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What is goBHB and How Does It Work?

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What is goBHB and How Does It Work?

The World’s Most Powerful Science Backed Ingredient.

goBHB® is the Gold Standard of cellular energy. It is a very high quality, patent-protected ketone body, commonly known as Beta-hydroxybutyrate (BHB). goBHB® is a breakthrough energy ingredient from Ketone Labs. Our BHB is bio-identical to the BHB produced endogenously when a person enters a low-carb state in which the body releases fat and the liver converts those fats into ketones, as an alternative, high energy source for the brain, heart, and muscles. BHB is the body’s preferred fuel.

To that note, BHB is used by the fetal brain for energy as they freely cross the placenta and are also incorporated into cerebral lipids and proteins, suggesting that BHB is an essential building block for the developing brain.

BHB also plays an important role in a newborn’s metabolism. For one, BHB is important for a baby’s brain development. Studies have shown that the newborn brain is much better at using ketone bodies as fuel compared to an adult brain (3). Ketones are also a precursor for important metabolites which supports brain development, including cholesterol and certain amino acids. During the most important time of your life, when your brain, heart and all your other major organs are developing, BHB aids in this development.

UNDERSTANDING THE MOLECULE BHB

BHB is Beta-Hydroxybutyrate, one of three molecules classically defined by physiologists as ketone bodies. Ketone bodies, such as B-hydroxybutyrate (BHB or B-OHB), acetone and acetoacetate (AcAc), are produced in the liver and serve as alternative energy sources for the brain, heart, and skeletal muscle cells. In the body (endogenous) they are produced by the liver during glucose deprivation (i.e. intermittent and regular fasting, starvation), or when consuming fat during a low-carbohydrate diet (Yudkoff et al., 2007; Branco et al., 2016). During prolonged fasting, glycogen stores (a source of glucose) are used first as energy and when those stores are exhausted, the level of total blood ketone bodies can increase up to 5-8 mM (Owen et al., 1969). At ketone levels of 0.5 mmol/L, it is clinically defined as a state of nutritional ketosis, which also prevents muscle loss (Veech, 2004; Paoli et al., 2015b), and may boost mitochondrial and neuronal metabolism for a myriad of physical and cognitive benefits (Achanta et al., 2017).

Biochemically, BHB is a water-soluble fat-derived energy metabolite. BHB is powerful. It rapidly crosses the blood brain barrier, accumulates in brain tissue and provides energy for the central nervous system (CNS) (Plecko et al., 2002; Yudkoff et al., 2007; Newman and Verdin, 2014; Achanta and Rae, 2017) with far more energy per gram than glucose. Preserving brain energy metabolism serves a very important evolutionary function with regard to the enormous energy demand of the human brain. Ketones help sustain that demand during glucose energy restriction, as well (Veech et al., 2001; Veech, 2004; Cahill, 2006).

During dietary glucose energy restriction from carbohydrate and protein restriction (ketogenic diet; KD), prolonged fasting, or heavy endurance, the human metabolism automatically shifts from burning glucose to burning fatty acids and ketones. In the brain exclusively, ketones become the predominate, preferred fuel for the massive energy requirements of the entire CNS (Cahill, 2006).

The ketone bodies—BHB and AcAc—are synthetized by liver cells’ mitochondria from fatty acids, which lead to ketosis when blood ketone levels rise above 0.5 mmol/L (Figure 1.; fatty acid metabolism in liver). These ketone bodies then reach the brain via blood vessels by transporter molecules. Similar to heart and skeletal muscle cells, ketone bodies can metabolize directly to aceyl CoA and provide energy for brain cells, as well as through the Krebs (ATP) cycle (Yudkoff et al., 2007; Newman and Verdin, 2014; Branco et al., 2016; Egan and D’Agostino, 2016; Achanta and Rae, 2017). While ketone metabolism may appear new, it is interesting to note that BHB is evolutionary molecule – designed to provide high energy when glucose was restricted. For example, many bacteria can synthetize BHB polymers to store energy (Cahill, 2006). Moreover, blood levels of BHB, and how BHB is metabolized and used, are all dependent on age, brain area and species. This suggests a different and diversified physiological role of BHB in the body of several species (Hawkins and Biebuyck, 1979; Achanta and Rae, 2017).

Figure 1. Synthesis and utilization of ketone bodies (from Branco et al., 2016; http://onlinelibrary.wiley.com/doi/10.1111/
eci.12591/full).

WHAT ARE THE BENEFITS OF BHB?

  • BHB is an alternative energy source to glucose and it is the body’s preferred energy source: Despite the fact that the human brain (weighing approximately 1.5 kg) represents 2-3% of body weight, it consumes 20% of the body’s total energy output. BHB represents an alternative form of energy that most of the body’s cells, including the brain, can use in many ways (Yudkoff et al., 2007; Pinckaers et al., 2017) (Figure 2.).

Here are the facts. The brain is shown to burn ketones preferentially over glucose in two ways: (1) In the developing brain, ketones preserve glucose for the pentose phosphate pathway, which results in ribose for DNA synthesis and NADPH for lipid biosynthesis and (2) under conditions of long-term starvation and KD, metabolism shifts from burning glucose to fatty acids and ketones as fuel. Under different conditions from above, glucose is the predominate fuel for the brain (Nehlig, 2004; Cahill, 2006).

The brain is like a hybrid engine, able to switch from ketones to glucose and vice versa. These observations show that the brain has a remarkable ability for adaptation and metabolic flexibility.

  • “The Fourth macronutrient”: BHB provides macronutritional mitochondrial energy (as a “high-octane” fuel). It can also provide unique signaling and health benefits that are completely independent of its role as an energy metabolite (Hashim and VanItallie, 2014; Newman and Verdin, 2014; Cox et al., 2016; Dyer, 2016; Egan and D’Agostino, 2016). This makes BHB one of the most versatile molecules in the human body
  • Reducing Reactive Oxygen Species (ROS) in lowering oxidative stress and inflammation: ROS causes cell damage, especially at the mitochondrial level. BHB when metabolized creates 46X LESS ROS compared to the metabolism of glucose. This magnitude of reduction in oxidative stress and inflammatory processes helps reduce cellular damage, and may improve the symptoms of different diseases such as Parkinson’s disease, Alzheimer’s disease, schizophrenia, amyotrophic lateral sclerosis (ALS), glucose transporter 1 (GLUT1)-deficiency syndrome, anxiety, autism, depression, cancer, and epilepsy not only in model animals of different human diseases but also in patients (Masino et al., 2009; Stafstrom and Rho, 2012; D’Agostino et al., 2013; Shimazu et al., 2013; Hashim and VanItallie, 2014; Poff et al., 2015; Youm et al., 2015; Ari et al., 2016; Branco et al., 2016; Chavan et al., 2016; Rogawski et al., 2016; Achanta and Rae, 2017; Bostock et al., 2017; Cheng et al., 2017; Rho, 2017; Simeone et al., 2017; Tefera et al., 2017).

Figure 2. Effect of ketone bodies on exercise metabolism. (from Pinckaers et al., 2017; https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC5309297/).

  • Improvement of cognitive functions: BHB improved cognitive functioning (e.g., working memory and executive function) in both memory-impaired patients and in healthy nondemented subjects (Reger et al., 2004; Krikorian et al., 2012; Ota et al., 2016).
  • Reduction of Normal Stress and Anxiety: BHB with MCT showed normal stress and anxiety were reduced by 39% (2019, Blind Comparison of Two Different Compositions of Exogenous Ketones and Their Impact on Anxiety, Weight, Lean Muscle Mass and Cognitive Function, Koche, Dituri, and Gracio)
  • Reduction in seizure activity: Approximately 50% reduction in seizure activity was demonstrated in 50-60% of children with drug-resistant childhood epilepsy after KD, which effect may be in relation, among others, to progressive elevation of serum ketone bodies/BHB (Ross et al., 1985; Groomes et al., 2011; Thammongkol et al., 2012; Kim et al., 2016).
  • Homeostatic role: BHB is one of the main components of homeostatic mechanisms, which allow us to survive prolonged starvation and other trying environmental factors. For example, BHB actively regulates its own synthesis and promotes effective use of fat tissue (as an energy store) under this circumstance (Taggart et al., 2005).
  • Longevity-enhancing effects: BHB could also have longevityenhancing effects (Newman and Verdin, 2014; Veech et al 2017). In C. elegans (roundworms), BHB was shown to increase lifespan through inhibiting histone deacetylase (HDAC) and reducing metabolic stress (Edwards et al, 2014).
  • Reduction of hunger and sugar craving and its effect on weight management: Nutritional ketosis/BHB plays a role in regulating food intake and body weight (Atkins, 2002; Paoli, 2014; Paoli et al., 2015a). Different hypotheses suggest the indirect and direct mechanisms by which KD/nutritional ketosis/ ketone bodies induce and evoke weight loss: (i) Losing energy by excretion of ketone bodies, (ii) gluconeogenesis (which converts protein to glucose and provides a major portion of the glucose needed for fuel during the initial period of KD) is an energy-demanding process leading to a “waste of calories”, (iii) higher satiety effect of proteins, which evoke reductions in appetite,(iv) increased lipolysis and decreased lipogenesis and (v) a possible direct suppressive effect of ketone bodies (e.g., BHB) on appetite/ hunger (Kekwick and Pawan, 1957; Atkins, 2002; Cahill, 2006; Feinman and Fine, 2007; Johnstone et al., 2008; Westerterp- Plantenga et al., 2009; Sumithran et al., 2013). In the Kekwick and Pawan study in 1957, the researchers showed that you can consume the same number of calories in fat, protein and carbs, but you expend the most energy (calories) when consuming fat. In other words, a calorie is not a calorie. Also, the ketogenic diet/nutritional ketosis is characterized by increased circulating free fatty acid levels, which may reduce food intake and glucose production through specific neurons from parts of the brain implicated in regulation of satiety and hunger (Paoli et al., 2015a). Thus, among others, beneficial effects of increased levels of both free fatty acids and BHB on body weight suggests that KD/ketosis may be a good way to manage weight. (ISSN 2001 KETAD Trial: Effects of exogenous ketones as an adjunct to low calorie diet on metabolic biomarkers, fat loss and health,Lopez, Raub,, et. al)
  • Insulin sensitivity: BHB enhances insulin sensitivity (Will et al., 1997; Veech, 2004; Park et al., 2011).
  • Improvement of reaction time and exercise performance: BHB may improve them both due to its use as an alternative substrate for ATP (Cox et al., 2016; Egan and D’Agostino, 2016). Additionally, BHB spares glycogen and Leucine (Nair et al, 1988). Brain reaction time was shown to increase by 9.9% (2019, Blind Comparison of Two Different Compositions of Exogenous Ketones and Their Impact on Anxiety, Weight, Lean Muscle Mass and Cognitive Function, Koche, Dituri, and Gracio).
  • Intermittent fasting: Consumption of BHB may preserve and maintain brain energy metabolism during periods of limited glucose availability without breaking a fast or interrupting autophagy.
  • Alleviation of the keto or low carb “flu” symptoms: Keto, low carb “flu” (or ketogenic/ ketosis flu, low-carb flu, induction flu, Atkins flu) is a withdraw symptom from glucose dependency experienced during carbohydrate restriction, which occurs during intermittent fasting, converting to a low carb or ketogenic diet. It’s really the side effect of when the body is adapting to burning ketones rather than glucose for its primary fuel. BHB decreases the symptoms of keto “flu” (e.g., fatigue, headache, nausea, dizziness, sleepiness, and difficulty focusing or brain fog), consumption of more fat, or BHB, may be recommended (Stanton, 2011).

WHY USE EXOGENOUS KETONES (BHB)?

Most people cannot withstand the rigors of maintaining a ketogenic or very low carb diet. It’s just too hard. And certainly, the mainstream population isn’t going to do it. This means their pathway to obtain the main benefits of ketones will be lost. The intermittent faster may also struggle to maintain that lifestyle even though its less rigorous, but nevertheless even intermittent fasting is limited to the number of ketones the body actually produces during an intermittent fast.

What needs to be understood is that the purpose of fasting, ketogenic diets, low carb diets, or calorie restriction diets is to put the body into a position of making more ketones than it already does and using those ketones to its benefit. Exogenous ketones for the first time provide access to ketones anytime you want or need them without having to follow a very restrictive diet. These exogenous ketones will always be used by the body in preference to glucose uptake. This is the power of exogenous ketones, the benefits without the hassles.

We now know through lots of science that BHB has the unique property of enhancing bioenergetic effects (much like creatine, but more versatile), thus consuming BHB as a supplement is the way to quickly enhance our overall metabolic health and even performance. (Abraham, 2015; Cox et al., 2016; Egan and D’Agostino, 2016; Pinckaers et al., 2017). For example, the use of BHB may be especially beneficial for populations of people that have insulin resistance or carbohydrate intolerance. Evidence suggests that BHB can enhance insulin sensitivity and may improve glucose disposal (Will et al., 1997; Veech, 2004; Park et al., 2011). A large percentage of the population above middle age has either signs of insulin resistance or is considered pre-diabetic.

It seems that the most promising application of exogenous ketones as a supplement is using this source of BHB daily as a source of energy to further augment anyone’s own diet or to enhance your intermittent fast (Veech, 2004; Paoli et al., 2013). Ketones are shown to be utilized regardless of glucose levels such as when someone might be on a Zone diet. (ISSN 2001 KETAD Trial: Effects of exogenous ketones as an adjunct to low calorie diet on metabolic biomarkers, fat loss and health, Lopez, Raub,, et. al).

When it comes to using BHB as a supplement together with intermittent fasting or a low carb diet, this may present several additional compelling benefits. For example, when one starts a KD, one’s brain essentially goes through a form of “glucose withdrawal” that can negatively impact physical and cognitive performance. This usually occurs over several days, or as long as two to four weeks, and causes lethargy, headaches and an overall decrease in mental well-being. But after several weeks the body adapts entirely to using fat and ketones (keto-adaptation) more efficiently for energy. Anecdotally, many users report that BHB makes this transition to a keto or low- carbohydrate diet more seamless by circumventing the need for extreme dietary restriction to elevate BHB levels.

This happens by providing an alternative form of energy that can help to restore and preserve normal brain energy metabolism in the face of carbohydrate restriction as described above. If following a KD, the use of BHB helps to bridge the gap into ketosis by supplying ketones to the brain and supplying a nongluconeogenic energy precursor that has less insulin potentiating effect than glucose or protein. Oral intake of BHB will not prevent endogenous ketone production from nutritional ketosis.

The other key application of exogenous ketones is their consumption during a period of time-restricted eating called intermittent fasting (IF). IF has been shown to have a broad range of health benefits, cognitively, physically and especially for metabolic health in resetting insulin resistance. It may have therapeutic effects alone or as an adjunct to increase the efficacy of the treatment of different diseases such as cancer, anxiety, neurological diseases and cognitive impairment (Park et al., 2011; Arnason et al., 2017; Hu et al., 2017; O’Flanagan et al., 2017; Singh et al., 2017). Anecdotally, the consumption of small amounts of ketone supplements during a period of intermittent fasting, can provide a person with greater sustained energy without impairing endogenous ketogenesis. Many of the aforementioned benefits are largely a function of preserving and maintaining brain energy metabolism during periods of limited glucose availability and mild hypoglycemia.

One of the main benefits of elevated BHB is that hunger cravings are controlled (satiety) as long as brain energy metabolism is not interrupted by fluctuations in glucose and insulin. Nutritional ketosis plays a vital role in stabilizing and regulating food intake control (Atkins, 2002; Paoli et al., 2015a). Regarding insulin, it has been shown that ingesting sodium-BHB did not change insulin secretion and was well tolerated without adverse effects in human studies (Plecko et al., 2002; Van Hove et al., 2003). More advanced formulas using BHB mineral electrolytes (i.e. in combination with MCTs) and new/more effective methods of their application are being developed to enhance and sustain ketone absorption and utilization and to evolve therapeutic procedures. For example, it has been demonstrated that not only intragastric gavage of BHB electrolytes, but also administration of its 4.2% solution (in drinking water) increased ketonemia/BHB level in rats, which may decrease fat mass and suggests that ketone supplements can increase the effectiveness of the treatment of obesity (Pawan and Semple, 1983; Caminhotto et al., 2017).

When it comes to performance, especially during periods of extreme exertion or extreme environment (e.g., military troops, emergency personnel, etc.), the use of BHB supplementation evoked mild ketosis. This may be leveraged to provide resilience in the face of limited glucose or oxygen levels without elevation of free fatty acids (Veech, 2004). It may also be noted the application of BHB as an exogenous fuel may be perceived as beneficial to exercise enthusiasts, high-performance athletes (e.g., elite athletes, and cyclists) and even to corporate executives functioning under high levels of stress due to limited sleep, limited food consumption and nonstop travel associated with their business activities. BHB in the form of BHB electrolytes may also add a critical hydration component by being able to deliver “free electrolytes” in the form of sodium, potassium, calcium and magnesium as the freely dissociate from the BHB acid upon ingestion and provide the body an instant supply of needed electrolytes. We call these PURE electrolytes. Indeed, it has been demonstrated that BHB may have distinct benefits for athletes looking to improve their reaction time and performance (Abraham, 2015; Paoli et al., 2015b; Cox et al., 2016; Egan and D’Agostino, 2016). Moreover, exogenous ketone supplements/ BHB as a food supplement may increase endurance performance of warfighters similar to high-performance athletes, providing an alternative substrate for oxidative phosphorylation (ATP), greater muscle fat oxidation and a sparing of muscle glycogen (Cox et al., 2016; Egan and D’Agostino, 2016). Elevating blood ketones may also enhance cardiac function (Puchalska and Crawford, 2017). For example, ketone bodies increased both the hydraulic efficiency of the heart by 28% and synthesis of adenosine triphosphate (ATP) (Kashiwaya et al., 1994).

The most promising application of BHB appears to be as a neurocognitive enhancement strategy and perhaps even a nootropic agent for improving cognitive function and reaction time, which has a broad range of implications for age- related cognitive decline (Newport et al., 2015; Ota et al., 2016; Mamelak, 2017). It has been demonstrated that BHB preserves the rat hippocampus (Izumi et al., 1998), a brain structure, which has a role for example in memory and cognition (it is interesting to note that the hippocampus is one of the first structures of the brain, which suffer damage in dementia generating among others shortterm memory loss). In human studies, BHB infusion and ketogenic meals- evoked increase in BHB levels improved cognitive functioning (e.g., working memory and executive function) not only in memory- impaired patients but also in healthy non-demented subjects (Reger et al., 2004; Krikorian et al., 2012; Ota et al., 2016). BHB increased the cerebral blood flow in healthy people (Hasselbalch et al., 1996), which may evoke ameliorating effect on cognitive functions. Moreover, ketone bodies may protect from cognitive impairment and moodiness evoked by obesity and weight gain (Yancy et al., 2009; Davidson et al., 2013).

WHY BHB ELECTROLYTES?

It doesn’t do anyone any good to produce a product no one will consume. Ever tasted a BHB ester? 1,3, butanediol (which is not a ketone body, but a pre-cursor alcohol that sometimes is used to create BHB)? They taste awful! BHB is attached to minerals (electrolytes) to create stability and consumability so they can be used in powder form, which is the most convenient form. A BHB electrolyte is created through an ionic bond with a mineral because BHB is not stable on its own in powder form. The BHB “electrolyte” (calcium, sodium, magnesium or potassium) makes the molecule way more palatable, and it’s also a very convenient way to deliver critical electrolytes that may otherwise be depleted under conditions of low-carbohydrate dieting or performance. Specifically, the consumption of BHB in a mineral electrolyte form buffers the ketone molecule to reduce the mild acidity that’s associated with the free acid form while supplying free-form electrolytes to aid in a low-carb diet or high performance activity.

It is important to consume BHB with balanced minerals in order to help absorption and maintain the proper electrolyte balance while being able to increase BHB levels. (Paoli et al., 2015b; Kesl et al., 2016; Caminhotto et al., 2017) (Figure 3.). Combining BHB with mineral electrolytes also allows BHB consumption in effective concentrations without leading to gastrointestinal (GI) distress It is interesting to note that ketone electrolytes may be effective in different intravenous and dialysis fluid therapies such as application of sodium- BHB in resuscitation fluids in combat casualties (Veech, 2004).

Figure 3. Effects of ketone supplementation on blood BHB level (from Kesl et al., 2016; https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC4743170/).

WHAT IS THE BEST WAY TO BALANCE THE MINERALS?

One way to balance BHB mineral electrolytes is to have sodium as the predominant mineral, since that can facilitate absorption of many molecules in the gut through co-transporter activation. Potassium, magnesium and calcium would represent at least 50% of the mineral content of the ketone electrolytes in a balanced ratio. This is one general guideline for formulation of a ketone electrolyte that is palatable and tolerable (Plecko et al., 2002; Van Hove et al., 2003; Azzam and Azar, 2013; Kesl et al., 2016).

BHB electrolytes contain BHB and sodium (Na+), potassium (K+), calcium (Ca2+) and/or magnesium (Mg2+) ions. As ketone bodies have diuretic effects and cause a loss of certain amounts of electrolytes BHB “electrolyte” content helps compensate for the loss without serious side effects if keeping to normal dosing (Veech, 2004). It should be noted that the sodium in sodium BHB is not sodium chloride (aka, table salt), the type of sodium people normally attribute to a rise in blood pressure. Ours is PURE sodium.

WHY BHB FREE ACID?

The best way to create a BHB RTD is using our BHB free acid which is a 50% solution. There are no solubility issues, no acidity issues, no flavoring issues or production issues. Dosing levels can be anything you want based off what you are trying to achieve.

APPROPRIATE DOSING FOR VARIOUS OUTCOMES (WEIGHT MGMT. (SATIETY), COGNITION, PERFORMANCE…)

The best dosing strategy for BHB electrolytes is to start at a relatively low dose – about 6 g per serving. Gradually increase the dose every three days in order to achieve the desired energy performance and GI tolerability. However, to achieve therapeutic levels of ketone bodies (1-5 mM) in the blood of a 70 kg man, it can range from 5.6g to 63 g/day of BHB salts (Veech, 2004), depending on the goal of the user and/or type of disease state. In dietary supplements, the typical therapeutic dose is in the 10g to 12g range. In some applications BHB can be combined with 2 to 3g of MCT for higher and more sustained levels of blood ketones. After ingesting a BHB supplement, increased levels of blood ketones may decrease to the normal physiological levels within several hours (Figure 3.). Thus, to achieve and maintain desired therapeutic levels of BHB, it’s wise to time your ketogenic/ BHB supplement to achieve your goal (e.g., before a meal, during intermittent fasting, prior to exercise, before difficult cognitive tasks, for long-lasting energy and other goals unique to you).

ARE THERE PATENTS ASSOCIATED WITH BHB?

Yes, Axcess Global Sciences currently holds the greatest number of BHB electrolyte and acid patents concerning BHB, the combination of BHB and MCT, and numerous other combinations of BHB and other ingredients. Ketone Labs is the official distributor of the patented BHB trademark goBHB™.

DOES TAKING EXOGENOUS KETONES ACTUALLY PUT SOMEONE INTO KETOSIS?

Yes, taking exogenous ketone supplements will elevate normal blood plasma BHB levels into a range that is clinically accepted as being in a state of ketosis (>0.5 mM) (Achanta and Rae, 2017).

CAN I BENEFIT FROM EXOGENOUS KETONES IF I’M NOT EATING KETOGENICALLY?

Yes, someone not eating a KD or carbohydrate-restricted diet can benefit from consumption of BHB electrolytes due to the fact that this will allow an elevation of BHB in the blood, which we know is linked to many health benefits described above; some of which have been documented in humans (Pinckaers et al., 2017). More research is needed to move the preclinical animal studies into human clinical studies to validate the use of BHB supplementation.

SHOULD THOSE IN NUTRITIONAL KETOSIS TAKE EXOGENOUS KETONES?

Yes. The use of exogenous ketones for performance applications has been exclusively in the realm of special operations forces and elite level endurance athletes that have described significant benefits for specific applications (Egan and D’Agostino, 2016; D’Agostion et. al., 2013; Abraham, 2015; Pinckaers et al., 2017). Similar to creatine supplementation, we will elucidate what types of exercise and what types of sports will benefit most from ketone supplementation as the science progresses (Cox et al., 2016). It will be important for the end-user to experiment with the dosing of ketones according to their own performance regimen since other factors, – including body size, type of exercise, duration, existing nutrition strategy and other supplements – will influence the performance-enhancing benefits of BHB supplementation (Pinckaers et al., 2017). Those already in a state of nutritional ketosis can also benefit from BHB supplementation by allowing the user to optimize blood levels of ketones that they have found correlate with optimal mental and cognitive performance.

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