INVESTIGATIVE REVIEW
HUMAN IN VIVO CLINICAL TRIALS

THE SCIENCE OF TRANSCRIPTION
PATHWAYS IN PROTEIN METABOLISM

DIRECTOR OF CLINICAL INVESTIGATIONS
PROTEIN RESEARCH PROJECT
Dr. Ann de Wees Allen
Chief of Biomedical Research
Glycemic Research Institute
Washington, D.C.

The Test Food, Protein-Glycoside-Matrix, contains biologically active components bound to protein molecules. Biologically active refers to natural compounds that affect the life processes of a human organism in a beneficial manner. The metabolic dynamic of the Protein-Glycoside-Matrix (PGM) composition appears to be multifaceted, and includes the stimulation of muscle protein synthesis (MPS) which provides positive net protein balance, resulting in hypertrophy, in an Anti-Ketogenic Matrix.

The glycosides in Protein-Glycoside-Matrix (PGM) lengthen the biological life of a protein molecule by decreasing the protein's rate of clearance from the blood. Additionally, the Protein-Glycoside-Matrix (PGM) compound helps the protein to fold properly, to stabilize the protein molecules, and to provide bioactivity.

The hypertrophic advantages in muscle-mass are evidenced in response to acute administration (short-term), and is particularly evidenced when administered orally over a chronic term (long-term).

Hypertrophy is defined as the increase in the volume of an organ or tissue due to the enlargement of its component cells. Muscle Hypertrophy is the increase in muscle tissue evidenced in response to stimuli.

One of the two most common and visible forms of organ hypertrophy occurs in skeletal muscles in response to strength training (known as muscle hypertrophy), and in response to oral ingestion of contractile proteins.

Contractile proteins participate in contractile processes, and include muscle proteins as well as those found in other tissues and cells in the body. These proteins partipate in localized contractile events in the cytoplasm, in motile activity, and in cell aggregation.

Oral administration of the Protein-Glycoside-Matrix results in significant gains in contractile protein content and muscle strength in humans. Additionally, a dose of 10 grams of protein enhances the inhibition of protein breakdown.

IMPROVED POST-PRANDIAL UTILIZATION OF DIETARY NITROGEN

Whey proteins, including isolates, as well as most anabolic proteins, are considered “Fast Proteins.” Fast Proteins are contraindicated in the anabolic state, as they induce over-rapid delivery of amino acids, which cannot support the anabolic requirement throughout the post-prandial period.

Slowly digested proteins (Slow Proteins) induce superior post-prandial utilization of dietary nitrogen than rapidly digested protein (Fast Proteins), despite the high chemical score of MSPI. The Test Food (Protein-Glycoside-Matrix) appears to metabolically switch whey proteins from acting like Fast Proteins to acting like Slow Proteins.

TRANSCRIPTION PATHWAY

Protein-Glycoside-Matrix (PGM) contains Patented anabolic amino acids and proteins, including natural Branched Chain Amino Acids (BCAAs), which are used to fuel working muscles and stimulate protein synthesis. The essential amino acids, found in Protein-Glycoside-Matrix (PGM), combined with glucose availability, is sensed by both AMPK and mTOR in human muscle, which enhances AKT/mTOR signalling to key regulators of translation initiation and elongation, thus inducing a potent and rapid increase in the rate of muscle protein synthesis.

In humans, rapamycin (mTOR) and AMP-activated protein kinase (AMPK) are important nutrient and energy-sensing and signalling proteins in skeletal muscle. AMPK activation decreases muscle protein synthesis by inhibiting mTOR signalling to regulatory proteins associated with translation initiation and elongation.

The specific amino acids found in Protein-Glycoside-Matrix (PGM) stimulate mTOR signalling and protein synthesis. These anabolic nutrients are sensed by both AMPK and mTOR, resulting in an acute and potent stimulation of human skeletal muscle protein synthesis via enhanced translation initiation and elongation. The Protein-Glycoside-Matrix (PGM) compound plays a key role in initiating the transcription pathway that fires up protein synthesis, which stimulates protein synthesis and aids in speeding recovery and adaptation to stress (exercise).

KETOSIS & CORTISOL: NEGATIVE METABOLIC STATES

Ketosis (from the root word ketones) is produced in the liver through the incomplete breakdown of fat. Unlike other proteins, the Test Food, Protein-Glycoside-Matrix (PGM) exhibits Non-Ketogenic properties. This is an extremely important facet in protein formulating, due to the negative physical events triggered by both Ketosis and Cortisol.

Ketosis is a buildup of partially broken-down fats (ketones) in the bloodstream and may occur if less than 50-100 grams of carbohydrates are consumed each day, or if protein is consumed without carbohydrates. As a result of ketone build-up in the blood, the body may produce high levels of uric acid, which is a risk factor for developing gout and kidney stones.

For pregnant women and people with diabetes or kidney disease, ketosis is especially dangerous.

SPARING PROTEINS & PREVENTING KETOSIS

Research has demonstrated that proteins and protein products that do not contain any carbohydrates, just protein, are ketogenic. This is metabolic suicide for protein metabolism and homeostasis. Proteins without carbohydrates instigate a ketogenic state in humans.

Carbohydrates are mandatory in protein synthesis

Maintaining a regular intake of carbohydrates will prevent protein from being used as an energy source. Further, an adequate amount of carbohydrates prevents the degradation of skeletal muscle and other tissues such as the heart, liver, and kidneys. The Test Food, Protein-Glycoside-Matrix, allows gluconeogenesis to slow down, allowing amino acids to be freed for the biosyntheses of enzymes, antibodies, receptors and other important proteins. More importantly, it prevents ketosis.

Although the brain will adapt to using ketones as a fuel, it preferentially uses carbohydrates and requires a minimum level of glucose circulating in the blood in order to function properly. Before the adaptation process occurs, sub-optimal hypoglycemic blood glucose levels typically cause headaches in response to a ketogenic state.

Although the processes of protein degradation and ketosis can create problems of their own during prolonged fasting, they are adaptive mechanisms during glucose shortages. The first priority of metabolism during a prolonged fast is to provide enough glucose for the brain and other organs that dependent upon it for energy in order to spare proteins for other cellular functions.

The second priority of the body is to shift the use of fuel from glucose to fatty acids and ketone bodies. From that point on, ketones significantly become more important as a source of fuel, while fatty acids and glucose become less important.

To prevent these ketotic symptoms, it is recommended that the average person consume at least 50 to 100 g of carbohydrates per day, and when ingesting dietary protein, include an appropriate ratio of protein-to-carbs symbiotic to protein synthesis.

KETOSIS CAUSES BODY FAT GAINS & SLOWS METABOLISM

High protein and/or low carbohydrate diets slow down metabolism. During high protein and/or low carbohydrate diets, weight loss may be realized but the type of weight that is actually lost includes muscle mass as well as fat. When muscle mass is reduced in humans in response to high protein and/or low carbohydrate diets, fat-burning slows down and metabolic rates decrease. This results in increased body fat and decreased lean muscle mass.

With reduced lean body mass, resting metabolic rates decrease since skeletal muscle requires more energy at rest and during exercise than adipose fat tissue. Diets and protein supplements that contain adequate Low Glycemic carbohydrates not only increase physical well being, but also contribute to body fat loss and maintenance of lean muscle mass.

KETOSIS & SPORTS PERFORMANCE

The Test Food, Protein-Glycoside-Matrix, was specifically formulated to provide a Metabolic Advantage to athletes. One of the components relative to this claim is the Anti-Ketogenic properties of the Test Food.

Ketosis is one of the most severe and negative states in protein synthesis and utilization, brain function, and fat-burning. Some classes of dietary amino acids are gluconeogenic, meaning glucose producing, while many amino acids are ketogenic and cannot enter the citric acid cycle.

Thus, the level of ketones in the body rises while levels of glucose fall, and many organs begin to function less efficiently, including the brain, which relies heavily on glucose. Proteins that do not contain carbohydrates exacerbate brain-focus-reduction, reducing mental focus and sports performance.

As an athlete’s performance and career ultimately depend on fast-brain-response, this athletes cannot afford reduced-sports-performance due to ketogenic proteins or diets. Neither the athlete nor the non-athlete can afford reduced-brain-function, or disrupted protein and fat metabolism.

In terms of added body fat and energy-synthesis, fats can only be metabolized (burned) when there is a adequate amount of glucose from carbohydrates present to produce oxaloacetate, which condenses with acetyl CoA in the citric acid cycle. Since fatty acids are degraded directly to acetyl CoA, they cannot be used as an energy source, and can be transformed in ketones.

High levels of ketones in the blood stream are dangerous, and low amounts of glucose (from dietary carbohydrates) in the blood can be detrimental to the brain and to sports performance.

PROTEIN THRESHOLD:
STORAGE CAPACITY OF PROTEINS

The storage capacity of protein in humans has been well established. Storage capacity relates to the maximum amount of protein the human body can process without negative consequences. In World-Class powerlifters, who weigh up to 400 pounds, the storage capacity of proteins does not exceed 30 grams within a 2-3 hour period.

In World-Class bodybuilders, such as Mr. Universe, who hold huge amounts of muscle mass, and low amounts of body fat, regardless of weight or size, or calories burned, or degree of muscle mass, the 30-gram protein rule does not change. The average, non-athlete does not require an intake of 30 grams of protein at one time, and can achieve protein homeostasis by ingesting specific forms and amounts of elemental protein throughout the day.

In large-size competing athletes, the homeostasis-dose of protein is 30 elemental grams. The 30-gram protocol should not be used in non-athletes, as this dose of protein cannot be metabolized or utilized in the body without benefit of high-muscle mass, as well as high-energy-output and high-caloric-burning. Using proteins at the 30-gram dose in an inappropriate ketogenic formula/product can cause serious medical problems, including ketosis, elevated liver enzymes, and liver damage.

In humans, ingestion of ketogenic proteins and meal replacement products results in increased body fat levels via elevation of insulin and LPL fat-storage in adipose tissue fat cells. Ketogenic protein drinks and meal replacements are contraindicated.

Additionally, protein drinks and products that only contain sugar alcohols, synthetic sweeteners, and other non-carbohydrate ingredients, do not achieve health protein storage capacity, and can cause ketosis and liver problems.

In terms of timing, protein drinks should not be consumed near bedtime, as this causes lowered Delta-stimulated GH and testosterone production.

PATHOLOGY OF CORTISOL’s MEDICAL IMPACT
IN HUMAN HEALTH

Cortisol is a corticosteroid hormone. The synthesis of Cortisol in the adrenal gland is stimulated by the anterior lobe of the pituitary gland. The highest levels of Cortisol in humans occur in early morning, with lowest levels in the evening and 2-3 hours following the onset of the sleep cycle.

Over-expression and over-elevation of Cortisol in humans is triggered by a variety of external biochemical events resulting in mild-to-serious medical problems, including reduction of sports performance in athletes, and excess adipose tissue body fat.

The down-regulation of Cortisol is an obvious advantage in protein metabolism, and the Test Food under investigation will provide substantiation of Cortisol-down-regulation. As of September 2009, no prior substantiated evidence of proteins that down-regulate Cortisol have been introduced.

CLAIMS SUBSTANTIATION

The Test Food duly submitted to the Glycemic Research Institute®, Protein-Glycoside-Matrix (PMG), is described as an advanced protein delivery system, that is undergoing independent government Certification Human In Vivo Clinical Trials, with the goal of clinical substantiation of metabolic properties and legal claims.

The proprietary PMG formula was designed to mitigate and/or eliminate blood glucose and insulin excursions in humans caused by ingestion of High Glycemic proteins, thus blunting Lipoprotein Lipase (LPL) fat-storage, adipose tissue fat-storage, body fat weight gains, and stimulation of fat cell replication.

In addition, PMG was designed to replace ketogenic protein supplements, and meal replacements that activate Cortisol and GLP-1.