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.
Most supplements rely on BHB as the source of their exogenous ketone bodies. BHB is converted to acetoacetic acid with a small quantity converted to acetone through a acetoacetate decarboxylase waste pathway. Some of the acetoacetic acid will enter the energy pathway using beta-ketothialase, which converts acetoacetic acid to two Acetyl-CoA molecules (see diagram below2).
The other option – which is the superior option – is the breakdown of fat into a fuel that can be used by the brain. This is a beautiful solution, because even the leanest individual will have weeks and weeks’ worth of energy stored as body fat. The body breaks down this fat in the liver and converts it into ketone bodies. The brain can then utilise these ketones as a fuel source – forgoing the need for stored glucose or constant consumption of carbohydrates. These ketones can also be used to make ATP.
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).
Every 7 days, animals were briefly fasted (4 h, water available) prior to intragastric gavage to standardize levels of blood metabolites prior to glucose and βHB measurements at baseline. Baseline (time 0) was immediately prior to gavage. Whole blood samples (10 μL) were taken from the saphenous vein for analysis of glucose and βHB levels with the commercially available glucose and ketone monitoring system Precision Xtra™ (Abbott Laboratories, Abbott Park, IL). Blood glucose and βHB were measured at 0, 0.5, 1, 4, 8, and 12 h after test substance administration, or until βHB returned to baseline levels. Food was returned to animals after blood analysis at time 0 and gavage. At baseline and week 4, whole blood samples (10 μL) were taken from the saphenous vein immediately prior to gavage (time 0) for analysis of total cholesterol, high-density lipoprotein (HDL), and triglycerides with the commercially available CardioChek™ blood lipid analyzer (Polymer Technology Systems, Inc., Indianapolis, IN). Low-density lipoprotein (LDL) cholesterol was calculated from the three measured lipid levels using the Friedewald equation: (LDL Cholesterol = Total Cholesterol - HDL - (Triglycerides/5)) [51, 52]. Animals were weighed once per week to track changes in body weight associated with hyperketonemia.
Personally, I think it is wise to include a regular carb meal in your diet if you are going to follow a ketogenic diet. Long term ketogenic diets do seem to downregulate your thyroid and metabolism, and a weekly carb meal (or carb day) can help avoid this. The Carb Nite diet by J. Kiefer is a good example of this. And BJJCaveman posted his labs showing how a weekly carb meal helped his thyroid HERE.
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.
Perfect Keto Base BHB Salt has everything you need in a BHB salt and nothing you don’t. For this reason, it shares the number one spot alongside their MCT oil powder as the best exogenous ketone supplements you can find. As far as price and value, many other BHB salts are more expensive, and lesser quality as they use additives and fillers. What gives Perfect Keto Base their edge outside of their proven raw ingredients quality is, taste. BHB salts are hard to make palatable. Perfect Keto has risen above when it comes to taste as well.

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.
Intermittent fasting will significantly help the body transition into ketosis as limiting your consumption of food for that many hours will help deplete the system of any excess glucose. It’s a shock to the system and research has shown that daily fasting can have other profound effects aside from weight control such as autophagy, lowering risks of heart disease and diabetes, as well as an improvement in cognitive function. So if you’re still wondering how to get into ketosis in 24 hours, then fasting will surely kick things into gear!
KE consumption decreased FFA from 0.6 to 0.2 mM, TG from 1.0 to 0.8 mM, and glucose from 5.5 to 4.7 mM by the end of the study (4 h). The effect was not altered by a meal (Figures 5A–C). Dextrose drinks also lowered FFA from 0.6 to 0.2 mM and TG from 1.0 to 0.7 mM (Figures 5A, B). This was likely mediated by the transient increase in glucose, which rose from 4.6 to 6.5 mM following the dextrose drink (Figure ​(Figure5C).5C). The anti-lypoytic effect of dextrose drinks was shorter than that of KE drinks as d-βHB concentrations were elevated for longer after KE drinks than glucose after dextrose drinks. Insulin increased to ~ 35 mU.ml−1 after both the meal and the dextrose drink, but also increased to 13 ± 2 mU.ml−1 when KE was consumed whilst fasted owing to the 15 g of glucose in the flavored drink used as a diluent (Figure ​(Figure5D5D).

Sometimes waiting for your body to make the switch from carbohydrate metabolism to beta hydroxybutyrate metabolism (aka ketosis) can be an uncomfortable and lengthy process. Another way to get beta hydroxybutyrate into your system so your body is using “clean” energy is by taking it supplementally or through nutrition. A betahydroxybutyrate supplement is what can be used in this scenario. This is an exogenous ketone. Exogenous means you get it from outside of your body. Think EX = exit = outside.


KE consumption decreased FFA from 0.6 to 0.2 mM, TG from 1.0 to 0.8 mM, and glucose from 5.5 to 4.7 mM by the end of the study (4 h). The effect was not altered by a meal (Figures 5A–C). Dextrose drinks also lowered FFA from 0.6 to 0.2 mM and TG from 1.0 to 0.7 mM (Figures 5A, B). This was likely mediated by the transient increase in glucose, which rose from 4.6 to 6.5 mM following the dextrose drink (Figure ​(Figure5C).5C). The anti-lypoytic effect of dextrose drinks was shorter than that of KE drinks as d-βHB concentrations were elevated for longer after KE drinks than glucose after dextrose drinks. Insulin increased to ~ 35 mU.ml−1 after both the meal and the dextrose drink, but also increased to 13 ± 2 mU.ml−1 when KE was consumed whilst fasted owing to the 15 g of glucose in the flavored drink used as a diluent (Figure ​(Figure5D5D).
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
Even Ben Greenfield Has Thyroid Problems While In Ketosis - “Ben describes one of the main side effects that he encountered being severe hypothyroidism… manifesting as severe sensitivity to cold, poor libido, and poor overall energy. The way they treated this was to eat a lot of liver, desiccated thyroid, and sweetbreads which seemed to fix things for him.”
When the results for the supplement and the placebo were within 0.2 (either % or mmol/L) of each other, we classed the supplement as neither “better” nor “worse” than the placebo. We gave a “winning brand” sticker to the brand that scored highest against the placebo for each marker, but not for physical performance, since none of the supplements performed better than the placebo for that marker.
Beta-hydroxybutyrate (BHB) is a ketone body produced in the liver naturally under conditions when glucose isn’t very available. Other types of ketones produced via the restriction of dietary carbohydrates are acetoacetate and acetone. A VLCHF or ketogenic diet provides the optimal conditions for this process. Fasting, exercise and/or basic caloric restriction are all also methods for promoting ketogenesis (literally, the making of ketones).
The other option – which is the superior option – is the breakdown of fat into a fuel that can be used by the brain. This is a beautiful solution, because even the leanest individual will have weeks and weeks’ worth of energy stored as body fat. The body breaks down this fat in the liver and converts it into ketone bodies. The brain can then utilise these ketones as a fuel source – forgoing the need for stored glucose or constant consumption of carbohydrates. These ketones can also be used to make ATP.
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.
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)
Possible GI distress (flatulence) at exceptionally high doses –  In the studies referenced in this article, exogenous ketones taken in large doses occasionally resulted in GI distress, especially flatulence. However, the cause of this is hypothesized to be due to the fact that ketones were mixed in a milky fluid that wasn’t very palatable. If you’re taking a nominal dose of exogenous ketones the likelihood of GI distress is rather low. Moreover, if some GI distress is prevalent, it should improve as you become accustomed to taking ketones.

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.”
Blood glucose concentrations are decreased during both exogenous and endogenous ketosis, although by different mechanisms. During endogenous ketosis, dietary carbohydrate deficit is the underlying cause of low blood glucose, along with reduced hepatic gluconeogenesis and increased ketone production (Cahill et al., 1966). With exogenous ketosis, carbohydrate stores are plentiful, yet ketones appear to lower blood glucose through limiting hepatic gluconeogenesis and increasing peripheral glucose uptake (Mikkelsen et al., 2015). One clinical use of the ketogenic diet is to improve blood glucose control, yet the elevated blood FFA may increase the risk of heart failure (Holloway et al., 2009). Thus, the ability of exogenous ketones to lower blood glucose without elevating blood FFA concentrations could deliver the desired effect of the diet, whilst also decreasing a potential risk.

When you restrict carbs, the kidneys excrete a lot of sodium. Not replacing this sodium can leave you feeling light headed. I recommend having a big glass of spring water with ½ teaspoon of Celtic sea salt twice a day (first thing in the morning and midafternoon are two times that work well). A long with this, make sure you use a lot of salt on your meals.
The main distraction which we have these days in our lives are the gadgets. Therefore, in order to fall asleep early, you need to make sure that you turn off your phones, tablets, computer, TV etc… at least 30 minutes before bedtime. This helps avoid insomnia as well as keep you away from the bright blue light which can interfere with your biorhythm.
Besides cutting carbs, it's important to increase your fat intake, and be moderate with protein. The fat you eat will keep you feeling energized and support ketone production. Protein is also important but if you go overboard with it, your body could enter into a process called gluconeogenesis. In gluconeogenesis, your body makes glucose from protein, and you want to avoid that.
Ketones may be a better source of fuel than glucose, and a far better beverage than Fruitopia, but it's a question of whether or not you can spare the extra fuel. Because just like adding sugar to a diet, it's like pressing pause on the fat burning process since the body preferentially burns it for fuel. Adding ketones to the diet does the same thing.
You see, when someone says ketosis is a natural state, they mean that ketosis is the body’s backup plan for those times when there isn’t any food to eat. It’s an evolutionary adaptation that developed over hundreds of thousands of years and springs from a time when our distant ancestors often had to go many days between decent meals. Fortunately, these days actual starvation is pretty rare so most people will never be in ketosis. But the physiological mechanism is still there, lurking in the background, readily accessible to anyone who is willing to trick their body into thinking it’s starving.

Ketones naturally exist in the body, being created during the process of fat metabolism and are therefore safe to consume even during pregnancy or breastfeeding. Supplements such as Ketologie’s PROBHB are simply providing ketones from an external (exogenous means literally ‘outside of the body’) source. However, if you suffer from any medical conditions and/or are on medications, it is always advisable to consult your health care provider prior to starting any new nutritional or dietary supplement.  
Humans in the hunter-gatherer era survived thanks to metabolic flexibility — the body’s ability to use different fuels for energy depending on the nutrients available. This adaptation was vital during a time when the source, quantity, and frequency of food was uncertain[*]. Most of the time, people were fasting, so their bodies ran on ketones, not glucose.

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