Authors Note: One of the fastest growing sports supplement product categories consists of "vasoactive" products, such as Nitric Oxide (NO) boosters, which are involved in improving blood flow, increasing the "Muscle Pump" and have other physiological functions.
Another new innovation in sports nutrition supplementation gaining popularity is aimed at increasing "Blood Building" via simulation of the body's red blood cell building hormone—Erythropoietin.
This article focuses on this newest trend of blood building sports supplements and related synergistic NO boosting benefits—Dual Action EPO and Nitric Oxide Stimulation.
EPO Blood Building: The New Rage In Bodybuilding And Sports Supplements
One of the hottest topics capturing the attention of athletes, coaches and trainers centers on using the drug rhEPO (recombinant erythropoietin). EPO (erythropoietin) is a hormone that is naturally produced in the body and primarily functions to stimulate the production of new red blood cells.
Increasing the amount of red blood cells increases the oxygen carrying capacity of the blood to deliver more oxygen to exercising muscles. The extra oxygen significantly increases the muscles' energy production and can therefore help to improve athletic performance output ability; higher intensity and longer duration. These benefits have led to the widespread use of synthetic rhEPO drug doping.
Due to the increase in oxygen carrying capacity and other vasoactive effects of interest, EPO has also gained interest among athletes outside of the endurance crowd; strength athletes, including bodybuilders, who are looking to increase exercise intensity, training session volume and quality of their workouts and those who are equally interested in achieving the "perpetual pump".
But there are even more interesting aspects to the EPO blood boosting story, including combating the fatigue causing drop in pH levels, a synergistic Nitric Oxide connection and enhanced nutrient delivery to stimulate muscle growth.
EPO-Red Blood Cells-Oxygen
From a straightforward athletic performance bio-energetic perspective, oxygen is required for the body to make energy (aerobically) to produce muscle contractions, in addition to anaerobic produced energy.
Within muscle cells, there are energy producing structures called mitochondria. Oxygen is used inside the mitochondria to drive the biochemical reactions that breakdown carbohydrates, fats and certain amino acids to produce energy in the form of ATP (adenosine tri-phosphate). This enables the body to convert the energy stored in foods to a form it can use in the body in the form of ATP.
These high energy ATP molecules are then used by the muscles as an energy source to power muscle contractions. So, more oxygen in the body/muscles yields more ATP generation, increasing muscle contractions, which results in improving athletic performance. This benefit of increasing oxygen in the body has lead to the reported use or suspected use of rhEPO by top endurance athletes.
Now, with the sports authorities cracking down on illegal rhEPO used in sports and the additional risk of potential harmful side effects of using rhEPO unsupervised, athletes are seeking alternative ways for boosting their own EPO and red blood cells, in addition to boosting their nitric oxide (NO) levels.
Natural EPO/Red Blood Cell Boosting
Athletes are now turning to natural EPO/red blood cell boosting performance enhancing products as alternatives to using the drug form, rhEPO. Sports science researchers have discovered that certain natural substances and nutrients can increase EPO levels, red blood cell production, plus additional related benefits for maximum endurance output, including increased blood flow.
Sports Performance Benefits of EPO
Medically, rhEPO is used to increase red blood cell count. Logically, since EPO accelerates red blood cell production, it also increases the oxygen carrying capacity of the blood and more oxygen to muscles and other tissues of the body. This primary benefit of rhEPO attracted the attention of the athletic community and led to the use (or alleged) of rhEPO by elite athletes.
Endurance Athletes and rhEPO
The use of rhEPO is reported by the athletic community to help increase oxygen carrying capacity of the blood, by building more red blood cells thereby improving athletic performance and reducing exercise fatigue.
This enables performance improvements in endurance type and other sports because of the extra oxygen carrying capacity. It is also believed that rhEPO and naturally produced EPO increases the metabolism and the healing process of muscles because the extra red cells carry more oxygen and nutrients, improving recovery ability.
Hardcore Bodybuilders Underground Use of EPO Boosting
Bodybuilders and other strength athletes using testosterone replacement drugs have long known the benefits of boosting EPO and red blood cells, as this is a secondary effect of this category of drugs.
Prior to the development of rhEPO, the popular anabolic steroid Anadrol was used to increase red blood cells. Anadrol has a reputation in bodybuilding for producing the best pumps and extreme vascularity. In addition to increasing muscle size and strength, noticeable improvements in workout endurance are reported to occur. To maximize these steroid induced EPO benefits, actual rhEPO use is suspected to be on the rise among bodybuilders and strength athletes.
Natural EPO Boosting Is The New Way To Go
The newest trend among rhEPO using athletes is to use legal specialized sports nutrition supplements designed to naturally boost their production of EPO. In taking the sports supplement route to boost their body's ability to maximize EPO, red cell building and oxygen uptake, this avoids taking illegal performance enhancing drug products.
Red Blood Cell (Erythrocytes) Building
Red blood cells, also known as erythrocytes or red corpuscles, primarily function in the transport of oxygen and carbon dioxide in the body. The red blood cells are specialized types of cells that are loaded with a substance called hemoglobin. Naturally produced EPO in the body stimulates the production of red blood cells from stem cells that originate in bone marrow.
Because blood cells have a short life in the bloodstream (only a few to several weeks) it is important to optimize this blood building process to maintain an optimum level of red blood cells. This is of particular importance to people who are more physically active, such as athletes, because intensive exercise will increase the breakdown of red blood cells.
Furthermore, it is additionally beneficial to maintain optimum levels of nutrients and substances that increase the red blood cell building stem cell populations, as well as to protect red blood cells once they are produced and delivered into the bloodstream.
Major Function of Hemoglobin
The major function of the hemoglobin molecules found densely packed in red blood cells is the transport of oxygen from the lungs through the bloodstream to the tissues and trillions of cells in the body.
During hemoglobin's functioning in the body, it will alternate between two physiological states based on if it is carrying oxygen molecules or not; oxyhemoglobin and deoxyhemaglobin. In the oxyhemoglobin state, hemoglobin is loaded up with oxygen. In the deoxyhemoglobin state, hemoglobin is devoid of oxygen, which is also known as empty hemoglobin.
Biochemically, hemoglobin is a specialized protein molecule, a conjugated globular protein, which consists of heme groups containing iron.
The iron components of hemoglobin function to "lock-on" to oxygen and also on to carbon dioxide molecules. Therefore, adequate dietary/supplement intake of iron is vital for the development and functioning of red blood cells. Forms such as ferrous fumarate are used in supplements as an "organic" alternative to iron oxide and other inorganic forms.
Carbon Dioxide Transport and Hemoglobin
In addition to carrying molecules of oxygen, hemoglobin also transports the metabolic waste product carbon dioxide from cells through the bloodstream and to the lungs where it is exhaled into the atmosphere. (Yes, humans are a source of CO2, refer to my related podcast about this).
As CO2 tissue levels build up during exercise, this contributes to the onset of fatigue, reducing the ability to maintain high-normal levels of exercise/athletic performance. It is therefore of paramount importance to have high levels of red blood cells, plus good blood circulation, to create the conditions in the bloodstream that will rapidly clear away CO2 from exercising muscles and eliminate it from the body.
Natural EPO and Red Blood Boosters
In a quest to find natural alternatives to rhEPO, that is, substances to naturally enhance EPO levels and boost red blood cell production, there is a growing list of research backed ingredients. Here are some nutrients/ingredients found in sports supplements that are reported to boost EPO and red blood cell production, function and duration, as well as produce other benefits of interest to athletes.
The EPO production stimulating effects of Arachidonic Acid are attributed to its involvement in the biochemical process leading to the actual production of EPO in the body and phospholipase activation in erythroid progenitor cell proliferation. Arachidonic Acid is abundant in the body and involved in many structural and biochemical functions.
Regarding EPO production, Arachidonic Acid is the precursor molecule in the production of eicosanoids, which are substances in the body found to be involved in stimulating the production of EPO. Additionally, recent research has reported anabolic muscle-building effects of Arachidonic Acid.
Cobalt is another key research based EPO/red blood cell production stimulator, which is needed by humans in small amounts. It is also a necessary component of vitamin B12. In the research report titled "Blood Doping by Cobalt", researchers reported that cobalt is a naturally occurring element that enhances erythropoiesis and angiogenesis (growth of new blood vessels), resulting in increasing red blood cell concentration and circulation. The proposed mechanisms of action include more efficient transcription of the erythropoietin gene.
More recent research has demonstrated that Echinacea stimulates production of erythroid (red blood cell) growth factors, induces erythropoiesis and increases the oxygen-transport capacity of the blood, in addition to its well-known role for beneficially stimulating the immune system.
The blood building and improved oxygen carrying capacity effects of taking standardized Echinacea supplements was reported in a recent study using male subjects. This research, along with other research studies, has found that the use of Echinacea containing supplements increased EPO levels, interleukin-3 (IL-3) levels, increased red blood cell count, increased the number and size of red blood cells, and increased maximal oxygen consumption VO2 max.
This essential vital vitamin that is required by the body for the formation of coenzymes NAD and NADP. Niacin also has vasodilation properties, especially for dilating the micro-circulatory system that is responsible for the delivery of oxygen, nutrients, and hormones to the muscle cells and clearance of metabolic waste products.
This botanical contains high concentration flavones that scientific research reports may improve the expression level of EPO and accelerate the generation of erythrocytes and hemoglobin.
Vitamin B-6 (As Pyridoxine HCl And Pyridoxine 5-Phosphate)
An essential vitamin needed for red blood cell production. Vitamin B-6 also helps increase the amount of oxygen carried by hemoglobin (the iron containing oxygen transport metallo-protein in red blood cells). Note that a vitamin B-6 deficiency can result in some health problems.
Vitamin B-12 (Methylcobalamin, Cyanocobalamin, Dibencozide)
This essential vitamin is vital for red blood cell production. Deficiency in Vitamin B-12 is responsible for a reduction in red blood cells and can lead to muscle fatigue and weakness.
EPO Blood Building and the Synergistic Effects of Nitric Oxide
While EPO and NO boosting have well-known distinct benefits, the question arises if boosting both EPO and NO will produce synergistic effects? The answer is unequivocally yes!
Let's examine how these two performance agents work in tandem to give athletes a new competitive edge. Here's a short recap of the science of NO. Major attention was first directed to NO when the Nobel Prize in Physiology or Medicine in 1998 was awarded to Robert F. Furchgott, Louis J. Ignarro and Ferid Murad for their discoveries concerning "the nitric oxide as a signaling molecule in the cardiovascular system".
One of the main functions performed by NO in the cardiovascular system is dilating blood vessels. This function helps to increase blood flow to muscle and other tissues in the body.
As more research has been focused on NO, more functions have been identified, such as NO's role as an important signaling molecule outside the cardiovascular system; signaling between nerve cells in the brain, enhancing the olfactory sense and immune system functioning.
Chief among NO's many functions in the sports nutrition product industry is its role in vasodilation—leading to achieving the resistance exercise induced PUMP. Vasodilating during exercise is vital to accommodate increasing blood volume and enhance blood flow rate for maximum delivery of oxygen, nutrients and anabolic hormones to muscle tissue, as well as improve metabolic waste clearance, such as fatigue causing carbon dioxide.
So, while EPO boosting provides a means to stimulate more red blood cells and higher nutrient and oxygen carrying capacity, NO provides the means to widen the blood vessels to promote greater blood flow. In this way, EPO and NO working together are the vasoactive cart and horse of maximizing performance enhancing enriched blood and blood vessel super-pumps.
Nitric oxide stimulates the blood vessel dilating effects, to create a wider circulatory system conduit for the EPO stimulated red blood cell enriched volumized bloodstream to deliver more oxygen and nutrients to the muscles and other tissues, with a new level of performance expected from these synergistic effects.
There are now hundreds of products featuring ingredients for promoting NO mediated vasodilation, primarily by two modes of action; precursors that are involved in NO production, and stimulators that are involved in stimulating the production of NO. Here are some of effective ingredients found being used in NO stimulating products, and are also contained in the newest class of dual action EPO-NO stimulating products.
NO Boosting Ingredients
Arginine is the key amino acid that is used to make nitric oxide in your body. NO products found on the shelves usually contain Arginine as a single ingredient or in other forms, for example, Arginine Alpha Keto Glutarate and Arginine Ethyl Ester.
Some products contain a multi-source Arginine blend claiming to ensure fast, complete and sustained absorption of the arginine molecule provided in free form and special organic complexes, such as with Alpha Keto Glutarate and Ethyl Ester for dynamic physiological action.
Citrulline is another amino acid found in NO stimulating supplements, primarily for its purported function of boosting the body's arginine levels and thereby supporting the NO production pathway.
Citrulline can be used on its own as a supplement, but it is typically included along with Arginine and other NO stimulating ingredients as a way of saturating the nitric oxide production pathways to ensure that peak nitric oxide production is achieved, as arginine has a variety of other functions in the body, in addition to NO production.
Citrulline also has other roles in the body that can benefit athletic performance, such as anti-fatigue properties in detoxification of ammonia amon.
This botanical ingredient is reported to be traditionally used to support already normal male sexual performance. However, modern research determined that a primary physiological function of this botanical is to increase the release of Nitric Oxide by cells lining the circulatory system, thereby promoting vasodilation.
This NO boosting effect reveals a viable reason for its traditional use for promoting normal male sexual function, as well as an ingredient used in NO boosting sports nutrition products.
This essential vitamin is involved in the hematopoietic system and is required for red blood cell production. Folate also has beneficial effects on endothelial function, as measured with the use of flow-mediated dilatation (FMD).
A recent study reported that folic acid improved endothelial function and increased flow-mediated dilation. Folate also lowers homocysteine levels, which is beneficial because a high level of homocysteine impairs cardiovascular function and blood flow. Furthermore, research revealed that folic acid is involved in the regeneration of tetrahydrobiopterin, which enhances nitric oxide synthase function and maximizes nitric oxide production.
Gypenosides extracted from Gynostemma pentaphyllum have been shown to elicit vasorelaxation and vasodilation through the direct release of endothelium-derived nitric oxide. In this way Gynostemma serves to directly stimulate NO levels in the cardiovascular system and plays a synergistic role with NO precursor substances, like arginine.
Norvaline is related to the branched chain amino acid Valine. Norvaline functions to inhibit the arginase enzyme, thus increasing arginine levels available for NO production. Norvaline can in this way optimize the NO boosting effects of a multi-ingredient NO boosting formula, in particular in formulas containing arginine and or citrulline, by optimizing the NO synthesizing biochemical pathway.
Methyltetrahydrofolate is reported to be a specialized bioactive compound found in specialized products that claims to have the unique ability to maximize the conversion of arginine to NO by augmenting all of the co-factors involved in arginine's conversion to Nitric Oxide within the series of biochemical pathways.
While arginine is the primary precursor used by the body to produce Nitric Oxide, there are other interactions along the Nitric Oxide synthesis pathway which influences Nitric Oxide production; both positive (NOS-Nitric Oxide Synthase) and negative or inhibitory factors (ADMA-asymmetric dimethylarginine and SOA-super oxide anion).
Vasofolate functions to increase the amount of arginine that converts into NO by combating negative factors, such as ADMA and SOA, which optimizes nitric oxide production biochemical pathways. Vasofolate is also reported to increase NOS-Nitric Oxide Synthase activity, which can further increase the production of NO.
Effects of Nitric Oxide Stimulation On Blood Vessels Compared to EPO + NO Stimulation
Nitric Oxide Stimulation
A blood vessel will be vasodilated from boosting Nitric Oxide levels. Without EPO stimulated blood building, there is a potential dilution effect of red blood cells and other substances in the bloodstream.
Dual Action EPO and Nitric Oxide Stimulation
A blood vessel will be in a "super-vasodilated" state from the synergistic effects of boosting Nitric Oxide levels, plus EPO stimulated blood building bloodstream contents. EPO stimulated red blood cells and other substances that may increase from the blood building effect may further enhance blood vessel dilation.
Exercise/Athletic Performance Significance
While NO boosting has well-established benefits in promoting vasodilation, there are additional important synergistic benefits for boosting EPO, red blood cell building, and red blood cell life span in the bloodstream.
NO mediated vasodilation alone will only provide minimal bloodstream related beneficial effects, unless red blood cell building and blood volume is also increased via EPO mediated and related physiological stimuli. For the advanced athlete, the overall benefits of maximizing EPO, red blood cell content, blood volume, NO, vasodilating, anabolic hormone levels, nutrients, and metabolic waste clearance can include:
- Increase oxygen carrying capacity for improved muscle endurance and work load.
- Increase removal of metabolic waste to prevent muscle fatigue and allow for greater workout capacity and muscle growth stimulation.
- Greater energy production to exercise harder more intensely.
- Enhancement of both the anaerobic and aerobic biogenic exercise capacity of muscle for maximum force production, lifting heaver workloads, and performing more reps and sets.
- Improved recovery between sets and workouts.
- Increase VO2max.
- Increase muscle building potential.
- Reducing training-induced red blood cell breakdown.
- Promotion of Angiogenesis (new blood vessel formation).
- Improved athletic performance.
Therefore, by ensuring that EPO mediated "blood building" is maximized, this can in turn optimize the vasodilation effects of NO to achieve a new level of exercise and athletic performance.
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