones, presumably mostly D-BOHB (Clarke 2012 and 2014). In a study involving lean athletes, an approximate 50 gram dose raised blood BOHB levels to 3 mM after 10 min and reached 6 mM by 20 min. Submaximal exercise resulted in increased ketone disposal from 2 to 3 hours and contributed significantly to whole body energy use during exercise (Cox 2016). This product has been shown to significantly reduce appetite after a single dose (Stubbs 2018) but its effect on body weight in humans over a longer period of time has not been studied, nor has its effect on blood glucose control been reported in humans with type 2 diabetes. However a single dose prior to a glucose tolerance test in healthy humans reduced blood glucose area-under-curve by 11% and non-esterified fatty acid area-under-curve by 44% (Myette-Cote 2018).
There are many different variations of intermittent fasting as well. Dr. Dom D’Agostino, the well-known ketogenic diet researcher, suggests doing a longer intermittent fast for 3 days, 3 times a year. This means not eating for 3 days, and eating normally until the next fast. Daily intermittent fasts are recommended as well. He says that it is ideal to have one to two meals after fasting for most of the day to reap the benefits of intermittent fasting every day.
Hello! We have a section on this in our weight loss plateau post—it’s fine to use them, but be careful if you have any digestive issues as a result of them, and make sure they’re not interfering with your weight loss goals. “In addition to potentially contributing too many calories, sources of fat like coconut oil (including concentrated supplements) contain medium chain triglycerides (MCT). These cannot be stored in body fat, meaning that whatever is consumed has to be promptly burned for energy. So you’re adding these sources on top of your dietary fat consumption for satiety, this type of fat takes priority. Often times people fall into the trap of adding supplements of coconut oil or straight up MCT oil and it ends up adding extra calories. Yes, it may raise your ketones a bit, but the overall cost may impact your weight loss.”
Exogenous ketones have a wide range of benefits that can enhance your fat-burning lifestyle. I personally use them daily as a strategy to heighten my mental performance and give my workouts an extra boost. For these purposes, I have also found it logical to combine exogenous ketones with other known health and performance boosting agents such as branched-chain amino acids and medicinal mushrooms.
I also concluded that post by discussing the possibility of testing this (theoretical) idea in a real person, with the help of exogenous (i.e., synthetic) ketones. I have seen this effect in (unpublished) data in world class athletes not on a ketogenic diet who have supplemented with exogenous ketones (more on that, below). Case after case showed a small, but significant increase in sub-threshold performance (as an example, efforts longer than about 4 minutes all-out).
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