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any endurance athletes out there?
- Thread starter triguy
- Start date
I was wondering what happened to you guys!?! Too much racing and training to post anymore? Triguy - I would ditch the Dbol like fhg recomended. Even with arimedex you probally have put on water weight. Shit GH and insulin with var would be great too. I wish I could afford GH! I'm going ala natural these days. Shoot some b12 in my glutes once a week and take some ALA basta! My weight is good now I'm afraid to juice again because it's taken me so long to lose the muscle. Is that Phytin stuff for real? Anyone used the kynoselen, amp, or atp injections? The amp and atp are available legal through vet sites. Kynoselen seems expensive. I could get 200mgs/ml of eq for the price of a bottle of kynoselen.
peace
peace
phytin first came out thru sopharma(tribestan fame) anything they make i agree with. Phytin's chemical or structure name is ip6, and now evryone is selling it. I would find a cheap place to measure blood work and do a pre & post test done on-hematocrit, hemoglobin, reticulycytes and see what happens.
On kynoselen, the main ingredient is heptaminol (banned by uci & some guys have gottten popped for it) Some cyclists on other boards have sworn by it.
road kill- I'm thinkin its the "slin" casuin the weight gain, also the gh is makin the ol' waist larger than it should be (gh gut?). Plus gh alone causes water weight gain.
On kynoselen, the main ingredient is heptaminol (banned by uci & some guys have gottten popped for it) Some cyclists on other boards have sworn by it.
road kill- I'm thinkin its the "slin" casuin the weight gain, also the gh is makin the ol' waist larger than it should be (gh gut?). Plus gh alone causes water weight gain.
for you ex. phys freaks
Overtraining
Fig. 1. Excessive exercise with inadequate rest can result in acute inflammation that evolves into a chronic response. A systemic immune response involves the central nervous system (CNS), the liver, and the immune system. [Figure is adapted from Smith, L. et al. (2000) Med. Sci. Sports Exerc.32:328.] Regular exercise can improve physical fitness, enhance overall well-being and may also strengthen the immune system.1,2 Prolonged excessive exercise, however, especially in conjunction with inadequate rest and other stresses, can result in an impairment of athletic performance. This is often associated with a complex of seemingly unrelated physical and psychological symptoms (see Table 1), a condition known as Overtraining Syndrome (OTS). Although overtrained individuals usually exhibit a variable number of the symptoms listed, upper respiratory tract infection is common and may suggest impaired immune function.3A number of hypotheses have been proposed to explain various symptoms associated with OTS, yet none have sufficiently accounted for all the manifestations of the syndrome. A recent article in Medicine and Science in Sport and Exercise presents an all-encompassing hypothesis focused on the role of cytokines in initiating and perpetuating OTS.4 The Cytokine Hypothesis suggests that exercise-induced muscle and connective tissue microtrauma triggers the release of proinflammatory cytokines (e.g. IL-1b, IL-6 and TNF-a), which when sufficient rest is allowed, can aid in the healing process. The acute inflammation that results from excessive exercise with inadequate rest, however, evolves into a chronic response resulting in a systemic immune response involving the central nervous system (CNS), liver, and immune system (see Figure 1). CNS function may be influenced by circulating cytokines. IL-1 and IL-6 receptors have been localized to the hypothalamus and thus may modulate both the hypothalamus-pituitary-adrenal (HPA) axis and the hypothalamus-pituitary-gonadal (HPG) axis. These systems are regulators of the stress hormones and reproductive hormones, respectively. Disruption of these systems may thus account for the blunted stress hormone response observed in overtrained athletes, i.e. decreased serum testosterone and amenorrhea. Interleukin receptors, especially IL-1 receptors, are also abundant in the hippocampus and therefore may be involved in the impaired cognitive abilities associated with overtraining, such as the inability to concentrate. In addition, the authors suggest that the previously reported correlation between circulating cytokines (IL-1, IL-6 and TNF-a) and depression may also hold for overtraining-induced depression.Decreased blood glutamine levels have been reported in overtrained individuals and because glutamine is required for lymphocyte proliferation and macrophage function, the decline in this amino acid may contribute to the putative decline in immune function in overtraining. The authors propose that systemic inflammation induces a catabolic state, driven in part by cytokines and glucocorticoids, which mobilize amino acids from skeletal muscle for hepatic gluconeogenesis and synthesis of acute phase proteins. The detrimental effect of overtraining on immune function may be compared to a model proposed to explain infection susceptibility of patients following surgery and injury.5,6 Following injury, inflammation is up regulated in an attempt to expedite cellular and humoral immune mechanisms. The body attempts to counter this hyperinflammatory response by producing a multitude of anti-inflammatory molecules. Systemic exposure to these anti-inflammatory molecules over an extended time period produces a state of immunosuppression, contributing to a high incidence of illness in overtrained athletes.Cytokines are proposed to play a central role in eliciting a large number of the symptoms associated with overtraining. The CNS, liver and immune system may be responding to a systemic hyperinflammatory response initiated by trauma to muscular, skeletal or joint systems. The Cytokine Hypothesis provides researchers with a framework for further study into the mechanisms responsible for the symptoms of OTS.
Table 1. Symptoms Associated with OTS
Physical · Decreased athletic performance · Fatigue · Elevated heart rate · Muscle and joint pain · Blood pressure changes · Sleep disturbances with or without night sweats · Loss of appetite · Thirst · Increased susceptibility to and severity of illness, colds and allergies · Flu-like symptoms · Swollen glands · Gastrointestinal disturbances Psychological · Depression · General apathy · Irritability · Inability to concentrate · Decreased libido · Increased sensitivity to environmental and emotional stress
Overtraining
Fig. 1. Excessive exercise with inadequate rest can result in acute inflammation that evolves into a chronic response. A systemic immune response involves the central nervous system (CNS), the liver, and the immune system. [Figure is adapted from Smith, L. et al. (2000) Med. Sci. Sports Exerc.32:328.] Regular exercise can improve physical fitness, enhance overall well-being and may also strengthen the immune system.1,2 Prolonged excessive exercise, however, especially in conjunction with inadequate rest and other stresses, can result in an impairment of athletic performance. This is often associated with a complex of seemingly unrelated physical and psychological symptoms (see Table 1), a condition known as Overtraining Syndrome (OTS). Although overtrained individuals usually exhibit a variable number of the symptoms listed, upper respiratory tract infection is common and may suggest impaired immune function.3A number of hypotheses have been proposed to explain various symptoms associated with OTS, yet none have sufficiently accounted for all the manifestations of the syndrome. A recent article in Medicine and Science in Sport and Exercise presents an all-encompassing hypothesis focused on the role of cytokines in initiating and perpetuating OTS.4 The Cytokine Hypothesis suggests that exercise-induced muscle and connective tissue microtrauma triggers the release of proinflammatory cytokines (e.g. IL-1b, IL-6 and TNF-a), which when sufficient rest is allowed, can aid in the healing process. The acute inflammation that results from excessive exercise with inadequate rest, however, evolves into a chronic response resulting in a systemic immune response involving the central nervous system (CNS), liver, and immune system (see Figure 1). CNS function may be influenced by circulating cytokines. IL-1 and IL-6 receptors have been localized to the hypothalamus and thus may modulate both the hypothalamus-pituitary-adrenal (HPA) axis and the hypothalamus-pituitary-gonadal (HPG) axis. These systems are regulators of the stress hormones and reproductive hormones, respectively. Disruption of these systems may thus account for the blunted stress hormone response observed in overtrained athletes, i.e. decreased serum testosterone and amenorrhea. Interleukin receptors, especially IL-1 receptors, are also abundant in the hippocampus and therefore may be involved in the impaired cognitive abilities associated with overtraining, such as the inability to concentrate. In addition, the authors suggest that the previously reported correlation between circulating cytokines (IL-1, IL-6 and TNF-a) and depression may also hold for overtraining-induced depression.Decreased blood glutamine levels have been reported in overtrained individuals and because glutamine is required for lymphocyte proliferation and macrophage function, the decline in this amino acid may contribute to the putative decline in immune function in overtraining. The authors propose that systemic inflammation induces a catabolic state, driven in part by cytokines and glucocorticoids, which mobilize amino acids from skeletal muscle for hepatic gluconeogenesis and synthesis of acute phase proteins. The detrimental effect of overtraining on immune function may be compared to a model proposed to explain infection susceptibility of patients following surgery and injury.5,6 Following injury, inflammation is up regulated in an attempt to expedite cellular and humoral immune mechanisms. The body attempts to counter this hyperinflammatory response by producing a multitude of anti-inflammatory molecules. Systemic exposure to these anti-inflammatory molecules over an extended time period produces a state of immunosuppression, contributing to a high incidence of illness in overtrained athletes.Cytokines are proposed to play a central role in eliciting a large number of the symptoms associated with overtraining. The CNS, liver and immune system may be responding to a systemic hyperinflammatory response initiated by trauma to muscular, skeletal or joint systems. The Cytokine Hypothesis provides researchers with a framework for further study into the mechanisms responsible for the symptoms of OTS.
Table 1. Symptoms Associated with OTS
Physical · Decreased athletic performance · Fatigue · Elevated heart rate · Muscle and joint pain · Blood pressure changes · Sleep disturbances with or without night sweats · Loss of appetite · Thirst · Increased susceptibility to and severity of illness, colds and allergies · Flu-like symptoms · Swollen glands · Gastrointestinal disturbances Psychological · Depression · General apathy · Irritability · Inability to concentrate · Decreased libido · Increased sensitivity to environmental and emotional stress
Thanks triguy
I looked up heptaminol on the IOC list and it's banned under stimulants.
What dosages are you doing of kynoselen?
Phytin by Sopharma has lactose in it as a filler. I'm lactose intolerant - maybe not such a good idea. Know of a good place to buy phytic acid or IP6 at a good price? What dosages a day are you doing? The sopharma website for phytin says 4-8 250mg tabs divided daily 30 minutes before meals.
nice overtraining post.
I looked up heptaminol on the IOC list and it's banned under stimulants.
What dosages are you doing of kynoselen?
Phytin by Sopharma has lactose in it as a filler. I'm lactose intolerant - maybe not such a good idea. Know of a good place to buy phytic acid or IP6 at a good price? What dosages a day are you doing? The sopharma website for phytin says 4-8 250mg tabs divided daily 30 minutes before meals.
nice overtraining post.
fhg43
New member
Sorry I haven't posted for awhile boys. Had lots of training and racing to take care of. Kudos to 'rider'-he posted some stuff earlier in the thread-he won a big race recently. He and I met up and did some training and racing.
IP6 is a form of inositol. Inositol is a B vitamin derivative. Inosine is similar if not the same to insoitol. I take a supp w/inosine in it and have found that it does work well. I haven't had my hematocrit done in awhile, but I know now that it is pretty high as my fitness is awesome. Some people have said that inositol can make you nauseaus in large doses. You need to take like 3gm+ to make a difference. And I think inosine/IP6/inositol just increases the amount of O2 your RBCs can carry not the actual number of RBCs. I found an article on how to naturally increase your bodies EPO production. I'll post it in another post.
FHG
IP6 is a form of inositol. Inositol is a B vitamin derivative. Inosine is similar if not the same to insoitol. I take a supp w/inosine in it and have found that it does work well. I haven't had my hematocrit done in awhile, but I know now that it is pretty high as my fitness is awesome. Some people have said that inositol can make you nauseaus in large doses. You need to take like 3gm+ to make a difference. And I think inosine/IP6/inositol just increases the amount of O2 your RBCs can carry not the actual number of RBCs. I found an article on how to naturally increase your bodies EPO production. I'll post it in another post.
FHG
fhg43
New member
Re: question
EQ-
1) quality muscle gain-doesn't promnote large rapid gains so sounds good for recovery
2) minor side effects-low water retention, hardly aromatizes
and last but not least-the magic phrase
3) promotes increased erythopoiesis....just like EPO (however the effect isn't near as great)
I'd say combine this with Anavar and you'd have an awesome stack. cycle it for eight weeks while putting in some quality workouts and you'll be flyin!!! EQ is currently used in race horses so it must be good for cyclists!!! however it has long detection times-could you be tested?
FHG
BadMoFo24 said:
EQ-
1) quality muscle gain-doesn't promnote large rapid gains so sounds good for recovery
2) minor side effects-low water retention, hardly aromatizes
and last but not least-the magic phrase
3) promotes increased erythopoiesis....just like EPO (however the effect isn't near as great)
I'd say combine this with Anavar and you'd have an awesome stack. cycle it for eight weeks while putting in some quality workouts and you'll be flyin!!! EQ is currently used in race horses so it must be good for cyclists!!! however it has long detection times-could you be tested?
FHG
Results
results on the anabolic program; greyhound
GH
slin
dbol
arimidex = too much muscle gain. 5 pds.
1 good thing. Dog grew crazy veins, so now his plumbing is better now to possibly enhance better oxygen exchange?
going to gh 2 i.u.'s EOD, w/halo low dose.
now that TT offers primo, wondering what would high dose primo would do for recovery?
Also anyone see how one of the top cycling mags called clenbuterol a steroid? F'ing morons
results on the anabolic program; greyhound
GH
slin
dbol
arimidex = too much muscle gain. 5 pds.
1 good thing. Dog grew crazy veins, so now his plumbing is better now to possibly enhance better oxygen exchange?
going to gh 2 i.u.'s EOD, w/halo low dose.
now that TT offers primo, wondering what would high dose primo would do for recovery?
Also anyone see how one of the top cycling mags called clenbuterol a steroid? F'ing morons
fhg43
New member
Here is that article on increasing natural EPO production-
ERYTHROPOIETIN[EPO]: NUTRITIONAL AND TRAINING INTERVENTIONS FOR INCREASING EPO
Bill Misner Ph.D.*
There is a distinct relationship between illegitimate EPO-drug or blood doping misuse and legal dietary interventions accompanied by specified training protocols. EPO increases performance from its influence on blood-oxygen carrying-capacity up to a point. Excessive substrates, dietary deficiencies, hormonal imbalances, and lack of specific hypoxic training stress may inhibit the endurance athlete from peaking naturally-induced optimal endogenous production of erythropoietin.
ERYTHROPOIETIN[EPO] is a naturally occurring hormone that stimulates the production of red blood cells (RBC). In the absence of erythropoietin, few RBCs are formed by the bone marrow. In normal adults, approximately 90% of human erythropoietin is produced in the kidneys. Endogenous production of erythropoietin is normally regulated by the level of tissue oxygenation. A reduction in the delivery of oxygen to the kidneys may occur when the hematocrit (Hct) is low, or as a result of changes in the way that hemoglobin (Hb) and oxygen interact. HYPOXIA and ANEMIA generally increase the production of erythropoietin, which in turn stimulates red blood cell production. Erythropoietin increases RBC production by stimulating the division and differentiation of specific cells in the bone marrow. An important effect of erythropoietin is to stimulate the production of "proerythroblasts." Erythropoietin causes these cells to mature rapidly, further accelerating the production of new RBCs. The regulation of red blood cell production resembles a complete feedback loop. ERYTHROPOIETIN[EPO] is released primarily by the kidneys in response to hypoxia, by sending a highly specific signal prompting cells in the bone marrow to produce RBCs. As a result, the oxygen-carrying capacity increases, the stimulus of hypoxia is alleviated, and the production of erythropoietin is decreased. Endogenous production of erythropoietin is normally regulated by the level of tissue oxygenation. Hypoxia and anemia generally increase the production of erythropoietin, which in turn stimulates erythropoiesis. In normal subjects, plasma erythropoietin levels range from 0.01 to 0.03 Units/mL, and increase up to 100- to 1000-fold during hypoxia or anemia. EPOETIN ALFA[PROCRIT] has been shown to stimulate erythropoiesis in anemic patients with CRF who do not require regular dialysis. The first evidence of a response to the three times weekly (T.I.W.) administration of the prescription drug EPOETIN ALFA[PROCRIT] is an increase in the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 14-42 days. Because of the length of time required for erythropoiesis -- several days for erythroid progenitors to mature and be released into the circulation -- a clinically significant increase in hematocrit is usually not observed in less than 14 days and may require up to 42 days in some patients. Once the hematocrit reaches the suggested target range (30-36%), that level can be sustained by adequate nutrition in the absence of iron deficiency and concurrent illnesses. Interval training hypoxia enhances EPO levels by the same mechanism which the prescription drug, EPOETIN ALFA[PROCRIT] does. When Procrit is administered 1-3 times per week, subsequent increases in plasma erythropoietin levels are 100- to 1000-fold.[1] Because EPO increases the hematocrit, it enables more oxygen to flow to the skeletal muscles. Some distance runners and cyclists have used recombinant EPO to enhance their performance. A model for the regulation of erythropoietin production has been examined. This model proposes that a primary O2-sensing reaction in the kidney is initiated by a decrease in ambient PO2, a rapid decrease in gas exchange in the lung, a diminished oxygen-carrying capacity of hemoglobin, a molecular deprivation of oxygen, or a decrease in renal blood flow. Some of the agents that are thought to be released during hypoxia, which may trigger the EPO cascade, are adenosine (A2 activation), eicosanoids (PGE2, PGI2, and 6-keto PGE1), oxygen-free radicals (superoxide and H2O2), and catecholamines with beta-2 adrenergic receptor agonist properties. It is further proposed that an INCREASE IN INTRACELLULAR CALCIUM LEADS TO THE INHIBITION OF ERYTHROPOIETIN BIOSYNTHESIS AND/OR SECRETION AND A DECREASE IN INTRACELLULAR CALCIUM INCREASES ERYTHROPOIETIN PRODUCTION. THE SPECIFIC MECHANISM BY WHICH CALCIUM REGULATES ERYTHROPOIETIN BIOSYNTHESIS AND SECRETION IS NOT WELL UNDERSTOOD. However, a good correlation is seen with several agents that decrease intracellular calcium and increase erythropoietin production as well as with other agents that increase intracellular calcium and decrease erythropoietin production. When INOSITOL TRIPHOSPHATE levels are increased, an increase in the mobilization of intracellular calcium from the endoplasmic reticulum or another intracellular pool occurs. This increased INTRACELLULAR CALCIUM probably activates a calcium calmodulin kinase and produces a phosphoprotein that inhibits erythropoietin production/secretion.[2] Although recombinant EPO has exactly the same sequence of amino acids as the natural hormone, the sugars attached by the cells used in the pharmaceutical industry differ from those attached by the cells of the human kidney. This difference can be detected by a test of the athlete's urine.
ERYTHROPOIETIN (EPO) LEVELS INCREASE DURING HYPOXIC EXERCISE AND PLASMA VOLUME DEPLETION Roberts et al., examined exercise-induced hypoxemia (EIH) and plasma volume contraction as modulators of serum ERYTHROPOIETIN (EPO) production. Five athletes cycled for 3 min at supra-maximal power outputs, at each of two different elevations (1,000 and 2,100 meters). Five subjects were exposed to normobaric hypoxia (F(I)O(2)=0.159), seven subjects underwent plasmapheresis to reduce plasma volume and eight subjects were time controls for Epo levels. Oxyhemoglobin saturation was significantly reduced during exercise and during normobaric hypoxia. The time period of haemoglobin oxygen saturation <91% was 24+/-29 s (mean+/-S.D., n=5) for exercise at 1000 m, 136+/-77 s (mean+/-S.D., n=5) for exercise at 2100 m and 178+/-255 s (mean+/-S.D., n=5) with resting hypoxic exposure. However, SIGNIFICANTLY INCREASED SERUM EPO LEVELS WERE OBSERVED ONLY FOLLOWING EXERCISE (21-27% at 1,000 m and 31-41% at 2,100 m). VOLUME CONTRACTION ALSO RESULTED IN INCREASED SERUM EPO 29-41% in spite of a significant rise in hematocrit of +2.2%. Despite similar degrees of arterial desaturation, ONLY THE HYPOXEMIA INDUCED BY EXERCISE WAS ASSOCIATED WITH AN INCREASE IN SERUM EPO. This finding indicates that other factors, in addition to hypoxemia, are important in modulating the production of Epo in response to exercise. VOLUME DEPLETION IN THE ABSENCE OF EXERCISE RESULTED IN INCREASES IN EPO LEVELS THAT WERE COMPARABLE WITH THOSE OBSERVED IN RESPONSE TO EXERCISE. The paradoxical responses of the increased hematocrit and the increase in Epo in subjects undergoing plasmapheresis suggests that PLASMA VOLUME MAY ALSO MODULATE THE PRODUCTION OF EPO.[3]
HOW DOES INTENSITY OF EXERCISE INCREASE ERYTHROPOIETIN RELEASE? Roberts & Smith set out to determine if the hypoxaemic stimulus generated by intense exercise results in the physiological response of increased erythropoietin production. Twenty athletes exercised for 3 min at 106-112% maximal oxygen consumption. Estimated oxyhemoglobin saturation was measured by reflective probe pulse oximetry (Nellcor N200) and was validated against arterial oxyhemoglobin saturation by CO-oximetry in eight athletes. Serum erythropoietin concentrations-as measured using the INCSTAR Epo-Trac radioimmunoassay-increased significantly by 19-37% at 24 h post-exercise in 11 participants, who also had an arterial oxyhemoglobin saturation < or = 91%. Decreased ferritin levels and increased reticulocyte counts were observed at 96 h post-exercise. However, no significant changes in erythropoietin levels were observed in nine non-desaturating athletes and eight non-exercise controls. Good agreement was shown between arterial oxyhemoglobin saturation and percent estimated oxyhaemoglobin saturation (limits of agreement = -3.9 to 3.7%). In conclusion, SHORT[3 MINUTES] SUPRAMAXIMAL EXERCISE CAN INDUCE BOTH HYPOXEMIA AND INCREASED ERYTHROPOIETIN LEVELS IN WELL-TRAINED INDIVIDUALS. The decline of arterial hypoxemia levels below 91% during exercise appears to be necessary for the exercise-induced elevation of serum erythropoietin levels. Furthermore, reflective probe pulse oximetry was found to be a valid predictor of percent arterial oxyhemoglobin saturation during supramaximal exercise when percent estimated oxyhemoglobin saturation > or = 86%.[4] Hence, fit athletes tend to gain more exercise-induced EPO from short 3-minute all-out intervals than do less fit athletes.
DIETARY INTERVENTIONS FOR INCREASING OXYGEN CARRYING CAPACITY AND REDUCING ANEMIA COMMON CAUSES OF ANEMIA Red blood cells that carry iron-rich hemoglobin, live only 120 days or four months. Unless there is a continual supply of iron, vitamin B12, vitamin C and folacin from either food or supplements, anemia will result in poorly formed red blood cells that are ineffective carriers of oxygen. Iron deficiency anemia is the most common form of anemia. Approximately 20% of women, 50% of pregnant women, and 3% of men are iron deficient. Iron is an essential component of hemoglobin, the oxygen carrying pigment in the blood. Iron is normally obtained through the food in the diet and by the recycling of iron from old red blood cells. The causes of iron deficiency are too little iron in the diet, poor absorption of iron by the body, and loss of blood (including heavy menstrual bleeding). It may also be related to lead poisoning or chemotherpy. Anemia develops slowly, after the normal stores of iron have been depleted in the body and in the bone marrow. Women, in general, have smaller stores of iron than men and have increased loss through menstruation, placing them at higher risk for anemia than men. In men and postmenopausal women, anemia is usually due to gastrointestinal blood loss associated with ulcers, the use of aspirin or nonsteroidal anti-inflammatory medications (NSAIDS), or colon cancer. High-risk groups include: women of child-bearing age who have blood loss through menstruation; pregnant or lactating women who have an increased requirement for iron; infants, children, and adolescents in rapid growth phases; and people with a poor dietary intake of iron through a diet of little or no meat or eggs for several years. Risk factors related to blood loss are peptic ulcer disease, long term aspirin use, colon cancer, or cancer-related chemotherapy treatment. Dietary sources of iron are red meat, liver, and egg yolks. Flour, bread, and some cereals are fortified with iron. If the diet is deficient in iron, iron should be taken orally and monitored by a physician.
The rate at which NATURAL ENDOGENOUS HEMATOCRIT increases varies with each subject but may be further enhanced when SPECIFIC DIETARY INTERVENTIONS ARE ADDED TO THE INTENSE HYPOXIC INTERVAL SESSIONS. The same dietary intervention observed to relieve Anemia symptoms is the ideal protocol for treating impaired blood oxygen capacity or increasing blood oxygen capacity of a normal-healthy endurance athlete. The most common cause is iron-deficiency anemia in red blood cells which are smaller than usual and pale in color due to improper amounts of hemoglobin (the molecule in red blood cells that binds to oxygen and carries it in the blood). This lack of iron for the production of hemoglobin is due to:
-Loss of iron from the body due to blood loss
-Poor absorption of iron from one's diet
-Lack of dietary iron
-Radiotherapy or Chemotherapy
-Anti-cancer drugs
-Certain types of viral infections
-Genetic reasons
-A result of malaria -AIDS
-A deficiency of vitamin B-12.
-A deficiency of folic acid.
-An imbalance between the ratio of B-12 & Folate
SYMPTOMS OF ANEMIA [Note: There may be no symptoms if anemia is mild.]
1. Tiredness and weakness
2. Lethargy
3. Dizziness, shortness of breath, and palpitations(rapid heart rate)
4. Headaches
5. Pale complexion
6. Brittle nails(due to lack of iron)
7. Irritability
8. Sore tongue
9. Unusual food cravings (called pica)
10. Decreased appetite
11. Headache - frontal
12. Blue tinge to sclerae (whites of eyes)
DIETARY INTERVENTIONS
PROTEIN ADEQUACY is a factor in erythropoietin (EPO) release mechanics. The erythroid response to Erythropoietin (EPO) is highly dependent on DIETARY PROTEIN. The mouse spleen is an erythropoietic organ which contains an EPO-responsive cell population that can be easily amplified by administration of the hormone. Researchers determined the effect of A PROTEIN-FREE DIET offered freely to mice up to two days after injection of r-Hu EPO (1000mU/200 ul) on the response of the above population. Splenic cell suspensions from control and experimental mice were prepared in microwells containing 400 mU r-Hu EPO and appropriate medium. The response to EPO was evaluated in terms of 3H-thymidine uptake. The results obtained indicate that acutely induced protein restriction suppressed the response of the EPO-responsive splenic cell population to EPO when it was imposed on mice immediately after hormone injection, and suggest the appearance of deficient rates of differentiation of erythropoietic units by protein restriction.[5] "ENOUGH PROTEIN" is 1.4-1.7 grams/kilogram body weight.
"ENOUGH FOOD", NOT FASTING is also a factor. In order to test the hypothesis that the early cessation of erythropoietin (Ep) production during hypobaric hypoxia is induced by lowered food intake, we have compared the plasma Ep titer of rats after exposure to continuous hypoxia (42.6 kPa = 7000 m altitude) for 4 days with that in FED OR FASTED RATS AFTER EXPOSURE TO DISCONTINUOUS HYPOXIA. We found that plasma Ep was rather low after 4 days of continuous hypoxia. However, the Ep titer significantly rose again, when rats were maintained normoxic for 18 h and then exposed to repeated hypoxia for 6 h. Because this was also found in rats which were deprived of food during the normoxic interval and the second hypoxic period, we conclude that the fall of the Ep titer during continuous hypoxia is not primarily due to reduced food intake. In addition, OUR FINDINGS SHOW THAT FASTING PER SE LOWERS THE EPO-RESPONSE TO HYPOXIA IN NORMAL RATS BUT NOT EXHYPOXIC RATS.[6] Maintaining caloric balance from exercise expense versus food intake is necessary for EPO-release.
OTHER HORMONAL AND CALORIC FACTORS INFLUENCE NATURAL EPO RATE EPO production also has hormonal-dependant roots complexly related to glucose metabolism, and caloric adequacy. The effect of T3 replacement and glucose supplementation on erythropoietin production was investigated in fasted hypoxic rats. It was found that 48 hr of fasting significantly reduced the circulating levels of thyroid hormones and the production of renal and extrarenal erythropoietin in response to hypoxia. These effects of fasting were completely abolished when the animals had free access to 25% GLUCOSE SOLUTION as drinking water, despite their lack of protein intake. REPLACEMENT DOSES OF T3 (0.5 micrograms/100 gm per day) RESTORED ERYTHROPOIETIN production in the fasted animals but also increased the response of the fed controls. To avoid the effect of endogenous T3, the experiments were repeated in thyroidectomized rats. ERYTHROPOIETIN PRODUCTION IN ATHYROID RATS WAS FOUND TO BE MARKEDLY DECREASED, WITH VALUES EQUIVALENT TO THOSE FOUND IN NORMAL FASTED ANIMALS, AND WERE NOT AFFECTED BY FASTING OR GLUCOSE SUPPLEMENTATION. Replacement doses of T3 increased erythropoietin production in all three groups, but the fasted animals needed five times as much T3 to obtain a response similar to that observed in the fed group. Glucose supplementation enhanced the effect of T3 in the fasted animals but did not completely restore it. THESE RESULTS INDICATE THAT CALORIC DEPRIVATION IS PRIMARILY RESPONSIBLE FOR THE DECREASED ERYTHROPOIETIN PRODUCTION INDUCED BY FASTING AND THAT THIS EFFECT IS PROBABLY MEDIATED BY BOTH A DECREASED LEVEL OF T3 AND A DECREASED RESPONSIVENESS TO IT.[7]
DIETARY IRON ABSORPTION INLUENCES ERYTHROPOIETIN
Dietary interventions may significantly advance nonheme IRON ABSORPTION during EPO production. It is most important to include foods that enhance nonheme iron absorption, when iron losses are exceptionally high, or when no heme iron is consumed[vegan diet]. Absorption of heme iron is very efficient; the presence of red meat may increase absorption of non-heme iron four times. Only 1-7% of the nonheme iron in vegetable staples such as rice, maize, black beans, soybeans and wheat is absorbed when consumed by itself. Meat proteins and vitamin C will improve the absorption of nonheme iron. Diets that include a minimum of 5 servings of fruits and vegetables daily, provide adequate vitamin C to boost nonheme iron absorption. Calcium, polyphenols and tannins found in tea, and phytates, a component of plant foods such as legumes, rice and grains, inhibit the absorption of nonheme iron. Some of the proteins found in soybeans may inhibit nonheme iron absorption. Most healthy individuals maintain normal iron stores when the diet provides a wide variety of foods. However, oxalates and phytates found in dark green leafy vegetables and whole cereal grains decrease the absorption of iron because they bind with iron in the gastrointestinal tract. A favorable absorption of heme iron is further influenced by other foods in the diet such as foods containing vitamin C and an acid environment found in the stomach. The Recommended Dietary Allowance (RDA) for iron is 10 milligrams for adult males and postmenopausal females. Males (ages 11 to 18) need 12 milligrams of iron per day. Females (ages 11 to 50 years) need 15 milligrams. Most endurance athletes consume too much iron from their daily menu. Iron is fortified in breads, cereals, and a number of packaged products. I performed dietary analysis on 16 endurance athletes' and 9 non-endurance athlete's iron intake from their reported food intake in a series of computer-generated Dietary Analysis data collected over a 3 year period. The results of this review are as follows:
AVERAGE MALE ENDURANCE ATHLETE'S DAILY IRON INTAKE FROM FOODS
N=9
AVERAGE=279%
AVERAGE FEMALE ENDURANCE ATHLETE'S DAILY IRON INTAKE FROM FOODS
N=7
AVERAGE=193%
AVERAGE MALE NON-ENDURANCE ATHLETE'S DAILY IRON INTAKE FROM FOODS
N=4
AVERAGE=158%
AVERAGE FEMALE NON-ENDURANCE ATHLETE'S DAILY IRON INTAKE FROM FOODS
N=5
AVERAGE=115%
Excessive iron overload is not healthy. Common side effects of iron overload include gastro-intestinal pain, constipation, nausea, and heartburn. Excess iron levels may generate a continuous low grade infection. Foods are the best source to assure iron adequacy. The best food source of iron is liver and red meats. These foods contain heme iron, which is better absorbed than non-heme iron. Non-heme iron can be found in dark green, leafy vegetables (spinach, chard and kale) and whole cereal grains (bran and whole wheat bread). Include dark green, leafy vegetables and whole cereal grains in the daily diet. Oxalates and phytates found in dark green leafy vegetables and whole cereal grains decrease the absorption of iron because they bind with iron in the gastrointestinal tract. Iron fortified cereals provide supplemental iron in the diet. Anemia may develop on a meat-free diet, if iron store or intake is low. Red meat contains arachidonic acid, an EPO-precursor nutrient, but it also contains high levels of saturated fats and cholesterol suggesting a little now and then is good but too much is harmful to cardiovascular lipid health. Adding iron to the diet in supplemental form is not recommended except under the supervision of a physician who is monitoring blood serum levels for a specific outcome. It has been shown that eating red meat 1-2 per week may contribute to advancing dietary substrates to regenerate EPO levels. This is shown in animal research. The ability of ARACHIDONIC ACID (AA), the bisenoic prostaglandin precursor to stimulate erythropoiesis and ERYTHROPOIETIN (EP) PRODUCTION in exhypoxic polycythemic mice and the programmed isolated perfused canine kidney was found to stimulate erythropoiesis when administered to exhypoxic polycythemic mice in the lowest dose tested(50 microgram/kg i.p.). Endogenously synthesized prostaglandins, their intermediates and/or other products of AA metabolism, such as prostacyclin and prostaglandins play an important role in the control Ep production.[8] Hematocrit levels are restored by getting adequate substrates[list below] that support the body's natural mechansims for producing the EPO it requires for handling imposed endurance exercise stress.
SUBSTRATES REQUIRED FOR ERYTHROPOIETIN[EPO] METABOLISM[9]
- Acidophilus - 2-8 Billion Count, Good Bacteria
- Coenzyme Q10 - 100-150 mg daily
- Garlic capsules - 2 capsules 3 x daily
- Germanium - 200 mg daily
- Kelp - 100-225 micrograms/day
- Vitamin B6 - 50 mg 1-3 daily
- Vitamin B12 - 200-1,000 mcg
- Folic Acid - 800 mcg
- Proteolytic enzymes - Bromelain & Papain - Selenium - 200 mcg daily
- Vitamin A - 15,000 IU daily or Beta Carotene
- 25,000 IU daily
- Vitamin B Complex - 50-100 mg/day
- Vitamin C plus Bioflavonoids - 1-3 grams daily [divided dose]
- Vitamin E - 400 IU daily
- Copper - 2 mg daily
- Zinc chelate or Picolinate- 50-80 mg daily ---->(Do not take zinc in amounts over 100 mg daily as it can impair the immune response.)
CONCLUSION Nutritional imbalances imposed from caloric restriction, overhydration, excessive supplemental calcium or inositol, dietary oxalates or phytates from dark green leafy vegetables or whole cereal grains, and lack of hypoxic interval training are factors which may inhibit the optimal natural production of Erythropoietin [EPO]. Manipulating diet, hydration, supplements, exercise intensity, and rest in order to maximize EPO for optimal hematocrit and oxygen carrying capacity is not without risk above 48% in men. Why limit hematocrit to 48%? When hematocrit levels exceed 48%, risk of insulin resistance syndrome and stroke exponentially increase. Men with hematocrits of 48 percent or higher have a fourfold increased rate of non-insulin-dependent-diabetes mellitus, according to a study from Royal Free Hospital School of Medicine in London. They followed over 7,000 middle-aged men for more than 12 years, and discovered that the risk of diabetes increases as the hematocrit increases.[10] The upper recommended levels for females is 45%.
Nutritional interventions and exercise balance are key to provoking optimal, not excessive levels of EPO. Nutritional and training interventions for resolving low EPO levels need to be periodically monitored to determine progress toward normal reference ranges of no higher than 48% in men, 45% in women. Regular physician-diagnostic blood labs are well-advised to confirm if such strategies are appropriate for resolving deficiencies and/or preventing performance inhibition.
REFERENCES
[1]-CLINICAL PHARMACOLOGY OF PROCRIT from the world wide web, cited 2-14-2002 @: http://www.procrit.com/profonly/nephrology/what_is_procrit/clinical_pharmaco logy.html
[2]-Fisher JW., Pharmacologic modulation of erythropoietin production. Annu Rev Pharmacol Toxicol. 1988;28:101-22.
[3]-Roberts D, Smith DJ, Donnelly S, Simard S., Plasma-volume contraction and exercise-induced hypoxaemia modulate erythropoietin production in healthy humans. Clin Sci (Lond). 2000 Jan;98(1):39-45.
[4]-Roberts D, Smith DJ., Erythropoietin concentration and arterial haemoglobin saturation with supramaximal exercise. J Sports Sci. 1999 Jun;17(6):485-93. Barrio Rendo ME. Related Articles
[5]-Depressed response of the erythropoietin-responsive splenic cell population to erythropoietin in acutely protein restricted mice. In Vivo. 1995 Jan-Feb;9(1):71-3.
[6]-Jelkmann W, Kurtz A, Bauer C., Effects of fasting on the hypoxia-induced erythropoietin production in rats. Pflugers Arch. 1983 Feb;396(2):174-5.
[7]-Caro J, Silver R, Erslev AJ, Miller OP, Birgegard G., Erythropoietin production in fasted rats. Effects of thyroid hormones and glucose supplementation. J Lab Clin Med. 1981 Dec;98(6):860-8.
[8]-Foley JE, Gross DM, Nelson PK, Fisher JW., The effects of arachidonic acid on erythropoietin production in exhypoxic polycythemic mice and the isolated perfused canine kidney. J Pharmacol Exp Ther. 1978 Nov;207(2):402-9.
[9]-As with any supplement, always confirm with your physician as to the appropriate level and selection prior to use.
[10]-Diabetes 45:576-579, 1997.
<<<This article is reproduced for informational purposes only. The poster is not taking credit for writing this article.>>>
ERYTHROPOIETIN[EPO]: NUTRITIONAL AND TRAINING INTERVENTIONS FOR INCREASING EPO
Bill Misner Ph.D.*
There is a distinct relationship between illegitimate EPO-drug or blood doping misuse and legal dietary interventions accompanied by specified training protocols. EPO increases performance from its influence on blood-oxygen carrying-capacity up to a point. Excessive substrates, dietary deficiencies, hormonal imbalances, and lack of specific hypoxic training stress may inhibit the endurance athlete from peaking naturally-induced optimal endogenous production of erythropoietin.
ERYTHROPOIETIN[EPO] is a naturally occurring hormone that stimulates the production of red blood cells (RBC). In the absence of erythropoietin, few RBCs are formed by the bone marrow. In normal adults, approximately 90% of human erythropoietin is produced in the kidneys. Endogenous production of erythropoietin is normally regulated by the level of tissue oxygenation. A reduction in the delivery of oxygen to the kidneys may occur when the hematocrit (Hct) is low, or as a result of changes in the way that hemoglobin (Hb) and oxygen interact. HYPOXIA and ANEMIA generally increase the production of erythropoietin, which in turn stimulates red blood cell production. Erythropoietin increases RBC production by stimulating the division and differentiation of specific cells in the bone marrow. An important effect of erythropoietin is to stimulate the production of "proerythroblasts." Erythropoietin causes these cells to mature rapidly, further accelerating the production of new RBCs. The regulation of red blood cell production resembles a complete feedback loop. ERYTHROPOIETIN[EPO] is released primarily by the kidneys in response to hypoxia, by sending a highly specific signal prompting cells in the bone marrow to produce RBCs. As a result, the oxygen-carrying capacity increases, the stimulus of hypoxia is alleviated, and the production of erythropoietin is decreased. Endogenous production of erythropoietin is normally regulated by the level of tissue oxygenation. Hypoxia and anemia generally increase the production of erythropoietin, which in turn stimulates erythropoiesis. In normal subjects, plasma erythropoietin levels range from 0.01 to 0.03 Units/mL, and increase up to 100- to 1000-fold during hypoxia or anemia. EPOETIN ALFA[PROCRIT] has been shown to stimulate erythropoiesis in anemic patients with CRF who do not require regular dialysis. The first evidence of a response to the three times weekly (T.I.W.) administration of the prescription drug EPOETIN ALFA[PROCRIT] is an increase in the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 14-42 days. Because of the length of time required for erythropoiesis -- several days for erythroid progenitors to mature and be released into the circulation -- a clinically significant increase in hematocrit is usually not observed in less than 14 days and may require up to 42 days in some patients. Once the hematocrit reaches the suggested target range (30-36%), that level can be sustained by adequate nutrition in the absence of iron deficiency and concurrent illnesses. Interval training hypoxia enhances EPO levels by the same mechanism which the prescription drug, EPOETIN ALFA[PROCRIT] does. When Procrit is administered 1-3 times per week, subsequent increases in plasma erythropoietin levels are 100- to 1000-fold.[1] Because EPO increases the hematocrit, it enables more oxygen to flow to the skeletal muscles. Some distance runners and cyclists have used recombinant EPO to enhance their performance. A model for the regulation of erythropoietin production has been examined. This model proposes that a primary O2-sensing reaction in the kidney is initiated by a decrease in ambient PO2, a rapid decrease in gas exchange in the lung, a diminished oxygen-carrying capacity of hemoglobin, a molecular deprivation of oxygen, or a decrease in renal blood flow. Some of the agents that are thought to be released during hypoxia, which may trigger the EPO cascade, are adenosine (A2 activation), eicosanoids (PGE2, PGI2, and 6-keto PGE1), oxygen-free radicals (superoxide and H2O2), and catecholamines with beta-2 adrenergic receptor agonist properties. It is further proposed that an INCREASE IN INTRACELLULAR CALCIUM LEADS TO THE INHIBITION OF ERYTHROPOIETIN BIOSYNTHESIS AND/OR SECRETION AND A DECREASE IN INTRACELLULAR CALCIUM INCREASES ERYTHROPOIETIN PRODUCTION. THE SPECIFIC MECHANISM BY WHICH CALCIUM REGULATES ERYTHROPOIETIN BIOSYNTHESIS AND SECRETION IS NOT WELL UNDERSTOOD. However, a good correlation is seen with several agents that decrease intracellular calcium and increase erythropoietin production as well as with other agents that increase intracellular calcium and decrease erythropoietin production. When INOSITOL TRIPHOSPHATE levels are increased, an increase in the mobilization of intracellular calcium from the endoplasmic reticulum or another intracellular pool occurs. This increased INTRACELLULAR CALCIUM probably activates a calcium calmodulin kinase and produces a phosphoprotein that inhibits erythropoietin production/secretion.[2] Although recombinant EPO has exactly the same sequence of amino acids as the natural hormone, the sugars attached by the cells used in the pharmaceutical industry differ from those attached by the cells of the human kidney. This difference can be detected by a test of the athlete's urine.
ERYTHROPOIETIN (EPO) LEVELS INCREASE DURING HYPOXIC EXERCISE AND PLASMA VOLUME DEPLETION Roberts et al., examined exercise-induced hypoxemia (EIH) and plasma volume contraction as modulators of serum ERYTHROPOIETIN (EPO) production. Five athletes cycled for 3 min at supra-maximal power outputs, at each of two different elevations (1,000 and 2,100 meters). Five subjects were exposed to normobaric hypoxia (F(I)O(2)=0.159), seven subjects underwent plasmapheresis to reduce plasma volume and eight subjects were time controls for Epo levels. Oxyhemoglobin saturation was significantly reduced during exercise and during normobaric hypoxia. The time period of haemoglobin oxygen saturation <91% was 24+/-29 s (mean+/-S.D., n=5) for exercise at 1000 m, 136+/-77 s (mean+/-S.D., n=5) for exercise at 2100 m and 178+/-255 s (mean+/-S.D., n=5) with resting hypoxic exposure. However, SIGNIFICANTLY INCREASED SERUM EPO LEVELS WERE OBSERVED ONLY FOLLOWING EXERCISE (21-27% at 1,000 m and 31-41% at 2,100 m). VOLUME CONTRACTION ALSO RESULTED IN INCREASED SERUM EPO 29-41% in spite of a significant rise in hematocrit of +2.2%. Despite similar degrees of arterial desaturation, ONLY THE HYPOXEMIA INDUCED BY EXERCISE WAS ASSOCIATED WITH AN INCREASE IN SERUM EPO. This finding indicates that other factors, in addition to hypoxemia, are important in modulating the production of Epo in response to exercise. VOLUME DEPLETION IN THE ABSENCE OF EXERCISE RESULTED IN INCREASES IN EPO LEVELS THAT WERE COMPARABLE WITH THOSE OBSERVED IN RESPONSE TO EXERCISE. The paradoxical responses of the increased hematocrit and the increase in Epo in subjects undergoing plasmapheresis suggests that PLASMA VOLUME MAY ALSO MODULATE THE PRODUCTION OF EPO.[3]
HOW DOES INTENSITY OF EXERCISE INCREASE ERYTHROPOIETIN RELEASE? Roberts & Smith set out to determine if the hypoxaemic stimulus generated by intense exercise results in the physiological response of increased erythropoietin production. Twenty athletes exercised for 3 min at 106-112% maximal oxygen consumption. Estimated oxyhemoglobin saturation was measured by reflective probe pulse oximetry (Nellcor N200) and was validated against arterial oxyhemoglobin saturation by CO-oximetry in eight athletes. Serum erythropoietin concentrations-as measured using the INCSTAR Epo-Trac radioimmunoassay-increased significantly by 19-37% at 24 h post-exercise in 11 participants, who also had an arterial oxyhemoglobin saturation < or = 91%. Decreased ferritin levels and increased reticulocyte counts were observed at 96 h post-exercise. However, no significant changes in erythropoietin levels were observed in nine non-desaturating athletes and eight non-exercise controls. Good agreement was shown between arterial oxyhemoglobin saturation and percent estimated oxyhaemoglobin saturation (limits of agreement = -3.9 to 3.7%). In conclusion, SHORT[3 MINUTES] SUPRAMAXIMAL EXERCISE CAN INDUCE BOTH HYPOXEMIA AND INCREASED ERYTHROPOIETIN LEVELS IN WELL-TRAINED INDIVIDUALS. The decline of arterial hypoxemia levels below 91% during exercise appears to be necessary for the exercise-induced elevation of serum erythropoietin levels. Furthermore, reflective probe pulse oximetry was found to be a valid predictor of percent arterial oxyhemoglobin saturation during supramaximal exercise when percent estimated oxyhemoglobin saturation > or = 86%.[4] Hence, fit athletes tend to gain more exercise-induced EPO from short 3-minute all-out intervals than do less fit athletes.
DIETARY INTERVENTIONS FOR INCREASING OXYGEN CARRYING CAPACITY AND REDUCING ANEMIA COMMON CAUSES OF ANEMIA Red blood cells that carry iron-rich hemoglobin, live only 120 days or four months. Unless there is a continual supply of iron, vitamin B12, vitamin C and folacin from either food or supplements, anemia will result in poorly formed red blood cells that are ineffective carriers of oxygen. Iron deficiency anemia is the most common form of anemia. Approximately 20% of women, 50% of pregnant women, and 3% of men are iron deficient. Iron is an essential component of hemoglobin, the oxygen carrying pigment in the blood. Iron is normally obtained through the food in the diet and by the recycling of iron from old red blood cells. The causes of iron deficiency are too little iron in the diet, poor absorption of iron by the body, and loss of blood (including heavy menstrual bleeding). It may also be related to lead poisoning or chemotherpy. Anemia develops slowly, after the normal stores of iron have been depleted in the body and in the bone marrow. Women, in general, have smaller stores of iron than men and have increased loss through menstruation, placing them at higher risk for anemia than men. In men and postmenopausal women, anemia is usually due to gastrointestinal blood loss associated with ulcers, the use of aspirin or nonsteroidal anti-inflammatory medications (NSAIDS), or colon cancer. High-risk groups include: women of child-bearing age who have blood loss through menstruation; pregnant or lactating women who have an increased requirement for iron; infants, children, and adolescents in rapid growth phases; and people with a poor dietary intake of iron through a diet of little or no meat or eggs for several years. Risk factors related to blood loss are peptic ulcer disease, long term aspirin use, colon cancer, or cancer-related chemotherapy treatment. Dietary sources of iron are red meat, liver, and egg yolks. Flour, bread, and some cereals are fortified with iron. If the diet is deficient in iron, iron should be taken orally and monitored by a physician.
The rate at which NATURAL ENDOGENOUS HEMATOCRIT increases varies with each subject but may be further enhanced when SPECIFIC DIETARY INTERVENTIONS ARE ADDED TO THE INTENSE HYPOXIC INTERVAL SESSIONS. The same dietary intervention observed to relieve Anemia symptoms is the ideal protocol for treating impaired blood oxygen capacity or increasing blood oxygen capacity of a normal-healthy endurance athlete. The most common cause is iron-deficiency anemia in red blood cells which are smaller than usual and pale in color due to improper amounts of hemoglobin (the molecule in red blood cells that binds to oxygen and carries it in the blood). This lack of iron for the production of hemoglobin is due to:
-Loss of iron from the body due to blood loss
-Poor absorption of iron from one's diet
-Lack of dietary iron
-Radiotherapy or Chemotherapy
-Anti-cancer drugs
-Certain types of viral infections
-Genetic reasons
-A result of malaria -AIDS
-A deficiency of vitamin B-12.
-A deficiency of folic acid.
-An imbalance between the ratio of B-12 & Folate
SYMPTOMS OF ANEMIA [Note: There may be no symptoms if anemia is mild.]
1. Tiredness and weakness
2. Lethargy
3. Dizziness, shortness of breath, and palpitations(rapid heart rate)
4. Headaches
5. Pale complexion
6. Brittle nails(due to lack of iron)
7. Irritability
8. Sore tongue
9. Unusual food cravings (called pica)
10. Decreased appetite
11. Headache - frontal
12. Blue tinge to sclerae (whites of eyes)
DIETARY INTERVENTIONS
PROTEIN ADEQUACY is a factor in erythropoietin (EPO) release mechanics. The erythroid response to Erythropoietin (EPO) is highly dependent on DIETARY PROTEIN. The mouse spleen is an erythropoietic organ which contains an EPO-responsive cell population that can be easily amplified by administration of the hormone. Researchers determined the effect of A PROTEIN-FREE DIET offered freely to mice up to two days after injection of r-Hu EPO (1000mU/200 ul) on the response of the above population. Splenic cell suspensions from control and experimental mice were prepared in microwells containing 400 mU r-Hu EPO and appropriate medium. The response to EPO was evaluated in terms of 3H-thymidine uptake. The results obtained indicate that acutely induced protein restriction suppressed the response of the EPO-responsive splenic cell population to EPO when it was imposed on mice immediately after hormone injection, and suggest the appearance of deficient rates of differentiation of erythropoietic units by protein restriction.[5] "ENOUGH PROTEIN" is 1.4-1.7 grams/kilogram body weight.
"ENOUGH FOOD", NOT FASTING is also a factor. In order to test the hypothesis that the early cessation of erythropoietin (Ep) production during hypobaric hypoxia is induced by lowered food intake, we have compared the plasma Ep titer of rats after exposure to continuous hypoxia (42.6 kPa = 7000 m altitude) for 4 days with that in FED OR FASTED RATS AFTER EXPOSURE TO DISCONTINUOUS HYPOXIA. We found that plasma Ep was rather low after 4 days of continuous hypoxia. However, the Ep titer significantly rose again, when rats were maintained normoxic for 18 h and then exposed to repeated hypoxia for 6 h. Because this was also found in rats which were deprived of food during the normoxic interval and the second hypoxic period, we conclude that the fall of the Ep titer during continuous hypoxia is not primarily due to reduced food intake. In addition, OUR FINDINGS SHOW THAT FASTING PER SE LOWERS THE EPO-RESPONSE TO HYPOXIA IN NORMAL RATS BUT NOT EXHYPOXIC RATS.[6] Maintaining caloric balance from exercise expense versus food intake is necessary for EPO-release.
OTHER HORMONAL AND CALORIC FACTORS INFLUENCE NATURAL EPO RATE EPO production also has hormonal-dependant roots complexly related to glucose metabolism, and caloric adequacy. The effect of T3 replacement and glucose supplementation on erythropoietin production was investigated in fasted hypoxic rats. It was found that 48 hr of fasting significantly reduced the circulating levels of thyroid hormones and the production of renal and extrarenal erythropoietin in response to hypoxia. These effects of fasting were completely abolished when the animals had free access to 25% GLUCOSE SOLUTION as drinking water, despite their lack of protein intake. REPLACEMENT DOSES OF T3 (0.5 micrograms/100 gm per day) RESTORED ERYTHROPOIETIN production in the fasted animals but also increased the response of the fed controls. To avoid the effect of endogenous T3, the experiments were repeated in thyroidectomized rats. ERYTHROPOIETIN PRODUCTION IN ATHYROID RATS WAS FOUND TO BE MARKEDLY DECREASED, WITH VALUES EQUIVALENT TO THOSE FOUND IN NORMAL FASTED ANIMALS, AND WERE NOT AFFECTED BY FASTING OR GLUCOSE SUPPLEMENTATION. Replacement doses of T3 increased erythropoietin production in all three groups, but the fasted animals needed five times as much T3 to obtain a response similar to that observed in the fed group. Glucose supplementation enhanced the effect of T3 in the fasted animals but did not completely restore it. THESE RESULTS INDICATE THAT CALORIC DEPRIVATION IS PRIMARILY RESPONSIBLE FOR THE DECREASED ERYTHROPOIETIN PRODUCTION INDUCED BY FASTING AND THAT THIS EFFECT IS PROBABLY MEDIATED BY BOTH A DECREASED LEVEL OF T3 AND A DECREASED RESPONSIVENESS TO IT.[7]
DIETARY IRON ABSORPTION INLUENCES ERYTHROPOIETIN
Dietary interventions may significantly advance nonheme IRON ABSORPTION during EPO production. It is most important to include foods that enhance nonheme iron absorption, when iron losses are exceptionally high, or when no heme iron is consumed[vegan diet]. Absorption of heme iron is very efficient; the presence of red meat may increase absorption of non-heme iron four times. Only 1-7% of the nonheme iron in vegetable staples such as rice, maize, black beans, soybeans and wheat is absorbed when consumed by itself. Meat proteins and vitamin C will improve the absorption of nonheme iron. Diets that include a minimum of 5 servings of fruits and vegetables daily, provide adequate vitamin C to boost nonheme iron absorption. Calcium, polyphenols and tannins found in tea, and phytates, a component of plant foods such as legumes, rice and grains, inhibit the absorption of nonheme iron. Some of the proteins found in soybeans may inhibit nonheme iron absorption. Most healthy individuals maintain normal iron stores when the diet provides a wide variety of foods. However, oxalates and phytates found in dark green leafy vegetables and whole cereal grains decrease the absorption of iron because they bind with iron in the gastrointestinal tract. A favorable absorption of heme iron is further influenced by other foods in the diet such as foods containing vitamin C and an acid environment found in the stomach. The Recommended Dietary Allowance (RDA) for iron is 10 milligrams for adult males and postmenopausal females. Males (ages 11 to 18) need 12 milligrams of iron per day. Females (ages 11 to 50 years) need 15 milligrams. Most endurance athletes consume too much iron from their daily menu. Iron is fortified in breads, cereals, and a number of packaged products. I performed dietary analysis on 16 endurance athletes' and 9 non-endurance athlete's iron intake from their reported food intake in a series of computer-generated Dietary Analysis data collected over a 3 year period. The results of this review are as follows:
AVERAGE MALE ENDURANCE ATHLETE'S DAILY IRON INTAKE FROM FOODS
N=9
AVERAGE=279%
AVERAGE FEMALE ENDURANCE ATHLETE'S DAILY IRON INTAKE FROM FOODS
N=7
AVERAGE=193%
AVERAGE MALE NON-ENDURANCE ATHLETE'S DAILY IRON INTAKE FROM FOODS
N=4
AVERAGE=158%
AVERAGE FEMALE NON-ENDURANCE ATHLETE'S DAILY IRON INTAKE FROM FOODS
N=5
AVERAGE=115%
Excessive iron overload is not healthy. Common side effects of iron overload include gastro-intestinal pain, constipation, nausea, and heartburn. Excess iron levels may generate a continuous low grade infection. Foods are the best source to assure iron adequacy. The best food source of iron is liver and red meats. These foods contain heme iron, which is better absorbed than non-heme iron. Non-heme iron can be found in dark green, leafy vegetables (spinach, chard and kale) and whole cereal grains (bran and whole wheat bread). Include dark green, leafy vegetables and whole cereal grains in the daily diet. Oxalates and phytates found in dark green leafy vegetables and whole cereal grains decrease the absorption of iron because they bind with iron in the gastrointestinal tract. Iron fortified cereals provide supplemental iron in the diet. Anemia may develop on a meat-free diet, if iron store or intake is low. Red meat contains arachidonic acid, an EPO-precursor nutrient, but it also contains high levels of saturated fats and cholesterol suggesting a little now and then is good but too much is harmful to cardiovascular lipid health. Adding iron to the diet in supplemental form is not recommended except under the supervision of a physician who is monitoring blood serum levels for a specific outcome. It has been shown that eating red meat 1-2 per week may contribute to advancing dietary substrates to regenerate EPO levels. This is shown in animal research. The ability of ARACHIDONIC ACID (AA), the bisenoic prostaglandin precursor to stimulate erythropoiesis and ERYTHROPOIETIN (EP) PRODUCTION in exhypoxic polycythemic mice and the programmed isolated perfused canine kidney was found to stimulate erythropoiesis when administered to exhypoxic polycythemic mice in the lowest dose tested(50 microgram/kg i.p.). Endogenously synthesized prostaglandins, their intermediates and/or other products of AA metabolism, such as prostacyclin and prostaglandins play an important role in the control Ep production.[8] Hematocrit levels are restored by getting adequate substrates[list below] that support the body's natural mechansims for producing the EPO it requires for handling imposed endurance exercise stress.
SUBSTRATES REQUIRED FOR ERYTHROPOIETIN[EPO] METABOLISM[9]
- Acidophilus - 2-8 Billion Count, Good Bacteria
- Coenzyme Q10 - 100-150 mg daily
- Garlic capsules - 2 capsules 3 x daily
- Germanium - 200 mg daily
- Kelp - 100-225 micrograms/day
- Vitamin B6 - 50 mg 1-3 daily
- Vitamin B12 - 200-1,000 mcg
- Folic Acid - 800 mcg
- Proteolytic enzymes - Bromelain & Papain - Selenium - 200 mcg daily
- Vitamin A - 15,000 IU daily or Beta Carotene
- 25,000 IU daily
- Vitamin B Complex - 50-100 mg/day
- Vitamin C plus Bioflavonoids - 1-3 grams daily [divided dose]
- Vitamin E - 400 IU daily
- Copper - 2 mg daily
- Zinc chelate or Picolinate- 50-80 mg daily ---->(Do not take zinc in amounts over 100 mg daily as it can impair the immune response.)
CONCLUSION Nutritional imbalances imposed from caloric restriction, overhydration, excessive supplemental calcium or inositol, dietary oxalates or phytates from dark green leafy vegetables or whole cereal grains, and lack of hypoxic interval training are factors which may inhibit the optimal natural production of Erythropoietin [EPO]. Manipulating diet, hydration, supplements, exercise intensity, and rest in order to maximize EPO for optimal hematocrit and oxygen carrying capacity is not without risk above 48% in men. Why limit hematocrit to 48%? When hematocrit levels exceed 48%, risk of insulin resistance syndrome and stroke exponentially increase. Men with hematocrits of 48 percent or higher have a fourfold increased rate of non-insulin-dependent-diabetes mellitus, according to a study from Royal Free Hospital School of Medicine in London. They followed over 7,000 middle-aged men for more than 12 years, and discovered that the risk of diabetes increases as the hematocrit increases.[10] The upper recommended levels for females is 45%.
Nutritional interventions and exercise balance are key to provoking optimal, not excessive levels of EPO. Nutritional and training interventions for resolving low EPO levels need to be periodically monitored to determine progress toward normal reference ranges of no higher than 48% in men, 45% in women. Regular physician-diagnostic blood labs are well-advised to confirm if such strategies are appropriate for resolving deficiencies and/or preventing performance inhibition.
REFERENCES
[1]-CLINICAL PHARMACOLOGY OF PROCRIT from the world wide web, cited 2-14-2002 @: http://www.procrit.com/profonly/nephrology/what_is_procrit/clinical_pharmaco logy.html
[2]-Fisher JW., Pharmacologic modulation of erythropoietin production. Annu Rev Pharmacol Toxicol. 1988;28:101-22.
[3]-Roberts D, Smith DJ, Donnelly S, Simard S., Plasma-volume contraction and exercise-induced hypoxaemia modulate erythropoietin production in healthy humans. Clin Sci (Lond). 2000 Jan;98(1):39-45.
[4]-Roberts D, Smith DJ., Erythropoietin concentration and arterial haemoglobin saturation with supramaximal exercise. J Sports Sci. 1999 Jun;17(6):485-93. Barrio Rendo ME. Related Articles
[5]-Depressed response of the erythropoietin-responsive splenic cell population to erythropoietin in acutely protein restricted mice. In Vivo. 1995 Jan-Feb;9(1):71-3.
[6]-Jelkmann W, Kurtz A, Bauer C., Effects of fasting on the hypoxia-induced erythropoietin production in rats. Pflugers Arch. 1983 Feb;396(2):174-5.
[7]-Caro J, Silver R, Erslev AJ, Miller OP, Birgegard G., Erythropoietin production in fasted rats. Effects of thyroid hormones and glucose supplementation. J Lab Clin Med. 1981 Dec;98(6):860-8.
[8]-Foley JE, Gross DM, Nelson PK, Fisher JW., The effects of arachidonic acid on erythropoietin production in exhypoxic polycythemic mice and the isolated perfused canine kidney. J Pharmacol Exp Ther. 1978 Nov;207(2):402-9.
[9]-As with any supplement, always confirm with your physician as to the appropriate level and selection prior to use.
[10]-Diabetes 45:576-579, 1997.
<<<This article is reproduced for informational purposes only. The poster is not taking credit for writing this article.>>>
New things to Research!
Valium helping with nervous system regenaration?
anyone hear take ice baths after training? or alternate hot/cold?
I love icing the legs after a hard workout.
anyone use tren alone an have no gyno?
there's gotta be something out there that can help with nervous system recovery. besides a good BJ!
starting to see "rhodiala" (a herb) used like siberian ginseng as a a recovery aid.
whats you guys opinion on phosphydital serine (sp)?
Valium helping with nervous system regenaration?
anyone hear take ice baths after training? or alternate hot/cold?
I love icing the legs after a hard workout.
anyone use tren alone an have no gyno?
there's gotta be something out there that can help with nervous system recovery. besides a good BJ!
starting to see "rhodiala" (a herb) used like siberian ginseng as a a recovery aid.
whats you guys opinion on phosphydital serine (sp)?
triguy- the only thing i know about valium is that its great if you need a solid 8-10hrs of sleep! as for nervous system recovery, i have spoken alot with Rick Crawford (Levi and Chann's coach) and he is huge into nervous system recovery, and from what he says the only thing is to be stress free, eliminate stress and keep the nervous system stimulated when training and it will recover. He tells his athletes to never do specific intervals because its boring for the nervous system, he claims its better to go do a hard group ride and get the intensity from that because your nervous system will be much more stimulated. He says you can do specific intervals but only if you are very very motivated at the time. Yah, i use ice baths alot after training, i shoot for a temp. of around +5 to +10 any colder than that and its too much of a shock. The alternating is good for a flush of the legs, if you feel like you have alot of lactic acid buildup then the alternating is good, but right after a good hard ride, i just do the 20mins in cold. And all that other shit you are talking about i have never heard of, but am interested in it nonetheless. ok, time to jump behind the scooter for 2hrs.. adios
rider
rider
fhg43
New member
Endurance athletes-
Lets hear your supplementation routines:
AM:
Calcium 50mg?
ALA 100mg
B-Complex
Twin Labs Multi Vitamin
Glucosamine/MSM 1000mg of each
Saw Palmetto 160mg
Milk Thistle 100mg
Vit C 1000mg
PM:
CoQ10 75mg
ALA 100mg
B-complex
Glutamine 2000mg
Amino acid supp
Vit E EOD
Iron 50mg EOD
Milk thistle 100mg
Saw Palmetto 160mg
Post ride:
B complex
ALA 200mg
Argine 100mg
Endurox R4 (53g carb/13g pro)
sublngual B12
Vit C 1000mg
protein shake (40g protein)
FHG
Lets hear your supplementation routines:
AM:
Calcium 50mg?
ALA 100mg
B-Complex
Twin Labs Multi Vitamin
Glucosamine/MSM 1000mg of each
Saw Palmetto 160mg
Milk Thistle 100mg
Vit C 1000mg
PM:
CoQ10 75mg
ALA 100mg
B-complex
Glutamine 2000mg
Amino acid supp
Vit E EOD
Iron 50mg EOD
Milk thistle 100mg
Saw Palmetto 160mg
Post ride:
B complex
ALA 200mg
Argine 100mg
Endurox R4 (53g carb/13g pro)
sublngual B12
Vit C 1000mg
protein shake (40g protein)
FHG
Injectable b12 - 3cc's a week
AlA - 300mg's per meal or 600mg's per high carb meal. 600mg's post race w/recoverydrink
recovery drink-(glutamine1000mg's,ribose1000mg's carbs 80grams,protein 40grams,)
Ribose- 1000mg's a day
IP6 w/calcium (Jarrow) - 1 gram 3x a day
Iron 50mg's 3x week
B complex multiple
Vit E 400 - 800 mgs a day
2000 - 4000 mg's vit.C (help's in B absorption)
MSM, Elecrtolytes, etc..
was using Tribulis 3 grams a day for a few weeks but just ran out
---------------------
AlA - 300mg's per meal or 600mg's per high carb meal. 600mg's post race w/recoverydrink
recovery drink-(glutamine1000mg's,ribose1000mg's carbs 80grams,protein 40grams,)
Ribose- 1000mg's a day
IP6 w/calcium (Jarrow) - 1 gram 3x a day
Iron 50mg's 3x week
B complex multiple
Vit E 400 - 800 mgs a day
2000 - 4000 mg's vit.C (help's in B absorption)
MSM, Elecrtolytes, etc..
was using Tribulis 3 grams a day for a few weeks but just ran out
---------------------
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AM- multi vitamin, flax seed oil, chlorella
after a hard ride- recovery shake (2scoops gator load 50g carb, 1 scoop whey protein 17g protein, and 1oz trace mineral supplement) sometimes will use some BCAA pills and also electrolyte pills if the weather was nice.
I have some injectable B12 but I have yet to use it, does anyone think itd be a good idea? I was thinking about scheduling an appointment to get my blood tested in hopes of being perscribed some iron injections as well as B12. Does anyone think that if i did a hard 5hr ride and then went right in and got my blood tested my levels would be low enough to warrant perscription? Maybe my test. levels would be low too!?! FHG- what is ALA? if anyone has any suggestions to my rather weak supplement routine id certainly appreciate it. Im also dieting pretty heavily right now (about 1500kcal a day deficet, with almost all kcal's coming from fats and protein) is there anything I should be taking so i dont lose too much strength?
rider
after a hard ride- recovery shake (2scoops gator load 50g carb, 1 scoop whey protein 17g protein, and 1oz trace mineral supplement) sometimes will use some BCAA pills and also electrolyte pills if the weather was nice.
I have some injectable B12 but I have yet to use it, does anyone think itd be a good idea? I was thinking about scheduling an appointment to get my blood tested in hopes of being perscribed some iron injections as well as B12. Does anyone think that if i did a hard 5hr ride and then went right in and got my blood tested my levels would be low enough to warrant perscription? Maybe my test. levels would be low too!?! FHG- what is ALA? if anyone has any suggestions to my rather weak supplement routine id certainly appreciate it. Im also dieting pretty heavily right now (about 1500kcal a day deficet, with almost all kcal's coming from fats and protein) is there anything I should be taking so i dont lose too much strength?
rider
Rider - There is a lot of info on ala on this board - do a search. It's an antioxidant that works somewhat like insulin and helps glucose metabolism. On a low cal diet it should help you get more nutrients out of your food. Take it when you eat something because it can give you heartburn. www.nutriteam.com has it for pretty cheap. If you have b12 use it! It will give you more energy and help in building in Red Blood Cells. You can get this online as well through pet pharmacy's.
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roadkill- Thanks alot for the advice, I went out and picked up some ALA tonight.. Ill start in on it tomorrow. Im a little nervous about the B12 as I've never given myself injections.. I also couldnt find any for sale on any pet pharmacy page, maybe you have a link or something? I have 2 10cc vials, how much should I be using a week? its called Tiaminal B12 and I got it in Mex. Thanks again for the advice.
rider
rider
diets?
Since you guys are all endurance athletes I was wondering if some of you can post some sample diets that you use?? Or types of foods you eat for endurance. I'm getting more into racing (converted from bodybuilding). What types of foods for energy on the go??? quick meals?
Since you guys are all endurance athletes I was wondering if some of you can post some sample diets that you use?? Or types of foods you eat for endurance. I'm getting more into racing (converted from bodybuilding). What types of foods for energy on the go??? quick meals?
rider - 2 bottles of 10cc's should last a while. You really only need 1cc a week. It's cheap so I generally load up a little more or do two injections a week - Tue and Thur. Here's a link for b-12.
http://www.jefferslivestock.com/sscproduct.asp?cid=2&bid=1&pf_id=16514
It can be kinda weird injecting yourself for the first time. Some guys do b12 in their delts with an insulin pin. I use a 1" 23 gauge in the glutes.Try www.getpinz.com if you need them. Get some alcohol swabs as well.
To inject, clean the area with an alcohol swab. Hang your right leg over a bed while kneeling with the other leg on the bed, then pull the skin tight on your right glute( on the side of your glute,centered) with your left hand using your thumb and forefinger. Holding the pen like a dart in one movement stick it in quickly. It will go in like butter and wont hurt if done swiftly and straight. Pull back on the plunger if it's tight and no blood comes into the syringe slowly inject the contents. This will make it less sore later. When done injecting pull the needle straight out and clean the area with an alcohol swab.
Practice on a tomato before sticking yourself to get the technique down if your nervous about it. Also clean the top of the bottles with an alcohol swab before loading up the syringe the next time you are going to inject.
Diet -
I eat 40/30/30 because it works for me. Just do what you normaly do but eat some easily digestible carbs on your hard/long endurance days and some recovery carbs/protein after. Then normal diet after. If you increase your carbs too much trying to compensate for your efforts you'll end up putting on weight. The day before a big event make sure your getting good carbs during lunch and dinner but you don't have to stuff yourself. Eat a normal breakfast the day of the event 3-4 hours before your start.
hope this helps
http://www.jefferslivestock.com/sscproduct.asp?cid=2&bid=1&pf_id=16514
It can be kinda weird injecting yourself for the first time. Some guys do b12 in their delts with an insulin pin. I use a 1" 23 gauge in the glutes.Try www.getpinz.com if you need them. Get some alcohol swabs as well.
To inject, clean the area with an alcohol swab. Hang your right leg over a bed while kneeling with the other leg on the bed, then pull the skin tight on your right glute( on the side of your glute,centered) with your left hand using your thumb and forefinger. Holding the pen like a dart in one movement stick it in quickly. It will go in like butter and wont hurt if done swiftly and straight. Pull back on the plunger if it's tight and no blood comes into the syringe slowly inject the contents. This will make it less sore later. When done injecting pull the needle straight out and clean the area with an alcohol swab.
Practice on a tomato before sticking yourself to get the technique down if your nervous about it. Also clean the top of the bottles with an alcohol swab before loading up the syringe the next time you are going to inject.
Diet -
I eat 40/30/30 because it works for me. Just do what you normaly do but eat some easily digestible carbs on your hard/long endurance days and some recovery carbs/protein after. Then normal diet after. If you increase your carbs too much trying to compensate for your efforts you'll end up putting on weight. The day before a big event make sure your getting good carbs during lunch and dinner but you don't have to stuff yourself. Eat a normal breakfast the day of the event 3-4 hours before your start.
hope this helps
Roadkill- Thanks so much for the info. I guess I need to just sac up and stick myself. Is it alright to take B12 for the entire season? and is there any other legal supplement that would help me out? maybe some injectable iron? A few guys I ride with are big into keno. it's just injectable vitamins, have you heard of this, and do you think itd be a good idea?
diet-
Pretty much just go really light on food, no bulking for us! right now im eating pretty much all fats and proteins to try and lose some weight but usually 2 days before an event I load up a bit on carbs to get the glycogen stores up. Thats about it, everyone has different theory's on diet so you'll just have to experiment and see what works for you. Hope this helps.
rider
diet-
Pretty much just go really light on food, no bulking for us! right now im eating pretty much all fats and proteins to try and lose some weight but usually 2 days before an event I load up a bit on carbs to get the glycogen stores up. Thats about it, everyone has different theory's on diet so you'll just have to experiment and see what works for you. Hope this helps.
rider
Thanks for the replies...any help is appreciated....Yeah I'm eating stuff like yogurt, fruit, clean meats (turkey, chicken, fish)...and trying to stay low on calories but eat every few hours......do you guys ever feel like you are losing muscle from not eating enough???? It seems so much different than bodybuilding so I'm trying to figure it all out....right now i'm on a winny/arimidex cycle also to maintain muscle while i figure the whole diet thing out.
yah man im always concerned about losing muscle while dieting but I think if all you are doing is riding then the body is gonna burn muscle from somewhere that is not being used as much, like i hope if im losing muscle that its coming from my arms! and you usually wont lose muscle unless you are in a caloric deficet of over 1000 a day. It sounds like your diet is good, but doesnt winny put weight on ya? what are your stats? good luck
rider
rider
Rider - I'm not convinced yet on injectable kynoselen,ATP,AMP, etc. Triguy was using it. Hey Triguy what do you think of this stuff?? Heptaminol works like a stimulant and makes some guys have insomnia. B-12, It's just a vitamin. Use it all the time.
check this site out for legal injectables
http://www.equinestar.com/
http://www.equinestar.com/kynoselen.htm
and this:
http://shop.store.yahoo.com/express...ormance-enhancers-injectable-medications.html
check this site out for legal injectables
http://www.equinestar.com/
http://www.equinestar.com/kynoselen.htm
and this:
http://shop.store.yahoo.com/express...ormance-enhancers-injectable-medications.html
I notice the winny won't put weight on me when i stay at maintenance calories or below...just keeps my muscles real hard....I take arimidex to keep water weight off.....Do you guys eat at maintenance calories or try and go for a deficit just about everyday to be sure to stay lean?
Thanks again for the info roadkill! wouldnt B12 be much more effective if you can get some iron injections? I've heard of people using both with really good results. As for calories, once I hit my racing weight I wont even bother counting, i just weigh myself every day and if I find myself to be up a pound or so I'll count kcals for a few days untill Im back at my ideal weight. Doing it this way keeps me a bit more sane than if I had to count every calorie for the entire season. Obviously once I get my ideal weight I dont go and max out on food, I still eat light and try to go to bed a little hungry but Im not obsessive like I am now. Hope this helps. adios
rider
rider
I have some injectable iron stocked away. You have to be careful with iron though. You can overdose pretty easy with it. I've got it but haven't used it. I don't think a doctor would give you a shot of iron unless you were anaemic. I just do an iron pill 3x a week. I don't think large doses of iron are going to do much good even with b12 but it will make you constipated! Try some ritalin(20mgs) and an ECA stack at your next crit that will get you going! I think ephedrine makes me cramp up during long races plus it reduces your bodies ability to replace ATP but for a crit once in a while this little stack will get you amped. 15 minutes prior to your start take everything; also chew the ritalin. Bon Voyage!
cycling performance
great discussion guys. i've been out of cycling for awhile due to clavicle fracture. i'm looking to get on the fast track to be competitive again by june or july. i have some sustanon, deca, winny tabs, and clomid. what kind of cycle would be helpful for a cyclist? stack? can i use the stuff i have or do i need something else. thanks in advance.
great discussion guys. i've been out of cycling for awhile due to clavicle fracture. i'm looking to get on the fast track to be competitive again by june or july. i have some sustanon, deca, winny tabs, and clomid. what kind of cycle would be helpful for a cyclist? stack? can i use the stuff i have or do i need something else. thanks in advance.
cycling performance
how long could i take the winnys before needing to give the liver a break? will the winnys really make that much difference? how many mg's per day and for how long? thanks for the guidance.
if i do use the sust and deca...what is considered low dosage...as the source recommended 500mg/week of sus and 200mg/week of deca.
how long could i take the winnys before needing to give the liver a break? will the winnys really make that much difference? how many mg's per day and for how long? thanks for the guidance.
if i do use the sust and deca...what is considered low dosage...as the source recommended 500mg/week of sus and 200mg/week of deca.
damn, did 4hrs in the 53x17 in the hills yesterday and felt pretty knackered, then did 2hrs medium plus another 2hrs behind the scooter at 55kph then cooled down for an hour (more than 200k total ride!) and was REALLY knackered! finally sacked up and shot myself w/ 2cc's of B12 and now, 3hrs later I feel fuckin awesome! anyone who is considering taking B12 injections.. Do it. my ass hurt for like an hour after but its all good now. I dont know if it's all mental but I certainly feel great. I also have a 1500kcal deficet today and im not hungry, which is strange because i keep hearing that b12 makes you hungry. hmmm. i got 5hrs tomorrow in the hills so ill post again and let you all know how i felt. adios
rider
rider
fhg43
New member
rider said:
Yeah I gotta work on that.
rider-I keep thinking I am going to go to TJ at somepoint and hook it up, but I think I am going to mailorder it. Did you use a slin needle? What were your teammates into keno? Is that like Kenocort and corticosteroid or was it Kyno like kynoselen(sp)? I found a site that sell Vit B and amino injections for vets and was wondering if the amino shot would be good also?
FHG
FHG- yah man get down to TJ and get on it, I jus went down and picked up 'Tiaminal B12' you can get it in a little box w/ 10cc's of B12 and 5 needles. Im not sure to the needle size but im guessing it's something close to a slin needle. None of my teamates were into kyno but I was just wondering about it as i know a few guys who are down w/ it. Im not gonna do it, injections suck and kyno is just vitamins that you can absorb from some pills. Im not sure about the amino shot, sounds like a good idea though. There are alot of vet sites that sell b12, most of them make it for horses and cows. It's mad cheap too, im gonna order some more today. Like 250ml is less than $10. and you can get pins online too www.getpinz.com let me know if you need a link to a vet site. later man
rider
ps- I did 5hrs today and didnt really feel that great, i was all jonsed up last night and felt like i could win the tour but today on the ride i wasent quite so chipper. although i definitly felt better than i would have if i rode like i did tuesday and wednesday and just drank protein shakes for recovery.
rider
ps- I did 5hrs today and didnt really feel that great, i was all jonsed up last night and felt like i could win the tour but today on the ride i wasent quite so chipper. although i definitly felt better than i would have if i rode like i did tuesday and wednesday and just drank protein shakes for recovery.
fina
I thought also fina/tren was a good choice for an endurance athlete, but I was wrong (at least, for me).
Trenbolone has a strong anti catabolic effect : it decrease cortisol at a very low level. It's good for gaining muscle, but not for endurance : I was always tired when I took it for my last cycle (240mg/week + 200mg test prop for 6 W). I couldn't recover after my workouts and I had an accelerated heart rate (70bpm instead of 50 usually).
I stopped it, and my energy levels get much higher within days.
When I was on tren, I felt like I was carrying a 30lbs weight on my back every day of the cycle. very bad feeling...
European pro bikers take gh, epo AND cortisone. Now I know why.
I must say though my look is much better now : really harder, leaner than before. good strength gains also. But it doesn't worth the pain and the exhaustion you feel all the day.
Just my opinion : maybe you can react well to tren, but i'll not use it anymore.
I thought also fina/tren was a good choice for an endurance athlete, but I was wrong (at least, for me).
Trenbolone has a strong anti catabolic effect : it decrease cortisol at a very low level. It's good for gaining muscle, but not for endurance : I was always tired when I took it for my last cycle (240mg/week + 200mg test prop for 6 W). I couldn't recover after my workouts and I had an accelerated heart rate (70bpm instead of 50 usually).
I stopped it, and my energy levels get much higher within days.
When I was on tren, I felt like I was carrying a 30lbs weight on my back every day of the cycle. very bad feeling...
European pro bikers take gh, epo AND cortisone. Now I know why.
I must say though my look is much better now : really harder, leaner than before. good strength gains also. But it doesn't worth the pain and the exhaustion you feel all the day.
Just my opinion : maybe you can react well to tren, but i'll not use it anymore.
oneradtec
hello all....
can someone explain to me why cortisone injections are good for cyclists? how does it ultimately improve performance? i have some good cortisone but surely i will not use it if i have no idea what it does. thanks.
also...i have some deca and winny that i may use...but also some sustanon. it seems that sustanon is a real no no based on what others have told me....as it will put on the weight.
hello all....
can someone explain to me why cortisone injections are good for cyclists? how does it ultimately improve performance? i have some good cortisone but surely i will not use it if i have no idea what it does. thanks.
also...i have some deca and winny that i may use...but also some sustanon. it seems that sustanon is a real no no based on what others have told me....as it will put on the weight.
Alll cortisone is not the same. Some cortisone is short term( hours)acting and some is long term (3 weeks) . Kenacort40 or kenalog40 (triamcinilone) is long term and one of the strongest. Everyone reacts slightly different. Some report a euphoric feeling while using although I didn't. Coritsone is an antiinflammatory. Imagine a very strong ibuprofen effect. Your legs don't ache and the soreness and pain goes away. When used intramuscularily in the glute it works systemically. It also has the effect of speeding up glycogen metabolism. Long term use will eat away at your muscles. Which is why body builders hate it. I found the effects to be fairly mild for me even when injecting 80mg's of kenalog 40. It probally wont make a huge difference to your form used alone.
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Back Baby!!!!!!!
Tren blows: gyno, limp dick, too much muscle gain.
winny: cool!
havent used kyno, atp, amp yet waiting for june,july. Ask about that in august.
here:s my vitamin program
liver extract
antioxidant
b-complex
saw palmetto
tribulis
CLA
siberian ginseng
ALA
Ip6
Phosphyldile serine (sp)?
Rhodilia (herb)
calcium pyruvate
ZMA
acetyl-l-carnitine
Tren blows: gyno, limp dick, too much muscle gain.
winny: cool!
havent used kyno, atp, amp yet waiting for june,july. Ask about that in august.
here:s my vitamin program
liver extract
antioxidant
b-complex
saw palmetto
tribulis
CLA
siberian ginseng
ALA
Ip6
Phosphyldile serine (sp)?
Rhodilia (herb)
calcium pyruvate
ZMA
acetyl-l-carnitine
fhg43
New member
road kill said:
I was wondering about cortisone aiding glucose metabolism-that is a definite benefit while racing. Sorry haven't posted mush lately-been busy!
Been feeling real lethargic lately. I need to get my B12 shots to pick it up-Also thinking Imight need some iron as I haven't had much red meat at all in...a few months!
FHG
Ive been feeling real lethargic lately too! and ive been using B12 (2cc's 2x/week) and Im not so sure if its making a huge difference. The first shot really made me feel awesome, but I havent felt like that since. Do the benefits take a while to get going? I also picked up Vitamin B complex plus off of jeffers livestock, is this the right stuff? it says only for animals on the side. Iron is something that I often wonder about, I always hear that you dont absorb pills or any kind of oral supplement for shit, but that injections are also dangerous as you can easily have too much iron in you. I guess the only thing to do is eat red meat!?? alright, time to hit the rollers for a few hrs. Gotta love the east, 36 and pouring down rain. sweet.
rider
rider
fhg43
New member
rider said:
Ahhh...Don't you miss the weather out here rider?
Willy Voet said the first thing he did with Virenque and Brochard was to get them off the cortisone-"They'll just waste away." The other bad thing about cortisone is that its an immuno depressant.
I need to see my doc about a checkup and some blood work. I'm sure I am just flat from peaking real early in the season. I kinda knew this would happen. I am starting to feel better though. I had to get motivated cause now we closing in the important summer races and don't want to suck for those. Rider PM or email sometime about your schedue and the nationals in TN.
FHG
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oneradtec
ok...how's this sound for my 8 week cycle...
weeks 1-8 deca 200mg
weeks 1-4 sustanon 250mg
weeks 5-8 winny tabs 30mg per day
it seems to me that the dosages are low enough to prevent any excess muscle mass type of weight gain that may impair performance. what do you guys think? i have some clomid also. i would appreciate some feedback...although i did start this cycle today. i threw in the sus just to help me build some strength initially that i hope will transfer into increased power output. my diet will be fairly lean for most of this cycle....so again..i hope the weight gain will not be a problem.
ok...how's this sound for my 8 week cycle...
weeks 1-8 deca 200mg
weeks 1-4 sustanon 250mg
weeks 5-8 winny tabs 30mg per day
it seems to me that the dosages are low enough to prevent any excess muscle mass type of weight gain that may impair performance. what do you guys think? i have some clomid also. i would appreciate some feedback...although i did start this cycle today. i threw in the sus just to help me build some strength initially that i hope will transfer into increased power output. my diet will be fairly lean for most of this cycle....so again..i hope the weight gain will not be a problem.
endurance athletes
that's why i'm here...to get constructive advice. it seems that there is an abundance of bodybuilding advice...but the endurance stuff is rather thin. i had assumed that 200mg of deca per week was the lowest dose possible to get results. bodybuilders are using 500 mg. a week or more. this is my first cycle..so perhaps i will not ask so many questions next time. comments like yours are appreciated. others welcome also. thanks in advance....and by the way..are you an endurance athlete that does 14-18 hours a week of cardio? just because you would get 20 lbs pumping iron..does that mean i'll get 20 lbs riding a bike?
that's why i'm here...to get constructive advice. it seems that there is an abundance of bodybuilding advice...but the endurance stuff is rather thin. i had assumed that 200mg of deca per week was the lowest dose possible to get results. bodybuilders are using 500 mg. a week or more. this is my first cycle..so perhaps i will not ask so many questions next time. comments like yours are appreciated. others welcome also. thanks in advance....and by the way..are you an endurance athlete that does 14-18 hours a week of cardio? just because you would get 20 lbs pumping iron..does that mean i'll get 20 lbs riding a bike?
you know I made a thread bout this too...
I just feel that for the endurance athlete (guessing now) that winnie, or an EQ or a primo, would be suffecient by themselves...... no need to stack
we are just looking for recovery aids, and a performance aid too.
not mass.....you have outlined a stack...something geared towards mass accumulation..especially running sustanon a deca together there
winstrol would help with both recovery and performance....and so would eq to a lesser degree I suspect........ primo would help in recovery almost only.....this is just my opinion
maybe a comprimise would be winnie at 50 mgs twice a week, and 1 shot of deca.......
just for recovery and performance.......I was thinking winnie alone would work just fine
I just feel that for the endurance athlete (guessing now) that winnie, or an EQ or a primo, would be suffecient by themselves...... no need to stack
we are just looking for recovery aids, and a performance aid too.
not mass.....you have outlined a stack...something geared towards mass accumulation..especially running sustanon a deca together there
winstrol would help with both recovery and performance....and so would eq to a lesser degree I suspect........ primo would help in recovery almost only.....this is just my opinion
maybe a comprimise would be winnie at 50 mgs twice a week, and 1 shot of deca.......
just for recovery and performance.......I was thinking winnie alone would work just fine
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endurance athletes
ok...the deca and winny plan makes alot of sense. maybe i am underestimating the sus and winny. i know that sus isn't the best choice..but i already had it and thought i might get some sort of benefit..as i have been injured and my watts are way down..so i am looking for some strength among other benefits...recovery being important also..as i work a job as well and do not get to lounge for a few hours a day. i guess in summary.."assumption is the lowest form of knowledge"
ok...the deca and winny plan makes alot of sense. maybe i am underestimating the sus and winny. i know that sus isn't the best choice..but i already had it and thought i might get some sort of benefit..as i have been injured and my watts are way down..so i am looking for some strength among other benefits...recovery being important also..as i work a job as well and do not get to lounge for a few hours a day. i guess in summary.."assumption is the lowest form of knowledge"
fhg43
New member
Re: oneradtec
A few things to be weary of:
1) Deca has a long detection time-so if you could be tested this is a poor choice-but I think you said you probably would NOT be tested-Correct?
2) Winny could cause some mild joint pain-however if you can take the Deca that should help ease the pain-
3) You will need something post cycle to help restart normal testes functions and you sex drive will drop off big time with the Deca
My thoughts-Good luck and remeber to train hard
FHG
oneradtec said:
A few things to be weary of:
1) Deca has a long detection time-so if you could be tested this is a poor choice-but I think you said you probably would NOT be tested-Correct?
2) Winny could cause some mild joint pain-however if you can take the Deca that should help ease the pain-
3) You will need something post cycle to help restart normal testes functions and you sex drive will drop off big time with the Deca
My thoughts-Good luck and remeber to train hard
FHG
oneradtech - winny gave me bad cramps. I heard this from others as well. Go with primo or anavar if you haven't already bought the other stuff.
rider - sounds like your just flat right now - get some rest. Take some time off your bike. Like 4 days and see how you feel. I'm feeling a little off right now as well from a lot of racing and my form has plateaued somewhat. Need a mental break this week. The b12 is fine at 1000mgs a week. Your body can only use so much and the rest is pissed out. I did an iron injection last week and it hurt like a bitch! My glute was sore all weekend! I had a metalic taste in my mouth all that day after I did it as well.
rider - sounds like your just flat right now - get some rest. Take some time off your bike. Like 4 days and see how you feel. I'm feeling a little off right now as well from a lot of racing and my form has plateaued somewhat. Need a mental break this week. The b12 is fine at 1000mgs a week. Your body can only use so much and the rest is pissed out. I did an iron injection last week and it hurt like a bitch! My glute was sore all weekend! I had a metalic taste in my mouth all that day after I did it as well.
roadkill- a buddy of mine acutally has some iron injects, Im not sure how much is in them but he said he'd hook me up. Think itd be a good idea? and would only using 1 help? im not so sure I can get more. Im starting to feel a little better on the bike now, took the last 2 days pretty easy just riding between 50-60k... i think some of my problem was mental as well, I just moved out of my house yesterday so hopefully the new training roads and new training partners will help. Thanks for your help.
rider
rider
Rider - why don't you get some blood work done so you know where your at. Call your doctor and tell him your suffering from fatigue and you want to get a blood test to see what's up. Get your iron levels tested, hematocrit, red blood cell count, get testosterone and dhea as well. Then you'll now what's going on. It will also be a good thing to get another blood test when your feeling good so you can compare the two.
draco-
I acutally dont live in so. cal, I just train there for the winter. Im from the east coast which is where I am now. What USCF championships are in cali? I know elite road nats are in Nashville. Either way, im not familiar w/ the course but FHG lives in so cal. so maybe ask him. Regards
rider
I acutally dont live in so. cal, I just train there for the winter. Im from the east coast which is where I am now. What USCF championships are in cali? I know elite road nats are in Nashville. Either way, im not familiar w/ the course but FHG lives in so cal. so maybe ask him. Regards
rider
rider,
sorry about that, for some reason I thought you lived in Ca. Anyway its just the uscf state rr champs. Not too big a deal, but I'll be there.
Let me ask you something, I just upgraded from 3 to 2. Out here a lot of the races are 2,1 pro combined. Well, I've been getting dropped on some of the climbs, By the time I chase back on, I'm either too knackered or too far back to put myself in contention for a top ten and end up finishing w/ the pack. I was wondering if you had any advice as to improving my climbing. ( the climbs out here aren't very long, either rollers or short and very steep.
Thanks a bunch, draco
sorry about that, for some reason I thought you lived in Ca. Anyway its just the uscf state rr champs. Not too big a deal, but I'll be there.
Let me ask you something, I just upgraded from 3 to 2. Out here a lot of the races are 2,1 pro combined. Well, I've been getting dropped on some of the climbs, By the time I chase back on, I'm either too knackered or too far back to put myself in contention for a top ten and end up finishing w/ the pack. I was wondering if you had any advice as to improving my climbing. ( the climbs out here aren't very long, either rollers or short and very steep.
Thanks a bunch, draco
Losing weight if you are over 6-8%body fat and gaining power will improve your climbing. For training 10 minute efforts at 5 - 10 beats below anarobic threshold; some with 90+ cadence, and some at 60- cadence. You don't need to go crazy with the training for improvement. The climbing will come with experience and weight loss. Try and position yourself at the front of the bunch so you can drift back and still reamain in the group over the top. Don't tense up before the climbs. Good Luck.
fhg43
New member
road kill said:
The current school of thought is train just below your threshold for extended periods of time to improve ability to operate above and at threshold AND to raise your threshold. Training over your LT is difficult to recover from and many coaches now think the same results can be derived from less intense training.
Road kill's info is perfect. I used to live in the flatlands, but when I moved to Boulder and then Cali I learned how to climb.
FHG
burn-out
Hey all,
long time no post... I've been racing all spring and for the past 2 weeks I don''t even want to look at my bike. I'm scared I'll never touch it again. I had a good spring though, several good results in some local races and I actually finished athens when it's not really my forte` and I was out of shape a little too. This is the first time ever in my five years of racing I've ever been burnt to the crisp like this without being injured. I feel really lethargic too, but I haven't been training too much at all and the heat really hasn't given me too much shit. I'm getting ready to start a clen cycle to see if that gives me some motivation... We'll see.
Rolfo
Hey all,
long time no post... I've been racing all spring and for the past 2 weeks I don''t even want to look at my bike. I'm scared I'll never touch it again. I had a good spring though, several good results in some local races and I actually finished athens when it's not really my forte` and I was out of shape a little too. This is the first time ever in my five years of racing I've ever been burnt to the crisp like this without being injured. I feel really lethargic too, but I haven't been training too much at all and the heat really hasn't given me too much shit. I'm getting ready to start a clen cycle to see if that gives me some motivation... We'll see.
Rolfo
TREN SUCKS FOR ATHLETES!
You guys are gonna be fucked in the mountains on fina. You'll pump up so bad you'll have to get off your bike and just stand there for 10+ minutes till you can bend your legs again. Not too mention the chronic fatigue feeling. And the fact your bodywieght will go up disproportionately to your strength. And my heart rate climbs ridiculously quick on the stuff and stays elevated for extended periods. It's horrible.
I just finished an 18 week test/winny cycle. Worked great. I added tren for 2 weeks, my second attempt with it, and put on 6 lbs in 3 weeks with what was supposed to be a kcal deficit.
DONT USE FINA......EVER
youve been warned.
You guys are gonna be fucked in the mountains on fina. You'll pump up so bad you'll have to get off your bike and just stand there for 10+ minutes till you can bend your legs again. Not too mention the chronic fatigue feeling. And the fact your bodywieght will go up disproportionately to your strength. And my heart rate climbs ridiculously quick on the stuff and stays elevated for extended periods. It's horrible.
I just finished an 18 week test/winny cycle. Worked great. I added tren for 2 weeks, my second attempt with it, and put on 6 lbs in 3 weeks with what was supposed to be a kcal deficit.
DONT USE FINA......EVER
youve been warned.
here's some info!!!!!!!
Alternatively, renal blocking agents were sought out. The premise is simple enough: If you can’t urinate the conjugates and other metabolites of AAS out of your system, then you can’t get caught. Probenecid was the most common offender in this category of agents. It retards the excretion of a variety of drugs, including AAS. Athletes taking masking agents could continue taking AAS closer to competition before discontinuing their use and still pass the drug tests. Once it was realized that athletes were using probenecid and related agents, these drugs were added to the banned substance list.
Alternatively, renal blocking agents were sought out. The premise is simple enough: If you can’t urinate the conjugates and other metabolites of AAS out of your system, then you can’t get caught. Probenecid was the most common offender in this category of agents. It retards the excretion of a variety of drugs, including AAS. Athletes taking masking agents could continue taking AAS closer to competition before discontinuing their use and still pass the drug tests. Once it was realized that athletes were using probenecid and related agents, these drugs were added to the banned substance list.
fhg43
New member
re: oops bought the wrong stuff Giancarlo and I got caught!!
In case anyone was wondering if their EPO was fake, check out the link below:
http://www.amgen.com/news/news02/release020506.html
Hopefully this will keep anybody from buying vials of saline solution like Dario Frigo. hehehehe
FHG
In case anyone was wondering if their EPO was fake, check out the link below:
http://www.amgen.com/news/news02/release020506.html
Hopefully this will keep anybody from buying vials of saline solution like Dario Frigo. hehehehe
FHG
hey guys,
The states RR this year suprised me. The race was like 110 miles and the course was hard. The climbs were tough, which everybody expected ,but the winds were brutal, and actually played a bigger part in the outcome than I expected.
There were attacks from the gun. A group got away, and the field got shredded. Webcor and Team Zombies did a really good job, and due to the winds and other factors, the group stayed away. Needless to say, I missed the break ( I was sure it wasn't going to stay away. Boy, was I wrong!!!)
Thats probably a little more than you were lookin for. Sorry.
Overall, it was a really fun race and I had a blast. I will try to avenge my loss in the seven race CAL CUP series in august. Draco
The states RR this year suprised me. The race was like 110 miles and the course was hard. The climbs were tough, which everybody expected ,but the winds were brutal, and actually played a bigger part in the outcome than I expected.
There were attacks from the gun. A group got away, and the field got shredded. Webcor and Team Zombies did a really good job, and due to the winds and other factors, the group stayed away. Needless to say, I missed the break ( I was sure it wasn't going to stay away. Boy, was I wrong!!!)
Thats probably a little more than you were lookin for. Sorry.
Overall, it was a really fun race and I had a blast. I will try to avenge my loss in the seven race CAL CUP series in august. Draco
Endurance Supps
Inositol hexakisphosphate acts as al allosteric protein modifier of hemoglobin very similar to 2,3 diphosphoglycerate (2,3 DPG). What this means is that it lowers hemoglobins affinity for oxygen once it has been oxygenated. this results in an increased release of oxygen to working tissues. At any given moment only about 25% of the oxygen bound to hemoglobin is released to tissues. There is a huge untapped reserve of oxygen that is waiting to be used. this is where allosteric modifiers can be very useful to an athlete. The way this would be used would be to take a gram or maybe two by IM injetion of pure inositol hexakisphosphate 3 to 4 hours before competition.
J Inorg Biochem 1993 Jun;50(4):263-72 Related Articles, Books, LinkOut
Cooperative effect of inositol hexakisphosphate, bezafibrate, and clofibric acid on the spectroscopic properties of the nitric oxide derivative of ferrous human hemoglobin.
Ascenzi P, Bertollini A, Coletta M, Desideri A, Giardina B, Polizio F, Santucci R, Scatena R, Amiconi G.
Department of Pharmaceutical Chemistry and Technology, University of Turin, Italy.
The cooperative effect of inositol hexakisphosphate (IHP), bezafibrate (BZF), and clofibric acid (CFA) on the spectroscopic (EPR and absorbance) properties of the nitric oxide derivative of ferrous human hemoglobin (HbNO) has been investigated quantitatively. In the presence of IHP, BZF, and CFA, the X-band EPR spectra and the absorption spectra in the Soret region of HbNO display the same basic characteristics described in the presence of 2,3-diphosphoglycerate (2,3-DPG), which have been attributed to a low affinity conformation of the tetramer. Addition to HbNO of two allosteric effectors together (such as IHP and BZF, or IHP and CFA) further stabilizes the low affinity conformation of the ligated hemoprotein (i.e., HbNO). Moreover, in the presence of saturating amounts of IHP, the affinity of BZF and CFA for HbNO increases by about fifteenfold. Likewise, in the presence of both IHP and BZF, as well as in IHP and CFA, the oxygen affinity for ferrous human hemoglobin (Hb) is reduced with respect to that observed in the presence of IHP, BZF, or CFA alone, which in turn is lower than that reported in the absence of any allosteric effector. All the data were obtained at pH 7.0 (in 1.0 x 10(-1) M N-[2-hydroxyethyl]-piperazine-N'-[2-ethanesulfonic acid]/NaOH buffer system plus 1.0 x 10(-1) M NaCl), as well as at 100 K and/or 20 degrees C. The results here reported represent clearcut evidence for the cooperative and specific (i.e., functionally relevant) binding of IHP, BZF, and CFA to Hb.
Inositol hexakisphosphate acts as al allosteric protein modifier of hemoglobin very similar to 2,3 diphosphoglycerate (2,3 DPG). What this means is that it lowers hemoglobins affinity for oxygen once it has been oxygenated. this results in an increased release of oxygen to working tissues. At any given moment only about 25% of the oxygen bound to hemoglobin is released to tissues. There is a huge untapped reserve of oxygen that is waiting to be used. this is where allosteric modifiers can be very useful to an athlete. The way this would be used would be to take a gram or maybe two by IM injetion of pure inositol hexakisphosphate 3 to 4 hours before competition.
J Inorg Biochem 1993 Jun;50(4):263-72 Related Articles, Books, LinkOut
Cooperative effect of inositol hexakisphosphate, bezafibrate, and clofibric acid on the spectroscopic properties of the nitric oxide derivative of ferrous human hemoglobin.
Ascenzi P, Bertollini A, Coletta M, Desideri A, Giardina B, Polizio F, Santucci R, Scatena R, Amiconi G.
Department of Pharmaceutical Chemistry and Technology, University of Turin, Italy.
The cooperative effect of inositol hexakisphosphate (IHP), bezafibrate (BZF), and clofibric acid (CFA) on the spectroscopic (EPR and absorbance) properties of the nitric oxide derivative of ferrous human hemoglobin (HbNO) has been investigated quantitatively. In the presence of IHP, BZF, and CFA, the X-band EPR spectra and the absorption spectra in the Soret region of HbNO display the same basic characteristics described in the presence of 2,3-diphosphoglycerate (2,3-DPG), which have been attributed to a low affinity conformation of the tetramer. Addition to HbNO of two allosteric effectors together (such as IHP and BZF, or IHP and CFA) further stabilizes the low affinity conformation of the ligated hemoprotein (i.e., HbNO). Moreover, in the presence of saturating amounts of IHP, the affinity of BZF and CFA for HbNO increases by about fifteenfold. Likewise, in the presence of both IHP and BZF, as well as in IHP and CFA, the oxygen affinity for ferrous human hemoglobin (Hb) is reduced with respect to that observed in the presence of IHP, BZF, or CFA alone, which in turn is lower than that reported in the absence of any allosteric effector. All the data were obtained at pH 7.0 (in 1.0 x 10(-1) M N-[2-hydroxyethyl]-piperazine-N'-[2-ethanesulfonic acid]/NaOH buffer system plus 1.0 x 10(-1) M NaCl), as well as at 100 K and/or 20 degrees C. The results here reported represent clearcut evidence for the cooperative and specific (i.e., functionally relevant) binding of IHP, BZF, and CFA to Hb.
Dichloroacetate
Int J Sports Med 1995 Apr;16(3):167-71
The effects of dichloroacetate on lactate accumulation and endurance in an exercising rat model.
Durkot MJ, De Garavilla L, Caretti D, Francesconi R.
U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA.
Abstract
Metabolism 1981 Jun;30(6):590-5
Dichloroacetate: effects on exercise endurance in untrained rats.
Schneider SH, Komanicky PM, Goodman MN, Ruderman NB.
Abstract
Am J Physiol 1998 Feb;274(2 Pt 1):E377-80
Muscle acetyl group availability is a major determinant of oxygen deficit in humans during submaximal exercise.
Timmons JA, Gustafsson T, Sundberg CJ, Jansson E, Greenhaff PL.
Department of Physiology and Pharmacology, University Medical School, Queen's Medical Centre, Nottingham, United Kingdom.
Abstract
Pflugers Arch 1993 May;423(3-4):251-4 Related Articles, Books, LinkOut
Effects of dichloroacetate on exercise performance in healthy volunteers.
Ludvik B, Mayer G, Stifter S, Putz D, Barnas U, Graf H.
Department of Nephrology, University of Vienna, Austria
Abstract
There are many more studies to support DCA as an aid to endurance athletes.
Int J Sports Med 1995 Apr;16(3):167-71
The effects of dichloroacetate on lactate accumulation and endurance in an exercising rat model.
Durkot MJ, De Garavilla L, Caretti D, Francesconi R.
U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA.
Abstract
Metabolism 1981 Jun;30(6):590-5
Dichloroacetate: effects on exercise endurance in untrained rats.
Schneider SH, Komanicky PM, Goodman MN, Ruderman NB.
Abstract
Am J Physiol 1998 Feb;274(2 Pt 1):E377-80
Muscle acetyl group availability is a major determinant of oxygen deficit in humans during submaximal exercise.
Timmons JA, Gustafsson T, Sundberg CJ, Jansson E, Greenhaff PL.
Department of Physiology and Pharmacology, University Medical School, Queen's Medical Centre, Nottingham, United Kingdom.
Abstract
Pflugers Arch 1993 May;423(3-4):251-4 Related Articles, Books, LinkOut
Effects of dichloroacetate on exercise performance in healthy volunteers.
Ludvik B, Mayer G, Stifter S, Putz D, Barnas U, Graf H.
Department of Nephrology, University of Vienna, Austria
Abstract
There are many more studies to support DCA as an aid to endurance athletes.
gettinhuge
New member
1/2 Ironman...
Need help on AS cycle. I have a 1/2 ironman 29 september. Please e-mail me...
Thanks,
M
Need help on AS cycle. I have a 1/2 ironman 29 september. Please e-mail me...
Thanks,
M
vinpocetine: possible ergogenic aid?
: Arzneimittelforschung 1990 Jun;40(6):640-3 Related Articles, Books, LinkOut
Effect of vinpocetine on oxygen release of hemoglobin and erythrocyte organic polyphosphate concentrations in patients with vascular dementia of the Binswanger type.
Tohgi H, Sasaki K, Chiba K, Nozaki Y.
Department of Neurology, Iwate Medical University, Japan.
Oxygen affinity of hemoglobin, erythrocyte 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP) concentrations were compared before and after oral administration of vinpocetine (TCV-3B) (15 mg/d), a primarily vasodilating agent, for three weeks in eight patients with vascular dementia of the Biswanger type which is characterized by diffuse myelin pallor and multiple lacunes in the cerebral white matter. After vinpocetine administration, oxygen affinity of hemoglobin (P50) was significantly increased (26.5 +/- 0.55 to 27.6 +/- 0.62 mmHg; mean and standard deviation, p less than 0.05), red blood cell (RBC) ATP concentrations were significantly increased (846 +/- 168 to 1,158 +/- 130 mumol/l RBC, p less than 0.05), while DPG concentrations were unaltered (4.46 +/- 0.48 to 4.59 +/- 0.57 mmol/l RBC). There was a significant positive correlation between the increase of P50 and the increase of erythrocyte ATP concentrations (r = 0.67, p less than 0.05). The effect of vinpocetine of enhancing oxygen release of hemoglobin may offer an additional benefit to its primary vasodilating action in the treatment of vascular dementia of the Binswanger type due to chronic ischemia.
: Arzneimittelforschung 1990 Jun;40(6):640-3 Related Articles, Books, LinkOut
Effect of vinpocetine on oxygen release of hemoglobin and erythrocyte organic polyphosphate concentrations in patients with vascular dementia of the Binswanger type.
Tohgi H, Sasaki K, Chiba K, Nozaki Y.
Department of Neurology, Iwate Medical University, Japan.
Oxygen affinity of hemoglobin, erythrocyte 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP) concentrations were compared before and after oral administration of vinpocetine (TCV-3B) (15 mg/d), a primarily vasodilating agent, for three weeks in eight patients with vascular dementia of the Biswanger type which is characterized by diffuse myelin pallor and multiple lacunes in the cerebral white matter. After vinpocetine administration, oxygen affinity of hemoglobin (P50) was significantly increased (26.5 +/- 0.55 to 27.6 +/- 0.62 mmHg; mean and standard deviation, p less than 0.05), red blood cell (RBC) ATP concentrations were significantly increased (846 +/- 168 to 1,158 +/- 130 mumol/l RBC, p less than 0.05), while DPG concentrations were unaltered (4.46 +/- 0.48 to 4.59 +/- 0.57 mmol/l RBC). There was a significant positive correlation between the increase of P50 and the increase of erythrocyte ATP concentrations (r = 0.67, p less than 0.05). The effect of vinpocetine of enhancing oxygen release of hemoglobin may offer an additional benefit to its primary vasodilating action in the treatment of vascular dementia of the Binswanger type due to chronic ischemia.
ProSportsCar
New member
Endurance Athletes out thar?
Hey,
All this talk of adding wheaties to TriGuys Meals and no one has posted any times!
I have been doing tri's for over 12 years. You can do all the fun stuff you want but without good training you are just another one to be passed.
What is your 10K split after bike? I usually average about 35:30.
I ride with some roadies with huge (enhanced ) legs but I say good bye to the fatboys when the big hills come.
Swim Bike Run!
Hey,
All this talk of adding wheaties to TriGuys Meals and no one has posted any times!
I have been doing tri's for over 12 years. You can do all the fun stuff you want but without good training you are just another one to be passed.
What is your 10K split after bike? I usually average about 35:30.
I ride with some roadies with huge (enhanced ) legs but I say good bye to the fatboys when the big hills come.
Swim Bike Run!
borderline elite marathon runner
I have a friend who has been running marathons for at least 5 years and is looking to get an Olympic Trials qualifying mark (2:20). At this time he is all natural (not even ephedrine, clenbuterol, b-12, not to even mention anabolics or EPO) and has a PR of around 2:28. He says that he is ready to do what it takes to get to the next level and asked me for some advice as far as what to take. I myself used to be a distance runner and a cyclist but have no idea what one would use as a marathoner outside of EPO which may be to risky for someone in his position. Any advice?
I have a friend who has been running marathons for at least 5 years and is looking to get an Olympic Trials qualifying mark (2:20). At this time he is all natural (not even ephedrine, clenbuterol, b-12, not to even mention anabolics or EPO) and has a PR of around 2:28. He says that he is ready to do what it takes to get to the next level and asked me for some advice as far as what to take. I myself used to be a distance runner and a cyclist but have no idea what one would use as a marathoner outside of EPO which may be to risky for someone in his position. Any advice?
fhg43
New member
Re: borderline elite marathon runner
I think your last statement is spot on. For endurance athletes there are few "easy to use" performance enhancers that make a difference. The problem with AAS for distance runners and cyclists is that they will cause weight gain. EPO can be life threatening if used improperly. I'd say the best things to try are ephedrine and caffeine and some b-12/iron. Caffeine is typically legal and has great endurance enhancing benefits. Ephedrine is banned but is helpful. B-12/iron have been working great for me. I had been feeling slow and tired and I started taking b-12 injections and iron supplements and I started to feel better and ride better. I haven't done AAS or EPO, but I know they work.
Your buddy and I are in the same boat: elite athletes on the edge. I know that I will get tested at certain races and I don't want to juice when I know I tweak my training and diet more. I know there is plenty of room for improvement in those fields so I'll explore that. Like many guys I'll look for good legal supps or borderline stuff. Your friend is probably frustrated and I can empathize. You can give him my email address. I could talk to him about legal options to pursue like diet/training/etc...I found that seeing a nutritionist, loosing a few pounds, and resting more helped a lot. Plus I quit stressing over getting results and tried to enjoy my sport more and then the results flowed in!!
FHG
roidzilla said:
I think your last statement is spot on. For endurance athletes there are few "easy to use" performance enhancers that make a difference. The problem with AAS for distance runners and cyclists is that they will cause weight gain. EPO can be life threatening if used improperly. I'd say the best things to try are ephedrine and caffeine and some b-12/iron. Caffeine is typically legal and has great endurance enhancing benefits. Ephedrine is banned but is helpful. B-12/iron have been working great for me. I had been feeling slow and tired and I started taking b-12 injections and iron supplements and I started to feel better and ride better. I haven't done AAS or EPO, but I know they work.
Your buddy and I are in the same boat: elite athletes on the edge. I know that I will get tested at certain races and I don't want to juice when I know I tweak my training and diet more. I know there is plenty of room for improvement in those fields so I'll explore that. Like many guys I'll look for good legal supps or borderline stuff. Your friend is probably frustrated and I can empathize. You can give him my email address. I could talk to him about legal options to pursue like diet/training/etc...I found that seeing a nutritionist, loosing a few pounds, and resting more helped a lot. Plus I quit stressing over getting results and tried to enjoy my sport more and then the results flowed in!!
FHG
Thanks for your comments fhg43 and I have passed them along to him along with your email address. I sincerely doubt that his weight is an issue right now since he only weighs 114lbs. Do you really think that AS such as EQ/Primo would not help (as long as he did watch his calorie intake so as not to gain weight) raise his hemocrit levels and speed his recovery? Also what about testosterones, winny, and anavar would they be of no use (again providing that he maintain his current weight?). Testing is not an issue right now (he has never been tested and most likely won't unless he comes top 3 in a major marathon which is way out of reach right now).
CAN I BUY IN BULK?????????????
DynEPO: A new form of EPO undetectable by the UCI's urine test
In the ongoing battle against doping in sport, it seems there's always a new substance on the horizon that the detection bodies don't know about or can't detect. The imminent release of DynEPO, a new version of the commonly-used EPO will require another round of modifications to the current testing regime, as Anthony Tan writes.
Bo Hamburger, the first rider accused of EPO use after a urine test
Photo: © AFP
A leading sports scientist has claimed that DynEPO - the latest drug approved by the European Union to fight kidney disease - poses a very serious threat to the cycling community. Although not wishing to be named for political reasons, the potential danger to endurance athletes, particularly within the sport of cycling, is clearly apparent:
"DynEPO is now much closer to the real thing - it looks just like normal human EPO, which means that even though it is produced via recombinant DNA techniques, the final product would not be detected by the urine test."
As the name implies, DynEPO (epoetin delta) is a variant of human erythropoietin - a hormone that stimulates "erythropoiesis", the natural production of red blood cells in the body. DynEPO has been designed for the treatment of anaemia related to chronic renal (kidney) disease - specifically for patients receiving or about to undergo dialysis, to elevate and maintain their red blood cell production.
"In theory, it would be undectectable by the urine test"
The claim that DynEPO will be undectable by the urine test developed by the French national doping laboratories in Châtenay-Malabry is of considerable concern, as the urine test has been the standard protocol for detection of EPO and its variants (such as NESP) since April 1 last year.
The good news is that the UCI is already aware of DynEPO. When Cyclingnews questioned Dr Mario Zorzoli, the high-profile Chief Medical Officer for the UCI, his response was:
"If you're talking about DynEPO, we're already on this one."
The bad news is that the UCI confirmed the urine test's inability to detect DynEPO:
"From what we have heard, DynEPO is produced naturally by human cells, not animal cells, so in theory, it would be undectectable by the urine test."
Legal wrangling delays global release
On March 26, 2002, the European Commission granted Transkaryotic Therapies (TKT), the biopharmaceutical company that has developed DynEPO, marketing authorisation for the fifteen countries of the European Union.
In a collaborative agreement, Transkaryotic Therapies will engage the services of Aventis Pharma, the pharmaceutical company of Aventis Worldwide, to propagate and market DynEPO for full-scale commercial production.
However TKT and Aventis are currently involved in litigation with both Amgen Inc and Kirin-Amgen Inc relating to the commercial production and sale of DynEPO.
California based Amgen is the world's largest biotechnology company, and are the proprietary owners for Epogen (Epoetin Alfa) - a substance much the same as Erythropoietin (EPO) - and Aranesp (NESP). Amgen developed EPO, Epogen and NESP to enable cancer and kidney disease patients to fight anemia.
Last year, the U.S. District Court for the District of Massachusetts concluded that DynEPO infringed several claims of patents asserted by Amgen, and the High Court of Justice in the United Kingdom ruled that DynEPO infringed one claim of a patent asserted by Kirin-Amgen.
In both the U.S. and U.K., TKT and Aventis have filed appeals with decisions expected by 2003. With appeals pending in both the U.S. and U.K., a launch of DynEPO has not yet been planned.
What is the difference between normal EPO and DynEPO?
EPO is a peptide hormone, which means it is composed of a relatively short sequence of amino acids, the building blocks of proteins - produced in the body to stimulate the production of red blood cells. Commercially-produced EPO is made using recombinant DNA techniques, and such is known as r-HuEPO (recombinant human EPO).
When human EPO is produced in this way using non-human cell lines (the most common being hamster ovary cells), it ends up with slightly different characteristics than the EPO produced by human cells. It still has the same effect, but the amount of sugars attached to the hormone vary.
As a result, r-HuEPO has a slightly different charge and weight than EPO produced naturally within the body. The urine test can detect these differences in charge and weight, and can therefore determine if someone has recently injected EPO (within two to four days).
In contrast, DynEPO, although commerically-produced using similar DNA techniques as r-HuEPO, is now sufficiently similar to the "real thing". The similarity being that DynEPO, like human erythropoietin, is produced using human cell lines, not via animal cells. This similarity will, in theory, make DynEPO indistinguishable from naturally produced EPO using the current urine test.
What about blood testing for EPO?
The blood testing procedure that was used in conjunction with the urine test at the Sydney Olympics and more recently, at the 2002 Winter Olympic Games in Salt Lake City, does not directly detect EPO use, but instead evaluates abnormalities based on the effects of EPO use over time.
And according to the UCI, this blood test could still detect DynEPO. This more extensive, more costly test differs from the current blood test used by the UCI, which is used as a "health check" that only enables a rider's haematological profile to be evaluated - which include one's haematocrit level and level of reticulocytes (young red blood cells).
Because all forms of EPO cause abnormally fast RBC production rates, the enhanced time-based blood test would still identify that something fishy was going on if DynEPO was the substance being used.
The UCI is aware of the limitations of the current blood test and recognises that its best chance of detecting EPO will be during the longer stage races. For the major one day races, the UCI's strategy consists of more frequent blood and urine test in the weeks preceding the race.
Urine test only partially effective, DynEPO or no DynEPO
Urine tests can only detect EPO use two to four days after injection. EPO is usually administered three to six weeks prior to competition (so that new red blood cells can have enough time to grow and mature); so urine testing alone, although accurate, is only partially effective.
Furthermore, current blood testing procedures are limited to a portion of the participants based on the available resources. For example, in a UCI-sanctioned one day race, blood tests are conducted on approximately 60 riders as part of the mandatory health checks. Assuming there are 180 participants and a particular athlete is using EPO, there is roughly a two in three chance of not being blood tested.
It is important to remember that the only riders who are tested for EPO use by the urine test are those that have haematocrit levels above the set limit or display anomalies considered unusual based on previous blood tests (as well as the race winner and two random draws). Therefore if some riders were using DynEPO a few days before a race and kept their haematocrit levels under the UCI limit, they would not be caught out, even if subjected to the urine test.
However Dr Mario Zorzoli, Chief Medical Officer at the UCI, has not altogether dismissed the urine test's inability to pick up DynEPO just yet:
"Some medical experts have told us that DynEPO, although produced naturally via human cells, is not produced by the kidney cells - which is where natural human EPO is produced. So based on this distinction, we may still be able to pick up use of DynEPO via the urine test."
Is it money stopping the UCI introducing more blood testing?
One of the few riders to admit EPO use, Chiotti gave his1996 MTB world's gold medal to Frischknecht
Photo: © AFP Presently the UCI conducts blood tests before races only as a method of selection for the urine test, so does it come down to a question of money?
Although it has been criticised for a lack of spending in the past, the UCI claims that it now invests nearly 10 percent of own annual budget (equal to 4.5 million euros in 2001) in the fight against doping. In addition, the various national federations contribute around 1.8 million euros each year to combat doping.
Enrico Carpani, Press Officer for the UCI, gave a somewhat vague answer when asked if the adoption of more blood tests would be worthwhile:
"We use blood tests throughout many other UCI races, but for us, it is not compulsory. The urine test is enough to detect EPO and NESP. Like Mr Verbruggen says, it is partly to do with money, but it also has something to do with logistics."
Logistics is definitely an issue: Bo Hamburger, the first rider to be tested positive for EPO use from the urine test was tested during an out-of-competition urine test, the day he competed in Fleche Wallonne on April 18, 2001.
Dr Mario Zorzoli supported his colleague Carpani on this issue:
"In fact, we conduct blood testing more often than most people think - riders are subject to both blood and urine testing at nearly all major UCI races.
"By the end of each Grand Tour, we manage to test all riders at least once and many twice. Before the Giro d'Italia, the UCI had already conducted around 2,300 blood tests."
So is it a question of reliability?
A blood test developed by the scientists at the Australian Institute of Sport has been used during the last two Olympic Games, and was instrumental in detecting the use of NESP (novel erythropoiesis stimulating protein or darbepoietin alpha, another synthetic form of EPO) by several cross-country skiers at Salt Lake City. However a quirk in the IOC rules meant they were allowed to keep their medals before subsequent testing, and were only stripped of medals won after the urine tests were also confirmed positive.
Capacity has been cited as an issue on a number of occasions. Only 10 to 15 athletes underwent the blood test for NESP at the Winter Olympics, because (according to the IOC) of the limited capacity of the laboratories - for example, over 30 hours of lab time were required to perform tests on the blood of Spanish cross-country skier Johann Muehlegg before he was declared positive.
"Too complicated, too hard, too expensive"
Hein Verbruggen
Photo: © AFP In November 2000, UCI President Hein Verbruggen was questioned over the events surrounding the Festina doping scandal. He said that the UCI "did not feel responsible if a rider is doping, or a soigneur gives them drugs."
"I am convinced that there is a small group of hardened cheaters, a much larger group that feels it's OK to take things not in excess, a group that takes legal drugs and finally, a few who do not take anything," he added. "The rider has the choice – nobody decides for him."
And just a few weeks later, Verbruggen was equally frank about the introduction of blood testing during major tours: "To use a (compulsory) blood and urine test for a cycle race such as the Tour de France would be too complicated, too hard, and too expensive."
Why create a new EPO?
If standard EPO is an effective therapy, why are pharmacological companies creating new forms? Once again, it's a question of money – not a lack of it, but everyone wanting a slice of the protein therapeutics pie that's worth over US$20 billion and growing.
Standard EPO has been in use since the 1970s to treat chronic renal failure, and the biotechnology firms that produce EPO have sought and obtained patent protection covering many of the genetic engineering techniques they use. Given the size of the market for protein therapeutics, those companies with a patent in place effectively raise the barriers of entry and at the same time, substantially increase their wealth.
A lesser reason is that conventional genetic engineering techniques for protein production may face technical limitations arising from the need to first clone the gene of interest. For certain proteins, this step adds to development times, increases costs and is technically challenging. Technical difficulties may also arise from the use of non-human production cell lines, which may result in the production of proteins that have therapeutically significant differences from those naturally produced by the cells of the human body.
Furthermore, production processes based on conventional genetic engineering may not have incorporated recent advances compared to processes originally developed over a decade ago.
In an effort to overcome these commercial barriers and technical limitations, Transkaryotic Therapies (TKT) has developed "gene activation" technology for the production of therapeutic proteins that does not rely on the manipulation of cloned genes.
Using its proprietary technology, TKT has succeeded in producing therapeutic proteins in human cells by bypassing regulatory DNA sequences set in the "off position" with regulatory DNA sequences set in the "on position" in order to activate the gene of interest (click here for a diagrammatic explanation).
Gene targeting is a technology by which DNA fragments can be "cut and pasted" precisely at pre-selected locations within the cell's genome. Gene targeting can be thought of as molecular surgery, with the surgical tools literally functioning at the molecular level.
Via gene targeting, cells have the capacity to align two homologous DNA sequences (two sequences that are quite similar) and exchange one with the other - allowing the cell to exchange the new active sequences in place of the old inactive ones. The new sequences must be introduced precisely in order to allow the proper initiation of gene expression.
The ability to detect use of these cloned cells will be the next challenge for the detection agencies.
DynEPO: A new form of EPO undetectable by the UCI's urine test
In the ongoing battle against doping in sport, it seems there's always a new substance on the horizon that the detection bodies don't know about or can't detect. The imminent release of DynEPO, a new version of the commonly-used EPO will require another round of modifications to the current testing regime, as Anthony Tan writes.
Bo Hamburger, the first rider accused of EPO use after a urine test
Photo: © AFP
A leading sports scientist has claimed that DynEPO - the latest drug approved by the European Union to fight kidney disease - poses a very serious threat to the cycling community. Although not wishing to be named for political reasons, the potential danger to endurance athletes, particularly within the sport of cycling, is clearly apparent:
"DynEPO is now much closer to the real thing - it looks just like normal human EPO, which means that even though it is produced via recombinant DNA techniques, the final product would not be detected by the urine test."
As the name implies, DynEPO (epoetin delta) is a variant of human erythropoietin - a hormone that stimulates "erythropoiesis", the natural production of red blood cells in the body. DynEPO has been designed for the treatment of anaemia related to chronic renal (kidney) disease - specifically for patients receiving or about to undergo dialysis, to elevate and maintain their red blood cell production.
"In theory, it would be undectectable by the urine test"
The claim that DynEPO will be undectable by the urine test developed by the French national doping laboratories in Châtenay-Malabry is of considerable concern, as the urine test has been the standard protocol for detection of EPO and its variants (such as NESP) since April 1 last year.
The good news is that the UCI is already aware of DynEPO. When Cyclingnews questioned Dr Mario Zorzoli, the high-profile Chief Medical Officer for the UCI, his response was:
"If you're talking about DynEPO, we're already on this one."
The bad news is that the UCI confirmed the urine test's inability to detect DynEPO:
"From what we have heard, DynEPO is produced naturally by human cells, not animal cells, so in theory, it would be undectectable by the urine test."
Legal wrangling delays global release
On March 26, 2002, the European Commission granted Transkaryotic Therapies (TKT), the biopharmaceutical company that has developed DynEPO, marketing authorisation for the fifteen countries of the European Union.
In a collaborative agreement, Transkaryotic Therapies will engage the services of Aventis Pharma, the pharmaceutical company of Aventis Worldwide, to propagate and market DynEPO for full-scale commercial production.
However TKT and Aventis are currently involved in litigation with both Amgen Inc and Kirin-Amgen Inc relating to the commercial production and sale of DynEPO.
California based Amgen is the world's largest biotechnology company, and are the proprietary owners for Epogen (Epoetin Alfa) - a substance much the same as Erythropoietin (EPO) - and Aranesp (NESP). Amgen developed EPO, Epogen and NESP to enable cancer and kidney disease patients to fight anemia.
Last year, the U.S. District Court for the District of Massachusetts concluded that DynEPO infringed several claims of patents asserted by Amgen, and the High Court of Justice in the United Kingdom ruled that DynEPO infringed one claim of a patent asserted by Kirin-Amgen.
In both the U.S. and U.K., TKT and Aventis have filed appeals with decisions expected by 2003. With appeals pending in both the U.S. and U.K., a launch of DynEPO has not yet been planned.
What is the difference between normal EPO and DynEPO?
EPO is a peptide hormone, which means it is composed of a relatively short sequence of amino acids, the building blocks of proteins - produced in the body to stimulate the production of red blood cells. Commercially-produced EPO is made using recombinant DNA techniques, and such is known as r-HuEPO (recombinant human EPO).
When human EPO is produced in this way using non-human cell lines (the most common being hamster ovary cells), it ends up with slightly different characteristics than the EPO produced by human cells. It still has the same effect, but the amount of sugars attached to the hormone vary.
As a result, r-HuEPO has a slightly different charge and weight than EPO produced naturally within the body. The urine test can detect these differences in charge and weight, and can therefore determine if someone has recently injected EPO (within two to four days).
In contrast, DynEPO, although commerically-produced using similar DNA techniques as r-HuEPO, is now sufficiently similar to the "real thing". The similarity being that DynEPO, like human erythropoietin, is produced using human cell lines, not via animal cells. This similarity will, in theory, make DynEPO indistinguishable from naturally produced EPO using the current urine test.
What about blood testing for EPO?
The blood testing procedure that was used in conjunction with the urine test at the Sydney Olympics and more recently, at the 2002 Winter Olympic Games in Salt Lake City, does not directly detect EPO use, but instead evaluates abnormalities based on the effects of EPO use over time.
And according to the UCI, this blood test could still detect DynEPO. This more extensive, more costly test differs from the current blood test used by the UCI, which is used as a "health check" that only enables a rider's haematological profile to be evaluated - which include one's haematocrit level and level of reticulocytes (young red blood cells).
Because all forms of EPO cause abnormally fast RBC production rates, the enhanced time-based blood test would still identify that something fishy was going on if DynEPO was the substance being used.
The UCI is aware of the limitations of the current blood test and recognises that its best chance of detecting EPO will be during the longer stage races. For the major one day races, the UCI's strategy consists of more frequent blood and urine test in the weeks preceding the race.
Urine test only partially effective, DynEPO or no DynEPO
Urine tests can only detect EPO use two to four days after injection. EPO is usually administered three to six weeks prior to competition (so that new red blood cells can have enough time to grow and mature); so urine testing alone, although accurate, is only partially effective.
Furthermore, current blood testing procedures are limited to a portion of the participants based on the available resources. For example, in a UCI-sanctioned one day race, blood tests are conducted on approximately 60 riders as part of the mandatory health checks. Assuming there are 180 participants and a particular athlete is using EPO, there is roughly a two in three chance of not being blood tested.
It is important to remember that the only riders who are tested for EPO use by the urine test are those that have haematocrit levels above the set limit or display anomalies considered unusual based on previous blood tests (as well as the race winner and two random draws). Therefore if some riders were using DynEPO a few days before a race and kept their haematocrit levels under the UCI limit, they would not be caught out, even if subjected to the urine test.
However Dr Mario Zorzoli, Chief Medical Officer at the UCI, has not altogether dismissed the urine test's inability to pick up DynEPO just yet:
"Some medical experts have told us that DynEPO, although produced naturally via human cells, is not produced by the kidney cells - which is where natural human EPO is produced. So based on this distinction, we may still be able to pick up use of DynEPO via the urine test."
Is it money stopping the UCI introducing more blood testing?
One of the few riders to admit EPO use, Chiotti gave his1996 MTB world's gold medal to Frischknecht
Photo: © AFP Presently the UCI conducts blood tests before races only as a method of selection for the urine test, so does it come down to a question of money?
Although it has been criticised for a lack of spending in the past, the UCI claims that it now invests nearly 10 percent of own annual budget (equal to 4.5 million euros in 2001) in the fight against doping. In addition, the various national federations contribute around 1.8 million euros each year to combat doping.
Enrico Carpani, Press Officer for the UCI, gave a somewhat vague answer when asked if the adoption of more blood tests would be worthwhile:
"We use blood tests throughout many other UCI races, but for us, it is not compulsory. The urine test is enough to detect EPO and NESP. Like Mr Verbruggen says, it is partly to do with money, but it also has something to do with logistics."
Logistics is definitely an issue: Bo Hamburger, the first rider to be tested positive for EPO use from the urine test was tested during an out-of-competition urine test, the day he competed in Fleche Wallonne on April 18, 2001.
Dr Mario Zorzoli supported his colleague Carpani on this issue:
"In fact, we conduct blood testing more often than most people think - riders are subject to both blood and urine testing at nearly all major UCI races.
"By the end of each Grand Tour, we manage to test all riders at least once and many twice. Before the Giro d'Italia, the UCI had already conducted around 2,300 blood tests."
So is it a question of reliability?
A blood test developed by the scientists at the Australian Institute of Sport has been used during the last two Olympic Games, and was instrumental in detecting the use of NESP (novel erythropoiesis stimulating protein or darbepoietin alpha, another synthetic form of EPO) by several cross-country skiers at Salt Lake City. However a quirk in the IOC rules meant they were allowed to keep their medals before subsequent testing, and were only stripped of medals won after the urine tests were also confirmed positive.
Capacity has been cited as an issue on a number of occasions. Only 10 to 15 athletes underwent the blood test for NESP at the Winter Olympics, because (according to the IOC) of the limited capacity of the laboratories - for example, over 30 hours of lab time were required to perform tests on the blood of Spanish cross-country skier Johann Muehlegg before he was declared positive.
"Too complicated, too hard, too expensive"
Hein Verbruggen
Photo: © AFP In November 2000, UCI President Hein Verbruggen was questioned over the events surrounding the Festina doping scandal. He said that the UCI "did not feel responsible if a rider is doping, or a soigneur gives them drugs."
"I am convinced that there is a small group of hardened cheaters, a much larger group that feels it's OK to take things not in excess, a group that takes legal drugs and finally, a few who do not take anything," he added. "The rider has the choice – nobody decides for him."
And just a few weeks later, Verbruggen was equally frank about the introduction of blood testing during major tours: "To use a (compulsory) blood and urine test for a cycle race such as the Tour de France would be too complicated, too hard, and too expensive."
Why create a new EPO?
If standard EPO is an effective therapy, why are pharmacological companies creating new forms? Once again, it's a question of money – not a lack of it, but everyone wanting a slice of the protein therapeutics pie that's worth over US$20 billion and growing.
Standard EPO has been in use since the 1970s to treat chronic renal failure, and the biotechnology firms that produce EPO have sought and obtained patent protection covering many of the genetic engineering techniques they use. Given the size of the market for protein therapeutics, those companies with a patent in place effectively raise the barriers of entry and at the same time, substantially increase their wealth.
A lesser reason is that conventional genetic engineering techniques for protein production may face technical limitations arising from the need to first clone the gene of interest. For certain proteins, this step adds to development times, increases costs and is technically challenging. Technical difficulties may also arise from the use of non-human production cell lines, which may result in the production of proteins that have therapeutically significant differences from those naturally produced by the cells of the human body.
Furthermore, production processes based on conventional genetic engineering may not have incorporated recent advances compared to processes originally developed over a decade ago.
In an effort to overcome these commercial barriers and technical limitations, Transkaryotic Therapies (TKT) has developed "gene activation" technology for the production of therapeutic proteins that does not rely on the manipulation of cloned genes.
Using its proprietary technology, TKT has succeeded in producing therapeutic proteins in human cells by bypassing regulatory DNA sequences set in the "off position" with regulatory DNA sequences set in the "on position" in order to activate the gene of interest (click here for a diagrammatic explanation).
Gene targeting is a technology by which DNA fragments can be "cut and pasted" precisely at pre-selected locations within the cell's genome. Gene targeting can be thought of as molecular surgery, with the surgical tools literally functioning at the molecular level.
Via gene targeting, cells have the capacity to align two homologous DNA sequences (two sequences that are quite similar) and exchange one with the other - allowing the cell to exchange the new active sequences in place of the old inactive ones. The new sequences must be introduced precisely in order to allow the proper initiation of gene expression.
The ability to detect use of these cloned cells will be the next challenge for the detection agencies.
A
Animal
Guest
Ever thought of doing EPO? Do it safely
Do any of you guys think there is a market for a hematocrit tester costing around $100. Current prototypes are being tested and are accurate. If there is enough demand they can go into production immediately.
Do any of you guys think there is a market for a hematocrit tester costing around $100. Current prototypes are being tested and are accurate. If there is enough demand they can go into production immediately.
A
Animal
Guest
Ok, I'll keep you posted.
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