The liver is always producing ketones to some small degree and they are always present in the bloodstream. Under normal dietary conditions, ketone concentrations are simply too low to be of any significant benefit. A ketogenic diet and exogenous ketone supplements will increase the amount of ketone in your body. The idea that  ketones are “toxic” is ridiculous. Ketones are a normal physiological substance that play many important roles in the human body.
If given all as a single salt, 50 grams per day of BOHB would mandate daily intakes of 5.8 g Mg++, 9.6 g Ca++, 11.0 g Na+, or 18.8 g K+. Even if divided up carefully as a mixture of these various salts, it would be problematic getting past 30 grams per day of BOHB intake. And again, most of the currently marketed ketone salt formulations are made with a mix of the D- and L-isomers of BOHB, so the actual delivered dose of the more desirable D-isomer is considerably less. The other concern with the salt formulations is that, as the salts of weak acids, they have an alkalinizing metabolic effect that might have a modest but cumulative effect on blood pH and renal function.

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 I have seen this effect in (unpublished) data in world class athletes not on a ketogenic diet who have supplemented with exogenous ketones (more on that, below).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).

Supplemental BHB’s are ideal for people new to the ketogenic way of eating. The changes that happen in your brain and body when adapting to a VLC diet are both immediate and profound. For example, our kidney’s start processing minerals salts much more efficiently. Ironically, after years of being advised to decrease our intake of salt (sodium), it turns out that for people transitioning away from the Standard American Diet (SAD diet) towards a lower carb or ketogenic diet there is actually a need to increase dietary mineral salts such as potassium, sodium, magnesium and calcium. During the process of becoming keto-adapted, it is very important to increase your intake of these essential minerals, in order to prevent the onset of unpleasant symptoms (known as “keto flu”).
Before the Nobel Prize was awarded to Yoshinori Ohsumi, other researchers were making groundbreaking discoveries about autophagy. In 2009, an article was published in Cell Metabolism entitled Autophagy Is Required to Maintain Muscle Mass. In this article, researchers described how deactivating an important autophagy gene resulted in a profound loss in muscle mass and strength.
The ketone supplements were associated with a 5.4% decrease in physical performance while the artificially-sweetened, non-caffeinated beverage I used as a placebo was associated with a 20.3% increase: a big difference in favour of the placebo. Before you go rushing out to buy some, remember that this experiment was not performed under fully-controlled, laboratory conditions, and we were working with too small a group to prove that the placebo caused an increase in physical performance. But what we can say is that we couldn’t find any correlation between ketone supplements and an increase in physical performance in this experiment. According to Brianna Stubbs, some of the work currently being done on new kinds of ketone salts is starting to show more promise in relation to physical performance, so there may be better news on this down the line.

Effects of ketone supplementation on blood βHB. a, b Blood βHB levels at times 0, 0.5, 1, 4, 8, and 12 h post intragastric gavage for ketone supplements tested. a BMS + MCT and MCT supplementation rapidly elevated and sustained significant βHB elevation compared to controls for the duration of the 4-week dose escalation study. BMS did not significantly elevate βHB at any time point tested compared to controls. b BD and KE supplements, maintained at 5 g/kg, significantly elevated βHB levels for the duration of the 4-week study. Two-Way ANOVA with Tukey’s post hoc test, results considered significant if p < 0.05. Error bars represent mean (SD)

Venous blood samples (2 ml) were obtained during all visits using a 22 G catheter inserted percutaneously into an antecubital vein. The catheter was kept patent using a saline flush following each sample collection. Additionally, during Study 1, arterialized blood from a catheter inserted into a heated hand (Forster et al., 1972) was collected into heparinized blood gas syringes (PICO 100, Radiometer, Copenhagen) from a subset of participants (n = 7) and immediately analyzed for pH and electrolytes using a clinical blood gas analyser (ABL, Radiometer, Copenhagen).
Calories do matter, even on a ketogenic diet. If you consume more calories than your body uses, you’re going to gain weight. Period. What you mean to say is that it’s very difficult to eat your entire day’s worth of calories on a ketogenic diet because fats are so satiating. This distinction is important to keep in mind for those who generally have a voracious appetite (like me).
So if you really want to jump start ketosis, do what the prehistoric humans did; don’t eat for 3 to 5 days. Keep the water bottle and multivitamins close and go on a strict fast. It might seem extreme and to a degree it is, but starving yourself will put you into ketosis. No ifs, ands, or buts about it. And it will cause you to lapse into a ketogenic state faster than if you tried to do so by manipulating the foods you eat (replacing carbs with fats). Once starvation has caused your body to transition to a ketogenic state, you can begin to introduce your low carb, high fat keto-friendly foods.
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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