Dominic D’Agostino has two in-depth interviews on The Tim Ferriss Show (Part 1, Part 2). Discussion includes exogenous ketones for mitigating the onset of neurodegenerative diseases, using ketones in place of fasting for chemo-protection, benefits of ketone supplementation when consuming carbohydrates, the risks and potential toxicities of ketones.

As I mentioned before, this was by no means a scientific experiment carried out under lab conditions, and this means we can only draw tentative conclusions from any of the data. Nonetheless, carrying out the testing in the way described above should give most people a good idea of how well the ketone supplements show the noticeable benefits they are marketed to have and provide a clear enough basis for a decision on whether or not to buy them.
The same question posed in a different way can be, what’s better, getting protein from powder or from a grass-fed steak or wild salmon? Omega-3 from supplements or from a variety of healthy wild fish? Just like with health supplements where you consume an isolated nutrient instead of the whole food where it comes from, if it’s possible to get what you need from whole food or nutrition, then that’s probably the best choice.

Most of the information regarding the effects of ketosis come from studies on the ketogenic diet, wherein ketones are made by the liver and become a major fuel source for the body. The ketogenic diet is currently under investigation for its potential therapeutic effects in a number of healthy and disease states. More recently, studies are beginning to reveal that many of the effects observed with the ketogenic diet are mechanistically attributable to ketones, which is a primary reason that exogenous ketones are being developed and studied. However, because they are such a new technology, there’s not a lot of data on exogenous ketones themselves. In a few pre-clinical studies, exogenous ketones have mimicked the therapeutic effects of the ketogenic diet”


It is a good idea to weigh the pros and cons before deciding to add a calcium supplement to your diet. This includes exogenous ketone supplements. If you have any risk factors for osteoporosis, have low bone density, or have issues that prevent you from consuming a nutrient-rich diet, then the benefits of calcium supplements will likely outweigh the risks. But don’t forget that there are other avenues to improving your bone density, like strength training, and, more importantly, a well-balanced diet.
Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...

Geek note: Technically speaking, beta hydroxybutyrate is NOT a legitimate ketone body. Ketone bodies, or ketones are technically molecules with carbonyl carbons which are bonded to two additional carbon atoms. One carbon has four available bonds. When that carbon is double bonded to oxygen and also has two single bonds to carbon, we have a ketone body. If you have a carbon atom that is double bonded to an oxygen (carbonyl group), which is also bound to an -OH group instead of two different carbon atoms, that would be a carboxylic acid, but that really doesn’t matter in this case. For all intents and purposes of the ketogenic diet, betahydroxybutyrate should be considered one of the three ketone bodies and a “ketone” nonetheless. Your body uses BHB pimarily for energy in the state of ketosis, so it’s a ketone, okay?


Even though there is mixed evidence regarding the association between calcium supplementation and cardiovascular events, there may be other reasons to avoid high calcium supplementation. In one of his studies, Dr. Bolland claimed that calcium supplements do not prevent hip fractures. Rather, they may lead to kidney stones, acute gastrointestinal events, and increased risk of myocardial infarction and stroke. Thus, the risks involved with high-calcium supplementation potentially outweigh the benefits[21].

Hi all…thanks for your articles and info. I am currently on a paleo diet, but want to lose more weight and bring it up a notch w/ ketogenic diet and be in ketosis. Not sure which product is best? Do you take the MCT oil and also a ketone powder. I know it may be difficult at first, but I am up for the challenge as we start the new year and would like to loose 40 lbs by May/June. Please advise as to what products are best so I can purchase. THANKS


Think about it like building muscle, good supplements can enhance your results, but if you don't eat right and exercise, supplements are just useless. You can't just sit on the couch to watch TV, eat potato chips all day and drink some supplements and expect to gain muscle. A supplement is not a miracle. It's just an addition and before you add it to your diet, you need to get the basics right first, which is dieting and exercise in the case of building muscles. The supplements are not going to lift the heavy weights for you. You do!
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)
A typical serving of racemic ketone salts contains around 12g of beta hydroxybutyrate, of which only half is the D- form (6g). Compared to the 40g ketone esters I consumed (which are 100% D- form), I would need to consume somewhere around seven to nine packets of ketone salts to get the same amount of D-β-hydroxybutyrate (some D- form is wasted burning of the L- form), along with the huge amount of salts contained and more than a gallon of water (since the powders must be mixed). Even if one could consume that amount of ketone salts, they will probably suffer from what people often refer as “disaster pants” (aka diarrhea) due to the amount of salt consumed.
Too low of sodium intake can be just as dangerous as getting too much. As with all essential nutrients, the graph for risk associated with sodium and health problems is actually u-shaped, such that both low and high quantities of sodium are associated with risk of cardiovascular disease and all-cause mortality[8]. Evidence also suggests that restricting sodium to the recommendations may rapidly increase plasma levels of renin, angiotensin II, and aldosterone, which can lead to complications in itself[9].
Ketone supplementation did not affect the size of the brain, lungs, kidneys or heart of rats. As previously mentioned, the rats were still growing during the experimental time frame; therefore, organ weights were normalized to body weight to determine if organ weight changed independently to growth. There could be several reasons why ketones influenced liver and spleen weight. The ratio of liver to body weight was significantly higher in the MCT supplemented animals (Fig. 5). MCTs are readily absorbed in the intestinal lumen and transported directly to the liver via hepatic portal circulation. When given a large bolus, such as in this study, the amount of MCTs in the liver will likely exceed the β-oxidation rate, causing the MCTs to be deposited in the liver as fat droplets [94]. The accumulated MCT droplets in the liver could explain the higher liver weight to body weight percentage observed with MCT supplemented rats. Future toxicology and histological studies will be needed to determine the cause of the observed hepatomegaly. It should be emphasized that the dose in this study is not optimized in humans. We speculate that an optimized human dose would be lower and may not cause hepatomegaly or potential fat accumulation. Nutritional ketosis achieved with the KD has been shown to decrease inflammatory markers such as TNF-α, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1 [8, 46], which may account for the observed decrease in spleen weight. As previously mentioned, Veech and colleagues demonstrated that exogenous supplementation of 5 mM βHB resulted in a 28 % increase in hydraulic work in the working perfused rat heart and a significant decrease in oxygen consumption [28, 41, 42]. Ketone bodies have been shown to increase cerebral blood flow and perfusion [95]. Also, ketone bodies have been shown to increase ATP synthesis and enhance the efficiency of ATP production [14, 28, 40]. It is possible that sustained ketosis results in enhanced cardiac efficiency and O2 consumption. Even though the size of the heart did not change for any of the ketone supplements, further analysis of tissues harvested from the ketone-supplemented rats will be needed to determine any morphological changes and to understand changes in organ size. It should be noted that the Harlan standard rodent chow 2018 is nutritionally complete and formulated with high-quality ingredients to optimize gestation, lactation, growth, and overall health of the animals. The same cannot be said for the standard American diet (SAD). Therefore, we plan to investigate the effects of ketone supplements administered with the SAD to determine if similar effects will be seen when the micronutrient deficiencies and macronutrient profile mimics what most Americans consume.

Ketones may be a better source of fuel than glucose, and a far better beverage than Fruitopia, but it's a question of whether or not you can spare the extra fuel. Because just like adding sugar to a diet, it's like pressing pause on the fat burning process since the body preferentially burns it for fuel. Adding ketones to the diet does the same thing.


Importantly, at Diet Doctor we do not think you need to spend any extra money at all in order to revolutionize your health. You can achieve radiant health just by enjoying authentic food that is naturally low in carbohydrates, getting plenty of sleep and some exercise (going for a walk is free) and reducing stress. A lot of you who answered the survey made exactly these points in your explanations of reasons for not taking the supplements. I whole-heartedly agree.
Humans in the hunter-gatherer era survived thanks to metabolic flexibility — the body’s ability to use different fuels for energy depending on the nutrients available. This adaptation was vital during a time when the source, quantity, and frequency of food was uncertain[*]. Most of the time, people were fasting, so their bodies ran on ketones, not glucose.

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