Animal procedures were performed in accordance with the University of South Florida Institutional Animal Care and Use Committee (IACUC) guidelines (Protocol #0006R). Juvenile male Sprague–Dawley rats (275–325 g, Harlan Laboratories) were randomly assigned to one of six study groups: control (water, n = 11), BD (n = 11), KE (n = 11), MCT (n = 10), BMS (n = 11), or BMS + MCT (n = 12). Caloric density of standard rodent chow and dose of ketone supplements are listed in Table 1. On days 1–14, rats received a 5 g/kg body weight dose of their respective treatments via intragastric gavage. Dosage was increased to 10 g/kg body weight for the second half of the study (days 15–28) for all groups except BD and KE to prevent excessive hyperketonemia (ketoacidosis). Each daily dose of BMS would equal ~1000–1500 mg of βHB, depending on the weight of the animal. Intragastric gavage was performed at the same time daily, and animals had ad libitum access to standard rodent chow 2018 (Harlan Teklad) for the duration of the study. The macronutrient ratio the standard rodent chow was 62.2, 23.8 and 14 % of carbohydrates, protein and fat respectively.
Neuroprotection: As humans age, the brain becomes more susceptible to neurodegeneration and subsequent conditions such as Alzheimer’s and Parkinson’s disease. Exogenous ketone supplementation appears to ameliorate the typical decline in cognitive function that comes with aging. The likely mechanism for this neuroprotective property is that ketone bodies reduce the inflammation and hyperexcitability that is normally exhibited as glucose metabolism declines in the brain.18, 19
After a few days of fasting, or of drastically reduced carbohydrate consumption (below 50 g/day), glucose reserves become insufficient both for normal fat oxidation via the supply of oxaloacetate in the Krebs cycle (which gave origin to the phrase ‘fat burns in the flame of carbohydrate') and for the supply of glucose to the central nervous system (CNS).4
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.
Despite the recent growth of the ketone salt market, there is very little published work analyzing the effects of these products on any biomarkers or performance measurements in humans. Several studies have been carried out in rats,6,7 with blood BHB levels being relatively low (<0.5 mM) post-consumption of salt drinks. In humans, ketone salts provided peak D-BHB levels of 1 mM, whereas the same amount of BHB in a ketone ester (BD-BHB) raised blood BHB to 2.8 mM.5

If you've tried this type of diet before, or if you've done some research about it beforehand, then you should know that these ten tricks are necessary to get into a ketogenic state quickly, but you will be surprised at the number of people who actually jump on the ketogenic bandwagon without knowing any of the basics first. Remember: A good working knowledge coupled with an effective meal plan can go a long way.


The Zenwise Keto Life BHB Salt uses a custom calcium, magnesium and sodium ketone complex to help access ketones for fuel without the low carb diet or fasting. This product is another all-natural option that goes as far as using turmeric for its added coloring. It is a proven product with hundreds of happy customers. They seem to have a strong grasp on the lemonade side of the exogenous market with their Raspberry Lemonade and Wild Limeade flavor choices.

Though research involving ketone supplements is still in the early stages, it seems promising. One study published in February 2018 in Obesity suggests exogenous ketone esters lower hunger hormones and act as appetite suppressors. That can lead to weight loss because “if we don’t feel hungry, gosh, we probably aren’t going to eat like we were,” Griffin says.
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.
These studies were approved by external Research Ethics Committees (London Queen's Square: 14/LO/0288 and South West Frenchay: 15/SW/0244) and were conducted in accordance with the Declaration of Helsinki (2008). Studies took place at the University of Oxford between September 2014 and September 2016. Participants were healthy, aged 21–57, non-smokers and had no history of major illness. Female participants were using oral contraception to minimize the effects of menstrual phase on results. Participants provided written informed consent prior to inclusion, and completed a confidential medical screening questionnaire to determine eligibility. Anthropometric characteristics are shown in Table ​Table1.1. Sample sizes were chosen following an estimated power calculation based on the effect size in previous work using KE drinks (Clarke et al., 2012b; Shivva et al., 2016).
What is the reason for needing to keep our stress levels down? Well the body reacts to stress, whether physical or emotional, by dumping glycogen and potentially glucose in your bloodstream, thus elevating insulin levels. This in turn blocks our bodies from entering ketosis. To keep your mental and emotional stress to a minimum, it may be wise to meditate, sleep, relax, or do something that is fun and care-free.
If Prüvit’s Keto OS-Max is “not a weight loss supplement” as stated in their disclaimer, why is the official website full of success stories of people who claim to have lost huge amounts of weight from taking the supplements? Ketōnd also feature a number of weight loss success stories on their site. I will get to why there is a problem with weight loss claims later on.
Currently, we lack enough evidence to change the recommendations for calcium intake. The Tolerable Upper Intake Level (UL) for adults 19-50 years old is 2500 mg. This is well over the RDA of 1000 mg for the same age group. Calcium supplements commonly contain 600-1200 mg. When assessing your own calcium intake, keep in mind that calcium from food sources and calcium from supplements may have different outcomes.

Anti-carcinogenic properties: Data seems to suggest that exogenous ketones are an effective anti-carcinogen. The reason behind this is that cancer cells are unable to use ketone bodies effectively, unlike most healthy tissues in the body. In fact, dietary ketone supplementation has been shown to increase survival rates of mice with systematic cancer by as much as 70%.17

The way you make an exogenous BHB is by attaching it to some type of other compound (sodium, potassium, calcium, or magnesium) so that your body can process the molecule by cleaving the bond between the salt and the beta hydroxybutyrate. BHB + bound to a salt = BHB salts, which is what most people in the ketosis community call exogenous ketones. There are also things called esters, which are basically unbound BHB molecules. These are really disgusting and cause massive digestive issues, so I like to ignore them until we can produce them in a more appealing way.


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.
Proper sleep is important for hormone function and repair of the body. Not getting enough sleep is tough on the adrenals and blood sugar regulation. Try to get at least seven hours of sleep per night. If you struggle with quality sleep, create an environment that is conducive for rest. This could be keeping your room cooler, turning off all electronic devices one to two hours before bedtime or using a sleep mask.
I’m already following a ketogenic diet and have been fat adapted for about 3 months. Since I’m already in ketosis would this product help me or hinder my fat loss? My thought is that if I’m already in a fat burning state and then I take exogenous ketones does my body stop burning my fat to burn the ingested ketones like taking a break or does the product enhance the fat burning that is already taking place?
Directions — — As a dietary supplement, mix 1 scoop of ketone powder with 8-12 oz of water To avoid gastrointestinal discomfort, start with 1/2 scoop (or even less) and gradually increase to a full serving. Best consumed prior to exercise to enhance performance. Do not exceed 3 scoops per day. As a dietary supplement take 1 serving of PX Ketotropin twice daily. Ideally the 1st servings (4 capsules) should be taken prior to the first meal of the day. Consume 2nd serving 30 minutes prior to strenuous physical activity. If no physical activity is performed please consumer 2nd serving prior to afternoon meal. Additional servings can be taken in between meals throughout the day if needed. Do not consume more than 6 servings of PX Ketotropin
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 metabolic phenotype of endogenous ketosis is characterized by lowered blood glucose and elevated FFA concentrations, whereas both blood glucose and FFA are lowered in exogenous ketosis. During endogenous ketosis, low insulin and elevated cortisol increase adipose tissue lipolysis, with hepatic FFA supply being a key determinant of ketogenesis. Ketone bodies exert negative feedback on their own production by reducing hepatic FFA supply through βHB-mediated agonism of the PUMA-G receptor in adipose tissue, which suppresses lipolysis (Taggart et al., 2005). Exogenous ketones from either intravenous infusions (Balasse and Ooms, 1968; Mikkelsen et al., 2015) or ketone drinks, as studied here, inhibit adipose tissue lipolysis by the same mechanism, making the co-existence of low FFA and high βHB unique to exogenous ketosis.
Second, take a look back at table 2. Kegenix Prime scored as the “winning brand” for 4 out of the 7 markers tested: mental performance, satiety, mental clarity and energy. Compared to the other supplements, it also scored highest for physical performance, although none of the supplements were listed as a “winner” since the placebo outperformed them all for that marker.
Alright, first of all, I tried every combination available for this product. I really loved the idea of adding it to my morning iced coffee with MCT, 1 tbs of heavy cream and stevia. To be honest, my morning coffee is one of my favorite things throughout my day and I was very dissppointed when it didn’t taste *exactly* like an iced mocha. I found it to be very bitter and tough to finish. Not to mention it was ruining my love for my morning coffee time.
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).
As repeated KE consumption would be required to maintain nutritional ketosis, we investigated the kinetics of drinks in series and of continuous intra-gastric infusion. During starvation, the accumulation of ketones (>4 mM) reportedly inhibited ketone clearance from the blood, however the underlying mechanism is unknown (Hall et al., 1984; Wastney et al., 1984; Balasse and Fery, 1989). In Study 3, βHB uptake and elimination were identical for the second and third KE drinks, suggesting that βHB may have reached a pseudo-steady state should further identical boluses have been given at similar intervals. Furthermore, when the KE was given at a constant rate via a NG tube, blood ketone concentrations remained ~3 mM. Therefore, repeated KE drinks effectively maintain ketosis at the intervals and doses studied here.
Effects of ketone supplementation on blood βHB. a, b Blood βHB levels at times 0, 0.5, 1, 4, 8, and 12 h post intragastric gavage for ketone supplements tested. a BMS + MCT and MCT supplementation rapidly elevated and sustained significant βHB elevation compared to controls for the duration of the 4-week dose escalation study. BMS did not significantly elevate βHB at any time point tested compared to controls. b BD and KE supplements, maintained at 5 g/kg, significantly elevated βHB levels for the duration of the 4-week study. Two-Way ANOVA with Tukey’s post hoc test, results considered significant if p < 0.05. Error bars represent mean (SD)
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.
Participants consumed 13.2 mmol.kg−1 of βHB (6.6 mmol.kg−1 or 1,161 mg/kg of KE) over 9 h, either as 3 drinks of 4.4 mmol.kg−1 of βHB at 3 h intervals (n = 12), or as an initial bolus of 4.4 mmol.kg−1 of βHB given through a nasogastric tube, followed by an infusion of 1.1 mmol.kg.h−1, beginning 60 min after the initial bolus, for 8 h (n = 4). Two participants completed both conditions (total n = 14). In both conditions, the KE was diluted to 1.5 L using the same citrus water as used in Study 2.
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.
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!
I interviewed Dr. Brianna Stubbs, a ketone researcher with a Ph.D. in Metabolic Physiology from the University of Oxford who is now Research Lead at HVMN, specializing in developing ketone esters. She told me that in terms of science on the ketone salts and their effect on physical performance, one of the most-cited benefits of ketone salts, the scientific studies that have been done show at best no effect on physical performance and that, currently, there is no peer-reviewed scientific research on the ketone salt products on the market.
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.*
Emerging evidence supports the therapeutic potential of the ketogenic diet (KD) for a variety of disease states, leading investigators to research methods of harnessing the benefits of nutritional ketosis without the dietary restrictions. The KD has been used as an effective non-pharmacological therapy for pediatric intractable seizures since the 1920s [1–3]. In addition to epilepsy, the ketogenic diet has elicited significant therapeutic effects for weight loss and type-2 diabetes (T2D) [4]. Several studies have shown significant weight loss on a high fat, low carbohydrate diet without significant elevations of serum cholesterol [5–12]. Another study demonstrated the safety and benefits of long-term application of the KD in T2D patients. Patients exhibited significant weight loss, reduction of blood glucose, and improvement of lipid markers after eating a well-formulated KD for 56 weeks [13]. Recently, researchers have begun to investigate the use of the KD as a treatment for acne, polycystic ovary syndrome (PCOS), cancer, amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI) and Alzheimer’s disease (AD) with promising preliminary results [14–26].
If you do the same calculations as I did above for estimating fat oxidation, you’ll see that EE in this case was approximately 13.92 kcal/min, while fat oxidation was only 67% of this, or 9.28 kcal/min, or 1.03 g/min. So, for this second effort (the test set) my body did about 5% less mechanical work, while oxidizing about 25% less of my own fat. The majority of this difference, I assume, is from the utilization of the exogenous BHB, and not glucose (again, I will address below what I think is happening with glucose levels).

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