Ketogenic diets have been successfully used to treat diseases that have an underlying metabolic component, effectively decreasing seizures in recalcitrant pediatric epilepsy (Kossoff et al., 2003), lowering blood glucose concentrations in type 2 diabetes mellitus (Feinman et al., 2015) and aiding weight-loss (Bueno et al., 2013). Emerging evidence supports several clinical uses of ketogenic diets, for example in neurodegenerative diseases (Vanitallie et al., 2005), specific genetic disorders of metabolism (Veech, 2004) and as an adjunct to cancer therapy (Nebeling et al., 1995). Ketone bodies themselves may underlie the efficacy of the ketogenic diet, either through their role as a respiratory fuel, by altering the use of carbohydrate, protein and lipids (Thompson and Wu, 1991; Cox et al., 2016), or through other extra- and intracellular signaling effects (Newman and Verdin, 2014). Furthermore, ketone metabolism may offer a strategy to improve endurance performance and recovery from exercise (Cox et al., 2016; Evans et al., 2017; Holdsworth et al., 2017; Vandoorne et al., 2017). However, achieving compliance to a ketogenic diet can be difficult for both patients and athletes and may have undesirable side effects, such as gastro-intestinal upset (Cai et al., 2017), dyslipidemia (Kwiterovich et al., 2003) or decreased exercise “efficiency” (Edwards et al., 2011; Burke et al., 2016). Hence, alternative methods to raise blood ketone concentrations have been sought to provide the benefits of a ketogenic diet with no other dietary changes.
The ketogenic journey should be more of a lifestyle than one that acts like a fad. So taking more than a day for your body to enter ketosis should not be the greatest of concern. It’s more important to stay discipline and to consistently keep your body in a fat-burning state. Although, if you are someone who has fallen out of ketosis after a cheat day, or rather somebody who is just starting out and finding it longer than expected to enter ketosis, then this article can definitely help in that respect. It’s nothing new, and it’s definitely no secret but strict dieting, fasting, exercise, controlling stress levels, sleep, and certain supplements can help you boost ketogenesis!
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.
However, we will not be commenting on ketone esters since there are big differences between them and ketone salts, and the ketone salts are the ones that have been heavily commercialized and marketed to the public over recent years. Ketone esters may be more difficult to market due to their having an unpleasant taste. We may look more deeply into the esters in the future.
In a keto-adapted individual where ketone metabolism is brisk with up to 100 grams or more being oxidized (i.e., ‘burned for energy’) daily, the small amount lost in breath and urine as acetone is minor. But because this breakdown occurs spontaneously without needing the help of enzymes, it also happens to AcAc in a stored beverage or food (even in an air-tight container), making the shelf-life of AcAc-containing products problematic. Thus all current ketone supplements consist of BOHB in some form rather than the naturally occurring mix of BOHB and AcAc produced by the liver.
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.
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.
If you have tried other ketone supplements that haven’t worked as promised or tasted terrible. Have no fear. This stuff is what a ketone supplement should be. It’s incredible what customers tell me. How it’s given them more energy, focus, drive. Helped them lose weight and suppress their appetite. Help them train harder at the gym and all kinds of great stories.*
Now I can make a full review on these Perfect Keto products. I purchased the Salted Chocolate first. When I got it, I was mixing it with room temperature coffee and outing it over ice and adding heavy whipping cream. I hated the taste but kept making it that ways bc it got me 5lbs lost in one week. One day I got lazy and just mixed it with water and added heavy cream and it was delicious!! I highly suggest just mixing with water, adding heavy cream and over ice. I've lost 10 lbs in 15 days.
Intellectual property covering uses of dietary ketone and ketone ester supplementation is owned by BTG Ltd., the University of Oxford, the National Institute of Health and TΔS Ltd. Should royalties ever accrue from these patents, KC and PC, as inventors, will receive a share of the royalties under the terms prescribed by the University of Oxford. KC is a director of TΔS Ltd., a company spun out of the University of Oxford to develop and commercialize products based on the science of ketone bodies in human nutrition. At the time of data collection and manuscript preparation, BS was an employee of TΔS Ltd., funded by the Royal Commission for the Exhibition of 1851. SH is an employee of NTT DOCOMO, Inc. (Japan). The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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”
Anti-cancer potential: Recent research suggests that ketogenic diets can blunt malignant tumor growth. This is due to the fact cancer cells can’t metabolize ketones effectively to nourish their growth and replication. Astonishingly, one study found that supplementing with BHB salts increases odds of survival in mice with systemic cancer by up to 70% in comparison to mice who didn’t receive exogenous ketones.
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]
Over the past couple years, I’ve tried a number of ketone supplements, generally to enhance a longer fast or to offer an edge before one of my Ultimate Frisbee evenings. This Kegenix variety is one I’d recommend. I’ve also used Quest Nutrition MCT oil powder with good results as well, but there are plenty of other solid formulations to choose from.
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).
In terms of epigenetic signaling, initial studies of the effects of BOHB on class-1 histone deacetylase activity against oxidative stress (Schimazu 2013), NLRP3 inflammasome suppression (Youm 2015), mouse longevity (Roberts 2017), and other epigenetic regulatory effects suggest that levels as low as 1 mM have potent effects. Furthermore, the association between very mild ketonemia and reduced coronary mortality with SGLT2 inhibitor use in patients with type 2 diabetes (Ferranini 2016) suggests that there might be clinical benefits with chronic BOHB levels as low as 0.3 mM (Gormsen 2017. Vetter 2017).
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.
Fortunately a new way to test ketosis has been developed - and that is by measuring acetone levels in the breath. This is rather new technology but based on the reports I have seen it does look reasonably reliable. The testing process is simple, you use a device like that made by Ketonix, you breathe into it, wait a minute or so and it will give you a color indicating the state of ketosis you are in. However, there are numerous downsides:
There’s also the issue of supplement safety in general. All supplements—whether you’re talking about vitamins, minerals, herbs, or other nutritional mixes—are only loosely regulated. “We know that there is contamination of supplements here in the U.S., often from products that are manufactured abroad,” Palumbo says. In that case, “the same concerns apply to this as for any other supplement.”
The many roles of magnesium include helping us maintain normal nerve and muscle function, as well as heart rate, supporting a healthy immune system, regulating blood glucose levels, and making energy production and protein synthesis possible. Magnesium is also involved in both aerobic and anaerobic energy production. ATP synthesis (the body’s energy source) depends on enzymes that are activated by magnesium.
For example, the popular Raspberry Ketones supplement is far different than what we have been discussing in this article. Raspberry ketones are unrelated to the ketones that are produced in the body and are not the same as the ketone salts that have been covered above. There are some limited studies that indicate raspberry ketones may be helpful for weight loss, but they are inconsistent. Raspberry ketones are the molecules that give raspberries their scent and flavor, and in some cases, aren’t even derived from raspberries at all.
Although most of the research has been done utilizing ketone esters, ketone salt supplementation has the potential to provide additional benefits through the extra electrolytes/nutrients that are required to make the ketones. While ketone esters are expensive due to the manufacturing process involved in making them, ketone salts might be a more convenient option for both inducing a state of ketosis and elevating blood ketone levels for various reasons we will discuss in another article.
North Americans typically live pro-inflammatory, pro-disease lives (think about your everyday: likely sitting in a flexed position for hours on end, not enough natural sunlight, not enough movement, artificial food stuffs, artificial colouring, going to bed late, blue light exposure, less in-person contact with our loved ones, late night snacks, the list goes on and on).
Nutritional ketosis induced with the KD has proven effective for the metabolic management of seizures and potentially other disorders [1–26]. Here we present evidence that chronic administration of ketone supplements can induce a state of nutritional ketosis without the need for dietary carbohydrate restriction and with little or no effect on lipid biomarkers. The notion that we can produce the therapeutic effects of the KD with exogenous ketone supplementation is supported by our previous study which demonstrated that acutely administered KE supplementation delays central nervous system (CNS) oxygen toxicity seizures without the need for dietary restriction . We propose that exogenous ketone supplementation could provide an alternative method of attaining the therapeutic benefits of nutritional ketosis, and as a means to further augment the therapeutic potential of the KD.
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).
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