It has been demonstrated by the italian pharmaceuticals company Pharmaguida that tesosterone in male body can be increased by 42% within 2 weeks by supplementing with the simple amino acid, D Aspartic acid. Leutinizing hormone was increased 33%, thus the natural pathway in the body was being used. The test was conducted on healthy men aged 27-37 years old. The effect on older men, who have low testosterone due to "aging" can be even more profound and much longer lasting.
Sports scientists at the University of Medical Sciences in Teheran conducted a study whereby they found that supplementing boron to men aged 29-50 resulted in an increase of bio available testosterone by 28% and a decrease in estradiol of 39%. Naturally, these nutrients are part of the Time Machine, in addition to many others. One of our ingredients is responsible for greatly increasing steriodogenic acute response protein, which carries cholesterol into the mitochondria of the leydig cells for conversion into testosterone. Now, aged leydig cells should repond to lutinizing hormone just like young leydig cells. This is a primary weapon for us.
In order to complete the strategies for raising testosterone, the regulatory pathways need to be addressed for optimal long term results. The male body has other mechnisms that are designed to regulate the levels of testosterone, which must be modified.
Testosterone (and estradiol) circulate in the bloodstream, bound mostly to Sex Binding Hormone Globulin (SHBG) and to a lesser extent serum albumin and corticosteroid-binding globulin (CBG) (AKA transcortin). Only a very small fraction of about 1-2% of testosterone is unbound, "free," or bio available". Only bio available testosterone is able to enter a cell and activate its receptor. SHBG inhibits the function of these hormones and renders them inactive.. So, the bioavailability of testosterone is affected by the level of SHBG. Part of the process of increasing testosterone involves inhibiting the binding of testosterone to SHBG.
Nettle root extract has the ability of inhibiting the binding of testosterone to SHBG by attaching itself to the SHBG molecule. SHBG has a good affinity for nettle root, thus it is part of the makeup of the Time Machine.
Furthermore, SHBG increases with age, and slowing this process down should be beneficial to increasing free testosterone. N Lecureuil et al, showed that SHBG is inhibited by IGF-1 in 1998. As you can see from this study, one of the most ideal approaches to raising testosterone is to address the levels of IGF-1. Since IGF-1 is triggered by growth hormone, we must address the issue of declining growth hormone in the male body. Since, from blood tests of Time Machine users, and from clinical trials using CDP Choline, we have shown that we can increase growth hormone 400%. This increases IGF-1, which, according to the research done by N Lecureuil et al, works to reduce SHBG, and thus helps to increase free testosterone. This is part of our solution offered in the Time Machine.
Another method that the male body has for regulating the levels of testosterone is to convert it to a form of estrogen, called estradiol. This process further reduces bio available testosterone. Elevated estradiol is associated with many unwanted health issues such as: double stroke risk, artery intima, heart attack, atherosclerosis, arthritis, blood clots, and prostate cancer and increases in fat.. This conversion of testosterone to estradiol is performed by the enzyme "aromatase". Aromatase is an enzyme produced by fat cells. The Time Machine has multiple ingredients that have been shown by clinical trials to reduce the activity of aromatase.
Stinging nettle root, along with indole 3 carbinol and other ingredients in the Time Machine can inhibit the activity of aromatase. The role that indole 3 carbinol actually plays in the male body is to convert the stronger estrogen, into the weaker estriol. These two nutrients help to elevate and protect bio available testosterone in the male body. Testosterone (as opposed to dihydrotestosterone) affect the cells that have androgen receptors, which would mean the muscle cells. Indole 3 Carbinol is a strong inhibitor of cancer caused by excess estrogen.
As mentioned above, aging men with low testosterone have an inability of the leydig cells (in the testicles) to respond efficiently to Leutinizing Hormone (LH). So, despite elevated levels of LH, testosterone is still low. Researcher have been confounded by this phenomena. The rate limiting factor is the decline in steroidogenic acute response protein, and (without divulging too many corporate secrets...) the Time Machine is equipped with the ingredients that have been shown to solve that issue. Part of that secret involves lowering cyclooxygenase 2 (COX2) in the leydig cells. The Time Machine has ingredients that directly lowering this inflammatory marker. by avoiding omega 6 fatty acids in the diet, one can make significant gains in testosterone production. In our opinion, the male body should be at a 2:1 or 3:1 ratio of omega 3 fatty acids to omega 6 fatty acids. The problem is, the typical american diet is too high in omega 6 fatty acids. This is conducive to systemic inflammation and a reduction in testosterone production. Taking the Time Machine and achieving a ratio of say 2:1 omega 3's to omega 6's, one can achieve results like those of Gary Butler (Time Machine user), who at age 59 went from the mid 600's to 903 ng/dl of serum testosterone. 903 is a very nice number for a 59 year old, and it represents a number you might find in a much younger man.
The usage and testing of the testosterone systems of the Brown Norway rats has given us insights as to what the issues are with low testosterone. The enzymes CYP11A, 3HSD, CYP17, and 17HSD are important links in the chain of the steroidogenic pathway of Leydig cells. When pituitary release of LH is suppressed by the administration of anabolic steroids, the Leydig cells regress because of lack of hormonal stimulation (by LH) losing expression of the steroidogenic enzymes (Ewing et al., 1983). Isolation of the regressed cells and then acute exposure of the cells to LH results in very little testosterone production, indicating the importance of steroidogenic enzyme expression for the synthesis of testosterone (Chen et al., 2002). Unfortunatley, in aged cells, mRNA and protein expression of the steroidogenic enzymes are reduced (Luo et al., 1996, 2005). Moreover, stimulation of the cells with saturating levels of intermediates of the steroidogenic pathway (e.g., pregnenolone, progesterone, etc.) demonstrates a correlated decline in steroid production (Luo et al., 1996). The decreased levels of the steroidogenic enzymes fit with stereological analysis indicating a reduced volume of mitochondria (Chen et al., 2002) and a significant regression of the microsomal volume of aged Leydig cells (Chen et al., 1994). Thus, a substantial contribution to the age-related reduced ability of Brown Norway rat Leydig cells to produce testosterone is the result of decreased expression of the enzymes responsible for the conversion of cholesterol to testosterone; this decreased expression limits the maximal amount of steroid metabolites through the steroidogenic pathway. However, it should be noted that age-related changes to the Leydig cell are a bit more complex than just a decreased expression of the steroidogenic enzymes. As described above, it has been known that the principal control step of steroidogenesis is the translocation of cholesterol from stores to the CYP11A1 enzyme located in the mitochondrial matrix (Stocco and Clark, 1996; Jefcoate, 2002). This step, involving transfer of cholesterol across the two mitochondrial membranes, is dependent on the presence of two proteins; steroidogenic acute response protein (StAR) and TSPO. Deletion of these two genes has been shown to disrupt the synthesis of steroids (Caron et al., 1997; Papadopoulos et al., 1997), and reduction in the levels of the StAR and TSPO proteins also negatively affect the ability of Leydig cells to make steroids (Hauet et al., 2005). Both StAR and TSPO, mRNA and protein levels are significantly diminished with age (Luo et al., 2005; Culty et al., 2002). In addition, the accumulation of hormonally recruited cholesterol into mitochondria is compromised in aged Leydig cells, arguing for age-related decline in mitochondrial cholesterol transfer with age (Culty et al., 2002). So it seems that not only is the ability of the Leydig cells to metabolize cholesterol to testosterone decreased with age, but the ability of the cell to provide the steroidogenic pathway with cholesterol substrate is decreased as well. Both the acute delivery of cholesterol to the steroidogenic machinery and the chronic maintenance of steroidogenic enzyme expression are regulated by cAMP production upon LH stimulation of its receptor (Payne and Youngblood, 1995; Stocco and Clark, 1996). With the multitude of hormone-dependent steps altered with age, it is seems reasonable that aged Leydig cells are under-stimulated by LH, even at sufficient levels. Exposure of isolated aged Leydig cells to LH for 0–20 min, a time window relevant to the acute production of testosterone by the cells, resulted in the production of significantly less cAMP than young cells (Chen et al., 2002). Additionally (important!) stimulation of aged cells with saturating concentrations of the cAMP analog dbcAMP for 3 days restored the maximal synthesis of testosterone to the level of young controls (Chen et al., 2004b). These findings show that diminished responsiveness to LH significantly contributes to diminished maximal testosterone synthesis in aged Leydig cells. An additional negative modulator of steroidogenesis in the aged Leydig cell is increased expression of the cyclooxygenase-2 (COX-2) enzyme, which increases DAX-1 (inhibitory protein). LH, in addition to its stimulation of cAMP synthesis, promotes the release of intracellular arachidonic acid (AA). AA release in steroidogenic cells may occur intramitochondrially through the action of a mitochondrial acyl-CoA thioesterase (Acot2) (Castillo et al., 2006), and/or via classical phospholipase A2-mediation (Irvine, 1982). The released AA is subsequently metabolized by cellular lipoxygenases, epoxygenases or cyclooxygenases. Lipoxygenase and epoxygenase AA metabolites are reported to stimulate steroidogenesis through enhanced expression of the StAR protein (Wang et al., 2002). However, metabolism of AA by the COX-2 enzyme has been shown to inhibit StAR gene expression and steroidogenesis (Wang et al., 2003). This may be relevant to aged rat Leydig cells; increased expression of COX-2 has been reported, and inhibition of COX-2 activity was found to enhance StAR protein levels and increase testosterone synthesis (Wang et al., 2005). (Reducing COX2 will reduce the inhibitory protein DAX-1, which allows a rise in StAR protein, which then moves cholesterol into the mitochondria of the leydig cells, which is then converted into testosterone!)
Having stated the above, let's discuss the (Time Machine) partial solution: D-Aspartate can be taken into testicles via the NMDA receptors, present in both Leydig and Sertoli cells of the testes. After being taking up into a cell, D-Aspartate appears to have the ability to induce testosterone release, although it tends to work synergistically with hCG (men and women both produce this) by increasing the efficacy of hCG on a testicular cell. This increase in testoterone synthesis is not seen after 1 hour of incubation, yet is seen after 16 hours, and can both increase cholesterol transport into the inner mitochondrial membrane by increasing expression of the StAR protein, which as previously discussed, is a transporter that brings cholesterol into the mitochondria. hCG treatment is able to increase expression of StAR itself via a cAMP dependent pathway, and incubation of a cell with D-Asparate can increase hCG-induced StAR mRNA upregulation 3.5-fold and protein content by 1.9-fold and can increase in cAMP levels by 3.1-fold at 0.1mM and 5.25-fold at 5.25mM.
Increasing the activity of the rate-limiting steps in steroidogenesis (steroid synthesis) in the testes may underlie the ability of D-aspartic acid to increase testosterone in otherwise healthy men. The Time Machine is also equipped with another ingredient (yes, it's a secret) that directly inhibits COX-2, which in turn lowers DAX-1, which then results in a dramatic increase in StAR, With these strategies, aged leydig cells can function similarly to young leydig cells, responding nicely to lutinizing hormone.
A new issue: Modern men who are experiencing low testosterone levels are typically also enduring elevated estradiol, elevated cholesterol, high blood pressure, and excess fat accumulation. In light of these additional issues, they are sometimes being told by medical professionals to reduce salt intake, reduce fat intake and reduce cholesterol consumption. Cutting fats and cholesterol is usually done by cutting fatty foods like red meats and eggs from the diet. Some men are also using "statin" drugs which limit the livers ability to make cholesterol. But, cholesterol is the precurser for testosterone, and also other hormones such as such as estrogen, progesterone, and DHEA. In our opinion, red meats, and eggs (which are rich in cholesterol) should be a part of the aging mans daily diet.A reduction in dietary fats has been shown to decrease testosterone by 12%. The trick is to make sure that your omega 6 fatty acids (a polyunsaturated fat) is low, and your omege 3 fatty acid intake is higher. Omega 6's supply the precoursers for inflammation, which reduces testosterone (by increasing COX2 as discussed above). Eggs yolks contain cholesterol, which is converted to testosterone by the leydig cells, especially when eaten in conjunction with the Time Machine. The Time Machine has other ingredients that will dramatically increase the bodies L Carnosine levels, which, acting as a chelator, will continue to clean the arteries of calcium and lipid deposits. Even in the face of a diet, consisting of red meats, bacon and eggs, the typical loss in blood pressure, as reported by users of the Time Machine is 5-10 points per month, in addition to increases total and free testosterone. The consumption of fats and cholesterol is essential for maximizing testosterone production. We agree that consumtion of fatty foods while being estrogen dominant should be avoided. However, if an aging man who is taking the Time Machine, has a better testosterone/estrogen balance (not estrogen dominant), then the consumption of fatty food, rich in cholesterol will help to increase testosterone, and should result in better health.
The accumulation of plaque in the arteries has more to do with the LDL to HDL ratio. Cholesterol does not travel through the body by itself. It is normally wrapped in a water soluble protein blanket. In essence, cholesterol is carried around in a pickup truck that knows what cells to deliver the cargo to. This pickup truck, called a "lipoprotien" can embed itself under the endothelial cell wall in the artery (Now it's called a plaque), in response to damage in that area. This is beleived to be a response to the damage, which can be brought on by inflammation. Inflammation in excess is bad for the body. Some of the contributors to excess inflammation is refined sugars and high glycemic index foods in the diet and an unfavorable ratio of omega 6 fatty acids to Omega 3 fatty acids. Modern science is suggesting a ratio of 1:1 to 4:1. The typical western diet is closer to 15 (omega 6) to 1 (omega 3). This has created a much higher risk for heart disease. The ratio can be changed by taking a fish oil supplement which is high in omega 3's. Cholesterol cannot be blamed for heart disease. Cholesterol is simply the cargo being carried by the lipoprotein. Cholesterol is needed by every cell in the body, and is needed for endothelial cell regeneration in the arterial wall. LDL can carry it in, but HDL carry it back out after endothelial repairs have been completed. Controlling inflammation and reducing intake of high glycemic foods (sugary junk foods) seems to be a big part of the method to reduce plaque in the arteries. Reducing cholesterol is not the way, and leads to reduced testosterone and serotonin, which can result in mood disorders.
The above method, in our opinion represents the right way (the safe way) to raise testosterone in aged men. We had to specifically identify the rate limiting factors (enzyme expression, and inflammation), and then attempt to fix those problems. The creator has been taking this formula since January 2012, with remarkable results, and no adverse effects. Testicular size and ejaculate volume are also maximized by the above method of raising testosterone, indicating that this method of raising testosterone is the right path.
The wrong way. The traditional method of testosterone hormone replacement therapy (HRT) involves administering cycled injections of testosterone or applying a transdermal patch. While this method will raise testosterone in the body, both of these traditional methods are associated with lower levels of leutinizing hormone and reduced testicular function, which results in testicular atrophy and a lowered sperm count. Testosterone HRT is also associated with Benign Prostatic Hyperplasia (BHP), prostate cancer (from the typical conversion to estradiol by armotase) and cardiovascular disease. This method absolutely avoids the real reasons why testosterone is low in the aging male.
Problematically, many doctors routinely prescribe men with erectile dysfunction to take androgen replacement therapy that can actually do a disservice to that man. Testosterone is believed to be the basis for a mans sexual desire and performance, but this is not the only cause of performance issues. The key to performance, and erectile hardness has much more to do with D2 receptor density, which can be upregulated by IGF-1, and sufficient nitric oxide production from the endothelial cells. When testosterone is injected into the male body, aromatase will convert much of this testosterone into estrogen, in particular estradiol (E2), which has been shown to downregulate D2 receptors. Desire can increase, but the ability of a man to perform, might not be significanlty changed. D2 receptor density has been linked to levels of IGF-1 (Thornton et al. Journal of GH and IGF Research Oct 99). A better approach would be to reduce estradiol and increase growth hormone, which will trigger an increase in IGF-1, which could increase D2 receptor density. Add to that, certain nutrients that increase the output of nitric oxide from the endothelial cells. Naturally, the ingredients that have been shown to benefit these areas are in the Time Machine.
Marketing pressure from the pharmaceutical companies further push the use of hormone replacement therapy. Below are some of the long-term negative effects of traditional testosterone replacement therapy:
• Complete suppression of natural testosterone production (leutinizing
hormone is shut down)
• Reduced sperm production that can ultimately lead to infertility
• Shrinking of the testicles
• Permanent testosterone dependence
• Increased risk of fluid retention, blood clots, stroke, and liver problems
• Increased difficulty with urination (from prostate growth)
• Promotes growth of prostate tissue (because of increased estrogen)
• Promotes growth of prostate cancer (because of increased estrogen)
• Breast enlargement (because of increased estrogen)
When you start testosterone replacement therapy (TRT), it is very difficult to stop. When patients stop TRT, they can experience depression, withdrawal and erectile dysfunction, in addition the inability to produce testosterone naturally.
When a patient is diagnosed with low testosterone, another hormone to check is prolactin. Prolactin in men seems to be primarily involved in the post orgasm refractory period. After orgasm, a surge of prolactin from the pituitary causes the penis to become flaccid. Testosterone and dopamine are inhibited, while oxytocin and serotonin take over to cause feelings of satiation.
Therfore, one of the simple approaches to raising testosterone is to lower prolactin (if it is too high). The holistic approach is to use vitamin E, along with 200 mg of pyridoxal hydrochloride, which is the synthetic form of vitamin B6. (the natural form will not do this) These two simple nutrients have been shown to reduce plasma prolactin by around 70%. In addition to raising testosterone, dopamine is less inhibited, and theorectically should result in faster, harder penile erections. But it's a very tricky stunt. B6 along with zinc has also been shown to strongly inhibit the 5 alpha reductase enzyme, which lowers dihydrotestosterone,....which kills your libido. Proper dosage is the key to getting desired results. The dosages used in the Time Machine have been carefully planned for optimal results.
Lastly, is the issue of serotonin reuptake inhibitors (SSRI's) such as St. Johns Wort, or the prescription drugs fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil) and others. These SSRI's increase the amount of time that serotonin stays in the synapse area between nerves, and serotonin inhibits the production of dopamine. For patients that are using some sort of SSRI, and complaining of erectile dysfunction, the root of the problem could be too much serotonin, which reduces dopamine. Dopamine is the trigger that fires the whole erection gun. Dopamine is like the gas pedal in a car. It causes you to go, speed up, take some action. Serotonin is the mediator that is like the brakes, it causes you to slow down, be calm and satisfied.. It slows the release of dopamine. For example, If your a man, do you remember how you feel when you go too long without food? Dopamine is enhanced, and you could actually feel like you could kill someone. Patience is shorter, your temper is hotter and your quicker to take action to get fed. Once you get a big meal into your stomach, you calm down. Your pleasant to be around. This is because, serotonin is produced in the gut, in the presence of food.
For erections, the process starts with dopamine. So, if serotonin is too high, this is where the root of the problem is. There are conflicting reports of whether SSRI's actually cause erectile dysfunction, but it's a fact that many patients who have taken SSRI's do complain of this.
For Bodybuilders who are taking HRT to a whole new level, there are additional issues to deal with. Bodybuliders use excessive amounts of synthetic testosterone hormones to increase muscle mass. This process definitely works, but keeping the muscle gains is tricky. After 5-8 weeks of using steroids, usually, the gains in muscle have flattened out. This is the point where most bodybulders opt to get off of the cycle. Once you quit the cycle, your own natural ability to produce testosterone is at a low point. It has been shut down for many weeks. So normally, you begin to lose those mucsle gains, and in fact; it it typical to lose everything. This is the point where cortisol is high, and testosterone is very low. Erectile dysfunction can set in, and since there is very little testosterone to support that new muscle, so it wastes away over the next several months. Some bodybuilders will simply go back on the steroids, in order to keep the muscle, but the health risks are increased.
Other solutions to this problem of keeping the new muscle involve using Clomid and Human Chorionic Gonadotropin, (HCG). Clomid has the ability to occupy the receptor sites designed for estrogen, in the hypothalamus. In the presence of Clomid, the hypothalamus is tricked into thinking that testosterone is low, so it releases more Gonadotropin Releasing Hormone (GnRH). This is turn causes a release of Leutinizing Hormone (LH) from the pituitary gland, which then signals to the Leydig cells in the testes to produce more testosterone. Clomids side effects include possible visual changes, pyospermia, and strangely enough, loss of libido and erectile dysfunction.
HCG is found in men and women. In women, it promotes the maintenance of the corpus luteum during the beginning of pregnancy. In men, it acts similar to LH. HCG stimulates the leydig cells of the testes to produce testosterone. HCG side effects in men include blood clots, headache, swelling or weight gain, irritability, and depression. There are many serious bodybuilders who use HCG post cycle, with satisfactory results.
The Time Machine can also be used to help preserve newly
gained muscle, and is arguably safer than Clomid or HCG.. Since the Time Machine
has ingredients that have been shown to increase growth hormone in clinical
trials, IGF-1 should also increase, which should down regulate Sex Hormone
Binding Globulin (SHBG).
This alone will increase free or bio available testosterone. The Time Machine
also has multiple ingredients that work to raise total testosterone. Therefore
it would seem that the Time Machine is a viable option for bodybuilders who
are trying to jumpstart their own testosterone production abilities. Below
is a video discussion of these topics.
One last thing to note about testosterone is the following: Alzheimers and Parkinson's have both been linked to the natural decline oftestosterone. Parkinson's disease is the loss of dopamine production in the substantia nigra part of the brain, and Alzheimers is a deterioration of neurons all across the brain. Alzheimers is pretty scary, in that the prevalance is almost 50% by age 85. Alzheimers also kills every one of it's victims. First, the memories fade, and eventually, basic functions such as breathing and swallowing are lost. Death follows. In Parkinson's it is the loss of dihydrotestosterone (DHT) that seems to be connected to the onset of this disease. The administration of DHT also seems to help the condition.
The latest research of both of these diseases suggest that the problem is, the neurons are suffering from a form of diabetes. The cells cannot take in enough glucose, and therefore get starved for fuel. Of course, the initial cause looks like the age related decline in testosterone.
Once these forms of dememtia take root, the only possible cure, other that raising testosterone seems to be the ingestion of medium chain tryglycerides (MCT). A good source is coconut oil. The MCT's cause the liver to create ketones, which can enter the brain cells, and be the source of fuel that is needed to restore the function of dying nerves. Ketones do not need insulin to enter the cells.
Knowing this connection between testosterone and demetia, it becomes apparent that keeping testosterone levels up, is vitally important for brain health. All the more reason to consider taking the Time Machine as a preventative measure.