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.

REFERENCES

  1. Lincoln BC, Des Rosiers C, Brunengraber H. 1987. Metabolism of S-3-hydroxybutyrate in the perfused rat liver. Arch. Biochem. Biophys. 259:149–56
  2. Webber RJ, Edmond J. 1977. Utilization of L(+)- 3-hydroxybutyrate, D(- )-3-hydroxybutyrate, acetoacetate, and glucose for respiration and lipid synthesis in the 18-day-old rat. J. Biol. Chem. 252:5222–26
  3. Desrochers S, Dubreuil P, Brunet J, Jette M, David F, et al. 1995. Metabolism of (R,S)-1,3-butanediol acetoacetate esters, potential parenteral and enteral nutrients in conscious pigs.Am. J. Physiol. 268:E660–67
  4. Gregoretti IV, Lee YM, Goodson HV. 2004. Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J. Mol. Biol. 338:17–31
  5. Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, et al. 2015. The ketone metaboliteB- hydroxybutyrate blocksNLRP3 inflammasomemediated inflammatory disease. Nat.Med. 21:263–69
  6. YudkoffM, Daikhin Y,Melo TM, Nissim I, Sonnewald U, Nissim I. 2007. The ketogenic diet and brain metabolism of amino acids: relationship to the anticonvulsant effect. Annu. Rev. Nutr. 27:415–30
  7. Sleiman SF, Henry J, Al-Haddad R, El Hayek L, Abou Haidar E, et al. 2016. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body B- hydroxybutyrate. eLife pii:e15092
  8. Bhaskara S, Knutson SK, Jiang G, Chandrasekharan MB, Wilson AJ, et al. 2010. Hdac3 is essential for the maintenance of chromatin structure and genome stability. Cancer Cell 18:436–47
  9. Fajas L, Egler V, Reiter R, Hansen J, Kristiansen K, et al. 2002. The retinoblastoma-histone deacetylase 3 complex inhibits PPARBand adipocyte differentiation. Dev. Cell 3:903–10
  10. Knutson SK, Chyla BJ, Amann JM, Bhaskara S, Huppert SS, Hiebert SW. 2008. Liver-specific deletion of histone deacetylase 3 disrupts metabolic transcriptional networks. EMBO J. 27:1017–28
  11. Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, et al. 2009. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58:1509–17
  12. Guan JS,Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N, et al. 2009.HDAC2negatively regulates memory formation and synaptic plasticity. Nature 459:55–60
  13. Peleg S, Sananbenesi F, Zovoilis A, Burkhardt S, Bahari-Javan S, et al. 2010. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 328:753–56
  14. Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH. 2007. Recovery of learning and memory is associated with chromatin remodeling. Nature 447:178–82
  15. Robinson AM, Williamson DH. 1980. Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiol. Rev. 60:143–87
  16. Kenyon CJ. 2010. The genetics of ageing. Nature 464:504–12
  17. Newman JC, Verdin E. 2014. Ketone bodies as signaling metabolites. Trends Endocrinol. Metab. 25:42–52
  18. Longo VD, Panda S. 2016. Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan. Cell Metab. 23:1048–59
  19. Mattson MP, Longo V, Harvie M. 2016. Impact of intermittent fasting on health and disease processes. Ageing Res. Rev. pii:S1568–1637(16)30251–3
  20. Zhang Y, Xie Y, Berglund ED, Coate KC, He TT, et al. 2012. The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. eLife 1:e00065
  21. Edwards C, Canfield J, Copes N, Rehan M, Lipps D, Bradshaw PC. 2014. D-beta-hydroxybutyrate extends lifespan in C. elegans. Aging 6:621–44
  22. Sleiman SF, Henry J, Al-Haddad R, El Hayek L, Abou Haidar E, et al. 2016. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body B- hydroxybutyrate. eLife pii:e15092
  23. Rahman M, Muhammad S, KhanMA, Chen H, Ridder DA, et al. 2014. TheB-hydroxybutyrate receptor HCA2 activates a neuroprotective subset of macrophages. Nat. Commun. 5:3944
  24. Berg JM, Tymoczko JL, Stryer L. 2012. Biochemistry. New York: Freeman
  25. Pellerin L, Bergersen LH, Halestrap AP, Pierre K. 2005. Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain. J. Neurosci. Res. 79:55–64
  26. Dobbins RL, Shearn SP, Byerly RL, Gao FF, Mahar KM, et al. 2013. GSK256073, a selective agonist of G-protein coupled receptor 109A (GPR109A) reduces serum glucose in subjects with type 2 diabetes mellitus. Diabetes Obes. Metab. 15:1013–21
  27. Graff EC, Fang H, Wanders D, Judd RL. 2016. Anti- inflammatory effects of the hydroxycarboxylic acid receptor 2. Metab. Clin. Exp. 65:102–13
  28. Robinson AM, Williamson DH. 1980. Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiol. Rev. 60:143–87
  29. Abraham R. Ketones: controversial new energy drink could be next big thing in cycling. 2015. http://www.cyclingweekly.co.uk/news/latest-news/ ketones-controversial-new-energy-drink-next-big-thing-cycling-151877. Accessed 14 June 2017
  30. Achanta LB, Rae CD. B-Hydroxybutyrate in the brain: One molecule, multiple mechanisms. Neurochem Res. 2017 Jan;42(1):35-49. doi: 10.1007/s11064-016-2099-2
  31. Achanta LB, Rowlands BD, Thomas DS, Housley GD, Rae CD. B-Hydroxybutyrate Boosts Mitochondrial and Neuronal Metabolism but is not Preferred Over Glucose Under Activated Conditions. Neurochem Res. 2017 Jun;42(6):1710-1723. doi: 10.1007/s11064-017-2228-6.
  32. Ari C, Kovács Z, Juhasz G, Murdun C, Goldhagen CR, Koutnik AP, Poff AM, Kesl SL, D’Agostino DP. Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/ Rijswijk Rats. Front Mol Neurosci. 2016 Dec 6;9:137. doi: 10.3389/ fnmol.2016.00137. eCollection 2016.
  33. Arnason TG, Bowen MW, Mansell KD. Effects of intermittent fasting on health markers in those with type 2 diabetes: A pilot study. World J Diabetes. 2017 Apr 15;8(4):154-164. doi: 10.4239/wjd.v8.i4.154
  34. Atkins RC. Dr. Atkins’ new diet revolution. New York: Avon, 2002.
  35. Azzam R, Azar NJ. Marked seizure reduction after MCT supplementation. Case Rep Neurol Med. 2013;2013:809151. doi: 10.1155/2013/809151.
  36. Bostock EC, Kirkby KC, Taylor BV. The current status of the ketogenic diet in psychiatry. Front Psychiatry. 2017 Mar 20;8:43. doi: 10.3389/ fpsyt.2017.00043. eCollection 2017
  37. Branco AF, Ferreira A, Simões RF, Magalhães-Novais S, Zehowski C, Cope E, Silva AM, Pereira D, Sardão VA, Cunha-Oliveira T. Ketogenic diets: from cancer to mitochondrial diseases and beyond. Eur J Clin Invest. 2016 Mar;46(3):285-98. doi: 10.1111/eci.12591
  38. Cahill GF Jr. Fuel metabolism in starvation. Annu Rev Nutr. 2006;26:1-22.
  39. Caminhotto RO, Komino ACM, de Fatima Silva F, Andreotti S, Sertié RAL, Boltes Reis G, Lima FB. Oral B-hydroxybutyrate increases ketonemia, decreases visceral adipocyte volume and improves serum lipid profile in Wistar rats. Nutr Metab (Lond). 2017 Apr 24;14:31. doi: 10.1186/s12986- 017-0184-4. eCollection 2017
  40. Chavan R, Feillet C, Costa SS, Delorme JE, Okabe T, Ripperger JA, Albrecht U. Liver-derived ketone bodies are necessary for food anticipation. Nat Commun. 2016 Feb 3;7:10580. doi: 10.1038/ncomms10580
  41. Cheng N, Rho JM, Masino SA. Metabolic dysfunction underlying autism spectrum disorder and potential treatment approaches. Front Mol Neurosci. 2017 Feb 21;10:34. doi: 10.3389/fnmol.2017.00034. eCollection 2017.
  42. Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL, Clarke K. Nutritional ketosis alters fuel preference and thereby endurance performance in athletes. Cell Metab. 2016 Aug 9;24(2):256-68. doi: 10.1016/j.cmet.2016.07.010.
  43. D’Agostino DP, Pilla R, Held HE, Landon CS, Puchowicz M, Brunengraber H, Ari C, Arnold P, Dean JB. Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats. Am J Physiol Regul Integr Comp Physiol. 2013 May 15;304(10):R829-36. doi: 10.1152/ ajpregu.00506.2012. Epub 2013 Apr 3.
  44. Davidson TL, Hargrave SL, Swithers SE, Sample CH, Fu X, Kinzig KP, Zheng W. Inter-relationships among diet, obesity and hippocampal dependent cognitive function. Neuroscience. 2013 Dec 3;253:110-22. doi:10.1016/j.neuroscience.2013.08.044.
  45. Denton, M. Beta Hydroxybutyrate. 2016. https://www.nootropedia.com/ beta-hydroxybutyrate/. Accessed 14 June 2017
  46. Dombrowski GJ Jr, Swiatek KR, Chao KL. Lactate, 3-hydroxybutyrate, and glucose as substrates for the early postnatal rat brain. Neurochem Res. 1989 Jul;14(7):667-75.
  47. Dyer E. Ketogenic diet and the “4th” macronutrient, 2016; http://www. esupplements.com/article/keto-diet-and-the-fourth-macro/. Accessed 14 June 2017
  48. Egan B, D’Agostino DP. Fueling performance: ketones enter the mix. Cell Metab. 2016 Sep 13;24(3):373-5. doi: 10.1016/j.cmet.2016.08.021
  49. Feinman RD, Fine EJ. Nonequilibrium thermodynamics and energy efficiency in weight loss diets. Theor Biol Med Model. 2007 Jul 30;4:27
  50. Gautschi M, Weisstanner C, Slotboom J, Nava E, Zürcher T, Nuoffer JM. Highly efficient ketone body treatment in multiple acyl-CoA dehydrogenase deficiency-related leukodystrophy. Pediatr Res. 2015 Jan;77(1-1):91-8. doi: 10.1038/pr.2014.154.
  51. Groomes LB, Pyzik PL, Turner Z, Dorward JL, Goode VH, Kossoff EH. Do patients with absence epilepsy respond to ketogenic diets? J Child Neurol. 2011 Feb;26(2):160-5. doi: 10.1177/0883073810376443.
  52. Hashim SA, VanItallie TB. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester. J Lipid Res. 2014 Sep;55(9):1818- 26. doi: 10.1194/jlr.R046599
  53. Hasselbalch SG, Madsen PL, Hageman LP, Olsen KS, Justesen N, Holm S, Paulson OB. Changes in cerebral blood flow and carbohydrate metabolism during acute hyperketonemia. Am J Physiol. 1996 May;270(5 Pt 1):E746-51.
  54. Hawkins RA, Biebuyck JF. Ketone bodies are selectively used by individual brain regions. Science. 1979 Jul 20;205(4403):325-7
  55. Hu Y, Yang Y, Zhang M, Deng M, Zhang JJ. Intermittent fasting pretreatment prevents cognitive impairment in a rat model of chronic cerebral hypoperfusion. J Nutr. 2017 May 17. pii: jn245613. doi: 10.3945/ jn.116.245613. [Epub ahead of print]
  56. Izumi Y, Ishii K, Katsuki H, Benz AM, Zorumski CF. Beta-Hydroxybutyrate fuels synaptic function during development. Histological and physiological evidence in rat hippocampal slices. J Clin Invest. 1998 Mar 1;101(5):1121- 32.
  57. Johnstone AM, Horgan GW, Murison SD, Bremner DM, Lobley GE. Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum. Am J Clin Nutr. 2008 Jan;87(1):44- 55.
  58. Kashiwaya Y, Sato K, Tsuchiya N, Thomas S, Fell DA, Veech RL, Passonneau JV. Control of glucose utilization in working perfused rat heart. J Biol Chem. 1994 Oct 14;269(41):25502-14.
  59. Kekwick A, Pawan GL. Metabolic study in human obesity with isocaloric diets high in fat, protein or carbohydrate. Metabolism. 1957 Sep;6(5):447- 60
  60. Kesl SL, Poff AM, Ward NP, Fiorelli TN, Ari C, Van Putten AJ, Sherwood JW, Arnold P, D’Agostino DP. Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats. Nutr Metab (Lond). 2016 Feb 4;13:9. doi: 10.1186/s12986-016-0069-y. eCollection 2016.
  61. Kim JA, Yoon JR, Lee EJ, Lee JS, Kim JT, Kim HD, Kang HC. Efficacy of the classic ketogenic and the modified Atkins diets in refractory childhood epilepsy. Epilepsia. 2016 Jan;57(1):51-8. doi: 10.1111/epi.13256.
  62. Klee CB, Sokoloff L. Changes in D(-)-beta-hydroxybutyric dehydrogenase activity during brain maturation in the rat. J Biol Chem. 1967 Sep 10;242(17):3880-3.
  63. Krikorian R, Shidler MD, Dangelo K, Couch SC, Benoit SC, Clegg DJ. Dietary ketosis enhances memory in mild cognitive impairment. Neurobiol Aging. 2012 Feb;33(2):425.e19-27. doi: 10.1016/j. neurobiolaging.2010.10.006.
  64. Mamelak M. Energy and the Alzheimer brain. Neurosci Biobehav Rev. 2017 Apr;75:297-313. doi: 10.1016/j.neubiorev.2017.02.001
  65. Masino SA. Ketogenic Diet and Metabolic Therapies: Expanded Roles in Health and Disease. Oxford University Press, 2016.
  66. Masino SA, Kawamura M, Wasser CD, Pomeroy LT, Ruskin DN. Adenosine, ketogenic diet and epilepsy: the emerging therapeutic relationship between metabolism and brain activity. Curr Neuropharmacol. 2009 Sep;7(3):257-68. doi: 10.2174/157015909789152164.
  67. Nehlig A. Brain uptake and metabolism of ketone bodies in animal models. Prostaglandins Leukot Essent Fatty Acids. 2004 Mar;70(3):265-75.
  68. Nehlig A, Pereira de Vasconcelos A. Glucose and ketone body utilization by the brain of neonatal rats. Prog Neurobiol. 1993 Feb;40(2):163-221.
  69. Newman JC, Verdin E. Ketone bodies as signaling metabolites. Trends Endocrinol Metab. 2014 Jan;25(1):42-52. doi: 10.1016/j.tem.2013.09.002.
  70. Newport MT, VanItallie TB, Kashiwaya Y, King MT, Veech RL. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer’s disease. Alzheimers Dement. 2015 Jan;11(1):99-103. doi: 10.1016/j. jalz.2014.01.006
  71. O’Flanagan CH, Smith LA, McDonell SB, Hursting SD. When less may be more: calorie restriction and response to cancer therapy. BMC Med. 2017 May 24;15(1):106. doi: 10.1186/s12916-017-0873-x.
  72. Ota M, Matsuo J, Ishida I, Hattori K, Teraishi T, Tonouchi H, Ashida K, Takahashi T, Kunugi H. Effect of a ketogenic meal on cognitive function in elderly adults: potential for cognitive enhancement. Psychopharmacology (Berl). 2016 Oct;233(21-22):3797-3802.
  73. Owen OE, Felig P, Morgan AP, Wahren J, Cahill GF Jr. Liver and kidney metabolism during prolonged starvation. J Clin Invest. 1969 Mar;48(3):574-83
  74. Paoli A. Ketogenic diet for obesity: friend or foe? Int J Environ Res Public Health. 2014 Feb 19;11(2):2092-107. doi: 10.3390/ijerph110202092.
  75. Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr. 2013 Aug;67(8):789-96. doi: 10.1038/ejcn.2013.116.
  76. Paoli A, Bosco G, Camporesi EM, Mangar D. Ketosis, ketogenic diet and food intake control: a complex relationship. Front Psychol. 2015a Feb 2;6:27. doi: 10.3389/fpsyg.2015.00027. eCollection 2015
  77. Paoli A, Bianco A, Grimaldi KA. The ketogenic diet and sport: A possible marriage? Exerc Sport Sci Rev. 2015b Jul;43(3):153-62. doi: 10.1249/ JES.0000000000000050.
  78. Park S, Kim DS, Daily JW. Central infusion of ketone bodies modulates body weight and hepatic insulin sensitivity by modifying hypothalamic leptin and insulin signaling pathways in type 2 diabetic rats. Brain Res. 2011 Jul 15;1401:95-103. doi: 10.1016/j.brainres.2011.05.040
  79. Pawan GL, Semple SJ. Effect of 3-hydroxybutyrate in obese subjects on very-low-energy diets and during therapeutic starvation. Lancet. 1983 Jan 1;1(8314-5):15-7.
  80. Pinckaers PJ, Churchward-Venne TA, Bailey D, van Loon LJ. Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype? Sports Med. 2017 Mar;47(3):383-391. doi: 10.1007/s40279-016- 0577-y.
  81. Plecko B, Stoeckler-Ipsiroglu S, Schober E, Harrer G, Mlynarik V, Gruber S, Moser E, Moeslinger D, Silgoner H, Ipsiroglu O. Oral B-hydroxybutyrate supplementation in two patients with hyperinsulinemic hypoglycemia: Monitoring of B-hydroxybutyrate levels in blood and cerebrospinal fluid, and in the brain by in vivo magnetic resonance spectroscopy. Pediatric Res. 2002;52:301-6; doi:10.1203/00006450-200208000-00025
  82. Poff AM, Ward N, Seyfried TN, Arnold P, D’Agostino DP. Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy. PLoS One. 2015 Jun 10;10(6):e0127407. doi: 10.1371/ journal.pone.0127407. eCollection 2015
  83. Puchalska P, Crawford PA. Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics. Cell Metab. 2017 Feb 7;25(2):262-284. doi: 10.1016/j.cmet.2016.12.022. Review. PubMed PMID: 28178565
  84. Reger MA, Henderson ST, Hale C, Cholerton B, Baker LD, Watson GS, Hyde K, Chapman D, Craft S. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol Aging. 2004 Mar;25(3):311-4.
  85. Rho JM. How does the ketogenic diet induce anti-seizure effects? Neurosci Lett. 2017 Jan 10;637:4-10. doi: 10.1016/j.neulet.2015.07.034
  86. Rogawski MA, Löscher W, Rho JM. Mechanisms of Action of Antiseizure Drugs and the Ketogenic Diet. Cold Spring Harb Perspect Med. 2016 May 2;6(5). pii: a022780. doi: 10.1101/cshperspect.a022780
  87. Ross DL, Swaiman KF, Torres F, Hansen J. Early biochemical and EEG correlates of the ketogenic diet in children with atypical absence epilepsy. Pediatr Neurol. 1985 Mar-Apr;1(2):104-8
  88. Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, Grueter CA, Lim H, Saunders LR, Stevens RD, Newgard CB, Farese RV Jr, de Cabo R, Ulrich S, Akassoglou K, Verdin E. Suppression of oxidative stress by B-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science. 2013 Jan 11;339(6116):211-4. doi: 10.1126/science.1227166.
  89. Simeone TA, Simeone KA, Rho JM. Ketone bodies as anti-seizure agents. Neurochem Res. 2017 Apr 10. doi: 10.1007/s11064-017-2253-5. [Epub ahead of print]
  90. Singh H, Kaur T, Manchanda S, Kaur G. Intermittent fasting combined with supplementation with Ayurvedic herbs reduces anxiety in middle aged female rats by anti-inflammatory pathways. Biogerontology. 2017 May 6. doi: 10.1007/s10522-017-9706-8. [Epub ahead of print]
  91. Stafstrom CE, Rho JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol. 2012 Apr 9;3:59. doi: 10.3389/fphar.2012.00059. eCollection 2012.
  92. Stanton J. The science behind the “low carb flu”, and how to regain your metabolic flexibility. 2011, April 26; http://www.gnolls.org/1984/ the-science-behind-the-low-carb-flu-and-how-to-regain-your-metabolicflexibility/
  93. Stilling RM, van de Wouw M, Clarke G, Stanton C, Dinan TG, Cryan JF. The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? Neurochem Int. 2016 Oct;99:110-32. doi: 10.1016/j.neuint.2016.06.011
  94. Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, Proietto J. Ketosis and appetite-mediating nutrients and hormones after weight loss. Eur J Clin Nutr. 2013 Jul;67(7):759-64. doi: 10.1038/ ejcn.2013.90.
  95. Taggart AK, Kero J, Gan X, Cai TQ, Cheng K, Ippolito M, Ren N, Kaplan R, Wu K, Wu TJ, Jin L, Liaw C, Chen R, Richman J, Connolly D, Offermanns S, Wright SD, Waters MG. (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem. 2005 Jul 22;280(29):26649-52.
  96. Tefera TW, Tan KN, McDonald TS, Borges K. Alternative fuels in epilepsy and amyotrophic lateral sclerosis. Neurochem Res. 2017 Jun;42(6):1610- 1620. doi: 10.1007/s11064-016-2106-7
  97. Thammongkol S, Vears DF, Bicknell-Royle J, Nation J, Draffin K, Stewart KG, Scheffer IE, Mackay MT. Efficacy of the ketogenic diet: which epilepsies respond? Epilepsia. 2012 Mar;53(3):e55-9. doi: 10.1111/j.1528- 1167.2011.03394.x
  98. Van Hove JL, Grünewald S, Jaeken J, Demaerel P, Declercq PE, Bourdoux P, Niezen-Koning K, Deanfeld JE, Leonard JV. D,L-3-hydroxybutyrate treatment of multiple acyl-CoA dehydrogenase deficiency (MADD). Lancet. 2003 Apr 26;361(9367):1433-5.
  99. Veech RL. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot Essent Fatty Acids. 2004 Mar;70(3):309-19.
  100. Veech RL, Chance B, Kashiwaya Y, Lardy HA, Cahill GF Jr. Ketone bodies, potential therapeutic uses. IUBMB Life. 2001 Apr;51(4):241-7.
  101. Veech RL, Bradshaw PC, Clarke K, Curtis W, Pawlosky R, King MT. Ketone bodies
  102. mimic the life span extending properties of caloric restriction. IUBMB Life. 2017
  103. May;69(5):305-314. doi: 10.1002/iub.1627. Epub 2017 Apr 3. Review. PubMed PMID: 28371201.
  104. Webber A. To ketone or not to ketone: Mineral salts. http://ketogenic.com/ nutrition/ketone-not-ketone-mineral-salts/. Accessed 14 June 2017
  105. Westerterp-Plantenga MS, Nieuwenhuizen A, Tomé D, Soenen S, Westerterp KR. Dietary protein, weight loss, and weight maintenance. Annu Rev Nutr. 2009;29:21-41. doi: 10.1146/annurev-nutr-080508-141056.
  106. Will JC, Strauss KF, Mendlein JM, Ballew C, White LL, Peter DG. Diabetes mellitus among Navajo Indians: findings from the Navajo Health and Nutrition Survey. J Nutr. 1997 Oct;127(10 Suppl):2106S-2113S
  107. Yancy WS Jr, Almirall D, Maciejewski ML, Kolotkin RL, McDuffie JR, Westman EC. Effects of two weight-loss diets on health-related quality of life. Qual Life Res. 2009 Apr;18(3):281-9. doi: 10.1007/s11136-009-9444- 8.
  108. Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, D’Agostino D, Planavsky N, Lupfer C, Kanneganti TD, Kang S, Horvath TL, Fahmy TM, Crawford PA, Biragyn A, Alnemri E, Dixit VD. The ketone metabolite B-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med. 2015 Mar;21(3):263-9. doi: 10.1038/ nm.3804
  109. Yudkoff M, Daikhin Y, Melø TM, Nissim I, Sonnewald U, Nissim I. The ketogenic diet and brain metabolism of amino acids: relationship to the anticonvulsant effect. Annu Rev Nutr. 2007;27:415-30

goBHB – Just Give Me the Facts – Serie 2

The World’s Most Powerful Science Backed Ingredient.

SERIES 2 – BHB, THE FOURTH MACRONUTRIENT:

Unveiling the Power of Beta-Hydroxybutyrate (BHB) in ATP Production

In the realm of nutrition and metabolism, the commonly recognized macronutrients are carbohydrates, proteins, and fats. However, emerging research highlights the significance of exogenous Beta- Hydroxybutyrate (BHB) as an already refined and potent “4th macronutrient.” Unlike its more familiar counterparts, BHB offers a unique and efficient pathway for adenosine triphosphate (ATP) production (the body’s energy currency), positioning BHB as a superior source of cellular energy with remarkable advantages over glucose.

This paper aims to elucidate the pivotal role of ATP in the body, the mechanisms of its production, and the exceptional efficacy of BHB in generating ATP with minimal oxidative stress.

The Energy Currency of Life: Understanding ATP

ATP, often referred to as the body’s energy currency of the cell, is indispensable for virtually all biological processes. It powers muscle contraction, nerve impulse propagation, chemical synthesis, and active transport across cell membranes. Structurally, ATP consists of an adenine base, a ribose sugar, and three phosphate groups. The energy is stored in the high-energy phosphate bonds, and when ATP is hydrolyzed into adenosine

diphosphate (ADP) an inorganic phosphate (Pi) releases the energy required for all cellular activities.ATP is primarily created in the mitochondria, the powerhouse of the cell, through a process called “oxidative phosphorylation” during cellular respiration. Additionally, ATP can be produced in the cytoplasm through glycolysis, albeit much less efficiently. The generation of ATP is analogous to electricity production from power plants that provides the electricity that powers our homes, cars, and tools. ATP fuels the biochemical machinery of life in our bodies.

Mechanism of ATP Production from Beta-Hydroxybutyrate (BHB)

Beta-Hydroxybutyrate (BHB) is a ketone body. It can be produced endogenously by the liver during periods of low carbohydrate intake, fasting, or ketogenic diets. BHB can also be administered exogenously now through goBHB. BHB serves as an alternative energy source to glucose, especially for the brain and muscles. Now it can be obtained through exogenous supplementation in a glucose fed state. Here’s a step-by-step explanation of how BHB is converted into ATP:

  • Transport into Cells:
    — BHB is transported from the bloodstream into cells via monocarboxylate transporters (MCTs).
  • Conversion to Acetoacetate:
    — Inside the cell, BHB is converted back to acetoacetate by the enzyme beta-hydroxybutyrate dehydrogenase. This reaction takes place in the mitochondria and involves the reduction of NAD+ to NADH.
  • Activation to Acetoacetyl-CoA:
    — Acetoacetate is then activated to acetoacetyl-CoA by the enzyme succinyl-CoA:3-oxoacid CoA transferase (also known as SCOT or OXCT1). This step bypasses the need for ATP, which is a significant advantage over glycolysis.)
  • Cleavage to Acetyl-CoA:
    — Acetoacetyl-CoA is cleaved into two molecules of acetylCoA by the enzyme thiolase. This acetyl-CoA can then enter the Krebs cycle (citric acid cycle).
  • Krebs Cycle and Oxidative Phosphorylation:
    — Krebs Cycle: The acetyl-CoA enters the Krebs cycle, where it undergoes a series of reactions to produce NADH and FADH2.
    — Electron Transport Chain (ETC): NADH and FADH2 donate electrons to the ETC in the inner mitochondrial membrane. The flow of electrons through the ETC drives the pumping of protons across the mitochondrial membrane, creating a proton gradient.
  • ATP Synthase:
    — The proton gradient powers ATP synthase, an enzyme that synthesizes ATP from ADP and inorganic phosphate (Pi).

BHB: A Superior Source of ATP

BHB, is referred to as the body’s preferred fuel. It provides an alternative energy source to glucose and has very efficient pathway for ATP production. BHB, can then be utilized by various tissues, especially the brain and muscles, as a direct energy source. Here is why BHB is a superior source for producing ATP:

  1. Enhanced ATP Yield: BHB metabolism produces more ATP per molecule compared to glucose. BHB enters the mitochondria and is converted into acetyl-CoA, which then enters the Krebs cycle. The subsequent oxidative phosphorylation of BHBderived substrates yields more ATP molecules with fewer steps compared to glucose metabolism.
  2. Reduced Reactive Oxygen Species (ROS) Production: One of the remarkable benefits of BHB metabolism is its lower production of ROS compared to glucose metabolism. ROS are byproducts of cellular respiration that can cause oxidative damage to cells and tissues, contributing to aging and various diseases. BHB’s cleaner ATP production process minimizes oxidative stress, promoting better cellular health.
  3. Gold Standard of Cellular Energy: Due to its efficient ATP production and reduced oxidative stress, BHB can be considered the gold standard of cellular energy. Its role in sustaining energy levels during metabolic states where glucose is scarce underscores its importance as a macronutrient.

Advantages of BHB in ATP Production

  1. Higher ATP Yield:
    — The conversion of BHB to ATP is more efficient than glycolysis and glucose metabolism, as BHB produces more reducing equivalents (NADH and FADH2) that feed into the ETC, resulting in a higher ATP yield.
  2. Reduced Reactive Oxygen Species (ROS) Production:
    — BHB metabolism produces fewer reactive oxygen species (ROS) compared to glucose metabolism. ROS are highly active and harmful byproducts that can damage cells and tissues. Lower ROS production means less oxidative stress and cellular damage.
  3. Alternative Energy Source:
    — BHB provides a crucial energy source during periods of low carbohydrate availability, ensuring that critical organs like the brain continue to receive a steady supply of energy.

Summary and Conclusion

The production of ATP from BHB involves a pathway that not only yields a higher amount of ATP, but also produces less oxidative stress compared to glucose metabolism, highlighting the efficiency and advantages of BHB as an energy source.

Beta-Hydroxybutyrate (BHB) stands out as a formidable 4th macronutrient, offering a superior pathway for ATP production compared to traditional glucose metabolism. Its efficient conversion to ATP with minimal ROS generation positions BHB as an exceptional source of cellular energy, potentially redefining our understanding of macronutrients. As research continues to unveil the benefits of BHB, its role in nutrition and metabolism may become increasingly prominent, offering new avenues for optimizing human health and performance.

goBHB – Just Give MeThe Facts – Serie 1

The World’s Most Powerful Science Backed Ingredient.

SERIES 1 – THE FACTS ABOUT 1,3 BUTANEDIOL

Beta Hydroxybutyrate (BHB) is considered the gold standard of clean cellular energy.

  • BHB is more efficient than glucose at producing energy. It can be converted into ATP (adenosine triphosphate), the body’s main energy currency, more quickly and easily than glucose.
  • BHB does not require insulin to carry it into the cell.
  • BHB is preferred by the brain, heart, kidney, and almost every other cell in the body over glucose.
  • BHB produces far less damaging free radicals (ROS) and increases levels of BDNF (brain-derived neurotrophic factor), a protein that helps to promote the growth and repair of cells.

The utilization of BHB in promoting superior performance and health is well documented.

What is 1,3 Butanediol? Chemically 1,3 butanediol IS AN ALCOHOL that can be converted through the liver into BHB. It ISN’T a ketone body like BHB. 1.3 butanediol is what you call a “ketone precursor,” a substance capable of converting into BHB in the liver to increase BHB levels in the blood. However, the ability of 1,3 butanediol to convert into BHB does not necessarily mean that supplementing with 1,3-butanediol will result in the desired increased levels of BHB in the blood or the side effects that come from the conversion.

The Process the Liver Goes Through to Convert 1,3-butanediol into BHB: Converting 1,3-butanediol into BHB must be done in the liver. Converting 1,3-butanediol to BHB is a complex enzymatic process that is subject to a variety of factors, including the individual’s metabolic state and the presence of other nutrients in the body necessary to fully metabolize the 1,3-butanediol. It cannot be directly absorbed into the blood like BHB. The conversion is done through a metabolic pathway known as the 1,3-butanediol pathway. In this pathway, because 1,3-butanediol is an alcohol, it must first be converted to beta-hydroxybutyraldehyde (BHBA) by the enzyme alcohol dehydrogenase (ADH). BHBA must then be oxidized to form BHB by the enzyme beta-hydroxybutyrate dehydrogenase (BDH).

The Energy Cost of Conversion: Converting 1,3 butanediol into BHB takes time and ATP energy. In a most recent study by NNB Labs entitled “The Impact of Different BHB Substates and Precursors on Liver ATP,” 1,3 butanediol consumed 89.1 mg/ min of ATP to convert 12.5g of 1,3 -butanediol into BHB. This is in contrast to BHB acid which provides 13.6 mg/min of ATP to the liver in transporting it into the blood within a 2 hour period of time. This equated to a comparative loss of 755% in ATP liver energy using 1,3, butanediol as a BHB source versus BHB acid in supplying BHB into the blood with similar dosages.

The Risks of 1,3, butanediol: While 1,3-butanediol is recognized as safe for consumption and even marketed as a vodka substitute (such as in products like Ketohol), its classification as an alcohol raises potential concerns. Similar to other alcohols, it necessitates processing by the liver, which could impact liver function over time. Additionally, from a performance perspective, 1,3-butanediol may pose challenges due to its impact on ATP energy levels, potentially impairing physical and cognitive function compared to non- alcoholic BHB sources.

For further information on Ketohol, you can visit their website:
https://shop.ketoneaid.com/products/hard-ketones

Here are some of the key concerns of 1,3 Butanediol:

  1. Dehydration: Alcohol is a diuretic, which means it increases urine production which can lead to dehydration. Dehydration can impair athletic performance, as it can lead to fatigue, muscle cramps, and decreased endurance.
  2. Impaired coordination: Alcohol can impair coordination, reaction time, and balance. This can be dangerous for athletes who require precision and coordination.
  3. Reduced muscle growth and recovery: Alcohol consumption can reduce protein synthesis, which is the process by which muscles grow and repair. This can lead to slower recovery times after exercise and reduced muscle growth over time.
  4. Decreased endurance: Alcohol consumption can decrease endurance and performance during aerobic exercise, such as running or cycling.
  5. Reduced mental focus: Alcohol consumption can impair cognitive function and reduce mental focus, making it more difficult for athletes to concentrate and perform at their best.

The Side Effects of 1,3 butanediol: The literature also identifies 1,3-butandiol can cause a range of adverse health effects, including drowsiness, dizziness, and loss of coordination. Additionally, long term consumption of 1,3-Butanediol has been linked to the development of liver and kidney damage, as well as respiratory problems such as asthma.

Here are a few studies highlighting the risks of using 1,3 butanediol:

  • In a recent study presented at the 4th International Keto Live® Conference in Switzerland, conducted by Csilla Ari, Dominic D’Agostino, and Zsolt Kovacs, called “Review of exogenous ketone supplements with enantiomer and concentration dependent effects,” showed the liver damage after administration of 1, 3, butanediol and ketone esters after 100 days in tissue histology. This is in contrast to administration of ketone salts (which contain BHB acid + electrolytes), and noted these are the most suitable exogenous ketones for chronic administration.
  • A study published in the journal “Clinical Toxicology” in 2006 found that 1,3-butanediol can cause kidney damage in rats. The study found that rats that were given high doses of 1,3-butanediol for 12 weeks had significant damage to their kidneys. This damage was similar to the damage that is seen in people who have kidney disease.
  • A study published in the journal “Neurotoxicology and Teratology” in 2008 found that 1,3-butanediol can cause neurotoxicity in rats. The study found that rats that were given high doses of 1,3-butanediol for 12 weeks had significant damage to their brains and spinal cords. This damage led to neurological problems, such as seizures, coma, and death.

The Taste is Horrible: Beyond 1,3 butanediol’s reduced effectiveness and inherent risks compared to BHB acid, 1,3-butanediol has an incredibly unpleasant taste. It is often described as having a very chemical or medicinal after taste, while BHB acid is often described as having a more natural or slightly sweet fruity taste. And from a price perspective, 1,3 butanediol is more expensive per gram than BHB acid in either a liquid or electrolyte acid powder form.

The Choice is Clear: 1,3 butanediol is a “want to be BHB,” and is no match for the authentic, gold standard of clean cellular energy of BHB.

Gamer’s Edge

The World’s Most Powerful Science Backed Ingredient.

Enhanced focus, reaction time, and cognitive function all result from taking BHB. Gamers Edge is formulated to support a. gamers’ demanding needs and habits when locked in digital competition, pushing the boundaries of strategy, focus and reflexes. Every click, every keystroke is a quest for the ultimate win, that is why gamers need Gamer’s Edge. Gamers represent a massive and engaged market eager for innovative solutions to elevate their experience. There are now over 3 billion gamers.

PRODUCT DESIGN:

Mental clarity and reaction time are crucial. This product combines the high mental sustained ATP energy of BHB with a unique set of other brain and eye enhancement micronutrients and electrolytes to fill the demands for optimal gaming performance without the distortion, crashes and fatigue from stimulants. Since gamers often maintain unconventional schedules, the formula must also promote better sleep quality and recovery.

TARGET AUDIENCES:

  • Competitive Gamers: eSport competitors seeking any edge to improve reaction times, focus, and endurance during intense matches and tournaments.
  • Serious Amateurs: Highly engaged players who want to perform their best in online competitions and ranked play.
  • Dedicated Streamers: Need consistent energy for long streaming sessions and to maintain a high level of interaction and entertainment.
  • Marathon Gamers: Prone to extended, all-night sessions; need to combat fatigue and maintain performance.
  • Completionists: Driven to finish games at 100%, often putting in long hours for achievement hunting.
  • Busy Professionals: Limited gaming time; want to maximize performance and enjoyment in short sessions.
  • Health-Conscious Gamers: Interested in alternatives to sugary energy drinks, seeking a more balanced and sustainable energy source.

POTENTIAL MESSAGING:

  • Gain the Edge: Enhance your reaction time, mental clarity, and overall performance with our unique blend of BHB ketones, cognitive boosters, and eye-health support.
  • Limitless Gaming: Designed for gamers who push their boundaries. Achieve sustained energy, razor-sharp focus, and optimize your mind and body for maximum gaming performance.

L-BHB – Entering and Maintaining the Flow State

The World’s Most Powerful Science Backed Ingredient.

INTRODUCTION

The Flow State, characterized by intense focus, effortless action, and intrinsic enjoyment, has been linked to brain energy metabolism. New evidence implicates a strong connection between brain energy metabolism and the ability to achieve this desirable state. We believe the L-enantiomer (L-BHB) is capable of inducing and maintaining Flow States.

UNDERSTANDING FLOW: A NEUROBIOLOGICAL PERSPECTIVE

Flow is associated with specific brain network configurations reflecting:

  • Reduced self-referential processing: Diminished activity in brain areas associated with introspection frees up cognitive resources for the task at hand.
  • Suppression of negative thought patterns: Dampened erratic energy patterns in regions linked to anxiety and worry promote mental clarity.
  • Activation of reward centers: Enhanced activity in neurotransmitters activating dopamine and norepinephrine, known to be involved in motivation, reward-related structures, reinforces positive feelings and focus.

UNLOCKING THE FLOW STATE

The Flow Model provides a framework for at least understanding the elusive state of flow, that is characterized by intense focus, effortless action, and intrinsic enjoyment. This model emphasizes a delicate balance between the perceived challenge of a task and an individual’s skill level in accomplishing that task. When those are in alignment the task appears easy to do and is often accomplished quickly with perceived ease and accuracy.

“When the challenge matches the skills to meet the challenge, where a state of super competence is reached without boredom, with an absence of real fear of failure, the “flow state” is attained.”

HERE ARE WHAT WE HAVE DETERMINED TO BE THE FLOW STATE CONDITIONS:

1.Skill vs. Challenge:

      • The Core of Flow: Flow arises from the delicate balance between perceived skill and the perceived challenge of a task. A person needs to feel capable, but not to the point of boredom. The challenge must stretch their abilities without causing overwhelming anxiety or doubt of capability.
      • High Skill, High Challenge: The optimal “flow zone” resides with a high level of both perceived skill and challenge. Tasks in this zone are motivating and lead to very high feelings of accomplishment.
      • Other Zones:
        – Boredom: Occurs with high skill but low challenge. Tasks feel monotonous and unfulfilling.
        – Anxiety: Arises when perceived challenge exceeds skill. People may feel overwhelmed, leading to worry and reduced performance.
        – Apathy: Results when both skill and challenge are low, leading to disinterest and lack of motivation.

      2. Action and Awareness Merging:

      • Immersion: In a flow state, one becomes fully engrossed in the task. The boundaries between the self and the activity seem to dissolve, creating a sense of effortlessness and a loss of time perception.

      3. Clear Goals:

      • Well-Defined Purpose: Flow experiences often occur in activities with well-defined goals that provide direction and focus.

      4. Immediate Feedback:

      • Informative Response: Flow thrives on rapid feedback helping adjust course and evaluating progress towards the goal. This immediate feedback helps maintain focus and engagement, thus keeping one “in the flow.”

      5. Sense of Control:

      • Feeling in Charge: Individuals in flow feel a sense of control over the situation despite the task’s difficulty. They believe they can influence outcomes through their actions.

      6. Distorted Perception of Time:

      • Time Flies: Time perception shifts in flow states. Hours might feel like minutes as immersion deepens.

      7. Autotelic Experience:

      Intrinsically Rewarding: Flow is its own reward. The activity itself is pleasurable and motivating, regardless of external goals or recognition. The state becomes intrinsically desirable in and of itself, pushing people to want that feeling all the time.

      IMPORTANT CONSIDERATIONS REGARDING THE FLOW STATE:

      • Individual Variability: While these factors generally promote flow, individual responses can vary. Some people may find it easier to enter flow states during specific activities or under certain conditions than others. This variability can be due to differences in personality, skill sets, and preferences.
      • Dynamic Nature: Flow is not a constant state; it naturally fluctuates. It’s unrealistic to expect to maintain a flow state indefinitely. Recognizing the ebb and flow of this experience can help manage expectations and avoid frustration when it dissipates.
      • Reproducibility Challenge: The most significant challenge with flow is its inherent unpredictability. Even when attempting to recreate the same conditions that previously induced flow, it may not always occur. This is a common frustration, highlighting the need for tools and techniques that can help individuals reliably access and sustain flow states.

      THE ROLE OF BETA-HYDROXYBUTYRATE (BHB) AS IT RELATES TO FLOW

      BHB, a ketone body endogenously produced during fasting or lowcarb diets, can also be supplemented exogenously, even when glucose is present. The brain can efficiently utilize BHB as an alternative energy source to glucose and often preferentially over glucose.

      HERE’S WHY BHB MIGHT BE THE KEY TO FLOW:

      • Enhanced Energy Stability: Compared to glucose, BHB provides a steadier, more sustainable energy supply for the brain. This is due to its efficient metabolism, which generates fewer harmful byproducts (reactive oxygen species) that can disrupt neural activity. BHB also supports mitochondrial function, boosting cellular energy production and minimizing distracting energy fluctuations.
      • Neurotransmitter Modulation: BHB influences neurotransmitters crucial for focus, relaxation, and cognitive function. It may enhance the production of GABA, the brain’s primary calming neurotransmitter, promoting a state of mental tranquility conducive to flow. Additionally, BHB could optimize glutamate signaling, facilitating the smooth, interconnected thought processes necessary for optimal performance.
      • Neuroplasticity and Neuroprotection: BHB may support neuronal health, adaptability, and resilience. It could promote the growth and strengthening of connections between neurons (synapses), enabling the fluidity of brain networks that characterize flow experiences. Furthermore, its potential antioxidant and anti-inflammatory properties might protect brain cells from stress and damage, preserving the focused state required for flow.

      THE SIGNIFICANCE OF L-BHB IN INDUCING FLOW

      D-BHB, is the enantiomeric form of BHB endogenously produced by the body through ketogenesis when glucose levels are low. D-BHB is the most widely studied and most often referred to as the BHB energy molecule. Although L-BHB can also serve as an enhanced ATP energy source, the emerging research suggests that the less-studied L-BHB potentially holds greater potential for flow induction.

      HERE’S WHY:

      • Astrocyte Preference: Astrocytes, star-shaped glial cells crucial for brain function, exhibit a preference for utilizing BHB as an energy source. This is particularly true of the L-BHB.
      • Neurotransmitter Modulation: The metabolism of L-BHB by astrocytes can influence the production and release of neurotransmitters like GABA and glutamate. Their regulation is crucial for maintaining the focused, relaxed mental state associated with flow.
      • Steady Energy for Neurons: Constant, reliable feeding of astrocytes by L-BHB could promote a stable energy supply for surrounding neurons. This minimizes the disruptive energy fluctuations commonly seen with glucose metabolism, which can derail flow.
      • Homeostatic Brain Energy Environment: By optimizing astrocyte function and energy delivery to neurons, L-BHB might promote a highly homeostatic brain energy environment. This steady state could be ideal for the activation and maintenance of brain networks necessary for flow experiences.

      THIS ALL LEADS TO:

      • Potential Superiority for Flow Induction: Preliminary evidence indicates L-BHB may possess unique properties affecting brain energy dynamics and signaling pathways highly relevant to inducing and sustaining flow states.
      • Brain Affinity of L-BHB: The effects of L-BHB on cognition and mental states, particularly the sectors of the flow model, could be the key to unlocking the reproducibility of inducing the flow state and the type of energy needed to maintain the flow state.

      PRELIMINARY OBSERVATIONS ON L-BHB AND FLOW EXPERIENCES

      While rigorous scientific investigation is on-going, preliminary observations linking L-BHB administration to the induction of flow states has strong preliminary evidence.

      • Study Description: In informal, self-reported studies, we administered 10g-15g doses of L-BHB to over 25 individuals. Participants were asked to characterize their experiences following L-BHB ingestion.
      • Reported Effects: All individuals reported subjective experiences consistent with flow states. Common descriptions included:
        – Enhanced ability to multitask and manage multiple cognitive processes simultaneously.
        – Increased perceptual clarity and heightened senses.
        – Simplified perception of tasks, making activities feel more effortless.
        – A sense of mental euphoria while engaged in activities.
        – Complete lack of fear, stress and anxiety when they resumed their activities, believing there was nothing stopping them from being successful.
      • Implications These preliminary observations, while not clinical in nature, require further scientific investigation to provide validation that L-BHB administered to promote mental conditions conducive to entering a flow state are noted as obvious and repeatable. Further research is being conducted to elevate the knowledge of these effects and determine the exact mechanisms involved for reproducing the flow state through administering L-BHB.

      GAMERS AND THE PROPENSITY FOR FLOW – USING L-BHB TO ENHANCE GAME FLOW

      Gamers may be particularly prone to experiencing flow states due to the inherent nature of well-designed games. Here’s why:

      • Skill-Challenge Alignment: Many games offer a carefully calibrated progression of difficulty, constantly matching challenges to the player’s developing skills.
      • Clear Goals and Feedback: Games provide well-defined objectives and immediate feedback systems, informing players of their progress and guiding their actions.
      • Immersive Environments: Games create captivating worlds and narratives that promote focused attention and a sense of merging with the activity.
      • Sense of Control: Well-designed games give players a sense of agency, allowing them to influence outcomes and to feel empowered within the virtual environment.

      THE POTENTIAL BENEFITS OF L-BHB FOR FLOW INDUCTION WERE PARTICULARLY PRONOUNCED FOR GAMERS. OUR PRELIMINARY OBSERVATIONS SUGGEST:

      • Easier Flow Access: Gamers who ingested L-BHB reported entering the flow state within the game much more readily.
      • Enhanced Game Performance: Participants described feeling a heightened sense of control, reduced fear of failure, and an increased ability to take calculated risks, leading to improved gaming performance.
      • Hypothesized Mechanisms: The brain energy stability, neurotransmitter modulation, and neuroplasticity effects of L-BHB could all contribute to enhanced focus, reaction times, and the mental state conducive to flow within the gaming context.

      CONCLUSION: L-BHB AND A NEW ERA IN REPEATABLE FLOW STATE INDUCTION

      Imagine a world where students learn effortlessly, artists and creators experience boundless artistic expression, and athletes shatter performance barriers. L-BHB might be the catalyst for this new era transformation.

      The evidence presented, while preliminary, illuminates a compelling potential for L-BHB to rewire the brain for flow. L-BHB’s macronutrient ATP energy producing capacity to optimize energy stability, power and regulate neurotransmitters could be the key to unlocking brain network configurations necessary for inducing and sustaining flow providing a state of sustained focus, effortless immersion, and rewarding experiences.

      The preliminary findings among both diverse individuals and in particular gamers, signal an exciting possibility that L-BHB could be an accessible daily tool for cultivating flow states across various activities. Its potential benefits extend far beyond the gaming realm, promising applications for boosting productivity, enhancing creativity, and promoting overall well-being.

      Our continued quest to understand and harness the power of flow represents a new frontier in neuroscience. As we unravel the complexities of how L-BHB interacts with the brain, developing optimal usage protocols for L-BHB in inducing flow, we may also discover fundamental insights into human consciousness and the boundless potential of the mind.

      Beta Hydroxybutyrate (goBHB) The King of Weight Loss and Type 2 Diabetic Support

      The World’s Most Powerful Science Backed Ingredient.

      Obesity and type 2 diabetes have reached epidemic proportions, posing a significant health burden globally. As the prevalence continues to rise, there is a pressing need for effective strategies to manage these conditions. One promising approach involves the use of Beta-Hydroxybutyrate (BHB), a naturally occurring molecule produced by the body during periods of low glucose availability. This paper aims to explore the potential benefits of BHB in weight loss and the management of type 2 diabetes.

      HERE ARE THE FACTS:

      Obesity and overweightness have grown at alarming rates globally over the past few decades. The World Health Organization (WHO) has provided some key statistics:

      • Global Overweight and Obesity: In 2021, more than 2 billion adults, 18 years and older, were overweight. Of these, over 1 billion were obese.
      • Increase Over Time: The prevalence of obesity nearly tripled between 1975 and 2021.
      • Childhood Obesity: In 2021 39 million children were overweight or obese. Once considered a high-income country problem, overweight and obesity are now on the rise in low and middle-income countries, particularly in urban settings.
      • Adolescent Overweight and Obesity: In 2021, over 340 million children and adolescents aged 5-19 were overweight or obese.
      • Consequences: Obesity is a major risk factor for several chronic diseases, including diabetes, cardiovascular diseases, and cancer.

      A study published in The Lancet in 2016 analyzed data from nearly 4 million individuals worldwide, finding that for those overweight, every 5 units of BMI above 25 kg/m² was associated with about a 30% higher overall mortality rate.

      AS TO TYPE 2 DIABETES:

      • Global Prevalence: According to the International Diabetes Federation (IDF), in 2019, approximately 463 million adults (20-79 years) were living with diabetes; by 2045 this number is expected to rise to 700 million. The majority of these cases are of type 2 diabetes.
      • Growth in Prevalence: The global prevalence of diabetes has nearly doubled since 1980, rising from 4.7% to 8.5% in the adult population, largely due to increases in type 2 diabetes.
      • Geographical Differences: In 2019, the Western Pacific had the highest number of people with diabetes (approximately 163 million), followed by the Southeast Asia region (approximately 88 million). However, the prevalence rate was highest in the Middle East and North Africa, where more than 12% of the adult population had diabetes.
      • Age Differences: The prevalence of type 2 diabetes increases with age, with the most significant number of people with diabetes being between the ages of 40 and 59.
      • Impact: Diabetes was the ninth leading cause of death in 2019, causing an estimated 4.2 million deaths globally. People with diabetes have a higher risk of developing several serious health problems, including cardiovascular disease, kidney disease, and certain types of cancer.

      WHY IS LOSING WEIGHT SO CRITICAL TO ONE’S HEALTH?

      • Reduced Risk of Chronic Diseases: High body fat, particularly when it’s concentrated around the abdomen, is associated with an increased risk of various chronic diseases, including heart disease, type 2 diabetes, certain cancers, and liver disease.
      • Improved Metabolic Health: Excess body fat can lead to insulin resistance, a precursor to type 2 diabetes. Losing fat can improve insulin sensitivity and overall metabolic function, which can help regulate blood sugar and cholesterol levels.
      • Better Cardiovascular Health: High body fat, especially visceral fat around the organs, is linked to increased blood pressure and higher levels of LDL (“bad”) cholesterol, both of which can contribute to heart disease. Reducing fat mass can improve these indicators of cardiovascular health.
      • Improved Mobility and Physical Function: Excess weight can put strain on the body, leading to joint pain and reduced mobility. Losing fat can alleviate these issues and improve overall physical function and quality of life.
      • Enhanced Mental Health: Body weight can impact mental health as well. Studies have linked obesity to a higher risk of depression and lower self-esteem. Weight loss, when done in a healthy manner, can potentially improve mental wellbeing.
      • Better Sleep: Excess weight, particularly around the neck, can contribute to sleep disorders like sleep apnea. Losing fat can lead to better sleep quality and reduce the risk of these disorders.

      IN PARTICULAR, WHY IS LOSING WEIGHT SO IMPORTANT TO THOSE WITH TYPE 2 DIABETES?

      • Improved Insulin Sensitivity: Excess body weight, particularly fat stored around the abdomen, can lead to insulin resistance. Losing weight can improve insulin sensitivity, enabling the body to use insulin more effectively to lower blood sugar levels.
      • Better Blood Sugar Control: Weight loss can help regulate blood sugar levels, making it easier for people with type 2 diabetes to manage their condition. Improved blood sugar control can reduce the risk of diabetes-related complications, such as nerve damage, kidney disease, and vision problems.
      • Reduced Need for Medications: When blood sugar levels are better controlled through weight loss and lifestyle changes, people with type 2 diabetes may require fewer medications or lower doses of their current medications, under the guidance of their healthcare provider.

      There is no doubt that weight loss improves general health and especially for those suffering from type 2 diabetes.

      THE MECHANICS OF ACHIEVING WEIGHT LOSS

      Weight loss doesn’t happen unless you are successful at creating a calorie deficit. But creating a calorie deficit puts strain on the body to find fuel to keep it running outside of the fuel you consume. There are two choices, use fat mass for fuel or use muscle mass for fuel, both will cause weight loss, but only diets that preserve muscle and burn fat will be successful in the long term and reduce the effects of recidivism, the regaining of weight after the conclusion of a calorie restricted diet.

      Science has proven a ketogenic or low carb diet outperforms a high carbohydrate diet in loosing fat mass versus muscle mass. This is because when the body does not have glucose to burn, nor the ability to convert muscle into glucose via a process called gluconeogenesis, it enters a state of ketosis when the body mobilizes its fat stores to provide triglycerides to the liver that converts the triglycerides into a high energy molecule called a ketone that can then fuel the body. It’s during this type of calorie restriction that the body loses fat, not muscle.

      WHAT ARE THE CHALLENGES OF A CALORIE RESTRICTIVE DIET TO LOSE WEIGHT?

      • Hunger and Cravings: Cutting back on calories often means eating less than you’re used to, which can lead to feelings of physical hunger and cravings for high-calorie foods, making it difficult to stick to the diet.
      • Lack of Satiety: Not all calories are created equal in terms of satiety. Diets that are low in protein and fiber, but high in refined carbohydrates, can leave you feeling unsatisfied, even if you’re consuming an adequate number of calories.
      • Social and Cultural Factors: Social gatherings, holidays, and cultural norms often revolve around food, which can make it challenging to stick to a calorie-restricted diet. There can be pressure to eat in social situations, or you might not have control over the food that’s available.
      • Sustainability: Long-term adherence to a calorie-restricted diet can be challenging. It requires consistent effort, planning, and willpower, and it’s not always compatible with a busy lifestyle. Many people find it hard to maintain this kind of diet over the long term.
      • Psychological Factors: Emotions, stress, and habits can all impact our eating behaviors. Emotional eating, for example, is a common struggle for many people on calorie-restricted diets. Moreover, old habits can be hard to break, and new ones can be hard to form.

      These challenges are both physiological and psychological and both challenges must be met to make any weight loss diet successful.

      USING goBHB FOR LOSING FAT AND SPARING MUSCLE IN CALORIE RESTRICTIVE DIETS

      One proven strategy is the supplementation of BetaHydroxybutyrate (BHB), a ketone body naturally produced during periods of low carbohydrate and calorie intake that essentially help the body mimic ketosis, the fat burning state, regardless of the calories restrictive diet selected.

      BHB supplements are exogenous sources of the ketone body BHB. They can mimic the physiological state of ketosis, where the body burns fat for fuel instead of glucose. While naturally occurring during fasting or a ketogenic diet, BHB supplements can significantly elevate ketone body levels in the body regardless of dietary intake, potentially offering unique metabolic and psychological advantages.

      BHB supplementation aids fat loss by promoting a metabolic shift from glucose to fat utilization, enhancing fat breakdown. It attacks the physiological diet challenges through appetite suppression by influencing hunger-related hormones, significant increase in energy levels, especially in the brain, spares muscle and lowers glucose and insulin levels.

      Studies show a correlation between elevated BHB levels from supplements and weight loss in:

      • Promoting Fat Metabolism: BHB supplements can provide the body with an external source of ketones, potentially signaling the body to continue using fat as its primary fuel source, even in the presence of dietary carbohydrates. One study in the Journal of Nutritional Science and Vitaminology showed that daily intake of BHB caused the average waist circumference to decrease of 9cm amongst healthy adults over a 9 week period and this was achieved without dietary restriction or exercise intervention.
      • Suppressing Lipogenesis: There is some evidence that BHB may in fact suppress the creation of new fat cells (a process known as lipogenesis), further promoting a state of fat burning in the body. One such study published in the International Journal of Environmental Research and Public Health showed that a state of ketosis suppressed lipogenesis and increased weight loss amongst obese human patients.
      • Suppressing Ghrelin and Lowering Appetite A study published in Obesity found that a cohort of healthy adults experienced decreased hunger, desire to eat and increased fullness after injesting exogenous ketones.

      Psychologically BHB supplementation has been shown to improve mood and relieve normal stress and anxiety. These psychological benefits help people make better food choices, reduce emotional and social eating issues, and maintain their discipline in sustaining their diet.

      SUMMARY OF BENEFITS OF goBHB ON WEIGHT LOSS AND TYPE 2 DIABETES SUPPORT

      Here is the bottom line of why BHB Supplementation is so powerful in promoting weight loss and supporting Type 2 diabetes on any diet:

      • Appetite Suppression: Some research suggests that BHB can help suppress appetite, potentially helping individuals maintain a calorie deficit, which is necessary for weight loss. This appetite suppression is due to BHB’s superior effect on hunger hormones, such as ghrelin.
      • Metabolic Shift: BHB is a ketone body, and taking BHB supplements can mimic the state of ketosis, where the body uses fat, rather than glucose, for fuel. This metabolic shift can help promote fat loss, especially when combined with a low carbohydrate diet.
      • Energy Levels: BHB provides a superior energy source for the brain and muscles. This can be especially beneficial during the early stages of any calorie restricted diet in preventing fatigue and support physical activity levels, thus maintaining high metabolic rates.
      • Muscle Preservation: During normal calorie restricted weight loss, the body can lose muscle as well as fat, sometimes more muscle than fat. BHB supplementation helps preserve muscle mass during calorie restrictive weight loss, due to its protein sparing effects.
      • Blood Sugar Control: BHB can help control blood sugar levels and improve insulin sensitivity, which can be beneficial for weight management and overall metabolic health.
      • Mood Enhancement: There is scientific evidence showing that BHB reduces normal stress and anxiety and promotes better mood. This psychological boost during a calorie restrictive diet goes a long way in helping to maintain the attitude and discipline to sustain the diet and reject behaviors that sabotage results.

      CONCLUSION

      By inducing a state of ketosis, even without a strictly low carb or ketogenic diet, BHB can help the body utilize stored fat for energy, promoting fat loss over muscle loss. This can be particularly beneficial for individuals on a calorie-restrictive diet, aiding in the preservation of lean muscle mass while promoting fat reduction. Moreover, the potential of BHB to reduce feelings of hunger and cravings can help individuals adhere to their calorie-restrictive diets more effectively, addressing one of the significant challenges of such diet protocols.

      Beyond weight loss, BHB’s role in improving cognitive function, reducing inflammation, and potentially improving insulin sensitivity may offer additional health benefits, contributing to an overall improvement in metabolic health.

      In conclusion, the use of Beta-Hydroxybutyrate (BHB) supplementation can serve as the perfect strategy to capture the benefits of a calorie-restrictive diet. Its potential to stimulate the body’s natural fat-burning processes, curb hunger pangs, and offer a high-powered energy source can enhance the weight loss journey, by reducing fat, sparing muscle, and improving mood. goBHB makes any calorie restrictive diet more efficient and sustainable.

      REFERENCES

      1. “Daily intake of D-B-Hydroxybutyrate Acid (D-BHB) Reduces Body Fat in Japanese Adult Participant: A Randomized, Double-Blnid, PlaceboControlled Study.” Kastsuya et al. The Journal of Nutrional Science and Vitaminology 2023
      2. “Ketogenic Diet for Obesity: Friend or Foe?” 2013 https://www.mdpi. com/1660-4601/11/2/2092
      3. “A Ketone Ester Drink Lowers Human Ghrelin and Appetite” Stubbs et al. Obesity Journal 2017 https://pubmed.ncbi.nlm.nih.gov/29105987
      4. “Impact of ketosis on appetite regulation—a review” Deemer et al. Nutrition Research Journal 2020 https://www.sciencedirect.com/science/ article/abs/pii/S0271531719309376?via%3Dihub
      5. “Ketogenic diets and Ketone suplementation: A strategy for therapeutic intervention”. Frontiers in Nutrition. 2022 Sarris et al. https://www.ncbi. nlm.nih.gov/pmc/articles/PMC9705794/
      6. “Metabolism of Exogenous D-Beta-Hydroxybutyrate, an Energy Substrate Avidly Consumed by the Heart and Kidney” https://www.frontiersin.org/ articles/10.3389/fnut.2020.00013/full, Frontiers in Nutrition 2020
      7. “Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans.” Nair et al. The Journal of Clinical Investigation 1988 https://www.jci.org/articles/ view/113570/pdf
      8. Effects of Exogenous Ketone Supplementation on Blood Glucose: A Systematic Review and Meta-analysis. Advanced Nutrition Journal. 2022 Falkenhain et al. https://pubmed.ncbi.nlm.nih.gov/35380602/
      9. “Ketogenic Diet and Inflammation: Implications for Mood and Anxiety Disorders” Karkafi et al. Neuroinflammation, Gut-Brain Axis and Immunity in Neuropsychiatric Disorders 2023

      goBHB vs. PeakATP (ATPDisodium) A ComparativeAnalysis of Cellular Energy Potential

      The World’s Most Powerful Science Backed Ingredient.

      The Cellular Energy Revolution – goBHB vs. ATP Disodium

      The quest for optimal cellular energy has led to the popularity of some ATP disodium supplements. However, the body has a far more powerful fuel source at its disposal – the powerful ketone body, beta-hydroxybutyrate (BHB). When comparing a mg to mg dosage, BHB unleashes an energy surge that ATP disodium simply cannot match. This isn’t just about raw ATP yield either. BHB has significant advantages that extend far beyond the ATP yield numbers.

      From BHB’s swift absorption and seamless entry into cells to its role as a potent signaling molecule, BHB reigns supreme as the body’s preferred energy currency. It’s a metabolic powerhouse designed to fuel our most critical functions, especially when traditional energy sources fall short of delivering the energy needed for all metabolic functions.

      This brief analysis delves into the multifaceted superiority of BHB, exposes the limitations of ATP disodium while highlighting BHB’s efficiency and advantages as the supreme fuel source. And well beyond BHB’s effortless cellular uptake BHB has a profound influence on metabolic signaling. BHB is not merely another ingredient, but the key cellular energy player in optimizing human performance and well-being.

      The following compares the efficiency in generating cellular ATP between the two energy substrates.

      Some Background

      • The Energy Currency: ATP (adenosine triphosphate) is the fundamental energy molecule used by cells. However, the body has many ways to generate and replenish ATP stores.
      • Ketone Power: Beta-hydroxybutyrate (BHB) is a ketone body that serves as a highly efficient alternative fuel source to glucose, and when taken exogenously provides a dual fuel aspect to further boost energy performance and metabolic flexibility.
      • Beyond Ingredient Hype: While ATP disodium supplements exist, it cannot produce it endogenously. BHB is produced endogenously from fat metabolism and can be supplemented exogenously.

      Calculating Basic ATP Yield

      • Theoretical Basis: We calculated the theoretical ATP yield from a 450mg dose of both BHB and ATP disodium.
      • BHB’s Advantage: BHB yields approximately 116 times more ATP molecules than the same mass of ATP disodium.

      Why BHB Is Superior?

      1.Direct vs. Indirect:

      – ATP disodium: One Step Removed: While ATP disodium offers one ATP molecule, that molecule isn’t ready for direct cellular use. It must first undergo a complex series of reactions within cellular respiration to actually generate a significant energy yield.

      – BHB: Metabolic Shortcut: BHB offers a shortcut in the energy production process. It is rapidly converted into acetyl-CoA, a molecule that directly fuels the same cellular respiration pathways. This streamlined conversion results in a higher net ATP yield compared to ATP disodium.

            2. Absorption:

            There’s surprisingly little research specifically investigating the absorption rate and bioavailability of orally ingested ATP disodium. This raises significant questions about whether intact ATP reaches cells in any meaningful quantity. Here are some of the scientific challenges:

            • Digestive Breakdown: ATP is a relatively large and complex molecule. The digestive system is designed to break down such molecules into smaller components before absorption. It’s likely that ATP disodium faces significant degradation, minimizing the amount of intact ATP available.
            • Transport Challenges: Even if some ATP molecules survive digestion, they face the challenge of crossing cell membranes. ATP is not readily transported into cells, requiring specific mechanisms usually not present in significant abundance for direct ATP uptake.
            • Metabolic Conversion: Any absorbed ATP would likely be quickly used or converted into other molecules by cells, making it difficult to track its direct impact on cellular ATP levels.

            BHB on the other hand is evolutionarily built for absorption. These factors have developed during the evolutionary life of BHB:

            • Small and Soluble: BHB is a relatively small, water-soluble molecule. This allows it to easily cross the digestive barrier and enter the bloodstream.
            • Direct Transport: BHB utilizes specific transporters (called MCTs) for cellular uptake. These transporters are present in various tissues, including the gut, liver, and brain, ensuring efficient distribution.
            • Metabolic Priority: Ketone bodies, especially during low glucose availability, are readily used by the body for energy. This promotes rapid uptake and utilization of BHB.

            BHB has superiority in its absorption to ATP disodium, but what needs to be called out is absorption and yield from ATP disodium is theoretical as strict science has not yet validated the quantification of efficacy of orally ingested ATP disodium in determining cellular energy yields.

            3. Metabolic Efficiency:

            • ATP disodium is likely broken down in digestion before significant absorption can occur. This requires energy for the breakdown. The body then needs to use existing energy stores to rebuild ATP, thus prior to yielding ATP, the body is spending ATP.
            • Exogenous BHB bypasses lengthy digestive processes and ketogenesis all together. It enters cells readily and is metabolized within the mitochondria – the cell’s powerhouses – with minimal ATP expenditure in the process.

            4. Cellular Signaling:

            • Metabolic Shift: BHB acts as a signal of altered energy availability. Elevated ketone levels trigger changes in gene expression and enzyme activity, favoring fat oxidation and optimizing cellular processes for using ketones as fuel.
            • Antioxidant and Anti-inflammatory Effects: BHB can reduce oxidative stress and inflammation through various pathways, impacting cellular health and disease prevention.
            • HDAC Inhibition: BHB acts as a natural inhibitor of histone deacetylases (HDACs), enzymes that modify gene expression. This influences a wide range of biological processes potentially impacting longevity and health span.
            • Other Signaling Roles: Research continues to uncover new signaling roles for BHB, suggesting it influences cell growth, differentiation, and responses to stress.
            • ATP Signaling Role: ATP’s main role is to store and release energy within cells. Its signaling impact is relatively limited compared to the multifaceted influence of BHB.
            • ATP Internal versus External: ATP signaling primarily occurs within cells as part of metabolic regulation. External ATP from a supplement like ATP disodium likely has minimal impact on these pathways.

            5. Cellular Context Matters:

            • In states of high energy demand or in the event of glucose scarcity, ketones become the singular preferred fuel for many tissues, including the brain. BHB’s efficiency is always amplified in these high demand scenarios.

            Practical Implications

            • Supporting Cellular Energy: BHB, whether produced naturally or through supplementation, provides a more potent and sustained energy source for cellular functions compared to direct ATP disodium supplementation.
            • Therapeutic Potential: Conditions where energy metabolism is compromised (neurological disorders, metabolic diseases) may benefit significantly from BHB’s superior ATP generation potential. For example, MADD disease can utilize BHB directly where it would not be able to utilize ATP disodium to generate vital metabolic energy. BHB has also been shown to impact epilepsy, brain disorders, glucose control, chronic inflammation, weight loss, stress and anxiety to just name a few.
            • Athletic Performance: During prolonged or high-intensity exercise, BHB in its dual fuel role can actually help modulate glucose usage, sparing glucose stores to fast twitch responses and other glucose dependent functions while providing the most reliable energy source for improving endurance.

            Conclusion

            While ATP is the final energy currency, BHB proves to be a far superior fuel source in terms of the net ATP it provides to cells. This analysis underscores the importance of understanding metabolic pathways and true net energy yields when choosing substrates that support cellular function.

            The effectiveness of BHB in boosting energy availability indirectly overshadows potential direct ATP supplementation studies, especially given absorption concerns.

            The Bottom Line

            The evolutionary, biological design of BHB ensures its efficient absorption and utilization as a cellular energy source. This scientifically contrasts the challenges and uncertainties associated with ATP disodium absorption and eventual cellular yield of ATP. This highlights the importance of utilizing actual biological yield determinations versus using theoretical calculated potential yields in assessing efficacy and performance.

            goBHB® (Beta-Hydroxybutyrate)vs. ElevATP®

            The World’s Most Powerful Science Backed Ingredient.

            ElevATP®

            ElevATP has made claims that the combination of Ancient Peat and Apple Polyphenols can significantly raise ATP levels in mitochondria (via the assumption that changes in ATP blood levels translate directly into increases in mitochondrial ATP) from a dose of 150mg. The key issue here is how does it do that since neither Ancient Peat nor Apply Polyphenols can be directly converted into ATP, the primary energy molecule in cells. They don’t even contain the necessary chemical structure to follow that conversion pathway.

            In order for Ancient Peat or Apply Polyphenols to increase ATP levels, it would need to be through indirect influence on some other pathway that would require the utilization of some other ATP generating substrate to create the ATP. Those pathways were never identified and to date there is no credible scientific evidence to support claims that Ancient Peat or Apple Polyphenols can directly stimulate ATP production in any significant way. While some Company sponsored study evidence suggests some potential indirect benefits to energy metabolism, Ancient Peat and Apply Polyphenols are far from a direct ATP source like ketones (BHB).

            This leads us to the conclusion that Ancient Peat and Apply Polyphenols are not macronutrients, contain no significant caloric energy and their ability to increase ATP levels is at best through a very indirect means.

            Here’s a bit more detail:

            • Lack of Direct ATP Energy Source: While peat and apple extracts do contain a variety of compounds, the primary carbohydrates of peat are cellulose, hemicellulose and lignin. These are long chain molecules that do not breakdown easily and what limited simple sugars that do remain are very small. Even if you were capable of extractions of simple sugars, harsh chemicals would be required to do the extraction.

            Apple polyphenols themselves don’t contain glucose as part of their molecular structure. While apple polyphenols don’t directly yield glucose, they might have a very minor and indirect influence on blood glucose levels, while apple polyphenols aren’t a source of glucose themselves.

            The key question is whether these specific compounds in ElevATP® have unique effects well beyond the substrate itself on triggering energy metabolism because the extracts themselves don’t have ATP producing capabilities. That pathway has not been discussed or shown in any of the company sponsored results.

            ElevATP is not a direct ATP fuel source, leaving only the claim that somehow the extracts stimulate increased ATP production blood cells translating directly to mitochondrial ATP through an unknown pathway.

            • Inability for Mitochondrial ATP Measurement: Increases in blood or general cellular ATP levels don’t necessarily translate into higher ATP within power-generating mitochondria of muscle cells. To definitively support that claim of improving mitochondrial ATP performance, researchers would need to measure ATP directly in muscle tissue during exercise. That was not shown. Since Ancient Peat and Apple Polyphenols contain no direct ATP generative pathway, it literally makes it impossible to calculate any level of comparable ATP yield that can easily be calculated from direct ATP macronutrient generative molecules like glucose, BHB and fatty acids.
            • Unclear Mechanism of Action: The claim that it supports the body’s own ATP production is very vague. There is no support for this claim on how it supposedly achieves this in order to make a convincing scientific case. As of now, this remains speculative at best.

            The reliance on company-sponsored studies without strong independent research raises validity concerns. Here’s what’s available:

            • Company-Sponsored Studies: Most readily available studies on ElevATP are sponsored by the company that produces it (FutureCeuticals). While these studies might show some positive results, they inherently carry a potential bias and require a more critical lens.
            • Lack of Independent University Research: We could not find independent, peer-reviewed University sponsored studies specifically focusing on the mechanism by which ElevATP supposedly increases mitochondrial ATP production.
            • Vague Marketing Materials: ElevATP’s marketing materials are vague about how the combination of ancient peat and apple polyphenols achieve their claimed increases in mitochondrial ATP. Without a clearly stated, scientifically supported mechanism of action, it’s impossible to find targeted research from any universities on this subject matter.

            BHB (Beta-Hydroxybutyrate)

            BHB is the main powerhouse ketone body. Ketones convert directly to ATP with known metabolic and measurable pathways. It provides energy for the body, especially the brain, and it has been shown in numerous research papers how much brain energy impacts the improvement in physical performance and reduces disease. 1 BHB has a very different metabolic pathway than glucose.

            Here is BHB:

            • Direct Mitochondrial ATP Fuel: BHB can be directly used by mitochondria to generate ATP. This offers a potential advantage over glucose-dependent pathways during periods of high energy demand and low oxygenation, exhibited during high intensity exercise.2
            • Potential Benefits: Some studies suggest that ketones also improve mitochondrial efficiency and cellular signaling pathways3, which could positively impact energy production, utilization and performance, while reducing Reactive Oxygen Species (ROS)4. This offers potential to put athletes into “The Zone” and enhance recovery.
            • Growing Research Landscape: Research on BHB and athletic performance is massive and ongoing, with promising results. Just compare how many studies focus today on BHB versus ancient peat and apple polyphenols to get a glimpse where the scientific community is focused.

            Where Things Stand

            • ElevATP®: Peat and Polyphenols are not direct sources of ATP. The potential mechanism of action for ElevATP® is unclear and would require clarification in order to be seen as credible. Its claimed real-world performance benefits in athletes also would require validated third party study results to be considered conclusive.

            Further, it isn’t appropriate to assume that increased blood level ATP translates to increased mitochondrial ATP, or in this case even muscle ATP under exercise conditions. There is a lack of scientific evidence demonstrating the product has a direct impact on actually boosting mitochondrial ATP production.

            • BHB: BHB produces mitochondrial ATP directly. That statement of fact might be enough in comparing the capabilities of these two ingredients. The verified, large body of clinical research on BHB offers an authenticated and straightforward metabolic picture suggesting BHB is a preferred macronutrient fuel that produces measurable ATP energy directly in mitochondria.

            BHB’s ability to produce mitochondrial ATP is definite and calculable. Its metabolic pathways are known. This is what makes BHB the impressive and unique molecule it is, and why it is considered the gold standard of cellular energy.

            References:

            1. Ketone Bodies and Brain Metabolism: New Insights and Perspectives for Neurological Diseases, Wilfredo López-Ojeda , Ph.D., M.S., and Robin A. Hurley, M.D., F.A.N.P.A.Published Online:14 Apr 2023https://doi.org/10.1176/ appi.neuropsych.20230017
            2. Metabolism of Exogenous D-Beta-Hydroxybutyrate, an Energy Substrate Avidly Consumed by the Heart and Kidney Front. Nutr., 19 February 2020 Sec. Nutrition and Metabolism Volume 7 – 2020 | https://doi.org/10.3389/fnut.2020.00013
            3. Beta-Hydroxybutyrate: A Dual Function Molecular and Immunological Barrier Function Regulator Jiancheng Qi, 1 , † Linli Gan, 1 , † Jing Fang, 1 , † Jizong Zhang, 1 Xin Yu, 1 Hongrui Guo, 1 Dongjie Cai, 1 Hengmin Cui, 1Liping Gou, 1 Junliang Deng, 1 Zhisheng Wang, 2 and Zhicai Zuo 1 , https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC9243231/
            4. Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation. Maalouf M 1, Sullivan PG, Davis L, Kim DY , Rho JM Author information Neuroscience, 18 Jan 2007, 145(1):256-264 https://doi.org/10.1016/j.neuroscience.2006.11.065 PMID: 17240074 PMCID: PMC1865572

            Dual Fuel Performance Stack – The Next Evolution in Workout Performance Nutrition

            The World’s Most Powerful Science Backed Ingredient.

            Shattering the Performance Plateau

            Today, there isn’t an integrated approach to performance workout nutrition. Almost all performance products focus on isolated moments of a workout, leaving you with energy spikes and crashes, incomplete recovery, and a constant struggle to reach your full potential.

            The truth is your body needs a continuous flow of optimized fuel and nutrients to power through each stage of your workout – and beyond

            The Dual Fuel Performance Stack is a revolutionary 3-phase system that works in harmony with your body’s natural workout rhythms, delivering the precise combination of energy (BHB + Glucose) and other key ingredients your muscles and mind crave pre, during and post workout.

            Dual Fuel. It’s time to experience a new level of performance, where your body and brain are in perfect sync, pushing your limits further than you ever thought possible.

            • Energy Synergy: Glucose provides rapid fast twitch energy while BHB offers sustained fuel and extreme cognitive benefits to keep you pushing hard.
            • Enhanced Performance: Improved endurance and clarity providing power output of exactly what and when you need it.
            • Optimized Recovery: Getting you ready for the next day through faster muscle repair, reduced soreness, and improved sleep quality.

            The Dual Fuel Performance Stack isn’t just another group of supplements – it’s a complete reimagining of how to fuel your workouts. It’s a 3-phase system leveraging BHB (BetaHydroxybutyrate) and glucose, for the first time ever, to maximize performance and recovery throughout your training:

            1. Pre-Workout Ignite:

              — Key Ingredients: BHB electrolytes, fast-acting glucose (dextrose, maltodextrin), creatine, L-citrulline, beta-alanine, taurine

              — Benefits: Immediate energy boost, enhanced muscle pump, delayed fatigue, heightened mental focus

            2. Intra-Workout Sustain:

              — Key Ingredients: BHB acid (for rapid ketone uptake), slower-digesting glucose (cluster dextrin), branched-chain amino acids (BCAAs)

              — Benefits: Sustained energy throughout workouts, reduced muscle breakdown, improved hydration, faster recovery

            3. Post-Workout Recovery:

              — Key Ingredients: BHB electrolytes (including magnesium), protein blend (whey, casein), glutamine, L-carnitine, zinc

              — Benefits: Replenishes glycogen stores, repairs muscle damage, reduces inflammation, promotes deeper sleep

              Target Audiences:
            • Athletes (professional, amateur, weekend warriors)
            • Fitness enthusiasts
            • Endurance, extreme athletes
            • Biohackers
            • Busy professionals
            • Anyone seeking sustained energy and peak performance

            A New Paradigm in Workout Performance

            The Dual Fuel Performance Stack isn’t just another set of supplements; it’s a paradigm shift in how you fuel your workouts and unleash your full potential. By seamlessly integrating BHB and Glucose with other key nutrients, this revolutionary 3-phase system empowers you to ignite your energy, sustain your power, and accelerate your recovery like never before.

            This provides the experience of unparalleled focus, endurance, and strength as you shatter plateaus and redefine your limits. The Dual Fuel Performance Stack is the future of performance in unlocking a level of physical and mental dominance never thought possible.

            Reducing Normal Stress and Anxiety Using goBHB

            The World’s Most Powerful Science Backed Ingredient.

            Normal stress and anxiety are common experiences that can have negative effects on physical and mental health. Understanding the size of the problem, the populations most affected, the causes, and ways to reduce stress and anxiety is important for reducing potential debilitation from stress and anxiety.

            According to the American Psychological Association (APA), stress levels in the United States have been steadily increasing in recent years. In the APA’s 2021 Stress in America survey, 84% of adults reported experiencing at least one emotion associated with prolonged stress in the past two weeks, such as anxiety, sadness, or anger. Additionally, 54% of adults reported that their stress levels had increased in the past year.

            Stress and anxiety can affect people of all ages, races, and ethnicities. However, some populations may be more affected than others. Women are more likely than men to experience anxiety disorders, while men are more likely to experience stressrelated disorders such as post-traumatic stress disorder (PTSD). Some racial and ethnic groups may be more likely to experience anxiety disorders, although the reasons for this are complex and not fully understood. Certain professions, such as those that involve high levels of stress or trauma, may also be more affected by stress and anxiety.

            Normal stress and anxiety can be defined as our natural responses to challenging or threatening situations and can help us to cope with difficult circumstances. Stress and anxiety are considered normal when they are proportional to the situation that is causing them, and they do not significantly interfere with daily activities or overall quality of life.

            But there are stressors or triggers that distort what might be considered proportional to a situation and in these cases normal stress and anxiety becomes excessive and can have negative effects on physical and mental health and lessen one’s ability to act towards stress and anxiety appropriately.

            There are many triggers that can lead to disproportionate stress and anxiety, and they can vary greatly depending on the individual. However, some common triggers include:

            • Social factors: Social factors, such as discrimination or social isolation, may contribute to the development of anxiety disorders.
            • Physical health conditions: Certain physical health conditions, such as chronic pain or heart disease, may increase the risk of developing anxiety disorders.
            • Lifestyle Factors: Lifestyle factors, such as diet, exercise, and sleep, can also play a role in the development of stress and anxiety.
            • Trauma: Traumatic events such as abuse, violence, or accidents can have a lasting impact on mental health and may lead to the development of anxiety disorders such as posttraumatic stress disorder (PTSD).
            • Situational stress: Situational stress can result from ongoing challenges in personal or professional life, such as financial difficulties, relationship problems, or a demanding job. If left unaddressed, it can turn into chronic stress and can lead to anxiety disorders.
            • Genetics: Anxiety disorders may run in families, and there may be a genetic component to their development. Research suggests that certain genes may increase the risk of developing anxiety disorders.
            • Substance use: Substance use, including alcohol and drugs, can contribute to the development of anxiety disorders.

            HOW DOES goBHB HELP REDUCE NORMAL STRESS AND ANXIETY?

            1. BHB reduces inflammation: Chronic inflammation can contribute to stress and anxiety. BHB has been shown to have anti-inflammatory effects, which may help to reduce inflammation and the associated stress and anxiety.

              One possible mechanism by which BHB works to reduce inflammation is through the activation of the NLRP3 inflammasome. The NLRP3 inflammasome is a protein complex that plays a key role in the inflammatory response, and its activation can lead to the production of pro-inflammatory cytokines. In a study done at Yale University, BHB has been shown to inhibit the activation of the NLRP3 inflammasome, which can help to reduce inflammation and the associated stress and anxiety.

              Additionally, BHB has been shown to have antioxidant effects, which can help to reduce oxidative stress (ROS) and inflammation. Oxidative stress occurs when there is an imbalance between the production of ROS and the body’s antioxidant defenses. ROS can damage cells and contribute to the development of stress and anxiety. BHB has been shown to increase the production of antioxidant enzymes, such as superoxide dismutase (SOD), which can help to reduce oxidative stress and inflammation.
            2. BHB increases GABA levels: GABA is a neurotransmitter that helps to regulate mood and reduce anxiety. BHB has been shown to increase GABA levels in the brain, which may help to reduce anxiety and promote feelings of calmness. GABA is an inhibitory neurotransmitter that plays a key role in regulating anxiety and promoting feelings of calmness. Low levels of GABA have been linked to the development of anxiety disorders. BHB has been shown to increase GABA levels in the brain, which can help to reduce anxiety and promote relaxation.

              One possible mechanism by which BHB works to increase GABA levels is through the inhibition of histone deacetylases (HDACs). HDACs are enzymes that play a key role in regulating gene expression, and they have been shown to decrease the expression of genes that encode GABAergic neurotransmitters. BHB has been shown to inhibit HDACs, which can increase the expression of GABAergic genes and lead to an increase in GABA levels in the brain.

              Another possible mechanism by which BHB works to increase GABA levels is through the activation of G-protein coupled receptors. BHB has been shown to activate the G-protein coupled receptor GPR109A, which is expressed on the surface of certain cells in the brain. Activation of GPR109A can lead to an increase in the production of GABA and the release of GABA from neurons.

            3. BHB improves brain function: BHB has been shown to increase brain-derived neurotrophic factor (BDNF), a protein that is important for brain function and cognitive health. Improving brain function may help to reduce stress and anxiety by improving the body’s ability to cope with stressors. BHB is the body’s preferred energy source for the brain that can provide more ATP energy than glucose. By providing a higher level and purer source of energy, BHB has been shown to improve cognitive function and memory in animal studies. This may be due to its ability to increase energy supply to the brain and improve neuroprotection and antioxidant activity. BHB can help to improve overall brain function and performance. This allows the brain to more easily and quickly deal with issues and situations such that they do not become disproportionate to the issue or situation improving coping and solution alternatives.

            4. BHB increases resilience to stress: BHB has been shown to increase the body’s ability to cope with stress by activating stress response pathways. This increased resilience to stress may help to reduce feelings of anxiety and promote a sense of well-being. BHB has been shown to increase resilience and improve the body’s ability to cope with stress. This can be particularly beneficial for individuals experiencing stress and anxiety, as it can help to reduce the negative effects of stress on brain function and cognitive performance.

            5. BHB improves sleep quality: Poor sleep quality can contribute to stress and anxiety. BHB has been shown to improve sleep quality by increasing levels of the hormone melatonin, which is important for regulating sleep-wake cycles. BHB has been shown to increase the production of melatonin, a hormone that helps to regulate the sleep-wake cycle. By increasing melatonin production, BHB can help to promote a more regular sleep-wake cycle and improve sleep quality.

              BHB is a high energy fuel source for the brain that can provide more energy than glucose, which is particularly beneficial during sleep. BHB has been shown to reduce sleep disturbances, allowing for deeper sleep, with reduced wakefulness and restlessness. This may be due to its ability to promote relaxation and improved energy metabolism.

            STUDIES SHOWING HOW BHB CAN HELP REDUCE NORMAL STRESS AND ANXIETY

            • A study published in the Frontiers of Psychiatry journal investigated the effects of a bhb supplement, which raises BHB levels, on anxiety in adult individuals. The study found that the ketone drink significantly alleviated anxiety levels.
            • Another study published in Frontiers in Psychiatry investigated the effects of a ketogenic diet, which increases BHB levels, as a mood stabilizer for patients with anxiety disorders. The study found that the ketogenic diet significantly improved perceived mood and reduced anxiety amongst human patients.
            • A study published in the journal Molecular Neuroscience investigated the effects of BHB on anxiety-like behaviors in mice. The study found that BHB administration reduced anxiety-like behaviors in the mice.
            • Another study published in the Scientific Reports Journal investigated the effects of BHB on stress levels amongst rodents with PTSD. The study found that BHB improved reduced anciety related behaviour, an anti-depressant effect and lessened stress responses in the rodents.
            • Another study entitled “Blind Comparison of Two Different Compositions of Exogenous Ketones and Their Impact on Anxiety, Weight, Lean Muscle Mass and Cognitive Function” found a reduction of 39% in normal stress and anxiety in a group of 56 adults.

            CONCLUSION

            BHB (beta-hydroxybutyrate) has several powerful benefits for reducing normal stress and anxiety. While the exact mechanisms by which BHB works to reduce stress and anxiety are not fully understood, there is significant evidence to suggest that it may involve several different mechanisms, including anti-inflammatory effects, increased GABA levels, and improved brain function.

            Overall, the available study evidence suggests that BHB may be one of most significant supplements in addressing the issue of normal stress and anxiety. It may be particularly beneficial for individuals who are looking for natural and non-pharmacological way to manage stress and anxiety daily.

            REFERENCES

            1. “Therapeutic Potential of Exogenous Ketone Supplement Induced Ketosis in the Treatment of Psychiatric Disorders: Review of Current Literature” Frontiers of Psychiatry 2019 https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC6543248/
            2. “Ketogenic Diet and Inflammation: Implications for Mood and Anxiety Disorders” Karkafi et al. Neuroinflammation, Gut-Brain Axis and Immunity in Neuropsychiatric Disorders 2023
            3. “Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats” Molecular Neuroscience Journal. Ari et al. https://www.frontiersin.org/ articles/10.3389/fnmol.2016.00137/full
            4. “Beta-hydroxybutyrate, an endogenous NLRP3 inflammasome inhibitor, attenuates anxiety-related behavior in a rodent post-traumatic stress disorder model” Scientific Reports 2020 Ymanashi et al. https://www. nature.com/articles/s41598-020-78410-2