Another important difference between endogenous and exogenous BOHB is that most synthetic BOHB used in dietary supplements is a mixture of the two ‘D’ and ‘L’ isomers, whereas endogenously produced BOHB consists of just the D-isomer. Metabolically, the two isomers are very different, and current published information indicates that most of the energy and signaling benefits of BOHB derive from the D-form. This is potentially problematic because the L-isomers are not metabolized via the same chemical pathways as the D-forms (Lincoln 1987, Stubbs 2017), and it remains unclear whether humans can convert the L-form to the D-form.
77. Volek JS, Sharman MJ, Gomez AL, Scheett TP, Kraemer WJ. An isoenergetic very low carbohydrate diet improves serum HDL cholesterol and triacylglycerol concentrations, the total cholesterol to HDL cholesterol ratio and postprandial pipemic responses compared with a low fat diet in normal weight, normolipidemic women. J Nutr. 2003;133(9):2756–61. [PubMed]
To determine the reason for the differences in blood d-βHB concentration, the KE and KS drinks were analyzed for enantiomeric purity. The KE contained >99% of the d-isoform, whereas ~50% of the KS βHB was the l-isoform (Figure (Figure1D).1D). Plasma samples from participants who consumed the high dose KS drink (n = 5) were analyzed to reveal higher l-βHB than d-βHB, the total βHB Cmax being 3.4 ± 0.2 mM (Figure (Figure1E),1E), with a total βHB AUC of 549 ± 19 mmol.min. After 4 h, plasma l-βHB remained elevated at 1.9 ± 0.2 mM; differences in urinary excretion of the two isoforms could not explain this observation as both d- and l-βHB were excreted in proportion to their blood AUCs (Figure (Figure1F).1F). Therefore, in order to determine the time required for l-βHB elimination, a follow-up experiment was undertaken in which subjects (n = 5) consumed 3.2 mmol.kg−1 of βHB as KE and KS with hourly blood and breath sample collection up to 4 h, plus additional samples at 8 h and 24 h post-drink. l-βHB was found to be 1.1 ± 0.1 mM at 4 h, and 0.7 ± 0.2 mM after 8 h, but undetectable after 24 h (Figure 1G). Low amounts of d-βHB (0.3 ± 0.1 mM) were present at 24 h, presumably due to endogenous production. Both ketone drinks significantly increased breath acetone concentration, but at a slower rate than blood d-βHB, reaching a peak after 3 h that was twice as high following the KE (87 ± 9 ppm) than the KS (44 ± 10 ppm), suggesting that d-βHB was readily converted to acetone, but l-βHB was not (p < 0.005, Figure Figure1H1H).
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 . 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 . 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.
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).
Funding. This work supported by an Industrial DPhil Fellowship to BS from the Royal Commission for the Exhibition of 1851. JM was supported by the EPSRC Doctoral Training Centre and Prize Fellowship; Ref: EP/M508111/1. The funding sources were not involved in the design, conduct or analysis of this study. TΔS Ltd. provided the ketone ester, ΔG®, and NTT DOCOMO Inc. provided the acetone meter for the study.
Bottom line: EK isn't the magic pill for instant weight loss. EK triggers ketosis which is a metabolic state where your body burns fat for fuel. EK increases satiety and feeling full, and boosts energy for exercise which helps you lose weight for the long term. You should always aim for the long term and sustainable weight loss and keep the weight off for good instead of looking for a quick fix.
Other studies have found that fasting was as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of chemotherapeutic drugs against melanoma, glioma, and breast cancer cells. Although this research may not apply to your life, it does suggest that intermittent fasting can help support your body in times of toxic stress.
For whatever reason, many patients won’t attempt a ketogenic diet—even if the evidence is clear that it could help. Doctors are often hesitant to recommend dramatic dietary shifts—even if they believe in their efficacy—to patients who are already dealing with difficult health issues. If you’ve got a picky kid with epilepsy, a pickier adult with Alzheimer’s, or a cancer patient who refuses to give up the familiar-yet-non-ketogenic foods that give him some small manner of comfort in this trying ordeal, exogenous ketones could make a big difference.
If you’ve done any reading about ketosis, you no doubt read at some point that ketosis is a “natural” state. You may have read on a bit more and learned what is meant by that statement or you may have simply skipped ahead to the keto success stories and decided to give it a try. But we’d like to direct your attention back to that little tidbit of information about keto being “natural” for a moment.
Intermittent fasting is using the same reasoning – instead of using the fats we are eating to gain energy, we are using our stored fat. That being said, you might think it’s great – you can just fast and lose more weight. You have to take into account that later on, you will need to eat extra fat in order to hit your daily macros (the most important thing). If you’re overeating on fats here, you will store the excess.
Measurements taken included whole blood glucose and BHB (every 5 minutes); VO2 and VCO2 (every 15 seconds); HR (continuous); RQ is calculated as the ratio of VO2 and VCO2. In the video of this post I explain what VO2, VCO2, and RQ tell us about energy expenditure and substrate use—very quickly, RQ typically varies between about 0.7 and 1.0—the closer RQ is to 0.7, the more fat is being oxidized; the reverse is true as RQ approaches 1.0
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From my personal experience, there are plenty of ketogenic supplements that certainly do work, but you do have to be careful of the "phonies." You can find highly recommended ketones products that are endorsed by celebrity life coaches such as Timothy Ferris and Joe Rogan; then you also have those infomercial products that are probably as effective as eating Tic Tacs, which is why it is really important to do your research before experimenting. Once you are finished scouring this website full of its information, you should be well-equipped to make a calculated decision on whether this whole thing is for you and that means our mission is complete.
Consuming exogenous ketones isn't the same as following a ketogenic diet–the ketones in the blood haven't been naturally produced by the breakdown of fat stores. However, scientists believe many of the health benefits of the keto diet and fasting (aside from weight loss) are triggered by ketones. Therefore, raising ketone levels through either endogenous or exogenous ketosis could help to improve health and performance by:
Getting into a state of ketosis normally involves eating a ketogenic diet consisting of around 80 percent fat, 15 percent protein, and 5 percent carbs. Over time, the body transitions from burning carbs for fuel to burning ketones—an alternative fuel source that the liver makes by breaking down fat, explains keto diet expert Amy Davis, RD, LDN. Since advocates say that ketosis can help you lose weight fast, think more clearly, and feel more energized, it’s tempting to try.
If you are having a weight loss plateau and you’ve been at the same weight for 3 or more weeks, try changing something to get back to that stable weight loss rate, like a ketone supplement. It would be exciting to lose more than that each week, but our bodies don’t adjust to dramatic changes well, and a slower rate of loss leads to more of the weight staying off in the future.
Effects of ketone supplementation on body weight: Rats administered ketone supplements gained less weight over the 4-week period; however, did not lose weight and maintained healthy range for age. KE supplemented rats gained significantly less weight during the entire 4-week study compared to controls. BMS + MCT, BMS, and BD supplemented rats gained significantly less weight than controls over weeks 2–4.MCT supplemented rats gained significantly less weight than controls over weeks 3–4, Two-Way ANOVA with Tukey’s post hoc test, results considered significant if p < 0.05. Error bars represent mean (SD)
The body will start making ketones when either we go extended periods without food, or we restrict the one dietary component that stops ketone formation – this being carbohydrates and also minimising protein intake as this also can halt ketone. In turn, your primary source of food is fat, with very little carbohydrate and a small amount of protein.”
Testing BHB levels in the blood is simple but can get pricey if you are doing it many times a day. The Precision Xtra blood glucose and ketone meter is a good buy at $28-$30. The expensive part is the ketone test strips here which can cost $4 each. If you are looking at testing yourself every day it is going to cost you $120 a month and the $30 meter. Here is a starter kit you can get on Amazon.
Thank you, Mark! I am an ME/CFS patient, and I have improved quite a bit on a ketogenic diet, which I have been following for the past 3 months. I am slowly losing weight (much needed) and I wondered, does using exogenous ketones inhibit fat loss? I’m trying to balance the benefits of continuing weight loss with benefits in dealing with ME/CFS symptoms. Thank you for any info you can offer!
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.
There are things you can do to get into ketosis faster. We explain how to get into ketosis and ways to make transitioning into ketosis easier. But first, we go over some facts about ketosis you need to understand before you start your keto journey. We will also explain the science behind ketosis, including how long it realistically takes for your body to make the switch.
If you ever wondered how to get into ketosis, know that getting into ketosis is easy and completely natural for your body. All you need to do is follow the ketogenic diet which involves cutting down on carbs and eating lots of fat. You can also get into ketosis through fasting. But if your goal is weight-loss and reaping all the benefits of ketosis, the ketogenic diet is a must.
LDL is the lipoprotein particle that is most often associated with atherosclerosis. LDL particles exist in different sizes: large molecules (Pattern A) or small molecules (Pattern B). Recent studies have investigated the importance of LDL-particle type and size rather than total concentration as being the source for cardiovascular risk . Patients whose LDL particles are predominantly small and dense (Pattern B) have a greater risk of cardiovascular disease (CVD). It is thought that small, dense LDL particles are more able to penetrate the endothelium and cause in damage and inflammation [82–85]. Volek et al. reported that the KD increased the pattern and volume of LDL particles, which is considered to reduce cardiovascular risk . Though we did not show a significant effect on LDL levels for ketone supplements, future chronic feeding studies will investigate the effects of ketone supplementation on lipidomic profile and LDL particle type and size.
I have tried the following preparations of exogenous ketones: BHB monoester, AcAc di-ester, BHB mineral salt (BHB combined with Na+, K+, and Ca2+). I have consumed these at different concentrations and in combination with different mixing agents, including MCT oil, pure caprylic acid (C8), branch-chained amino acids, and lemon juice (to lower the pH). I won’t go into the details of each, though, for the sake of time.
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