Exogenous ketones have become a popular nutritional supplement since their introduction in 2014. Unfortunately there is a lot of inaccurate information and marketing you have to read through to find the truth about them. This article does the hard work for you. It gets right to the true benefits and drawbacks of exogenous ketones supported by research studies.
A growing number of people are giving it a try, thanks to exogenous ketone supplements that claim to launch your body into a state of ketosis within two and a half days—even if you’ve been living on pasta and cookies instead of following a low-carb diet. How can that be, though? And can that kind of rapid transformation actually be safe? Here’s what you should know.
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.
If you are new to ketosis and don’t know much about it, it is a metabolic state, where your body preferentially uses ketones (instead of glucose) for energy. This can lead to a host of different health benefits. If you’d like to learn more about ketosis, what ketones are, and how to benefit from these, feel free to read through our guides: What is Ketosis? What is the Ketogenic Diet? What Are Ketones?
Personally, I do this on Friday night to Saturday night, so if something happens and my hunger hasn't crashed by Sunday morning, I have another day that I can go zero carb to keep the momentum going. While the body will trigger ketosis as soon as you run out of glycogen, hunger is attached to your triglyceride and insulin levels, which might take an extra day to normalize.
Hello, I’ve tried several different Exogenous Ketone supplements and I believe Perfect Keto may be the best I’ve tried. Thus far I’ve had Keto//OS from Pruvitt, Kegenix, KetoForce, KetoCaNa and Ketond. Out of all these brands both Perfect Keto and Ketond have been the products that hack me into Ketosis quick and for longer periods of time. Perfect Keto is less expensive that Ketones from Pruvitt mainly because Pruvitt and their Network Marketing is all about making money. The flavors of Perfect Keto are much better than Pruvitt.
Keep these studies in mind as your body tries to play tricks on you during your first day of fasting. Even after three days of fasting, health complications are highly unlikely. However, it is important to know about the possible issues that can be caused by fasting. If you choose to incorporate fasting into your daily diet, you typically want to eat every day as well. Occasionally going on a longer period of fasting.
It was explained to me that exogenous ketones inhibit lipolysis (breaking down of fat cells), therefore triglycerides should be expected to go down. They theorize that ketones may promote transfer of triglycerides from blood into cells, which primes the pump for fat burning, but to verify would require conducting biopsies to measure blood versus tissue.
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.
One other thing I must point out is also that we are talking about being in ketosis and not being fully keto adapted. You enter ketosis when your body starts producing ketones above a specified level, being fully keto adapted means that your body is full adapted to use fat as your primary energy source and that the production of certain enzymes in your body is fully adapted. This doesn’t happen in one day and it takes about 1 month on average to be fully keto adapted. But we are not looking for this as we just want to end the most unpleasant period and to start losing weight.
The CNS cannot use fat as an energy source; hence, it normally utilizes glucose. After 3–4 days without carbohydrate consumption the CNS is ‘forced' to find alternative energy sources, and as demonstrated by the classic experiments of Cahill and colleagues4 this alternative energy source is derived from the overproduction of acetyl coenzyme A (CoA). This condition seen in prolonged fasting, type 1 diabetes and high-fat/low-carbohydrate diets leads to the production of higher-than-normal levels of so-called ketone bodies (KBs), that is, acetoacetate, β-hydroxybutyric acid and acetone—a process called ketogenesis and which occurs principally in the mitochondrial matrix in the liver.6
Serial drinks or a continuous NG infusion of KE effectively kept blood ketone concentrations >1 mM for 9 h (Figure (Figure6).6). With drinks every 3 h, blood d-βHB rose and then fell, but had not returned to baseline (~ 0.1 mM) when the next drink was consumed. There was no significant difference in d-βHB Cmax between drinks 2 and 3 (3.4 ± 0.2 mM vs. 3.8 ± 0.2 mM p = 0.3), as the rate of d-βHB appearance fell slightly with successive drinks (0.07 ± 0.01 mmol.min−1 and 0.06 ± 0.01 mmol.min−1 p = 0.6). d-βHB elimination was the same after each bolus (142 ± 37 mmol.min, 127 ± 45 mmol.min; and 122 ± 54 mmol.min). When KE was given via a nasogastric tube, the initial bolus raised blood d-βHB to 2.9 ± 0.5 mM after 1 h, thereafter continuous infusion maintained blood d-βHB between 2–3 mM. Total d-βHB appearance in the blood was identical for both methods of administration (Serial drinks AUC: 1,394 ± 64 mmol.min; NG infusion AUC: 1,305 ± 143 mmol.min. p = 0.6).
That said, there also remains the question of the relative benefits of AcAc versus BOHB, both as independent signaling molecules and as redox modulators in peripheral (aka non-hepatic) tissues. Seen from this perspective, AcAc generated in the liver acts as a NAD+ donor for the periphery, whereas pure BOHB taken orally, to the extent that it is retro-converted to AcAc (Sherwin 1975), potentially deprives the periphery of NAD+.
If you are not on a vigorous exercise plan, I wouldn't go more than about a scoop a day (if you are a 30min/day, low carb person like me) because some of the research available says that if you get into ketosis using diet only and supplement with extra ketones, you may experience a slower rate of weight loss since you are getting your ketones from a supplement rather than the body transforming fat to ketones. As I progress, I will probably move up to 2 scoops per day.
Skipping breakfast on a keto diet is a popular way to boost ketone levels. Despite the age-old myth that breakfast is the most important meal of the day, research shows that breakfast skipping is not only safe but beneficial. Skipping breakfast causes intermittent ketosis and also suppresses appetite . Make sure your next meal of the day isn't too late in the evening as studies show that eating meals late at night causes weight gain and impairs fat metabolism .
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!
Look around your grocery store, and you’ll soon start to see “Fortified with Calcium” on a variety of different labels, along with calcium supplements everywhere you look. Calcium is essential for cardiovascular health, but several studies have found too much calcium to be associated with cardiovascular events and even death. One study found that consumption of 1000+ mg of supplemental calcium per day was associated with an increased risk of death from cardiovascular disease in men but not women. Dietary calcium intake (i.e., calcium from incorporated foods such as milk, etc.), on the other hand, was not associated with death from cardiovascular disease in men or women. Additionally, a different study found 1000 mg of supplemental calcium to be associated with an increase in rates of cardiovascular events in women.
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.
Even though endurance athletes can train in a carb depleted state, they will generally consume carbohydrates in the lead up to a race (the athlete is seeking to increase the ability to run off fats by training in a carb depleted state, then benefiting from both fats AND carbs come race day). Likewise, with the brain, even though the brain can function off ketones, does it mean it’s the best state for brain function?
Again, there are very interesting animal studies plus some single case reports and small uncontrolled trials of humans with neurodegenerative disease and cancer given ketogenic diets and/or exogenous ketones (Murray 2016, Poff 2015, Roberts 2017, Newport 2015, Cunnane 2016). In some cases where the patient does not have the cognitive resources to comply with a well-formulated ketogenic diet, or where target blood levels of BOHB that work in animals are hard to achieve in humans by diet alone, supplemental ketones may have an important role to play in the prevention, management, or reversal of these disease categories.
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
As ketone drinks can deliver nutritional ketosis without fasting, we investigated the effect of food on KE uptake and metabolism. It is well documented that food in the gut can slow, or prevent, the uptake of small hydrophilic hydrocarbons, such as βHB (Melander, 1978; Toothaker and Welling, 1980; Horowitz et al., 1989; Fraser et al., 1995), so decreased gut βHB uptake is probably the cause of lower blood βHB following the meal. Despite higher blood βHB concentrations in the fasted state, the meal did not alter plasma AcAc. This suggests that the rate of conversion of βHB to AcAc may not match the rate of appearance of βHB following KE consumption. Alternatively, meal-induced changes in the hepatic ratio of NAD+:NADH may have altered the conversion of βHB to AcAc (Himwich et al., 1937; Desrochers et al., 1992).
Plasma glucose, free fatty acids (FFA), triglycerides (TG) and urinary d-βHB were assayed using a commercial semi-automated bench-top analyzer (ABX Pentra, Montpellier, France), and insulin was measured using a commercially available ELISA assay (Mercodia, Uppsala, Sweden). Both the pure liquid KS and KE, and a subset of plasma (n = 5) and urine (n = 10) samples from a subset of participants in Study 1 underwent analysis using GC-MS and a chiral column, and the concentrations of l-βHB was calculated using the enzymatically determined concentration of d-βHB and the ratio of the d/l-βHB peaks obtained through GC-MS. Acetoacetate was assayed using an enzymatic method (Bergmeyer, 1965), and breath acetone was measured using GC-MS (Study 1) or with a handheld electrochemical device (Study 2; NTT DOCOMO, Japan) (Toyooka et al., 2013).
The difference in peak blood d-βHB concentrations between matched amounts of βHB as ester or salts arose because the salt contained l-βHB, as the blood concentrations of d- plus l-βHB isoforms were similar for both compounds. It is unclear if kinetic parameters of KE and KS drinks would be similar if matched d-βHB were taken in the drinks. Unlike d-βHB, blood l-βHB remained elevated for at least 8 h following the drink, suggesting an overall lower rate of metabolism of l-βHB as urinary elimination of l-βHB was in proportion to plasma concentration. Despite similar concentrations of total βHB, breath acetone was ~50% lower following KS drinks compared to KE, suggesting fundamental differences in the metabolic fates of D- and L-βHB. These findings support both previous hypotheses (Veech and King, 2016) and experimental work in rats (Webber and Edmond, 1977), which suggested that the l-isoform was less readily oxidized than the d-isoform, and is processed via different pathways, perhaps in different cellular compartments. It seems that l-βHB is not a major oxidative fuel at rest, and may accumulate with repeated KS drinks. However, the putative signaling role of l-βHB in humans remains unclear. In rodent cardiomyocytes, l-βHB acts as a signal that modulates the metabolism of d-βHB and glucose, Tsai et al. (2006) although no differences in blood glucose were seen here. Furthermore, L-βHB can act as a cellular antioxidant, although to a lesser extent than D-βHB (Haces et al., 2008).
There are many different variations of intermittent fasting as well. Dr. Dom D’Agostino, the well-known ketogenic diet researcher, suggests doing a longer intermittent fast for 3 days, 3 times a year. This means not eating for 3 days, and eating normally until the next fast. Daily intermittent fasts are recommended as well. He says that it is ideal to have one to two meals after fasting for most of the day to reap the benefits of intermittent fasting every day.
There are enticing anecdotes of supplemental ketones being used to boost human physical performance in competitive events, notably among elite cyclists. Given that BOHB can deliver more energy per unit of oxygen consumed than either glucose or fatty acids (Sato 1995, Cox 2016, Murray 2016), this makes sense. But what we do not know is if there is any required period of adaptation to the use of exogenous ketones, and thus how to employ them in training. It is clear that exogenous ketones decrease adipose tissue lipolysis and availability of fatty acids, the exact opposite to what happens on a well formulated ketogenic diet. This distinction between exogenous ketones and ketogenic diets on adipose tissue physiology and human energy balance underscores an important reason why these two ketone-boosting strategies should not be conflated.
Meanwhile Brinkworth, et al., in their 2009 paper "Long-term Effects of a Very Low-Carbohydrate Diet and a Low-Fat Diet on Mood and Cognitive Function" looked at the effects on ketogenic diet on cognitive function and mood. The study participants ate a ketogenic diet for a year and the researchers found that mood levels decreased when compared to a group eating a high carb/low fat diet. They go on to remark “there was no evidence that the dietary macronutrient composition of LC and LF diets affected cognitive functioning over the long term, as changes in cognitive function were similar for both diets”.
I’m often asked if it’s necessary to buy and use keto products like urine sticks. They’re small test strips that you dip in urine to see if your body is producing ketones (and therefore indicate if you’ve entered ketosis.) There's very little information on how to know that you are in ketosis other than using these ketones supplements because they are as accurate as can be in determining your current state. Outside of that, you can only guess if you are in it or not by your body's performance.
In Study 2 a Student's unequal variance t-test with equal SD was used to compare urine βHB concentrations. Additionally, a linear mixed effects model was constructed to estimate partitions of variance in R, using the lme4 and blme packages (Chung et al., 2013; Bates et al., 2015). Feeding state and visit number were fixed effects in this model, and inter-participant variability was a random effect. Inter-participant variability was calculated according to the adjusted generalized R2 metric (as proposed by Nakagawa and Schielzeth, 2013), to partition variance between the fixed effects of feeding, inter-participant variability, and residual variability. The coefficient of variation for βHB Cmax and AUC were calculated using the method of Vangel (1996).
Interestingly, the effects of exogenous ketones on blood substrate concentrations were preserved with the metabolic stimulus of a mixed meal. Following KE drinks, FFA and glucose fell and remained low in both fed and fasted subjects, despite higher insulin throughout the fed arm, suggesting that there was no synergistic effect of insulin and βHB to further lower blood glucose or FFA. In agreement with previous work, the threshold for the effects of βHB on glucose and lipids appears to be low (<1 mM), as there was no significant dose-response relationship between increasing blood βHB and the small changes in plasma FFA, TG or glucose across all of the study drinks (Mikkelsen et al., 2015).
Remember how important it is to measure ketone blood levels accurately? Same goes for food tracking. A food tracking app, like MyFitnessPal, provides insight into macronutrient intake and thus the ability to tweak the diet to achieve ketosis. Tracking diet (inputs) and measuring ketones levels (outputs) delivers the best shot at optimizing the keto diet plan.
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