The World’s Most Powerful Science Backed Ingredient.
IT’S REALLY ALL ABOUT KETONES (BHB)
The rise in internet traffic for the word “keto” and “ketone” is nearly unprecedented. There has been a flurry of interest and talk regarding the benefits of adding exogenous ketones into people’s diets and lives via beta-hydroxybutyrate (as goBHB®). Although weight management is a very powerful benefit of exogenous ketones, it’s not the most powerful story behind BHB and the longterm opportunity behind the most powerful energy molecule that is called the “body’s preferred fuel.”
Beta hydroxybutyrate (as goBHB®) is a multi-patented, noncarbohydrate energy source with an ATP producing potential that is up to 2.5X that of glucose, when calculated per unit carbon consumed and per molecule of oxygen utilized in animal models. BHB has two stereoisomers: D and L (think of them as “lefthanded” and “right-handed” molecules).
The D-BHB isomer is often called the “natural” isomer because it is the BHB that is synthesized in the liver from acetoacetate during normal ketogenesis (the synthesis of new ketone bodies) from triglycerides as a result of fat breakdown (lipolysis).
The L-BHB isomer is only created in small amounts in the body in the mitochondria and appears to be a powerful neuronal activator and signaling molecule. A lot more investigation is going on regarding L-BHB than ever before as to its exact metabolic pathways and distinct benefits and characteristics.
Of the many important advancements in ketogenic research, one of the most important includes discovering ketones (BHB) are the preferred energy source of the brain and heart. Additionally, researchers have discovered that D-BHB does much more than simply provide cellular energy or fuel.
This Formulator’s Guide focuses mainly on D-BHB and DL – BHB as not as much is known about L-BHB in terms of its metabolic pathways and functionality. The guide aims to provide you with our knowledge of how to take advantage of the already known benefits of our D-BHB and DL- BHB (goBHB®) in your product formulations.
USING D-BHB
D-BHB is the naturally occurring, endogenously (“inside the body”) generated isomer produced through human metabolism of acetoacetate in the ketogenic process. D-BHB can be measured by conventional ketone blood meters like the Keto Mojo and Precision-Xtra. Once D-BHB enters the blood, it does not reconvert to acetoacetate, and is directly metabolized rapidly within the mitochondria for energy.
Benefits include:
Rapid and readily available bioenergetic fuel source for body and brain via oxidation in mitochondria through the TCA cycle
Rapid effects on satiety and insulin sensitivity/ glucose tolerance
High aerobic capacity and energy for low to moderate intensity continuous exercise performance and muscular endurance performance
Indirect antioxidant effects via endogenous enzyme upregulation; Direct OH- free radical scavenging and antioxidant potential
Class I and II HDAC inhibition (increased gene expressionFOXO3a, antioxidant defense enzymes Catalase, SOD2, Metallothionein II, etc.)
Increased cytoplasmic NAD+ pool (NAD+:NADH ratio) over glucose metabolism
“BHB-lation” of histone (epigenetic effects on gene expressionPPAR, mitochondrial enzymes for oxidative phosphorylationElectron Transport Chain, proteasome, etc.)
HCAR2 receptor activation (reduces dysregulated lipolysis from fat cells, anti-inflammatory effects, neuroprotection, gut integrity)
FFAR3 modulation for regulating inflammation
USING DL-BHB
The racemic form of BHB appears to be the most versatile. It combines the benefits of both D-BHB and L-BHB to address a variety of issues in a much broader format than perhaps either D-BHB or L-BHB address alone.
Benefits include:
A blend of both readily available energy/ fuel supply with the D-BHB plus a sustained reservoir of L-BHB for a prolonged ketosis effect
Applications for individuals looking for optimal health span and human performance from exposure to increased blood concentrations of BHB
NLRP3 inflammasome inhibition was demonstrated in a direct study using the DL-BHB form
USING L-BHB
L-BHB is the so-called “cellular” isomer of BHB that appears to reside within mitochondrial cells, as an intermediate, under normal conditions of fatty acid ß-oxidation. It must be consumed exogenously (“from outside the body”). This particular isomer has not been extensively studied and is still speculative as to its functionality, but it appears to have great functional benefits. There is not a simple way to measure the amount of L-BHB within the body as it cannot be detected through current ketone blood meters like D-BHB can. We will continue to update you on our research into this exciting molecule as more knowledge unfolds.
Benefits include:
L-BHB is metabolized slowly, creating a more sustained and prolonged elevation of ketones in the blood for up to 8 hours in humans
Increased exposure time “may” provide an opportunity to elicit a more consistent, or robust signaling response for HDAC, NLRP3 inflammasome, HCAR2 inhibition, and ‘BHB-lation’ of histones, chaperone-mediated autophagy and direct/indirect antioxidant defense & resilience
Better suited for “signaling” purposes due to prolonged duration and residence time in the body, many of which do not appear to be “stereospecific” to D- vs. L, but to BHB in general
Appears to still be involved in most of the “direct” signaling responses that do not require D-BHB catabolism
Indirect antioxidant effects via endogenous enzyme upregulation; Direct OH- free radical scavenging and antioxidant potential
L-BHB is already contained within the cell; thus it might have an additional beneficial effect for protecting against DNA damage and cellular inflammation that contribute directly to disease
Some studies show that L-BHB is better at synthesizing fats, thus it may be more effective in weight loss and treating obesity
THE FORMS OF BHB
BHB is not a stable molecule on its own. So it needs to either be bound to a mineral to stabilize it or dissolved in a aqueous solution of greater than 50% water. The most common minerals are sodium, calcium, magnesium and potassium, and the finished ingredient is called a “BHB electrolyte.” In the preferred embodiment of using either D-BHB or DL-BHB you should consider what form of BHB do you want to have in your end product. Is it going to be used in an RTD, a capsule, as a dissolvable powder, in a gummy, in a food product, etc.? Below is a table to suggest which form is best in what embodiment.
SUMMARY
Taking the current research in its entirety, D-BHB may be superior in energy performance, L maybe the superior signaling molecule and DL-BHB has the widest range of application. What is exciting about the ketone field of research is the number of future combinations and formulation iterations still undiscovered. We’re still at the beginning stages of learning how L-BHB will work, but we are always striving to help you optimize your exogenous BHB experience by continuing future research for the answers.
[References are located on the following page]
USE CHART FOR goBHB®
Here is the list of BHB by functionality to help you decide how best to utilize (goBHB) in products to accomplish the functionality you desire:
REFERENCES
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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
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
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
Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, et al. 2015. The ketone metabolite- hydroxybutyrate blocksNLRP3 inflammasome- mediated inflammatory disease. Nat.Med. 21:263–69
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
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 – hydroxybutyrate. eLife pii:e15092
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
Fajas L, Egler V, Reiter R, Hansen J, Kristiansen K, et al. 2002. The retinoblastomahistone deacetylase 3 complex inhibits PPAR and adipocyte differentiation. Dev. Cell 3:903–10
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
Guan JS,Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N, et al. 2009. HDAC2negatively regulates memory formation and synaptic plasticity. Nature 459:55–60
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
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
Robinson AM, Williamson DH. 1980. Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiol. Rev. 60:143–87
Kenyon CJ. 2010. The genetics of ageing. Nature 464:504–12
Newman JC, Verdin E. 2014. Ketone bodies as signaling metabolites. Trends Endocrinol. Metab. 25:42–52
Longo VD, Panda S. 2016. Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan. Cell Metab. 23:1048–59
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
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Edwards C, Canfield J, Copes N, Rehan M, Lipps D, Bradshaw PC. 2014. D-betahydroxybutyrate extends lifespan in C. elegans. Aging 6:621–44
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 – hydroxybutyrate. eLife pii:e15092
Rahman M, Muhammad S, KhanMA, Chen H, Ridder DA, et al. 2014. The-hydroxybutyrate receptor HCA2 activates a neuroprotective subset of macrophages. Nat. Commun. 5:3944
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K. 2005. Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain. J. Neurosci. Res. 79:55–64
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
NNB Labs has recently released two groundbreaking studies on BHB, shedding new light on how to determine the true efficacy of BHB supplements and ketone precursors (substances that are not BHB but can convert into BHB). Traditionally, the effectiveness of BHB supplements and precursors (BHB sources) have been measured by their peak levels they reach in the blood.
However, this method is flawed as it only captures a fleeting moment, neglecting the overall impact of BHB sources efficacy. These studies challenge the traditional focus on peak BHB levels and emphasize the importance of considering the total quantity of ketones over time and the net ATP yield of each BHB source—the two key metrics that reveal the real value of different BHB sources.
The two new NNB studies dive deep into comparing the main sources of BHB in the market, in particular goBHB acid/powders (powders being acid + electrolytes), 1,3-butanediol (a ketone precursor), BHB mono esters (one BHB bonded to 1,3-butanediol), and BHB diesters (two BHBs bonded to 1,3-butanediol).
BEYOND THE PEAK: MEASURING BLOOD KETONES (BHB) WITH AREA UNDER THE CURVE (AUC)
Traditional blood ketone meters focus on peak BHB levels to determine effectiveness. This approach is limited because it only captures a fleeting glimpse of the BHB source’s impact, neglecting the total quantity and duration of BHB in the blood. A more accurate measure is the Area Under the Curve (AUC), which considers the total BHB presence over time, providing a clearer picture of the source’s efficacy.
Study Highlights
In the study “Beyond the Peak: Comparing the Duration and Quantity of Ketones from Three D-BHB Sources,” NNB Labs demonstrated that the total quantity of ketones generated over a two-hour period was relatively equivalent among different D-BHB sources, despite differences in peak levels.
THE TRUE STORY OF BHB SOURCES: NET ATP PRODUCTION
The real value of BHB lies in its ability to yield ATP, the primary energy currency of the body. To accurately assess a BHB source’s efficacy, one must examine its net ATP yield—the amount of ATP generated after accounting for the energy cost of converting the BHB source into bioavailable BHB.
Key Findings
The NNB Labs study “Impact of Different BHB Substrates and Precursors on Liver ATP” revealed significant differences in net ATP yield among various BHB sources. Both goBHB D-BHB and L-BHB enantiomers provided a substantial and continuous ATP boost to the liver. In contrast, 1,3-butanediol and all esters were found to consume excessive amounts of ATP during their conversion process. Specifically, 1,3-butanediol required over seven times the ATP to convert to BHB compared to BHB acid itself.
Furthermore, numerous studies indicate that 1,3-butanediol not only lacks efficacy, but also poses potential risks to liver and kidney health due to its alcohol nature. BHB mono esters contain 41% 1,3-butanediol, and BHB diesters contain 21% 1,3-butanediol.
For example, Karen Clarke from Oxford and Delta G Ketones writes in marketing materials, “…ketone products that contain straight 1,3 butanediol, the alcoholic ketogenic precursor, should never be consumed in an attempt to raise blood ketones for performance, as they will carry the same deleterious effects one would see from ethanol consumption.”
Refer to our detailed paper on 1,3-butanediol for more information.
BEYOND EFFICACY: ADDITIONAL ADVANTAGES OF goBHB
Taste and Flavoring: goBHB, in both its liquid acid and electrolyte acid powder forms, offers a significantly better flavor profile compared to 1,3-butanediol and esters, which are known for their unpleasant taste. This makes goBHB a much more consumer-friendly option.
Electrolyte Benefits: goBHB can exist in an electrolyte acid powder form, and upon ingestion releases BHB acid and valuable electrolytes that aid in hydration and electrolyte balance. This is crucial for athletes and individuals with specific workout and lifestyle regimens who need a combination of energy and hydration.
Formulation Flexibility: goBHB liquid acids and electrolyte acid powders enable the creation of liquid or powdered supplements, offering versatile formulation options. In contrast, 1,3-butanediol and esters are primarily available in liquid form, limiting their use and convenience.
Alcohol Concerns: 1,3-Butanediol, being an alcohol, poses potential health risks. Its metabolism can increase the burden on the liver and kidneys, raising concerns about long-term use.
Cost-Effectiveness: goBHB is less expensive per kilogram compared to other BHB sources.
MEASURING L-BHB: THE NEW UNTAPPED POTENTIAL OF BHB TECHNOLOGY
Current ketone measurement devices only measure D-BHB, overlooking the significant presence and potential of L-BHB. This leads to an incomplete understanding of the true power of ketone sources. In one study, L-BHB was finally measured and showed a much higher peak and duration than D-BHB. goBHB is the only brand that can provide both D-BHB and L-BHB in any desired ratio and in both liquid acid and electrolyte acid powder forms.
The Hidden Power of L-BHB
Recent research has revealed that L-BHB fully metabolizes in the body and can play a crucial role in energy production, metabolic regulation, and cellular signaling. While D-BHB is widely studied and appears to be the body’s primary energy source, L-BHB’s unique metabolic pathways and impact might be even more profound. Emerging evidence suggests that L-BHB significantly contributes to the body’s energy dynamics, metabolic signaling, and overall metabolic functionality.
For example, we are working with hospitals on rare diseases using goBHB. One of those diseases, MADD (Multiple Acyl-CoA Dehydrogenase Deficiency), a rare genetic disorder that affects the body’s ability to break down certain fats and proteins for energy.
It was originally believed that D-BHB could be administered to these patients as a fuel source, it was soon discovered that in order for BHB to be effective in supplying energy, it required both L-BHB and D-BHB.
goBHB: THE GOLD STANDARD OF CELLULAR ENERGY
Studies clearly show that D-BHB and L-BHB acid are superior sources of cellular energy. They deliver a direct and sustained ATP boost, aligning with our evolutionary need for stable, efficient fuel during periods of food scarcity.
Fueling Your Success: The Smart Choice for Ketone Supplements
When choosing ketone supplements, focus on the science-backed evidence pointing to ATP production rather than flashy claims about peak BHB levels. It is evident that goBHB is the gold standard. Understanding the true metabolic costs and benefits of different BHB sources empowers you to make informed choices about ingredients that will optimize cellular energy and deliver the most power in a supplement. Based on the positive results from the NNB studies Ketone Labs is moving forward to perform additional human studies on the impact of goBHB on metabolic ATP production.
Unveiling the Truth: Net ATP Production
Science-backed evidence highlights net ATP production as the true measure of a ketone supplement’s efficacy. ATP, the body’s primary energy currency, fuels cellular processes and drives performance. Research has unequivocally demonstrated that BHB acid reigns supreme in net ATP production, outperforming all other BHB sources, especially 1,3-butanediol.
EMPOWERING YOUR PRODUCTS WITH goBHB
By aligning your brand with the scientifically proven superiority of goBHB and leveraging our 81 patents to protect your brand’s use of goBHB, you provide your customers with the most efficient and sustainable energy source. Unlike other BHB sources that deplete cellular energy and pose potential health risks, goBHB delivers the best, clean, powerful boost to cellular function without compromising safety, all at the lowest cost per kilogram.
Are You Ready to Help Fuel Your Success?
NNB Labs’ studies unequivocally demonstrate the superior net ATP production and sustained energy benefits of goBHB compared to other BHB sources, particularly 1,3-butanediol. We at Ketone Labs invite you to choose goBHB, the gold standard of cellular energy for your brand.
goBHB-RTD is a proprietary and patented aqueous blend of pure BHB acid and BHB-K salt. goBHB-RTD is unique due to its exceptional bioavailability. It is our fastest absorbing liquid BHB blend designed to deliver an immediate BHB elevation that is noticeably experienced in seconds following ingestion.
WHY DOES goBHB-RTD HAVE SUCH UNIQUE “DUAL ACTION” ABSORPTION CAPABILITIES?
goBHB-RTD exhibits the distinctive dual ability to be absorbed both sublingually and gastrointestinally. This not only delivers an instantaneous and perceptible impact through sublingual absorption; the absorption through the stomach further elevates and sustains its effects. Finally, BHB does not need to be broken down by the liver, resulting in even quicker absorption and the delivery of clean ketone energy directly into the blood stream and to the cells. goBHB-RTD delivers fast fuel to the body and brain.
WHAT IS THE RELATIONSHIP BETWEEN LIPID SOLUBILITY AND SPEED OF ABSORPTION?
BHB is highly lipid-soluble (able to dissolve in lipids or fats), it is the most lipid soluble ketone body, meaning that it can be quickly and completely dissolved and absorbed through the tissues of the mouth. BHB effortlessly crosses through cell membranes and is transported into the bloodstream to provide energy for cellular utilization, throughout the body, targeting the brain, heart, kidneys, and the entire central nervous system. In addition, BHB delivers 2.5 times the ATP (cellular energy) and requires no transport mechanism, produces more power and uses less oxygen compared with glucose. goBHB-RTD delivers fast fuel to the body and brain.
Highly lipid-soluble substances can be absorbed sublingually. Sublingual (‘Under the tongue’) absorption is the process of absorbing substances through the cell walls of the mouth. The substance, such as lipid soluble BHB, gets absorbed and dissolved into the mucous membranes in the mouth. The tiny blood capillaries under the tongue allow rapid absorption of BHB directly into the system, while bypassing the gastrointestinal tract and liver.
This allows an unrivalled speed of delivering energy to cells. For the consumer, this translates to a perceptible feeling just a few seconds after ingesting our goBHB-RTD. This makes our formula remarkably powerful and unique—and the consumer will notice the elevation in energy and focus immediately.
HOW CAN NOOTROPICS, LIKE CAFFEINE COMPLEMENT THE POWER OF goBHB-RTD’S?
Nootropics (aka ‘Smart Drugs”) are predominantly absorbed through the gastrointestinal (GI) tract. They are designed to be broken down in the stomach and intestines, where the active ingredients are absorbed into the bloodstream and transported to the brain. Thus, in combination with goBHB-RTD, they act
to further the duration and intensify the effects of goBHB-RTD. Nootropics, like caffeine, are central nervous system stimulants that can increase alertness, improve mood, and enhance physical performance by stimulating neurons.
However, nootropics do not provide any real cellular energy (ATP) and this is where the beauty of combining BHB with caffeine comes in.
Caffeine being a nootropic stimulant works by blocking the action of adenosine, a neurotransmitter that promotes sleep and suppresses arousal. This can provide neuronal activity providing a sense of alertness and upregulation of brain activity in the short term.
Beta hydroxybutyrate (BHB), on the other hand, is a macronutrient molecule that provides true cellular energy (ATP) and has been scientifically proven to improve cognitive function and demonstrates neuroprotective effects through feeding the brain with actual energy. This energy provides a much longer term brain activity.
CAFFEINE + BHB SYNERGIES INCREASE EFFICACY
Caffeine and BHB can work synergistically by enhancing cognitive function through two different biochemical mechanisms. While both compounds have been shown to improve cognitive performance, they accomplish it differently and thus act as symbiotic catalysts and increase each other’s effects. In our studies, we have observed that on consuming caffeine with BHB, you experience the stimulating benefits of caffeine without the so called “crash” once caffeine’s effect dissipates.
BHB also has another powerful synergistic effect on caffeine. BHB appears to offset caffeine’s overstimulating capacity to cause the “jitters”, which translates too often to headaches, nausea, anxiety, once the adenosine blocking effect of caffeine disappears.
Another possible synergy of caffeine and BHB is through their combined effects on energy metabolism. Caffeine has been shown to increase metabolism and fat oxidation, while BHB itself is a potent fat-burning ketone. Together, these effects could lead to increased energy generation as well as fat loss.
goBHB-RTD delivers dual bioavailability of clean and sustained energy combined with the synergistic impact of caffeine. goBHB-RTD presents a unique opportunity that delivers unrivaled instant, yet long lasting energy for consumers.
CONCLUSION
With or without nootropics, goBHB-RTD provide the highest energy formulation for RTD’s that can be easily felt in its effects. It provides the ONLY true replacement for RTD’s containing sugar, and trumps any caffeinated RTD because of its ability to provide true cellular energy, not just neuronal stimulation that ends in a “crash.”
goBHB has a unique ability to enhance mood and happiness. Studies have shown that BHB can mitigate the effects of stress and anxiety by influencing neurotransmitter balance in the brain by calming neurotransmitters and providing a unique, alternative brain energy source shown to improve cognitive function and overall mental well-being. In a US Census Bureau report, almost a third of the USA population expressed anxiety and depression symptoms in 2023.
PRODUCT DESIGN:
This product would harness the power of a patented combination of BHB and C8 MCT to create a natural stress-reducing and mood-boosting powder. An AGS clinical study demonstrated a significant 39% reduction in stress levels with this unique combination. BHB and C8 MCT coupled with a few other unique ingredients would support a calmer, more positive mental state by providing the body with a unique combination of alternative energy sources. It would balance neurotransmitters while also promoting overall well-being.
TARGET AUDIENCES:
Stressed-out professionals/First responders: Individuals in high-pressure jobs seeking ways to manage daily stress, enhance their focus, and improve their overall productivity.
People with anxiety: Those experiencing generalized anxiety or milder forms who want supplementary support to manage symptoms and promote calmness.
Wellness enthusiasts: Individuals interested in natural health solutions, biohacking, and optimizing their mental and emotional well-being.
Busy parents/caregivers: People juggling the demands of parenting or caregiving, needing help to manage stress and emotional balance.
Parents seeking to cope with their children: Individuals looking for ways to better manage the stress and emotional challenges that come with parenting.
Students: Individuals facing academic pressure who want to reduce test anxiety, improve focus, and enhance their study performance.
Anyone seeking a mood boost: People desiring a natural way to feel happier, more positive, and cultivate a more optimistic outlook.
POTENTIAL MESSAGING:
Calm your mind. Fuel your focus. Conquer your day: Address being overwhelmed, find the clarity you need to excel, boost mental energy, unlock your true potential at work and GET HAPPY.
Feed your inner calm with this Superfuel: Harness the power of BHB and MCTs for natural stress reduction and a happier state of mind.
Nutritional strategies have long been used to enhance athletic performance. In recent years, there has been growing interest in using exogenous ketones like beta-hydroxybutyrate (BHB) to improve athletic performance. BHB can be metabolized quickly to produce ATP, which is the primary source of energy for the body. The production of ATP from BHB can increase energy production while reducing oxidative stress in the body, improving athletic performance.
There are key reasons BHB can improve athletic performance:
BHB Produces More Energy: BHB produces 279 kilocalories of total energy from a single BHB molecule while glucose can only produce 248. Also, because ketones are generated from fat endogenously, 1g of fat (ketones) produces 2.5 times the ATP than on 1g of carbohydrate (glucose). The reality is ketones are a much better and richer energy source for the brain than glucose because of their more efficient pathway.
Reduced oxidative stress: BHB has been shown to reduce oxidative stress, which occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them. Oxidative stress can significantly impair athletic performance by causing muscle damage and impairing recovery. BHB’s ability to reduce oxidative stress helps to improve athletic performance and recovery.
Enhanced mitochondrial function: Mitochondria are the power factories of the cell. They are the cellular organelles responsible for energy production in the body. BHB has been shown to enhance mitochondrial function, which can increase the efficiency of energy production and improve athletic performance.
Reduced inflammation: During exercise, the body undergoes a series of physiological and metabolic changes that can lead to inflammation, which is the body’s natural response to tissue damage. While acute inflammation is a normal response to exercise, chronic inflammation can impair muscle function, reduce athletic performance, and delay recovery from exercise. Reducing inflammation through the use of BHB supplementation has been shown to improve athletic performance, particularly in endurance athletes.
Enhanced muscle protein synthesis: BHB has been shown to enhance muscle protein synthesis in animal studies. Muscle protein synthesis is a process by which the body builds new muscle tissue, which is essential for muscle growth and strength. Thus, in body building BHB supplementation can be valuable to increase muscle mass.
THE CHALLENGES OF IMPROVING ATHLETIC PERFORMANCE
Improving athletic performance can be challenging, as it requires a combination of factors to be optimized. Some key challenges to improving athletic performance include:
Genetics: Genetics can play a significant role in determining athletic performance, as certain genetic factors can influence factors such as muscle fiber type, oxygen utilization, and other factors that impact athletic performance.
Training: Optimal training is essential for improving athletic performance, but finding the right balance of frequency, intensity, and volume can be challenging. Overtraining can lead to fatigue, injury, and reduced performance, while undertraining can limit progress and fail to stimulate adaptation.
Nutrition: Proper nutrition is essential for fueling workouts, supporting recovery, and optimizing body composition. However, finding the right balance of macronutrients and micronutrients can be challenging, an individual needs can vary based on factors such as age, gender, body composition, and activity level.
Recovery: Adequate recovery is essential for allowing the body to adapt to training and improving athletic performance. However, balancing the right amount of rest, sleep, and other recovery strategies can be challenging, particularly when balancing other demands such as work or school.
Mental factors: Mental factors, such as motivation, focus, and confidence, can also impact athletic performance. Overcoming mental barriers and developing mental toughness can be challenging and may require the help of a mental health professional or other support system.
Epigenetics: Epigenetics can play a role in athletic performance by influencing gene expression and modifying an individual’s response to training and exercise.
THE ROLE OF BHB IN MITIGATING THE CHALLENGES AND ENHANCING PERFORMANCE
There isn’t a lot BHB can do to overcome genetics in improving athletic performance, but BHB can play a major role in mitigating the other five challenges.
Training: By creating less inflammation and providing more clean energy, BHB allows an athlete to train longer and harder and recover much quicker. This allows for longer, better training sessions.
Nutrition: Being in a ketogenic state allows the body to preserve its glycogen stores until needed. Using exogeneous BHB in conjunction with glucose provides a whole new “dual fuel” concept by delaying the onset of fatigue, allowing athletes to perform longer and with greater intensity at the end of a workout or event. This is very similar to the principle behind a hybrid automobile, utilizing gas power for the long haul and utilizing glucose for quick acceleration in stop and go traffic.
Recovery: BHB has been shown to reduce oxidative stress. Oxidative stress can lead to muscle damage during exercise. By reducing oxidative stress, BHB may help to protect muscles from damage and improve recovery after workouts. BHB also produces less lactic acid.
Mental Factors: There is no doubt athletes understand the terms “being in the zone,” “going with the flow,” and other states of mind that reduce anxiety, improve mood, and provide that feeling of being invincible. This all helps to reduce distractions and allows for better focus, reduce distractions, and improved mental clarity.
Epigenetics: BHB provides the additional mitochondrial energy to impact epigenetic switching, allowing for all the lights to come on at once, putting someone at their highest performance threshold. A study published in the Journal of Nutritional Biochemistry found that BHB can increase the expression of genes related to antioxidant defense and other metabolic processes through epigenetic modifications. The study suggested that these epigenetic effects of BHB may be related to its ability to reduce oxidative stress and improve metabolic health leading to better performance.
THE STUDIES AND SCIENCE OF USING goBHB FOR ENHANCED ATHLETIC PERFORMANCE
There have been several studies investigating the effects of exogenous beta-hydroxybutyrate (BHB) supplementation on athletic performance. Here are a few examples:
A study published in the journal Nutrients found that ketones improved endurance performance in trained cyclists. The study found that BHB increased energy efficiency and quickened recovery times.
Another study published in the Journal of Cell Metabolism found that BHB supplementation improved cycling time trial performance in trained cyclists. The study found that BHB increased power output and reduced lactate production during the time trial, suggesting improved metabolic efficiency.
A study published in the Journal of Nutrition and Metabolism found that BHB supplementation improved endurance performance in trained runners. The study found that BHB increased time to exhaustion during a treadmill run and improved cognitive function during and after the run.
A study published in the Journal of Exercise Rehabilitation found that elevated bhb levels from reduced oxidative damage and improved recovery after overload exercise training in Taekwondo athletes.
A study on athletes in the journal Nutrients demonstrated that elevated ketone levels delayed mental fatigue and improved reaction time amongst athletes during and after exertion.
Overall, these studies suggest that exogenous BHB supplementation can improve athletic performance by increasing energy efficiency, improving power output, reducing lactate production, improving cognitive function, and reducing muscle damage and improving recovery.
BHB AND ENHANCED EXERCISE RECOVERY
The recovery period after exercise is critical for athletes. It’s when the body repairs damaged tissues, replenishes energy stores, and adapts to the training stimulus its undergoing. BHB can play a significant role in optimizing several key aspects of this recovery process:
1. Faster Glycogen Replenishment: Glycogen is the primary fuel source for muscles during high-intensity exercise. After exercise, the body needs to refill these glycogen stores. BHB has been shown to increase the rate of glycogen synthesis, helping muscles recover their energy reserves more quickly. This can lead to improved performance in subsequent workouts.
2. Reduced Muscle Damage and Soreness: Intense exercise can cause micro-tears in muscle fibers, leading to soreness and inflammation. BHB has been shown to reduce markers of muscle damage and inflammation, such as creatine kinase and C-reactive protein. This can help athletes feel less sore and recover faster, allowing them to return to training sooner.
3. Enhanced Protein Synthesis: Muscle growth and repair depend on protein synthesis. BHB appears to stimulate protein synthesis pathways, aiding in muscle repair and potentially contributing to increased muscle mass over time.
4. Improved Mitochondrial Function: Mitochondria are the powerhouses of cells, responsible for energy production. Exercise can stress mitochondria, but BHB has been found to enhance mitochondrial biogenesis (the creation of new mitochondria) and function. This can lead to improved energy production and overall recovery.
5. Reduced Oxidative Stress: Exercise generates reactive oxygen species (ROS) that can damage cells and contribute to fatigue. BHB acts as an antioxidant, neutralizing ROS and reducing oxidative stress. This may help protect muscles and other tissues from damage.
6. Neurological Recovery: Exercise can also impact the nervous system. BHB may play a role in neurological recovery by reducing inflammation in the brain and promoting neurogenesis (the growth of new neurons). This could potentially improve cognitive function and reduce mental fatigue after exercise.
TIMING AND DOSAGE
The timing of BHB supplementation is be important for maximizing its recovery benefits. Some studies suggest that consuming BHB immediately after exercise may be most effective for glycogen replenishment. However, we believe that consuming BHB during exercise further optimizes recovery through reducing ROS during the exercise phase helping to achieve various recovery goals.
CONCLUSION
Beta-hydroxybutyrate (BHB) is a ketone body that has benefits for improving athletic performance. BHB can serve as primary and dual fuel source, increase energy production, reduce muscle damage, enhance cognitive function, and improve recovery. These effects can help athletes to exercise longer and with greater intensity, while also improving their ability to recover and adapt to training.
Studies investigating the effects of exogenous BHB supplementation on athletic performance have found promising results, suggesting that BHB can improve endurance performance, power output, cognitive function, and recovery.
Athletes should strategically build their training programs, determining how often to us BHB supplementation to ensure optimal outcomes. In addition, athletes should focus on optimizing their training, nutrition, and recovery strategies to maximize their potential and improve their performance, while also working with professionals to manage any genetic or other factors that may impact their athletic performance.
Overall, BHB supplementation provides significant benefits for improving athletic performance.
GLP-1 (semaglutide) medications have triggered a true paradigm shift in weight loss treatment. Their ability to significantly reduce appetite and promote substantial weight loss with less effort is highly attractive. As a result, millions of people in the USA are currently utilizing GLP-1s. HOWEVER, there are significant side effects. Our patented BHB offers significant and unique support both during and after GLP-1 treatment through mitigating potential side effects like fatigue, nausea, vomiting, GI issue, increased heart rate, and most significantly preserves muscle mass. BHB also offers critical ongoing support after stopping GLP-1 treatments, in helping individuals maintain their weight and body composition goals and overall metabolic health.
PRODUCT DESIGN:
This patented product would synergistically work with GLP- 1 medications to provide valuable support during and after treatment. During GLP-1 use, BHB can help mitigate side effects like nausea and fatigue by offering an alternative energy source to depleted glucose, while further boosting appetite suppression. BHB’s unique ability to preserve muscle during weight loss is exceptional. This enhances GLP-1 fat loss effectiveness. Post-treatment, the product assists in maintaining weight loss, promoting metabolic health, providing sustained energy levels and continued appetite suppression. This multifaceted formulation makes it a powerful, needed companion to GLP-1 treatments.
TARGET AUDIENCES:
Current GLP-1 Users: Individuals actively using GLP- 1 medications who seek ways to manage common side effects such as nausea, fatigue, GI issues, and muscle loss. Those wanting to maintain weight loss success and healthy metabolic function even after stopping GLP-1 therapy.
Potential GLP-1 Users: Individuals with obesity or significant weight loss goals who are considering GLP-1 medication, but are concerned about side effects and want proactive, natural solutions for optimal and prolonged long term success.
Post GLP-1 Users: Struggling to keep the weight off, now seeking lower cost solutions rather than returning to another round of GLP-1 treatment.
POTENTIAL MESSAGING:
Optimize your GLP journey: Minimize the discomfort, maximize fat loss results. Our BHB formula supports you during GLP-1 treatment by reducing side effects and promoting a smoother weight management experience.
Protect Your Gains. Achieve Your Goals: Keep your muscle, lose your fat and keep the weight off forever. Our BHB formula provides ongoing support after GLP-1 treatment, helping you achieve lasting results.
Beta-hydroxybutyrate (BHB) is the primary ketone body “a refined macronutrient” that is either produced during ketosis or fasting and now for the first time BHB can be taken exogenously. Emerging research suggests that BHB may be the most effective mitochondrial support supplement ever produced, surpassing any other popular options. Let’s compare BHB to other popular “mitochondrial support” supplements in terms of their effects on the actual mitochondrial processes:
BHB: A MULTIFACETED MITOCHONDRIAL ENHANCER
BHB not only outperforms other “mitochondrial support” supplements in individual mitochondrial processes, but also offers additional benefits:
Gene Expression: BHB influences gene expression, promoting the production of proteins essential for mitochondrial health and longevity.
Signaling Pathways: BHB activates various signaling pathways that promote mitochondrial biogenesis, function, and resilience to stress.
CONCLUSION:
Emerging research suggests that BHB may be the most comprehensive and effective mitochondrial support supplement ever. By outperforming other supplements in various mitochondrial processes and offering additional benefits, BHB has earned the title of “King of Mitochondrial Support.”
Dogs are the most cherished pet in the USA, with 48% of all USA households having one. As a key member of most peoples households, they deserve to experience the same benefits of BHB that humans do. Help them live their happiest, healthiest life with K-9 Thrive, a powerful BHB formula designed specifically to support canine well-being. Harness the power of BHB to promote mental calmness, clarity and over all physical well-being while keeping your beloved dog in the best shape ever.
PRODUCT DESIGN:
Patented BHB and MCT Blend: Our unique formula optimizes BHB and C8 MCTs in a specialized bone broth to support your dog’s specific metabolic needs.
Additional Calming Ingredients: Ingredients like chamomile or L-theanine (pending safety research in dogs) may be included for enhanced relaxation benefits.
Delicious, Easy-to-Administer: K-9 Thrive can be offered as a tasty bone broth powder to mix with food, or it can be made into a gravy.
KEY BENEFITS:
Stress and Anxiety Support: Promotes calmness, focus, and resilience in stressful situations and presents the highest potential for significant impact on a dog’s quality of life helping dogs cope with various anxiety triggers.
Anti-Inflammatory Potential: Reducing chronic inflammation is crucial for alleviating pain, improving mobility, and potentially slowing the progression of age-related conditions in dogs.
Cognitive Support: Maintaining cognitive function is essential for older dogs. BHB can promote brain health and reduce agerelated cognitive decline.
Weight Management Aid: Canine weight management is critical in maintaining health in so many ways. BHB could be a powerful supplementary tool.
TARGET AUDIENCES
Owners of anxious dogs, senior dogs, and any owner seeking natural, holistic health and well-being support for their dog.
In 2013 Gary Millet and Rob Rogers were introduced to the concept of being able to exogenously harness the energy of Beta Hydroxybutyrate (BHB), the most powerful energy molecule the body produces when it enters a catabolic state of ketosis through glucose deprivation.
After studying BHB they concluded that exogenous BHB could be externally ingested in an anabolic fed state, despite normal glucose levels, and utilized by the body for numerous benefits. We believed exogenous BHB could play a major, long-term role in human nutrition in aiding certain morbidities to an ever-growing sicker human population. This technology discovery spawned the birth of Axcess Global Sciences (AGS).
The decision to invest in exogenous BHB technology launched our efforts towards building a strong IP Platform that would allow us control over the use of exogeneous BHB electrolytes and acids worldwide. Our first step towards building our IP Platform came through the licensing of a patent called Weight Loss Medication and Method followed shortly after by licensing a patent from the University of South Florida called Compositions and Methods for Producing Elevated and Sustained Dietary Ketosis.
For AGS to accomplish their vision of a comprehensive IP Platform around BHB they assembled the necessary team and resources to create and patent our own IP technology. AGS now controls 33 granted domestic Composition Patents and 21 Composition Patents Pending in our US IP Platform with 7 Foreign Composition Patents and 87 PCT patent filings in key foreign markets.
In May 2021 AGS licensed its IP Platform to Ketone Labs to sell BHB to select companies for the production and sale of approved BHB and BHB related products. This relationship has been instrumental in pioneering a fast growth market of qualified companies who join us in our belief that BHB has significant, long term, sustainable growth potential in impacting worldwide health and wellness issues.
AGS and Ketone Labs now control the single licensing source of BHB ingredients within the supplement marketplace.
UTILIZING THE AGS IP PLATFORM
Ketone Labs is selective in their relationships for the use of the AGS IP Platform. These are the key technical aspects the IP Platform delivers:
Competitive Advantage of Using BHB in a Product. Adding BHB to a product offering creates a significant competitive advantage and creates new opportunities in select market spaces.
Market Protection. The strength and depth of our IP deters and prevents competitors from entering the market with “me too” products.
Real Efficacy. The science around BHB is strong. It does what the science says it does and we have studies to prove it.
Continued Innovation. AGS will continue to innovate and deepen its IP Platform and provide its partners access to that innovation.
Technical Help. AGS can help with formulations, creative product ideas, and unique delivery systems for BHB.
Market Awareness. Ketone Labs can help provide vital information that can be used to advance the awareness of the benefits of BHB to human health and performance.
COMPETITIVE FUNCTIONAL ADVANTAGES OF USING BHB IN A PRODUCT
BHB is a high cellular energy molecule. BHB is the body’s preferred fuel, producing 2.5 times more energy than glucose. A true fatigue fighter. BHB can be utilized by the body even in a “glucose fed” state.
BHB is immediately up taken by the brain. BHB can stimulate brain energy metabolism, increase brain speed, improve mental clarity and sharpness and improve memory. It can also increase cognitive performance and shows promising results in delaying related onset brain aging diseases.
BHB is protective. Ketosis protects against hypoglycemia and muscle loss during dieting, thus no “low-carb flu,” when entering a low carb state. This reduces tiredness, hunger and irritability on any diet.
BHB is effective in reducing normal anxiety and stress. ï BHB is effective in promoting better sleep.
BHB is highly effective in weight loss. It suppresses appetite and carb cravings. Helps reduce “weight loss plateauing” because the brain is well-fed and the body maintains its normal metabolism rather than down regulating its energy level because it thinks it is starving during any caloric restricted diet.
BHB supplementation allows people to enjoy the benefits of ketones without the harsh dietary restrictions to produce ketones endogenously. It leverages any diet plan.
BHB is the only macro-nutritional ingredient that can be consumed during a fasting period that will not break a fast.
BHB salts has been shown to be very effective in supporting hydration.
BHB helps to lower insulin and glucose levels, which aids in and reduces the risk of Type 2 Diabetes while improving insulin sensitivity.
BHB helps to improve human endurance and stamina, with no insulin/glucose crashes.
BHB enhances mental and motor performance, helping to improve human performance such as athletics, and bodybuilding/body shaping.
BHB produces fewer free radicals (Reactive Oxygen Species). This is extremely important in curbing and preventing aging, workouts, and improving cellular health.
BHB reduces inflammation by interrupting inflammation pathways.
BHB has special affinity for the heart and kidneys. There are numerous studies showing heart health and kidney function improvement.
BHB has now been shown to have strong anti-viral effects and immunity boosting qualities.
BHB has proven to be a very ineffective growth fuel for cancer cells. A great deal of research is currently being performed on ketones and cancer.
REAL EFFICACY
There are now dozens of new research studies being performed on BHB, ketones, ketogenic diets and exogeneous ketones. We believe the best studies are the ones you do yourself. We have conducted two significant human clinical study trials on BHB and numerous animal studies. Both Human Study 1 and Human Study 2 resulted in regulatory attorney approved Structure, Function Claims covering the following:
Weight Loss
Fat Loss
Improvement in Lean to Fat Ratios
Reduction of Hip Circumference
Lowering of Normal Insulin Levels
Lowering of Normal Cholesterol Levels
Increased Brain Speed
Reduction in Normal Anxiety and Stress
TECHNICAL HELP
Our deep understanding of BHB in all its forms (acids, electrolytes, acid/electrolytes), how it performs, how it tastes, how it reacts to other substances, etc. provides us the ability to quickly innovate perfect applications and create new delivery methods for BHB. We have developed and formulated these classes of BHB products.
BHB Powders
BHB Powders with MCT
BHB Capsules
Keto Gummies
Keto Shots
Keto Collagen
Keto Protein
Keto Bars
Keto Chips
Keto Popcorn
Keto RTDs
BHB MARKET AWARENESS AND GROWTH
BHB is in its infancy in terms of both its potential and the understanding of its TRUE health and wellness value by consumers. The nature of BHB and its efficacy provides sustainability and continuous opportunity to utilize BHB in different formulations and in different delivery systems. The more consumers experience the benefits of BHB, the greater the demand will be for BHB.
The World’s Most Powerful Science Backed Ingredient.
goBHB® is the Gold Standard of cellular energy. It is a very high quality, patent-protected ketone body, commonly known as Beta-hydroxybutyrate (BHB). goBHB® is a breakthrough energy ingredient from Ketone Labs. Our BHB is bio-identical to the BHB produced endogenously when a person enters a low-carb state in which the body releases fat and the liver converts those fats into ketones, as an alternative, high energy source for the brain, heart, and muscles. BHB is the body’s preferred fuel.
To that note, BHB is used by the fetal brain for energy as they freely cross the placenta and are also incorporated into cerebral lipids and proteins, suggesting that BHB is an essential building block for the developing brain.
BHB also plays an important role in a newborn’s metabolism. For one, BHB is important for a baby’s brain development. Studies have shown that the newborn brain is much better at using ketone bodies as fuel compared to an adult brain (3). Ketones are also a precursor for important metabolites which supports brain development, including cholesterol and certain amino acids. During the most important time of your life, when your brain, heart and all your other major organs are developing, BHB aids in this development.
UNDERSTANDING THE MOLECULE BHB
BHB is Beta-Hydroxybutyrate, one of three molecules classically defined by physiologists as ketone bodies. Ketone bodies, such as B-hydroxybutyrate (BHB or B-OHB), acetone and acetoacetate (AcAc), are produced in the liver and serve as alternative energy sources for the brain, heart, and skeletal muscle cells. In the body (endogenous) they are produced by the liver during glucose deprivation (i.e. intermittent and regular fasting, starvation), or when consuming fat during a low-carbohydrate diet (Yudkoff et al., 2007; Branco et al., 2016). During prolonged fasting, glycogen stores (a source of glucose) are used first as energy and when those stores are exhausted, the level of total blood ketone bodies can increase up to 5-8 mM (Owen et al., 1969). At ketone levels of 0.5 mmol/L, it is clinically defined as a state of nutritional ketosis, which also prevents muscle loss (Veech, 2004; Paoli et al., 2015b), and may boost mitochondrial and neuronal metabolism for a myriad of physical and cognitive benefits (Achanta et al., 2017).
Biochemically, BHB is a water-soluble fat-derived energy metabolite. BHB is powerful. It rapidly crosses the blood brain barrier, accumulates in brain tissue and provides energy for the central nervous system (CNS) (Plecko et al., 2002; Yudkoff et al., 2007; Newman and Verdin, 2014; Achanta and Rae, 2017) with far more energy per gram than glucose. Preserving brain energy metabolism serves a very important evolutionary function with regard to the enormous energy demand of the human brain. Ketones help sustain that demand during glucose energy restriction, as well (Veech et al., 2001; Veech, 2004; Cahill, 2006).
During dietary glucose energy restriction from carbohydrate and protein restriction (ketogenic diet; KD), prolonged fasting, or heavy endurance, the human metabolism automatically shifts from burning glucose to burning fatty acids and ketones. In the brain exclusively, ketones become the predominate, preferred fuel for the massive energy requirements of the entire CNS (Cahill, 2006).
The ketone bodies—BHB and AcAc—are synthetized by liver cells’ mitochondria from fatty acids, which lead to ketosis when blood ketone levels rise above 0.5 mmol/L (Figure 1.; fatty acid metabolism in liver). These ketone bodies then reach the brain via blood vessels by transporter molecules. Similar to heart and skeletal muscle cells, ketone bodies can metabolize directly to aceyl CoA and provide energy for brain cells, as well as through the Krebs (ATP) cycle (Yudkoff et al., 2007; Newman and Verdin, 2014; Branco et al., 2016; Egan and D’Agostino, 2016; Achanta and Rae, 2017). While ketone metabolism may appear new, it is interesting to note that BHB is evolutionary molecule – designed to provide high energy when glucose was restricted. For example, many bacteria can synthetize BHB polymers to store energy (Cahill, 2006). Moreover, blood levels of BHB, and how BHB is metabolized and used, are all dependent on age, brain area and species. This suggests a different and diversified physiological role of BHB in the body of several species (Hawkins and Biebuyck, 1979; Achanta and Rae, 2017).
Figure 1. Synthesis and utilization of ketone bodies (from Branco et al., 2016; http://onlinelibrary.wiley.com/doi/10.1111/ eci.12591/full).
WHAT ARE THE BENEFITS OF BHB?
BHB is an alternative energy source to glucose and it is the body’s preferred energy source: Despite the fact that the human brain (weighing approximately 1.5 kg) represents 2-3% of body weight, it consumes 20% of the body’s total energy output. BHB represents an alternative form of energy that most of the body’s cells, including the brain, can use in many ways (Yudkoff et al., 2007; Pinckaers et al., 2017) (Figure 2.).
Here are the facts. The brain is shown to burn ketones preferentially over glucose in two ways: (1) In the developing brain, ketones preserve glucose for the pentose phosphate pathway, which results in ribose for DNA synthesis and NADPH for lipid biosynthesis and (2) under conditions of long-term starvation and KD, metabolism shifts from burning glucose to fatty acids and ketones as fuel. Under different conditions from above, glucose is the predominate fuel for the brain (Nehlig, 2004; Cahill, 2006).
The brain is like a hybrid engine, able to switch from ketones to glucose and vice versa. These observations show that the brain has a remarkable ability for adaptation and metabolic flexibility.
“The Fourth macronutrient”: BHB provides macronutritional mitochondrial energy (as a “high-octane” fuel). It can also provide unique signaling and health benefits that are completely independent of its role as an energy metabolite (Hashim and VanItallie, 2014; Newman and Verdin, 2014; Cox et al., 2016; Dyer, 2016; Egan and D’Agostino, 2016). This makes BHB one of the most versatile molecules in the human body
Reducing Reactive Oxygen Species (ROS) in lowering oxidative stress and inflammation: ROS causes cell damage, especially at the mitochondrial level. BHB when metabolized creates 46X LESS ROS compared to the metabolism of glucose. This magnitude of reduction in oxidative stress and inflammatory processes helps reduce cellular damage, and may improve the symptoms of different diseases such as Parkinson’s disease, Alzheimer’s disease, schizophrenia, amyotrophic lateral sclerosis (ALS), glucose transporter 1 (GLUT1)-deficiency syndrome, anxiety, autism, depression, cancer, and epilepsy not only in model animals of different human diseases but also in patients (Masino et al., 2009; Stafstrom and Rho, 2012; D’Agostino et al., 2013; Shimazu et al., 2013; Hashim and VanItallie, 2014; Poff et al., 2015; Youm et al., 2015; Ari et al., 2016; Branco et al., 2016; Chavan et al., 2016; Rogawski et al., 2016; Achanta and Rae, 2017; Bostock et al., 2017; Cheng et al., 2017; Rho, 2017; Simeone et al., 2017; Tefera et al., 2017).
Figure 2. Effect of ketone bodies on exercise metabolism. (from Pinckaers et al., 2017; https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC5309297/).
Improvement of cognitive functions: BHB improved cognitive functioning (e.g., working memory and executive function) in both memory-impaired patients and in healthy nondemented subjects (Reger et al., 2004; Krikorian et al., 2012; Ota et al., 2016).
Reduction of Normal Stress and Anxiety: BHB with MCT showed normal stress and anxiety were reduced by 39% (2019, Blind Comparison of Two Different Compositions of Exogenous Ketones and Their Impact on Anxiety, Weight, Lean Muscle Mass and Cognitive Function, Koche, Dituri, and Gracio)
Reduction in seizure activity: Approximately 50% reduction in seizure activity was demonstrated in 50-60% of children with drug-resistant childhood epilepsy after KD, which effect may be in relation, among others, to progressive elevation of serum ketone bodies/BHB (Ross et al., 1985; Groomes et al., 2011; Thammongkol et al., 2012; Kim et al., 2016).
Homeostatic role: BHB is one of the main components of homeostatic mechanisms, which allow us to survive prolonged starvation and other trying environmental factors. For example, BHB actively regulates its own synthesis and promotes effective use of fat tissue (as an energy store) under this circumstance (Taggart et al., 2005).
Longevity-enhancing effects: BHB could also have longevityenhancing effects (Newman and Verdin, 2014; Veech et al 2017). In C. elegans (roundworms), BHB was shown to increase lifespan through inhibiting histone deacetylase (HDAC) and reducing metabolic stress (Edwards et al, 2014).
Reduction of hunger and sugar craving and its effect on weight management: Nutritional ketosis/BHB plays a role in regulating food intake and body weight (Atkins, 2002; Paoli, 2014; Paoli et al., 2015a). Different hypotheses suggest the indirect and direct mechanisms by which KD/nutritional ketosis/ ketone bodies induce and evoke weight loss: (i) Losing energy by excretion of ketone bodies, (ii) gluconeogenesis (which converts protein to glucose and provides a major portion of the glucose needed for fuel during the initial period of KD) is an energy-demanding process leading to a “waste of calories”, (iii) higher satiety effect of proteins, which evoke reductions in appetite,(iv) increased lipolysis and decreased lipogenesis and (v) a possible direct suppressive effect of ketone bodies (e.g., BHB) on appetite/ hunger (Kekwick and Pawan, 1957; Atkins, 2002; Cahill, 2006; Feinman and Fine, 2007; Johnstone et al., 2008; Westerterp- Plantenga et al., 2009; Sumithran et al., 2013). In the Kekwick and Pawan study in 1957, the researchers showed that you can consume the same number of calories in fat, protein and carbs, but you expend the most energy (calories) when consuming fat. In other words, a calorie is not a calorie. Also, the ketogenic diet/nutritional ketosis is characterized by increased circulating free fatty acid levels, which may reduce food intake and glucose production through specific neurons from parts of the brain implicated in regulation of satiety and hunger (Paoli et al., 2015a). Thus, among others, beneficial effects of increased levels of both free fatty acids and BHB on body weight suggests that KD/ketosis may be a good way to manage weight. (ISSN 2001 KETAD Trial: Effects of exogenous ketones as an adjunct to low calorie diet on metabolic biomarkers, fat loss and health,Lopez, Raub,, et. al)
Insulin sensitivity: BHB enhances insulin sensitivity (Will et al., 1997; Veech, 2004; Park et al., 2011).
Improvement of reaction time and exercise performance: BHB may improve them both due to its use as an alternative substrate for ATP (Cox et al., 2016; Egan and D’Agostino, 2016). Additionally, BHB spares glycogen and Leucine (Nair et al, 1988). Brain reaction time was shown to increase by 9.9% (2019, Blind Comparison of Two Different Compositions of Exogenous Ketones and Their Impact on Anxiety, Weight, Lean Muscle Mass and Cognitive Function, Koche, Dituri, and Gracio).
Intermittent fasting: Consumption of BHB may preserve and maintain brain energy metabolism during periods of limited glucose availability without breaking a fast or interrupting autophagy.
Alleviation of the keto or low carb “flu” symptoms: Keto, low carb “flu” (or ketogenic/ ketosis flu, low-carb flu, induction flu, Atkins flu) is a withdraw symptom from glucose dependency experienced during carbohydrate restriction, which occurs during intermittent fasting, converting to a low carb or ketogenic diet. It’s really the side effect of when the body is adapting to burning ketones rather than glucose for its primary fuel. BHB decreases the symptoms of keto “flu” (e.g., fatigue, headache, nausea, dizziness, sleepiness, and difficulty focusing or brain fog), consumption of more fat, or BHB, may be recommended (Stanton, 2011).
WHY USE EXOGENOUS KETONES (BHB)?
Most people cannot withstand the rigors of maintaining a ketogenic or very low carb diet. It’s just too hard. And certainly, the mainstream population isn’t going to do it. This means their pathway to obtain the main benefits of ketones will be lost. The intermittent faster may also struggle to maintain that lifestyle even though its less rigorous, but nevertheless even intermittent fasting is limited to the number of ketones the body actually produces during an intermittent fast.
What needs to be understood is that the purpose of fasting, ketogenic diets, low carb diets, or calorie restriction diets is to put the body into a position of making more ketones than it already does and using those ketones to its benefit. Exogenous ketones for the first time provide access to ketones anytime you want or need them without having to follow a very restrictive diet. These exogenous ketones will always be used by the body in preference to glucose uptake. This is the power of exogenous ketones, the benefits without the hassles.
We now know through lots of science that BHB has the unique property of enhancing bioenergetic effects (much like creatine, but more versatile), thus consuming BHB as a supplement is the way to quickly enhance our overall metabolic health and even performance. (Abraham, 2015; Cox et al., 2016; Egan and D’Agostino, 2016; Pinckaers et al., 2017). For example, the use of BHB may be especially beneficial for populations of people that have insulin resistance or carbohydrate intolerance. Evidence suggests that BHB can enhance insulin sensitivity and may improve glucose disposal (Will et al., 1997; Veech, 2004; Park et al., 2011). A large percentage of the population above middle age has either signs of insulin resistance or is considered pre-diabetic.
It seems that the most promising application of exogenous ketones as a supplement is using this source of BHB daily as a source of energy to further augment anyone’s own diet or to enhance your intermittent fast (Veech, 2004; Paoli et al., 2013). Ketones are shown to be utilized regardless of glucose levels such as when someone might be on a Zone diet. (ISSN 2001 KETAD Trial: Effects of exogenous ketones as an adjunct to low calorie diet on metabolic biomarkers, fat loss and health, Lopez, Raub,, et. al).
When it comes to using BHB as a supplement together with intermittent fasting or a low carb diet, this may present several additional compelling benefits. For example, when one starts a KD, one’s brain essentially goes through a form of “glucose withdrawal” that can negatively impact physical and cognitive performance. This usually occurs over several days, or as long as two to four weeks, and causes lethargy, headaches and an overall decrease in mental well-being. But after several weeks the body adapts entirely to using fat and ketones (keto-adaptation) more efficiently for energy. Anecdotally, many users report that BHB makes this transition to a keto or low- carbohydrate diet more seamless by circumventing the need for extreme dietary restriction to elevate BHB levels.
This happens by providing an alternative form of energy that can help to restore and preserve normal brain energy metabolism in the face of carbohydrate restriction as described above. If following a KD, the use of BHB helps to bridge the gap into ketosis by supplying ketones to the brain and supplying a nongluconeogenic energy precursor that has less insulin potentiating effect than glucose or protein. Oral intake of BHB will not prevent endogenous ketone production from nutritional ketosis.
The other key application of exogenous ketones is their consumption during a period of time-restricted eating called intermittent fasting (IF). IF has been shown to have a broad range of health benefits, cognitively, physically and especially for metabolic health in resetting insulin resistance. It may have therapeutic effects alone or as an adjunct to increase the efficacy of the treatment of different diseases such as cancer, anxiety, neurological diseases and cognitive impairment (Park et al., 2011; Arnason et al., 2017; Hu et al., 2017; O’Flanagan et al., 2017; Singh et al., 2017). Anecdotally, the consumption of small amounts of ketone supplements during a period of intermittent fasting, can provide a person with greater sustained energy without impairing endogenous ketogenesis. Many of the aforementioned benefits are largely a function of preserving and maintaining brain energy metabolism during periods of limited glucose availability and mild hypoglycemia.
One of the main benefits of elevated BHB is that hunger cravings are controlled (satiety) as long as brain energy metabolism is not interrupted by fluctuations in glucose and insulin. Nutritional ketosis plays a vital role in stabilizing and regulating food intake control (Atkins, 2002; Paoli et al., 2015a). Regarding insulin, it has been shown that ingesting sodium-BHB did not change insulin secretion and was well tolerated without adverse effects in human studies (Plecko et al., 2002; Van Hove et al., 2003). More advanced formulas using BHB mineral electrolytes (i.e. in combination with MCTs) and new/more effective methods of their application are being developed to enhance and sustain ketone absorption and utilization and to evolve therapeutic procedures. For example, it has been demonstrated that not only intragastric gavage of BHB electrolytes, but also administration of its 4.2% solution (in drinking water) increased ketonemia/BHB level in rats, which may decrease fat mass and suggests that ketone supplements can increase the effectiveness of the treatment of obesity (Pawan and Semple, 1983; Caminhotto et al., 2017).
When it comes to performance, especially during periods of extreme exertion or extreme environment (e.g., military troops, emergency personnel, etc.), the use of BHB supplementation evoked mild ketosis. This may be leveraged to provide resilience in the face of limited glucose or oxygen levels without elevation of free fatty acids (Veech, 2004). It may also be noted the application of BHB as an exogenous fuel may be perceived as beneficial to exercise enthusiasts, high-performance athletes (e.g., elite athletes, and cyclists) and even to corporate executives functioning under high levels of stress due to limited sleep, limited food consumption and nonstop travel associated with their business activities. BHB in the form of BHB electrolytes may also add a critical hydration component by being able to deliver “free electrolytes” in the form of sodium, potassium, calcium and magnesium as the freely dissociate from the BHB acid upon ingestion and provide the body an instant supply of needed electrolytes. We call these PURE electrolytes. Indeed, it has been demonstrated that BHB may have distinct benefits for athletes looking to improve their reaction time and performance (Abraham, 2015; Paoli et al., 2015b; Cox et al., 2016; Egan and D’Agostino, 2016). Moreover, exogenous ketone supplements/ BHB as a food supplement may increase endurance performance of warfighters similar to high-performance athletes, providing an alternative substrate for oxidative phosphorylation (ATP), greater muscle fat oxidation and a sparing of muscle glycogen (Cox et al., 2016; Egan and D’Agostino, 2016). Elevating blood ketones may also enhance cardiac function (Puchalska and Crawford, 2017). For example, ketone bodies increased both the hydraulic efficiency of the heart by 28% and synthesis of adenosine triphosphate (ATP) (Kashiwaya et al., 1994).
The most promising application of BHB appears to be as a neurocognitive enhancement strategy and perhaps even a nootropic agent for improving cognitive function and reaction time, which has a broad range of implications for age- related cognitive decline (Newport et al., 2015; Ota et al., 2016; Mamelak, 2017). It has been demonstrated that BHB preserves the rat hippocampus (Izumi et al., 1998), a brain structure, which has a role for example in memory and cognition (it is interesting to note that the hippocampus is one of the first structures of the brain, which suffer damage in dementia generating among others shortterm memory loss). In human studies, BHB infusion and ketogenic meals- evoked increase in BHB levels improved cognitive functioning (e.g., working memory and executive function) not only in memory- impaired patients but also in healthy non-demented subjects (Reger et al., 2004; Krikorian et al., 2012; Ota et al., 2016). BHB increased the cerebral blood flow in healthy people (Hasselbalch et al., 1996), which may evoke ameliorating effect on cognitive functions. Moreover, ketone bodies may protect from cognitive impairment and moodiness evoked by obesity and weight gain (Yancy et al., 2009; Davidson et al., 2013).
WHY BHB ELECTROLYTES?
It doesn’t do anyone any good to produce a product no one will consume. Ever tasted a BHB ester? 1,3, butanediol (which is not a ketone body, but a pre-cursor alcohol that sometimes is used to create BHB)? They taste awful! BHB is attached to minerals (electrolytes) to create stability and consumability so they can be used in powder form, which is the most convenient form. A BHB electrolyte is created through an ionic bond with a mineral because BHB is not stable on its own in powder form. The BHB “electrolyte” (calcium, sodium, magnesium or potassium) makes the molecule way more palatable, and it’s also a very convenient way to deliver critical electrolytes that may otherwise be depleted under conditions of low-carbohydrate dieting or performance. Specifically, the consumption of BHB in a mineral electrolyte form buffers the ketone molecule to reduce the mild acidity that’s associated with the free acid form while supplying free-form electrolytes to aid in a low-carb diet or high performance activity.
It is important to consume BHB with balanced minerals in order to help absorption and maintain the proper electrolyte balance while being able to increase BHB levels. (Paoli et al., 2015b; Kesl et al., 2016; Caminhotto et al., 2017) (Figure 3.). Combining BHB with mineral electrolytes also allows BHB consumption in effective concentrations without leading to gastrointestinal (GI) distress It is interesting to note that ketone electrolytes may be effective in different intravenous and dialysis fluid therapies such as application of sodium- BHB in resuscitation fluids in combat casualties (Veech, 2004).
Figure 3. Effects of ketone supplementation on blood BHB level (from Kesl et al., 2016; https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC4743170/).
WHAT IS THE BEST WAY TO BALANCE THE MINERALS?
One way to balance BHB mineral electrolytes is to have sodium as the predominant mineral, since that can facilitate absorption of many molecules in the gut through co-transporter activation. Potassium, magnesium and calcium would represent at least 50% of the mineral content of the ketone electrolytes in a balanced ratio. This is one general guideline for formulation of a ketone electrolyte that is palatable and tolerable (Plecko et al., 2002; Van Hove et al., 2003; Azzam and Azar, 2013; Kesl et al., 2016).
BHB electrolytes contain BHB and sodium (Na+), potassium (K+), calcium (Ca2+) and/or magnesium (Mg2+) ions. As ketone bodies have diuretic effects and cause a loss of certain amounts of electrolytes BHB “electrolyte” content helps compensate for the loss without serious side effects if keeping to normal dosing (Veech, 2004). It should be noted that the sodium in sodium BHB is not sodium chloride (aka, table salt), the type of sodium people normally attribute to a rise in blood pressure. Ours is PURE sodium.
WHY BHB FREE ACID?
The best way to create a BHB RTD is using our BHB free acid which is a 50% solution. There are no solubility issues, no acidity issues, no flavoring issues or production issues. Dosing levels can be anything you want based off what you are trying to achieve.
APPROPRIATE DOSING FOR VARIOUS OUTCOMES (WEIGHT MGMT. (SATIETY), COGNITION, PERFORMANCE…)
The best dosing strategy for BHB electrolytes is to start at a relatively low dose – about 6 g per serving. Gradually increase the dose every three days in order to achieve the desired energy performance and GI tolerability. However, to achieve therapeutic levels of ketone bodies (1-5 mM) in the blood of a 70 kg man, it can range from 5.6g to 63 g/day of BHB salts (Veech, 2004), depending on the goal of the user and/or type of disease state. In dietary supplements, the typical therapeutic dose is in the 10g to 12g range. In some applications BHB can be combined with 2 to 3g of MCT for higher and more sustained levels of blood ketones. After ingesting a BHB supplement, increased levels of blood ketones may decrease to the normal physiological levels within several hours (Figure 3.). Thus, to achieve and maintain desired therapeutic levels of BHB, it’s wise to time your ketogenic/ BHB supplement to achieve your goal (e.g., before a meal, during intermittent fasting, prior to exercise, before difficult cognitive tasks, for long-lasting energy and other goals unique to you).
ARE THERE PATENTS ASSOCIATED WITH BHB?
Yes, Axcess Global Sciences currently holds the greatest number of BHB electrolyte and acid patents concerning BHB, the combination of BHB and MCT, and numerous other combinations of BHB and other ingredients. Ketone Labs is the official distributor of the patented BHB trademark goBHB™.
DOES TAKING EXOGENOUS KETONES ACTUALLY PUT SOMEONE INTO KETOSIS?
Yes, taking exogenous ketone supplements will elevate normal blood plasma BHB levels into a range that is clinically accepted as being in a state of ketosis (>0.5 mM) (Achanta and Rae, 2017).
CAN I BENEFIT FROM EXOGENOUS KETONES IF I’M NOT EATING KETOGENICALLY?
Yes, someone not eating a KD or carbohydrate-restricted diet can benefit from consumption of BHB electrolytes due to the fact that this will allow an elevation of BHB in the blood, which we know is linked to many health benefits described above; some of which have been documented in humans (Pinckaers et al., 2017). More research is needed to move the preclinical animal studies into human clinical studies to validate the use of BHB supplementation.
SHOULD THOSE IN NUTRITIONAL KETOSIS TAKE EXOGENOUS KETONES?
Yes. The use of exogenous ketones for performance applications has been exclusively in the realm of special operations forces and elite level endurance athletes that have described significant benefits for specific applications (Egan and D’Agostino, 2016; D’Agostion et. al., 2013; Abraham, 2015; Pinckaers et al., 2017). Similar to creatine supplementation, we will elucidate what types of exercise and what types of sports will benefit most from ketone supplementation as the science progresses (Cox et al., 2016). It will be important for the end-user to experiment with the dosing of ketones according to their own performance regimen since other factors, – including body size, type of exercise, duration, existing nutrition strategy and other supplements – will influence the performance-enhancing benefits of BHB supplementation (Pinckaers et al., 2017). Those already in a state of nutritional ketosis can also benefit from BHB supplementation by allowing the user to optimize blood levels of ketones that they have found correlate with optimal mental and cognitive performance.
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