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.

This is another point that Brianna Stubbs put me onto: often, ketone-salt companies use terms such as “technology developed by Dominic D’Agostino” as a tool to market their products. Dom D’Agostino holds the patent for the technology being used but is not associated with the products and does not necessarily promote them. In many cases, this feels like a marketing strategy that name-drops a famous keto expert in order to make a product sound more legitimate. There is an example of this on Real Ketones’ website.


Other ingredients: Many of the supplements contain large amounts of caffeine – the supplement we tested from Prüvit contains the same amount as a 16 oz cup of coffee! Some supplements also contain malic acid, which is “known for its ability to increase energy and tolerance to exercise”. This leaves the nagging doubt: if the experiment shows an increase in energy and physical performance, for example, how do we know it is the (expensive) BHB causing the effect and not the (inexpensive) other ingredients?


In the second of these posts I discuss the Delta G implications of the body using ketones (specifically, beta-hydroxybutyrate, or BHB, and acetoacetate, or AcAc) for ATP generation, instead of glucose and free fatty acid (FFA). At the time I wrote that post I was particularly (read: personally) interested in the Delta G arbitrage. Stated simply, per unit of carbon, utilization of BHB offers more ATP for the same amount of oxygen consumption (as corollary, generation of the same amount of ATP requires less oxygen consumption, when compared to glucose or FFA).

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.
Second, there are inherent metabolic differences between boosting ketones via diet and boosting ketones via supplements. On a ketogenic diet, ketones go up because you’re converting body and dietary fat into ketone bodies. A rise in endogenous ketones means you’re burning fat and building the requisite machinery to metabolize the new energy source. On exogenous ketones, ketones go up because you ate some ketones; conversion of body and dietary fat into ketone bodies goes down if anything.
It's also a smart idea to start slowly with this supplement. We can thank Dave Asprey for the term “disaster pants” which has been used by those who try MCT oil at too high a dose when they first start using it. There is a chance that you can experience the same unpleasant gastrointestinal effect with exogenous ketones if you start with too high a dose, or if you maintain a higher carbohydrate diet while using this supplement. Used in appropriate doses, it gets absorbed through your stomach into your liver, then sent out to the rest of your body.
Interestingly, the effects of exogenous ketones on blood substrate concentrations were preserved with the metabolic stimulus of a mixed meal. Following KE drinks, FFA and glucose fell and remained low in both fed and fasted subjects, despite higher insulin throughout the fed arm, suggesting that there was no synergistic effect of insulin and βHB to further lower blood glucose or FFA. In agreement with previous work, the threshold for the effects of βHB on glucose and lipids appears to be low (<1 mM), as there was no significant dose-response relationship between increasing blood βHB and the small changes in plasma FFA, TG or glucose across all of the study drinks (Mikkelsen et al., 2015).
Animal research findings report that BHB supplementation also enhances oxygen utilization, especially in the central nervous system (CNS).[11] While molecular oxygen is a crucial molecule for health and longevity, too much of it can be potentially toxic and speed the effects of aging in tissues throughout the body.Therefore, using a BHB supplement can effectively mitigate the toxic buildup of molecular oxygen, particularly in the CNS/brain.

The blood levels of BOHB that can be achieved with the salts or ester formulations are in the 1-3 mM range, similar to what can be achieved with a well-formulated ketogenic diet in insulin sensitive humans, but well below levels achieved after a 4-7 days of total fasting (Owen 1969). In more insulin resistant humans, the ester formulation may deliver higher blood levels than a sustainable diet (as opposed to short term fasting). For example, in the Virta IUH Study of over 200 patients with type 2 diabetes, blood ketone mean levels were 0.6 mM at 10 weeks and 0.4 mM after 1 year.
They’ve got enough science behind them to suggest they do work very well indeed, but watch out for the online ads featuring the raspberry ketone fat burners. Their name is little more than a parlour trick because this is not related in any way to ketones, a ketogenic diet or nutritional ketosis. They are merely the natural substance that gives raspberries their sweet aroma and flavour. Just because they’re marketed at the must-have fat burner, doesn’t mean they work and are one of the most widely spread Internet scams. There aren’t any human studies to back up raspberries claims so exercise a handful of caution when choosing your ketone supplier. Make sure they’re reputable, can be held accountable and are Australian made to set yourself up to become leaner while increasing your stamina.

As ketone drinks can deliver nutritional ketosis without fasting, we investigated the effect of food on KE uptake and metabolism. It is well documented that food in the gut can slow, or prevent, the uptake of small hydrophilic hydrocarbons, such as βHB (Melander, 1978; Toothaker and Welling, 1980; Horowitz et al., 1989; Fraser et al., 1995), so decreased gut βHB uptake is probably the cause of lower blood βHB following the meal. Despite higher blood βHB concentrations in the fasted state, the meal did not alter plasma AcAc. This suggests that the rate of conversion of βHB to AcAc may not match the rate of appearance of βHB following KE consumption. Alternatively, meal-induced changes in the hepatic ratio of NAD+:NADH may have altered the conversion of βHB to AcAc (Himwich et al., 1937; Desrochers et al., 1992).
Given that blood βHB after identical ketone drinks can be affected by factors such as food or exercise (Cox et al., 2016), the accuracy of tools for non-invasive monitoring of ketosis should be investigated. Breath acetone and urinary ketone measurements provide methods to approximate blood ketosis without repeated blood sampling (Martin and Wick, 1943; Taboulet et al., 2007). However, breath acetone did not change as rapidly as blood βHB following KE and KS drinks. Acetone is a fat-soluble molecule, so may have been sequestered into lipids before being slowly released, resulting in the differences observed here. Similarly, significant differences in blood d-βHB between study conditions were not reflected in the urinary d-βHB elimination. As the amount of d-βHB excreted in the urine (≈0.1–0.5 g) represented ~1.5% of the total consumed (≈23.7 g), it appears that the major fate of exogenous d-βHB was oxidation in peripheral tissues. These results suggest that neither breath acetone nor urinary ketone measurements accurately reflect the rapid changes in blood ketone concentrations after ketone drinks, and that blood measurement should be the preferred method to quantitatively describe ketosis. That said, it should be noted that although commercial handheld monitors are the most practical and widely available tool for measuring blood ketones, they can overestimate blood D-βHB compared to laboratory measures (Guimont et al., 2015) and these monitors do not measure L-βHB and so may not provide accurate total blood ketone concentrations, especially if a racemic ketone salt has been consumed.

Also, this experiement should be of interest. Two men followed a ‘traditional Eskimo’ diet for 1 year. After the year eating a low carb high fat diet, it was found that the men had a diminished tolerance to carbohydrates, something that did not occur in Eskimos eating the same diet. It took the mean nearly a month of eating a ‘normal diet’ before their glucose tolerance returned to baseline. 
Ketogenic Diets and Physical Performance – Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis. (http://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-1-2)
I had heard horror stories about how bad ketone esters tasted (like “rocket fuel”!) so was prepared for the worst. I followed their instructions and drank the contents of the bottle in one gulp, then chased it with a sip of sparkling mineral water. While not the most pleasant aftertaste, the flavor wasn’t any worse than after a shot of well tequila. Within 15 minutes I was already well into therapeutic ketosis, and after 30 minutes my ketone meter displayed a “HI” error message (meaning my level was greater than 8.0 mmol/L)!

When our cells undergo the process of autophagy, non-essential parts like damaged proteins are recycled and invading microorganisms and toxic compounds are removed. This means that autophagy plays an important role in stopping the aging process, reversing disease, and preventing cancer, but it doesn’t happen all the time. Fasting, protein restriction, and carbohydrate restriction are the three main ways that can initiate different autophagic processes — all of which are not the same. This is part of the reason why a ketogenic diet has so many positive effects, and it also shows you why intermittent fasting is a way to improve your diet even more.


All of the data I’ll present below were from an experiment I did with the help of Dominic D’Agostino and Pat Jak (who did the indirect calorimetry) in the summer of 2013. (I wrote this up immediately, but I’ve only got around to blogging about it now.) Dom is, far and away, the most knowledgeable person on the topic of exogenous ketones. Others have been at it longer, but none have the vast experiences with all possible modalities (i.e., esters versus salts, BHB versus AcAc) and the concurrent understanding of how nutritional ketosis works. If people call me keto-man (some do, as silly as it sounds), they should call Dom keto-king.

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