Ketogenesis is the metabolism of fatty acids by β-oxidation. 4 This process gives acetyl CoA which then leads to β-hydroxy-β-methyglutaryl-CoA (HMG-CoA) as seen below5. HMG-CoA converts into Acetoacetone which can switch back and forth to BHB. Acetoacetone to Acetone conversion is irreversible (on the left below). Acetoacetate and BHB (via acetoacetate) are used to produce energy when converted back into acetyl-CoA within a cell’s mitochondria whilst Acetone is excreted in the breath and urine.4
Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. – Glucose is the brain’s principal energy substrate. In Alzheimer’s disease (AD), there appears to be a pathological decrease in the brain’s ability to use glucose. Neurobiological evidence suggests that ketone bodies are an effective alternative energy substrate for the brain. Elevation of plasma ketone body levels through an oral dose of medium chain triglycerides (MCTs) may improve cognitive functioning in older adults with memory disorders. On separate days, 20 subjects with AD or mild cognitive impairment consumed a drink containing emulsified MCTs or placebo. Significant increases in levels of the ketone body beta-hydroxybutyrate (beta-OHB) were observed 90 min after treatment (P=0.007) when cognitive tests were administered. beta-OHB elevations were moderated by apolipoprotein E (APOE) genotype (P=0.036). For 4+ subjects, beta-OHB levels continued to rise between the 90 and 120 min blood draws in the treatment condition, while the beta-OHB levels of 4- subjects held constant (P<0.009). On cognitive testing, MCT treatment facilitated performance on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) for 4- subjects, but not for 4+ subjects (P=0.04). Higher ketone values were associated with greater improvement in paragraph recall with MCT treatment relative to placebo across all subjects (P=0.02). Additional research is warranted to determine the therapeutic benefits of MCTs for patients with AD and how APOE-4 status may mediate beta-OHB efficacy. (http://www.ncbi.nlm.nih.gov/pubmed/15123336)
Some people follow more of an Ultra Low Carb diet approach. This is generally around 50g or less of carbs per day. A ULC is more supportive of reaching a ketogenic state, but again total carbs are not the only variable when it comes to reaching ketosis (other factors such as types of carbs, protein consumption, portion size, ingredients, supplements used etc. all play a role and will be covered in more detail below). 
The other potentially important distinction between nutritional ketosis and chemically-induced ketosis is the potential metabolic role played by liver AcAc production and redox status. Although the ratio of BOHB to AcAc in venous blood is typically 80% to 20%, classic studies by Cahill (1975) have observed important hepatic vein and peripheral arterio-venous gradients for this ratio in keto-adapted patients. What these observations imply is that the liver produces a higher proportion of AcAc than is found in the peripheral blood, and that this is due to uptake of AcAc in peripheral cells (principally muscle) with re-release as BOHB. In the process, the reduction of AcAc to BOHB produces NAD+, which is beneficial to mitochondrial redox state and mitochondrial function (Verdin 2015, Newman 2017).
Safety Warning — KEEP OUT OF REACH OF CHILDERN. This product is only intended to be consumed by healthy adults 18 years of age or older. Do not use if you are pregnant, trying to become pregnant, breast feeding, have known medical conditions (including but not limited to diabetes, kidney, heart, or liver disease) or are taking prescription or OTC medication(s). Consult with your health care practitioner before using this product These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. —

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


The fate of excess ketones: In the event someone has an excessive amount of ketones in the blood, the body (specifically the kidneys) will work as quickly as possible to filter out ketones via urine rather than converting them to adipose tissue.9 This is not to say that you can’t gain fat if you consume an exorbitant amount of exogenous ketones, but that they are less prone to be converted to fat than other nutrients.

Once the body is able to generate energy with the help of exogenous ketones which are present in the bloodstream, it would start looking for other sources of ketones. This would encourage the body to tap into the vast reserve of fat which is accumulated in the body. Thus, the process of ketosis is accelerated when you consume extra exogenous ketones. This also leads to quicker weight loss and the body entering ketosis faster.
The effects of ketone drinks on endogenous insulin secretion are unclear. Whilst the small increase in plasma insulin after KE and KS drinks may have been due to the small quantity of dextrose in the diluent, it has been proposed that ketones could potentiate or even stimulate insulin secretion. Isolated pancreatic islets secreted insulin when stimulated by ketones at glucose concentrations of >5 mM (Biden and Taylor, 1983), and small amounts of insulin are secreted in vivo following exposure to exogenous ketones in animals (Madison et al., 1964; Miles et al., 1981). In response to an intra-venous 10 mM glucose clamp, ketone ester drinks increased glucose uptake and plasma insulin (Holdsworth et al., 2017). The increases in insulin with ketone drinks taken whilst fasted were small compared to the increases seen when the ketone ester drink was consumed with a meal and with consumption of a dextrose drink. Furthermore, the lack of difference in peak plasma insulin between the two latter conditions indicates that nutritional ketosis did not inhibit or increase normal carbohydrate induced insulin production.

2. Shimazu, T., Hirschey, M.D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C.A., Lim, H., Saunders, L.R., Stevens, R.D., Newgard, C.B., Farese Jr, R.V., De Cabo, R., Ulrich, S., Akassoglou, K., and Verdin, E. (2013). Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339, 211-214.


I followed 30g carbs as my limit each day, moderate protein, increased fat intake (avocado at each main meal plus carefully chosen oils, eggs and nuts) and have upped green veg to the bucket load and incorporated a juiced lemon in water to my morning, as well as my usual water consumption. I also did intermittent fasting Mon to Thur, 18 hours fasting each day.
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).
BHB supplementation can drastically enhance your insulin sensitivity, resulting in better shuttling of blood glucose into cells.[10] With type-2 diabetes and insulin resistance becoming growing concerns, BHB supplementation may provide a promising alternative for healthy blood glucose regulation in the coming years.Even for everyday gym goers and fitness enthusiasts, increasing insulin sensitivity via BHB supplementation can be a great benefit as this puts your body in a better position for partitioning nutrients/carbohydrates to energetically demanding, glycolytic tissues, such as skeletal muscle.
In a subset of participants (n = 7) the effect of 3.2 mmol.kg−1 of βHB as KE and KS on blood pH and electrolytes after ketone drinks was investigated. Blood d-βHB kinetics were similar to those in the initial experiment (Figure ​(Figure3A).3A). After 60 min, blood pH declined from 7.41 to 7.31 following a KE drink (p < 0.001, Figure ​Figure3B).3B). Bicarbonate fell significantly from 23.6 ± 0.7 to 17.0 ± 0.8 mM following KE drinks (p < 0.001), but remained within the normal range (Figure 3C). Both ketone drinks significantly decreased blood potassium concentrations by 0.7 mM (both drinks p < 0.05, Figure 3D) and increased sodium and chloride concentrations (Sodium: both drinks p < 0.05, Chloride: KE = p < 0.05, KS = p < 0.005, Figures 3E,F).
The challenge for me is what 80% fat looks like. If I eat 1500 calories a day – mostly veggies and protein – how do I best get the fat? I can eat an avocado with my meals, olive oil on my salads, cook my eggs in coconut oil, but I am not clear on how to eat so much fat the healthy way while keeping calories at a lower amount. I eat once – twice a day. I am not a fan of eating tons of saturated fat – bacon on everything is bad advice I have seen pushed out on other pages. Eating Keto does not mean eating high fat meats for your fat. Healthy is the focus. How to eat a heavy veggie, low protein, high fat diet the most healthy way? The calculations are challenging on a tight schedule for one trying to get started :)I would love some solid advice.
The challenge for me is what 80% fat looks like. If I eat 1500 calories a day – mostly veggies and protein – how do I best get the fat? I can eat an avocado with my meals, olive oil on my salads, cook my eggs in coconut oil, but I am not clear on how to eat so much fat the healthy way while keeping calories at a lower amount. I eat once – twice a day. I am not a fan of eating tons of saturated fat – bacon on everything is bad advice I have seen pushed out on other pages. Eating Keto does not mean eating high fat meats for your fat. Healthy is the focus. How to eat a heavy veggie, low protein, high fat diet the most healthy way? The calculations are challenging on a tight schedule for one trying to get started :)I would love some solid advice.
Electrolyte Imbalance – The physiological reasoning behind electrolytes becoming depleted during a state of ketosis is due to lack of water retention and frequent urination. When supplementing with exogenous ketones, the acute state of ketosis will likely increase the frequency of urination, but it won’t deplete glycogen stores. Therefore, it may be useful to drink an electrolyte solution if you are urinating a lot after taking exogenous ketones, but it’s dependent upon how you feel.
It might sound absolutely crazy to go that long without food. Especially when you consider traditional diets that recommend eating 3-5 small meals each day, starting with breakfast – the “most important” meal of the day. But if you think back to hunter gatherer times, human beings didn’t always have food accessible to us. Farming and agriculture hadn’t existed so our first meal each day would vary quite vastly. If you think about the word itself, ‘breakfast’ means to break-fast. We didn’t have a set time where we would consume our first meal – it was dependent on accessibility. So if you’re wondering how you’re going to survive without going for food for 16 hours, the answer is straight forward – you can! Let’s simplify this and break down what this may potentially look like.
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?
Effects of ketone supplementation on basal blood ketone and basal blood glucose levels: Rats administered ketone supplements did not have a significant change in basal blood ketone levels (a) or basal blood glucose levels (b) for the four week study. Two-Way ANOVA with Tukey’s post-hoc test, results considered significant if p < 0.05. Error bars represent mean (SD)

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:


The blood levels of BOHB that can be achieved with the salts or ester formulations are in the 1-3 mM range, similar to what can be achieved with a well-formulated ketogenic diet in insulin sensitive humans, but well below levels achieved after a 4-7 days of total fasting (Owen 1969). In more insulin resistant humans, the ester formulation may deliver higher blood levels than a sustainable diet (as opposed to short term fasting). For example, in the Virta IUH Study of over 200 patients with type 2 diabetes, blood ketone mean levels were 0.6 mM at 10 weeks and 0.4 mM after 1 year.
Blood, breath, and urine ketone kinetics following mole-matched ketone ester (KE) and ketone salt (KS) drinks, at two amounts, in 15 subjects at rest. Values are means ± SEM. (A) Blood d-βHB. (B) Tmax of blood d-βHB. (C) AUC of blood d-βHB. (D) Isotopic abundance (%) of d- and l-chiral centers in pure liquid KE and KS. (E) Blood d-βHB and l-βHB concentrations in subjects (n = 5) consuming 3.2 mmol.kg−1 of βHB in KS drinks. (F) d-βHB and l-βHB concentrations in urine samples from subjects (n = 10) consuming 3.2 mmol.kg−1 of βHB in KS drinks. (G) Blood d- and l-βHB after 4, 8, and 24 h in subjects (n = 5) consuming 3.2 mmol.kg−1 of βHB in KS drinks. (H) Breath acetone over 24 h in subjects (n = 5) consuming 3.2 mmol.kg−1 of βHB in KE and KS drinks (ppm = parts per million). (I) Urine d-βHB excreted over 4 h after KE and KS drinks (n = 15). (J) Urine pH 4 h after drink, dotted line indicates baseline. †p < 0.05 KE vs. equivalent amount of KS, *p < 0.05 difference between 1.6 vs. 3.2 mmol.kg−1 of βHB, §p < 0.05 difference between amounts of d- and l-βHB, p < 0.05 difference between baseline and post-drink level.
Think about it like building muscle, good supplements can enhance your results, but if you don't eat right and exercise, supplements are just useless. You can't just sit on the couch to watch TV, eat potato chips all day and drink some supplements and expect to gain muscle. A supplement is not a miracle. It's just an addition and before you add it to your diet, you need to get the basics right first, which is dieting and exercise in the case of building muscles. The supplements are not going to lift the heavy weights for you. You do!
How to get into ketosis in 24 hours you ask? Can it be done? Yes, it can happen. But only for people who have already been keto-adapted and may have dropped out of ketosis for a short period of time, like after a cheat day. Those people can follow these steps to get back into ketosis quickly. However, if you are just starting keto you have a lot of work to do before your body will let you get into ketosis.
Hi Mark, sorry this is off topic but not sure where to send a question for a future Ask Mark. I’m about to go into my yearly physical and I am wondering if there is any specific bloodwork that you like to do for your annual check up. I’m 47 year’s old and the than the basic blood work like lipid panel, etc..I’m going to ask my doctor to test my testosterone, HbA1C, fasting insulin, and Vitamin D levels. I’m also going to ask my doctor to do a stool test to check for parasites or other infections I may have picked up from open water swimming for triathlons. Can you recommend any other blood work that might be useful? Thanks!

Let’s briefly discuss some organic chemistry. Two molecules that are “the same” but mirror images of each other (like your hands) are known as enantiomers, a type of spatial isomer. Beta hydroxybutyrate comes in two forms, D-β-hydroxybutyrate (“right-handed”) and L-β-hydroxybutyrate (“left-handed”). D-β-hydroxybutyrate is the form that is naturally produced in the body and is most bioavailable when taken exogenously.


Pruvit v Perfect Keto: One of the more popular brands for BHB salts is Pruvit (Keto OS). Pruvit is a good brand, but they do use some additives. Also, Pruvit is an MLM company that has tons of people pushing their products as the best weight loss product in the world. And you have to use one of their representatives’ referral codes to buy it. Learn more about the two in this Pruvit vs Perfect Keto comparison article.
Taking exogenous ketones not only eliminates the need to follow a strict ketogenic diet to achieve ketosis (so you can have your high carb cake and eat it too), it can also help users get there faster. “They can expedite the process of getting into ketosis and becoming fat adapted,” Davis explains. “They can also help people push past the keto flu and potentially experience more mental energy and clarity than from diet alone.”

Your body is trained to use glucose as its main energy source, but when you decrease your consumption of carbs, your body turns to another source of energy that is naturally produced by our own bodies--fat. Therefore, a great way to lose weight faster is to consume low-carb fruits, vegetables and other food that are specially designed for a low-carb diet.

Over five visits, participants (n = 16) consumed either 4.4 mmol.kg−1 of βHB (2.2 mmol.kg−1 or 395 mg/kg of KE; 1 mole of KE delivered 2 moles of d-βHB equivalents): twice whilst fasted, and twice following a standardized meal, or an isocaloric dextrose drink without a meal. To improve palatability, drinks were diluted to 500 ml with a commercially available, citrus flavored drink containing 65 kCal (5 g of carbohydrate) (Glaceau, UK). The dextrose drink was taste-matched using a bitterness additive (Symrise, Holzminden, Germany). The standard meal consisted of porridge oats (54 g), semi-skimmed milk (360 ml) and banana (120 g), giving 600 kCal per person, with a macronutrient ratio of Carbohydrate: Protein: Fat of 2:1:1.
“Imagining that everyone is going to go on a ketogenic diet is very unlikely. I’ve done it myself, and it is hard as a diet to sustain for a long period of time,” said Verdin. “The interest for us in BHB is [if] can we recapitulate all the beneficial effects that we are seeing from the ketogenic diet simply by administering BHB as a food or as a drug, whatever you want to call it.”

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