HYPERADE: The King of Endurance

Accumulating evidence indicates a strong connection between amino acids and plasma glucose levels. Branched-chain amino acids have been demonstrated to play a big role in glucose consumption and utilization.

The mechanism behind the greater uptake of glucose, when combined with amino acids, is due to enhanced GLUT1 and GLUT4 translocation to the plasma membrane of the muscle by a process that may be unique to amino acid stimulation.

Collectively, BCAA regulates the expression and translocation of muscular or intestinal glucose transporters through insulin-dependent or insulin-independent ways. These findings have important implications in that BCAA could enhance muscle growth and intestinal development by increasing the local glucose uptake.

Fig: Isoleucine up-regulates intestinal and muscular transporters. GLUT1 and GLUT4 are vital glucose transporters in muscle. SGLT1 and GLUT2 are important glucose transporters in the small intestine. Isoleucine could potentially increase muscle growth and intestinal development and health by up-regulating the protein expression of GLUT1 and GLUT4 in muscle and enhancing the expression of SGLT1 and GLUT2 in the small intestine. Ref: https://pubmed.ncbi.nlm.nih.gov/28127425/

Fig: Effects of BCAA on glucose uptake in isolated soleus muscle from CCl4 rats. Soleus muscle isolated from CCl4 rats after 17 h of fasting (Fast) was incubated in tubes with 2 mM Leu, Ile, or Val or saline (None) for 20 min and then incubated for another 20 min with double-labeled glucose as described previously. *P < 0.05 vs. None. Ref: https://pubmed.ncbi.nlm.nih.gov/15591158/

References:

• - J Appl Physiol (1985). 2012 Jul;113(1):97-104 https://pubmed.ncbi.nlm.nih.gov/22604888/
• - Biochem Biophys Res Commun. 2003 Dec 26;312(4):1111-7. https://pubmed.ncbi.nlm.nih.gov/14651987/
• - J Anim Sci Biotechnol. 2017; Jan. 23;8: 10 https://pubmed.ncbi.nlm.nih.gov/28127425/

Hyperade ingredients and what makes it so powerful.

What are Electrolytes?

Chemically, electrolytes are substances that become ions in solution and acquire the capacity to conduct electricity. Electrolytes are present in the human body, and the balance of the electrolytes in our bodies is essential for normal function of our cells and our organs.

Common electrolytes that are measured by doctors with blood testing include sodium, potassium, chloride, and phosphorous. The functions and normal range values for these electrolytes are described below.

Sodium

Sodium is the major positive ion (cation) in fluid outside of cells. The chemical notation for sodium is Na+. When combined with chloride, the resulting substance is table salt.

Excess sodium (such as that obtained from dietary sources) is excreted in the urine. Sodium regulates the total amount of water in the body. The transmission of sodium into and out of individual cells plays a role in critical body functions. Many processes in the body, especially in the brain, nervous system, and muscles, require electrical signals for communication.

The movement of sodium is critical in the generation of these electrical signals. Therefore, too much or too little sodium can cause cells to malfunction, and extremes in the blood sodium levels (too much or too little) can be fatal.

Increased sodium (hypernatremia) in the blood occurs whenever there is excess sodium in relation to water. There are numerous causes of hypernatremia; these may include kidney disease, too little water intake, and loss of water due to diarrhea and/or vomiting.

A decreased concentration of sodium (hyponatremia) occurs whenever there is a relative increase in the amount of body water relative to sodium. This happens with some diseases of the liver and kidney, in patients with congestive heart failure, in burn victims, and in numerous other conditions.

A Normal blood sodium level is 135 - 145 milliEquivalents/liter (mEq/L), or in international units, 135 - 145 millimoles/liter (mmol/L).

Potassium

Potassium is the major positive ion (cation) found inside of cells. The chemical notation for potassium is K+. The proper level of potassium is essential for normal cell function. Among the many functions of potassium in the body are the regulation of the heartbeat and the function of the muscles.

A seriously abnormal increase in potassium (hyperkalemia) or a decrease in potassium (hypokalemia) can profoundly affect the nervous system and increases the chance of irregular heartbeats (arrhythmias), which, when extreme, can be fatal.

Increased potassium is known as hyperkalemia. Potassium is normally excreted by the kidneys, so disorders that decrease the function of the kidneys can result in hyperkalemia. Certain medications may also predispose an individual to hyperkalemia.

Hypokalemia, or decreased potassium, can arise due to kidney diseases, excessive losses due to heavy sweating, vomiting, diarrhea, eating disorders, certain medications, or other causes.

The normal blood potassium level is 3.5 - 5.0 milliEquivalents/liter (mEq/L), or in international units, 3.5 - 5.0 millimoles/liter (mmol/L).

Chloride

Chloride is the major anion (negatively charged ion) found in the fluid outside of cells and in the blood. An anion is the negatively charged part of certain substances such as table salt (sodium chloride or NaCl) when dissolved in liquid. Chloride plays a role in helping the body maintain a normal balance of fluids.

The balance of chloride ion (Cl-) is closely regulated by the body. Significant increases or decreases in chloride can have deleterious or even fatal consequences.

Increased chloride (hyperchloremia) may be seen in diarrhea, certain kidney diseases, and sometimes in overactivity of the parathyroid glands.

Decreased chloride (hypochloremia): Chloride is normally lost in the urine, sweat, and stomach secretions. Excessive loss can occur from heavy sweating, vomiting, adrenal gland and kidney disease.

The normal serum range for chloride is 98 - 108 mmol/L.

Phosphorous

Phosphorus is an element that plays an important role in the body. In the body, almost all phosphorus is combined with oxygen, forming phosphate. Phosphate is one of the body's electrolytes, which are minerals that carry an electric charge when dissolved in body fluids such as blood, but the majority of phosphate in the body is uncharged.

Bone contains about 85% of the body’s phosphate. The rest is located primarily inside cells, where it is involved in energy production.

Phosphate is necessary for the formation of bone and teeth. Phosphate is also used as a building block for several important substances, including those used by the cell for energy, cell membranes, and DNA (deoxyribonucleic acid).

Cluster Dextrin

Cluster Dextrin sometimes known as Highly Branched Cyclic Dextrin (HBCD), is a new advanced breed of maltodextrin. It differs from other high glycemic index (GI) carbohydrates like dextrose and maltodextrin because it provides a sustained release of energy as opposed to a sudden spike in blood sugar resulting in a large insulin response.  It has a high molecular weight, is soluble, and has an osmotic pressure near zero.  Essentially, it passes through your stomach much faster than other carbohydrate supplements, making it more readily available for your body to burn as energy.

How does Cluster Dextrin act?

Cluster Dextrin sustains a slow-release which offers an ideal interface between carbohydrate breakdown and the normal release of free fatty acids from fat cells.  This results in a superior carbohydrate that delivers smooth, constant energy and replenishes muscle glycogen stores without spiking blood sugar levels. 

Sports drinks include HBCD as a carbohydrate because it has high solubility, low viscosity, and is tolerant to retrogradation.  Gastric emptying time is shorter for drinks containing HBCD compared to glucose and standard dextrin due to having a much lower osmotic pressure. 

This also results in less gastrointestinal disorders developing in humans during exercise. Therefore, Cluster Dextrin increases performance, promotes fat burning, and decreases nausea during vigorous exercise.

Research proven to:

• - Enhance endurance performance
• - Promotes fast gastric emptying times
• - Lower markers for stress hormones (i.e. cortisol) after exhaustive exercise compared to other carbohydrate sources.
• - No other carbohydrate source can demonstrate clinical data like cluster dextrin.

Cluster Dextrin has the same molecular weight as maltodextrin but with more “branching.”

Branching refers to short chains of poly- and oligosaccharides that “branch” out from the main starch molecule which enhances digestion. Research on Cluster Dextrin has demonstrated that it has faster gastric emptying time, reducing the potential for upset stomachs, and improves endurance performance. 

The mechanism responsible seems to be associated with the ability of HBCD to supply glucose energy for a longer period and its shorter gastric emptying time. This is why it is the primary carbohydrate in our HYPERADE glycogen & electrolyte formula.

Fig: Relationship between the Mean Swimming Time to fatigue and carbohydrate ingestion 10 min after onset of swimming through a cross-experiment.  Ref: https://pubmed.ncbi.nlm.nih.gov/10664836/

References:

• - Biosci Biotechnol Biochem, 2014;78(12):2117-9. https://pubmed.ncbi.nlm.nih.gov/25080121/
• - Int J Sports Med.  2005 May;26(4):314-9.  https://pubmed.ncbi.nlm.nih.gov/15900642/
• - Food Science and Technology Research  Volume: 10 Issue: 4 Pages: 428-431 https://www.jstage.jst.go.jp/article/fstr/10/4/10_4_428/_article/-char/ja/
• - J Sports Med Phys Fitness. 2014 Oct;54(5):622-30.  https://pubmed.ncbi.nlm.nih.gov/25270782/
• - Biosci Biotechnol Biochem. 1999 Dec;63(12):2045-52. https://pubmed.ncbi.nlm.nih.gov/10664836/

Glutamine

Glutamine is not an essential amino acid, but it is considered to be conditionally essential. Usually, glutamine is produced in sufficient amounts in the body. However, in some cases of stress, inflammation, and injuries, some bodily functions may use significantly more glutamine than usual [2, 3].

Our muscles account for 70% of all glutamine production in the body.

The main organs that use glutamine are muscle, kidneys, liver, and small intestine.

Scientists think glutamine is a critical amino acid for the immune system and for keeping the nitrogen levels in your body in check. It makes up to 60% of the free amino acids in the bones.

Overview of Glutamine Uses:

• - A building block for body proteins
• - Fuel for cells that line the gut
• - Fuel for immune cells, such as macrophages
• - Maintaining nitrogen balance
• - Preventing the burning of other amino acids for energy

Fig: Serum IL-2 levels in the glutamine ( ) and alanine ( ) groups. Mice in the glutamine group were fed with the 1·0 % glutamine þ basal diet, while mice in the alanine group were fed with the 1·22 % alanine þ basal diet. dpi, Days post-infection. * P,0·05; ** P,0·01. Ref: https://pubmed.ncbi.nlm.nih.gov/23351361/

 References:

• - Ann Surg. 1994 Aug;220(2):212-21. https://pubmed.ncbi.nlm.nih.gov/8053744/
• - J Crit Care. 2010 Dec;25(4):661.e1-6.
• - The Journal of Nutrition, Volume 131, Issue 9, September 2001, Pages 2515S–2522S https://academic.oup.com/jn/article/131/9/2515S/4687557
• - Br J Nutr. 2013 Sep 28;110(6):1053-60 https://pubmed.ncbi.nlm.nih.gov/23351361/

Leucine

Leucine is a branched-chain amino acid that is sold as a supplement. The other two BCAAs are valine and isoleucine, but leucine is the most popular of the three as a bodybuilding supplement.

Leucine supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.

Leucine is an essential amino acid, meaning that it cannot be produced in the body and needs to be taken in through diet. It increases energy and protein (therefore, muscle) production.

Similar to many other amino acids, leucine is found in many foods that are high in protein. Examples include meats (such as fish, chicken, and turkey), dairy products (such as yogurt and cheese), and soybeans. Other foods like eggs, nuts, seeds, and fruit also contain leucine, but to a lesser extent.

L-leucine is the natural version of the amino acid, is found in the proteins of the body, and is the main form used as a supplement.

Solid evidence supports the use of branched-chain amino acids (including leucine) for reducing fatigue and exertion after prolonged or intense exercise.

Exercise leads to branched-chain amino acid (BCAA) breakdown, especially in the muscles.

Scientists believe that BCAAs help protein synthesis and prevent protein degradation, which in turn helps prevent muscle fatigue and soreness.

In a study of 30 healthy adults, squat exercises caused muscle fatigue and soreness. Those that received BCAA supplementation had less soreness in the following days, while those that did not receive supplementation showed prolonged periods of soreness.

Muscle fatigue after exercise also decreased with BCAA supplementation.

Additional research on individual BCAAs should be done to see if these amino acids can produce the desired effects individually (such as leucine).

Also, scientists found that leucine increased two muscle-building pathways in rats (AKT by 98% and mTOR by 49%) and decreased muscle protein breakdown. More clinical trials on leucine are needed.

Fig: mTOR protein phosphorylation in arbitrary unit (AU) in the control group (C), treated with leucine (L), denervated (D), and denervated treated with leucine (DL). V.  Ref: https://pubmed.ncbi.nlm.nih.gov/25852565/

References:

• - Arch Biochem Biophys. 1984 Aug 15;233(1):10-8. https://pubmed.ncbi.nlm.nih.gov/6540547/
• - Nutrients. 2017 Oct; 9(10): 1047. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5691664/
• - J Biol Chem. 1975 Jan 10;250(1):290-8.  https://pubmed.ncbi.nlm.nih.gov/1141208/
• - The Journal of Nutrition, Volume 136, Issue 2, February 2006, Pages 529S–532S, https://academic.oup.com/jn/article/136/2/529S/4664393
• - Front Physiol. 2015 Mar 18;6:73. https://pubmed.ncbi.nlm.nih.gov/25852565/

L-Isoleucine

L-Isoleucine is one of the three branched-chain amino acids alongside both leucine and valine.

Relative to the other two BCAAs, isoleucine is intermediate for its ability to induce muscle protein synthesis (stronger than valine, but much weaker than leucine) but is able to significantly increase glucose uptake and the usage of glucose during exercise. Isoleucine does not promote glycogen synthesis, however.

Via a PI3K/aPKC dependent mechanism (which is notable since this is neither mediated by the more common AMPK mechanism seen with supplements like berberine nor muscle contraction-mediated uptake) isoleucine can increase glucose uptake into a muscle cell.

Leucine also appears to have this ability, but due to leucine stimulating a protein known as S6K (required for protein synthesis) leucine reduces its own efficacy by hindering insulin-stimulated uptake. In other words, while isoleucine and leucine both stimulate glucose uptake, leucine then shoots itself in the foot and hinders itself while isoleucine just acts in a predictable and linear manner.

Although extensive human testing has not been conducted yet, isoleucine can be seen as the BCAA which mediates glucose uptake (into a cell) and breakdown (into energy) to a larger degree than other amino acids and may serve a role as a hypoglycemic (in diabetics) or as a performance enhancer (if taken pre-workout in a carbohydrate replete state).

Fig: Differentiated C2C12 myotubes were starved for 2 h in a buffer A containing 5 mM glucose and 18 mM mannitol before the experiments were performed. The medium was removed and the buffer A, 5 mM glucose, and 8–17 mM mannitol, together with 1 mM leucine, isoleucine or valine, was added. The osmolality of the medium was adjusted to a constant range with mannitol. At time zero and after 4 h, 5 lL of the medium was collected and the glucose concentration was measured by the glucose oxidase method. Glucose consumption (GC) was calculated by subtracting the remaining glucose at 4 h from that in the medium at time zero. Data are expressed as means ± SD (n = 4). Asterisks represent a significant difference from the value in the respective control group: Student’s t test ***p < 0.001 Ref: https://pubmed.ncbi.nlm.nih.gov/14651987/

References:

• - Doi M, et al. Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubes. Biochem Biophys Res Commun (2003)
• - Biochem Biophys Res Commun. 2003 Dec 26;312(4):1111-7. https://pubmed.ncbi.nlm.nih.gov/14651987/

L-Valine

L-Valine is one of the three branched-chain amino acids (BCAAs) alongside leucine and isoleucine. 

In isolation, there is currently no hugely significant benefit of valine supplementation that cannot be replicated by either leucine or isoleucine supplementation. The possession of a 'branched chain' itself confers some bioactivity, but this is shared to a degree between all of the BCAAs.

This may simply be due to lack of evidence because many times when valine is researched in studies, it is due to it being tested as a branched-chain amino acid (and valine is randomly used). The bioactivities of valine just haven't been purposefully investigated much.

It seems to be more similar to leucine than it is to isoleucine, but the transient state of insulin resistance occurs faster than with leucine (isoleucine causes glucose uptake) while the muscle-building effects of valine are likely less than both leucine and isoleucine.

Fig. 1. Animals were fasted for 20 h before the start of an OGTT. Leucine, isoleucine, or valine was delivered separately as a 3% aqueous solution (0.3 g/kg bw/10 mL) by oral gavage 30 min before the glucose bolus. OGTT was performed by administration of a 2 g bolus of glucose/kg of body weight by gavage as a 50% solution of glucose in water. Blood samples were collected by tail bleeding 60 min before the glucose bolus (basal), and 30, 60, and 120 min after the glucose bolus.  The increase in the plasma glucose was calculated by subtraction of the basal value from the 30, 60 or 120 min value for each rat. Data are expressed as means ± SD (n = 7). Asterisks represent a significant difference from the value in the respective control group: Dunnett’s test*p < 0:05, **p < 0:01.

References:

• - Exp Neurol. 2010 Nov;226(1):218-30

L-Lysine  

Lysine is an essential amino acid that plays an important role in the creation of proteins in the body. The human body is unable to produce lysine itself. This means that lysine must come from external sources — primarily food.

Some biological functions of lysine include:

• - Serving as a building block for proteins
• - Playing an important role in histone modification (which affects gene expression)
• - Providing structure to collagen
• - Regulation of calcium levels

Lysine, as an oral supplement or lip balm, is often used for treating and preventing cold sores. Some other popular purported health benefits include improving athletic performance, canker sore symptoms, and schizophrenia symptoms.

References:

• - Adv Biol Regul. 2016 Jan;60:144-150. https://pubmed.ncbi.nlm.nih.gov/26482291/
• - Heredity (Edinb). 2010 Jul;105(1):24-37. https://pubmed.ncbi.nlm.nih.gov/20442736/

L-Threonine  

Threonine is an essential amino acid. Amino acids are the building blocks the body uses to make proteins. The "essential" amino acids are those that cannot be made by the body and must be obtained from the diet.

People use threonine for conditions such as a muscle control disorder marked by involuntary movements and muscle tightness (spasticity), multiple sclerosis (MS), inherited disorders marked by weakness and stiffness in the legs (familial spastic paraparesis or FSP), and Lou Gehrig's disease (amyotrophic lateral sclerosis or ALS), but there is no good scientific evidence to support these uses.

The way it works is that threonine is changed in the body to a chemical called glycine. Glycine works in the brain to reduce constant and unwanted muscle contractions (spasticity).

L-Methionine

Methionine is an amino acid found in many proteins, including the proteins in foods and those found in the tissues and organs of your body.  In addition to being a building block for proteins, it has several other unique features.

One of these is its ability to be converted into important sulfur-containing molecules.

Sulfur-containing molecules have a variety of functions, including the protection of your tissues, modifying your DNA, and maintaining proper functioning of your cells.

These important molecules must be made from amino acids that contain sulfur. Of the amino acids used to make proteins in the body, only methionine and cysteine contain sulfur.

Although your body can produce the amino acid cysteine on its own, methionine must come from your diet.

Additionally, methionine plays a critical role in starting the process of making new proteins inside your cells, something that is continuously occurring as older proteins break down.

For example, this amino acid starts the process of producing new proteins in your muscles after an exercise session that damages them.

References:

• - The Journal of Nutrition, Volume 136, Issue 6, June 2006, Pages 1636S–1640S https://academic.oup.com/jn/article/136/6/1636S/4664439
• - J Nutr. 2004 Mar;134(3):489-92. https://pubmed.ncbi.nlm.nih.gov/14988435/
• - Sports Med. 2014 May;44 Suppl 1(Suppl 1):S71-7 https://pubmed.ncbi.nlm.nih.gov/24791918/

L-Phenylalanine

Phenylalanine is an essential amino acid that is used to produce proteins and signaling molecules. It has been studied as a treatment for several medical conditions, but is dangerous for those with a specific genetic disorder phenylketonuria (PKU). 

Your body needs phenylalanine and other amino acids to make proteins.  Many important proteins are found in your brain, blood, muscles, internal organs, and virtually everywhere else in your body.

What’s more, phenylalanine is crucial for the production of other molecules, including:

• - Tyrosine: This amino acid is produced directly from phenylalanine. It can be used to make new proteins or converted into other molecules on this list.
• - Epinephrine and norepinephrine: When you encounter stress, these molecules are vital for your body’s “fight or flight” response.
• - Dopamine: This molecule is involved in feelings of pleasure in your brain, as well as forming memories and learning skills

References:

• - J Nutr. 2007 Jun;137(6 Suppl 1):1539S-1547S
• - Biochemistry. 5th edition
• - Compr Physiol. 2015 Jan;5(1):1-15
• - J Nutr 2007 Jun;137(6 Suppl 1):1539S-1547S

L-Tryptophan

Tryptophan is an essential amino acid that serves several important purposes, like nitrogen balance in adults and growth in infants. It also creates niacin, which is essential in creating the neurotransmitter serotonin.  There are a number of health benefits from the naturally-occurring tryptophan found in foods. Most of these health benefits come from the potential increase of niacin and thus serotonin.

The benefits of more serotonin include:

• - Promoting healthier and better quality sleep
• - Relief from depression and anxiety
• - Increased emotional well-being
• - Managing pain tolerance

References:

• - Psychiatry Res. 1998 Feb 27;77(3):167-74.
• - Neurosci Biobehav Rev. 2016 May;64:346-58

L-Histidine  

Histidine (L-histidine) is one of the 20 amino acids that make up the proteins in our body. These building blocks are generally classified as either nonessential or essential. Nonessential amino acids are those that the body can produce by itself, while essential amino acids must be acquired through diet.

Histidine is an essential amino acid. A long-term study demonstrated that adults who consume a diet deficient in histidine over long periods of time may experience negative health effects such as reduced hemoglobin (the protein that carries oxygen in red blood cells) levels.

Histidine is produced by the liver in small quantities. Hence, it must be consumed in the diet to maintain necessary histidine levels in the body. Here, it is converted into a number of important substances such as histamine and carnosine.

Function

Histidine is required for the growth and repair of tissues, red blood cell production, and protecting tissues from damage from radiation and heavy metals. It is especially necessary for the formation of myelin sheaths, which are layers surrounding nerves that enables faster transmission of signals to the brain.

In both human and animal studies, histidine functioned in maintaining normal levels of hemoglobin, the protein responsible for delivering oxygen from the lungs to the tissues of the body.

Urocanic acid, produced through histidine, is a major absorber of ultraviolet (UV) radiation, which protects skin cells from damage.

Additionally, it is converted to histamine, a messenger molecule involved in immunity, digestion, and sexual function.

It is also a major component (along with β-alanine) of carnosine, an important antioxidant that slows the progression of multiple degenerative diseases and reduces plaque buildup in the arteries. It may also help improve muscle performance for high-intensity exercise.

References:

• - Nutrition. 1998 Jan;14(1):143-8.  https://pubmed.ncbi.nlm.nih.gov/9437700/
• - Proc Natl Acad Sci U S A. 1988 May;85(9):3175-9. https://pubmed.ncbi.nlm.nih.gov/3362866/
• - Microb Biotechnol. 2014 Jan; 7(1): 5–25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896937/
• - J Nutr. 1984 Feb;114(2):369-84 https://pubmed.ncbi.nlm.nih.gov/6693997/
• - Photochem Photobiol Sci. 2008 Jun;7(6):655-67  https://pubmed.ncbi.nlm.nih.gov/18528548/
• - Br J Pharmacol. 2006 Jan; 147(Suppl 1): S127–S135.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1760721/
• - Amino Acids. 2013 Jun;44(6):1477-91. https://pubmed.ncbi.nlm.nih.gov/23479117/

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