Ketosis is a metabolic state where most of the body’s energy supply comes from ketone bodies in the blood, in contrast to a state of glycolysis where blood glucose provides most of the energy. Ketosis is characterised by serum blood concentrations of ketone bodies over 0.5 millimolar with low and stable levels of insulin and blood glucose. However, with ketone supplementation (as you’ll learn about later in this article) ketosis can actually be induced even when there are high levels of blood glucose
So I’ve been primarily on a Keto diet for almost 6 months. During this time, I have fine tuned a lot to get my ketone levels up (Eating more fat and less protein). Most recently, I have used blood measurements for my ketone levels and I fluctuate between .6 and 2.6. The higher readings I get on the days I workout in the morning (about 5 hours before I draw blood and take a reading). I don’t have any problems sticking to the diet. It only seems to get easier. I’ve also incorporated 16 hour fasts which also are becoming easier over time. My priority and motivation for doing a keto diet is first and foremost weight loss. So far I have lost 40 pounds and I need to lose about 20 more. I do however want to improve my performance (running) and strength (I am doing the Stronglifts 5×5 program now).
Administration of ketone supplementation significantly reduced blood glucose over the course of the study (Fig. 3a, b). MCT (5 g/kg) decreased blood glucose compared to control within 30 min which was sustained for 8 h at baseline and at week 1. MCT (10 g/kg) likewise decreased blood glucose within 30 min and lasted through the 12 h time point during weeks 2, 3, and 4. BMS + MCT (5 g/kg) lowered blood glucose compared to control from hours 1–8 only at week 1. BMS + MCT (10 g/kg) lowered blood glucose compared to control within 30 min and remained low through the 12 h time point at weeks 2, 3, and 4. Rats supplemented with BMS had lower blood glucose compared to control at 12 h in week 4 (10) (Fig. 3a). Administration of BD did not significantly change blood glucose levels at any time point during the 4-week study. KE (5 g/kg) significantly lowered blood glucose levels at 30 min for week 1, 2, 3, and 4 and was sustained through 1 h at weeks 2–4 and sustained to 4 h at week 3. (Fig. 3b).
Once the body is able to generate energy with the help of exogenous ketones which are present in the bloodstream, it would start looking for other sources of ketones. This would encourage the body to tap into the vast reserve of fat which is accumulated in the body. Thus, the process of ketosis is accelerated when you consume extra exogenous ketones. This also leads to quicker weight loss and the body entering ketosis faster.
So if your high-fat diet includes a high amount of roasted seeds or roasted nuts, nut butters, heated oils such as heated coconut oil or heated extra virgin olive oil, barbecued meats or meats cooked at very high temperatures, then your triglyceride count is going to go up. You should have triglycerides that are less than 150mg/dL, and a triglyceride to HDL ratio that is no more than 4:1, and in most of the healthiest people I’ve worked with, triglycerides are under 100 and the triglyceride to HDL ratio is less than 2:1. If your ratio is whacked, your ketogenic diet isn’t doing you any favors.’
Exogenous ketones can lower appetite during a fast. After an overnight fast, normal weight human subjects either drank a ketone ester supplement or a calorie-matched glucose drink. Compared to the glucose drinkers, the ketone drinkers had lower insulin, lower ghrelin, greater satiety, and less hunger. This can be useful for people trying to extend their fast who don’t want to or can’t yet deal with the hunger. You’re still taking in energy, but the metabolic profile remains similar to that of a fasted person.
Another source of the D-BOHB isomer is an evolutionarily ancient energy source for micro-organisms. Poly-BOHB is a long chain of D-BOHB molecules strung end-to-end. It functions in many single-cell organisms as a concentrated energy source similar to glycogen in mammals, but whereas glycogen breakdown releases individual glucose molecules, poly-BOHB hydrolysis releases single D-BOHB molecules.
At day 29 of the study, animals were euthanized and brain, lungs, liver, kidneys, spleen and heart were harvested and weighed. Organ weights were normalized to body weight. Ketone supplementation did not significantly change brain, lung, kidney, or heart weights compared to controls (Fig. 5a, b, d, f). MCT supplemented animals had significantly larger livers compared to their body weight (p < 0.05) (Fig. 5c). Ketone supplements BMS + MCT, MCT and BD caused a significant reduction in spleen size (BMS + MCT p < 0.05, MCT p < 0.001, BD p < 0.05) (Fig. 5e). Rats administered KE gained significantly less weight over the entire study compared to controls. BMS + MCT, BMS, and BD supplemented rats gained significantly less weight than controls during weeks 2 – 4, and MCT animals gained less weight than controls at weeks 3 – 4 (Fig. 6). Increased gastric motility (increased bowel evacuation and changes to fecal consistency) was visually observed in rats supplemented with 10 g/kg MCT, most notably at the 8 and 12-h time points. All animals remained in healthy weight range for their age even though the rate of weight gain changed with ketone supplementation [53–54]. Food intake was not measured in this study. However, there was not a significant change in basal blood glucose or basal blood ketone levels over the 4 week study in any of the rats supplemented with ketones (Fig. 7).
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.
Our bodies are produce three types of ketone bodies for fuel: beta-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone. Each is used by the body differently. Acetone is the least abundant, produced in much smaller amounts, and is usually exhaled through the lungs rather than being used as fuel.3 Acetoacetate is part of the metabolic pathway whereby humans make and use ketones, but it tends to be found in the blood at lower levels than BHB.
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...
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)!
As for MCT oil (and oil powders), powder formulations tend to cause less digestive distress (e.g. probiotics), but some folks object to the additional ingredients like sunflower lecithin or soluble corn fiber). Even if you’d like to eventually settle on an oil, I’d recommend starting with a powder to see how you respond and to give your body the chance to adapt over time.
Also, it’s important to remember that just because something may be SAFE (and to reiterate, I’m not saying a long term ketogenic diet is safe), it doesn’t mean it’s good for you or beneficial. Running Marathons could be considered safe (especially if it’s on a closed race circuit), but does this mean it’s good for you? Or should you be out running marathons every day?
Animal research findings report that BHB supplementation also enhances oxygen utilization, especially in the central nervous system (CNS). 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.
For the ketone esters, on the other hand, repeated doses of 20-30 grams in any one day may be possible. Thus these products may be able to maintain a modest level of ketonemia without dietary carbohydrate restriction. Thus some of the cardiac and brain fueling benefits may follow, not to mention the epigenetic effects limiting oxidative stress and inflammation. But given the recent observation that administered ketone esters markedly reduce circulating free fatty acids (Myette-Cote 2018) — possibly due to an insulin-tropic effect or direct suppression of lipolysis (Taggart 2005) — their sustained use in people with underlying insulin resistance may compromise their long-term benefits by promoting weight gain unless combined with carbohydrate restriction.
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.
International Patent # PCT/US2014/031237, University of South Florida, D.P. D’Agostino, S. Kesl, P. Arnold, “Compositions and Methods for Producing Elevated and Sustained Ketosis”. P. Arnold (Savind) has received financial support (ONR N000140610105 and N000140910244) from D.P. D’Agostino (USF) to synthesize ketone esters. The remaining authors have no conflicts of interest.
For all studies, the area under the curve (AUC) of blood [βHB] was calculated using the trapezium rule. In Study 3, for each of the three drinks, the initial rate of d-βHB appearance was estimated using d-βHB concentrations at baseline and 30 min post-drink, and d-βHB elimination was estimated using the AUC between the post-drink peak (60 min) and trough (180 min) d-βHB concentrations, with a baseline correction to the value at 180 min.
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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