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Witch hunt against performance-enhancing drug users

SARMs

“Was the government to prescribe to us our medicine and diet, our bodies would be in such keeping as our souls are now.” — Thomas Jefferson

While it is understandable that competitive sports event organizers want to keep their events clear from the performance-enhancing drugs due to their values, the aim to extend that policy to laymen with a threat of a felony level (sic!) criminal offense seems clearly less justified both economically and morally. It can be reasoned that punitive laws are not in the interest of taxpayers. Average cost of per recruit in a cohort study is about ten dollars for offline recruitment and the cost can be further reduced by a third if online recruitment methods such as Facebook are used [1]. On the other hand, cost per year spent in prison is at least 30 000 dollars [2]. It would be more reasonable and cheaper to label the the said performance-enhancing drug users as “test subjects” and investigate them than label the said experimenters as “offenders” and put them into the jail. If the nonmedical use of substances could be epidemiologically monitored with compulsory following of a study protocol, then it should satisfy both moderate authoritarians and libertarians. If the use of SARMs is positioned clearly as that of performance-enhancement rather than that of medical, it should unburden medical and pharmaceutical regulatory authorities from some of the responsibility. On the other hand, it would position the sports authorities as major stakeholder, as seems to be the case (pharmaceutical industry does not seem to be major stakeholder because use of SARMs is not at odds with their major economic interests). In order to draw the boundaries that would allow the laypersons to use SARMs, the concerns of sports authorities must be taken into the account, and We suggest that science would be perfect arbiter while observation with the right to cancel the study due to health concerns is not sufficient means of regulation.

[1] https://www.ncbi.nlm.nih.gov/pubmed/28249833
[2]https://www.marketplace.org/2017/05/19/how-much-does-it-cost-send-someone-prison/

The Proposed SARMs Control Act

SARMs

There is new bill in Congress that would ban SARMs. Should possession of SARMs become a dangerous criminal act then? 

United States senators are pushing a bill that would reclassify SARMs as illegal substances (Schedule III) that would be treated similarly with anabolic steroids and some other drugs such as ketamine or buprenorphine. The parties that are interested in banning SARMs in USA are US Anti-Doping Agency, Council for Responsible Nutrition and Federal Law Enforcement Officers Association. While it is already clear that FDA has not approved SARMs as pharmaceuticals, the parties that are interested in enacting punitive laws pertinent to SARMs capitalize on possible negative health consequences. On the other side of the coin, a more plausibly benevolent argument is that under the less strict laws it is more difficult to stop the unscrupulous vendors who include SARMs as unlisted ingredients in their “food supplements”, which has been the concern of Council of Responsible Nutrition. Without saying, such cheating of consumers is already illegal. The bill aimed at making possession of a SARM a felony did not pass in April 24, 2018 [1]. What are the probable implications of this bill passing? “Once that happens, state and local police can arrest for SARMs, so that possessors are only one unexpected car stop or one bitter ex-spouse phone call away from a set of handcuffs.”[2].

[1] https://www.govtrack.us/congress/bills/115/s2742
[2] https://www.steroidlaw.com/2019/01/the-proposed-sarms-control-act/

New SARM SR9011 available

SARMs, SARMs online shop

We have added new SARM SR9011 to our product list.

SR9011 is a novel circadian clock amplifier not yet tested in humans but is already a suspected performance enhancing agent. In mice, it has reduced blood fat and sugar levels while it increased energy expenditure and appetite. SR9011 had mild or nightlong interaction with wakefulness depending on light conditions, has anti-inflammatory properties and does not have overt toxicity. In a few cell lines it did not interfere with proliferation of normal cell lines specifically. Hence, Rev-ErbA? agonists, as shown by at least four lines of evidence, seem to have a broad spectrum of effects.

Read more about SR9011 or buy SR9011 in our store.

How does yohimbine interact with caffeine?

Nootropics

In 1989 there was a study that investigated the behavior of animals. Caffeine was anxiogenic in the context of exploration and social interaction while yohimbine was anxiogenic in the context of exploration but displayed anti-conflict properties in social interaction [1]. Unexpectedly, caffeine and yohimbine cancelled each others’ effects out.

An interesting study investigated rat vocalizations under the influence of either caffeine, yohimbine or amphetamine. 22 kHz sounds were interpreted as signals of alarm or distress while 50 kHz voice were interpreted as response to rewarding stimuli while mentioning that it is unknown whether the same signal is associated with anxiety [2]. Caffeine and amphetamine increased 50 kHz calls, yohimbine did not. In addition, it was shown that while caffeine and amphetamine were locomotor stimulants, yohimbine was not.

Yohimbine can promote fat loss by mildly increasing lipolysis when not counteracted by eating because after a meal the lipolysis-enhancement does not work [3]. In lower doses it does not increase blood pressure, heart rate or cause anxiety as much as ephedrine but larger doses have both cardiovascular and anxiogenic effects.

A human cardiology study [4]investigated caffeine, ephedrine and yohimbine in obese women during exercise (handgrip and cycloergometer). Caffeine and ephedrine increased heart ejection fraction during cycling (amount of blood pumped out of left ventricle, an increase may be considered usually beneficial) and did not alter the hemodynamics while resting. Addition of yohimbine increased diastolic blood pressure (that may be considered quite undesirable in this context) and heart rate (same interpretation) but decreased ejection fraction (same interpetation) and stroke index during rest (same interpretation). During exercise, yohimbine decreased ejection fraction during both exercises and increased cardiac load during exercise.

 

Bottom line: while yohimbine seems useful for fasted long-duration low-intensity fat burning training, it seems that combining it with substantial amounts of caffeine may be asking for trouble. Most importantly, yohimbine seems a very unwise choice for hard exercise (weightlifting, sprint, high-intensity interval training, intense cardio, and, if I may suggest, also pushing the limits with rough sex).

[1] https://www.ncbi.nlm.nih.gov/pubmed/2707309
[2] https://www.ncbi.nlm.nih.gov/pubmed/29909426
[3] https://www.ncbi.nlm.nih.gov/pubmed/12323115
[4] https://www.ncbi.nlm.nih.gov/pubmed/9545623

Effects and adverse effects of ibutamoren

SARMs

Ibutamoren (MK-677) has been researched with aims of increasing muscle mass, improving healing of injures and increasing quality of sleep. But there are also some side-effects related to blood pressure.

Growth hormone deficiency, if present, is associated with lower blood pressure independent of the time of the day [1] with normal response to exercise in humans. In rats whose hypophysis (part of brain that produces growth hormone) was removed, growth hormone lowered blood pressure, instead [2]. Mechanistically, alterations of growth hormone level may modify the blood pressure indeed but the exact dose relationship is unknown, and human studies must be considered more informative.

Growth hormone release amplifier MK-677 or ibutamoren is also relevant from the perspective of cardiovascular health: a study with obese humans has shown that ibutamoren moderately but significantly increased both diastolic blood pressure (mean 84 vs 79) and heart rate (mean 61 vs 56) [3]. In the first administration of ibutamoren, a transient elevation of prolactin and cortisol was observed, while the long term result was increase of fat free mass[4]. On the other hand, ibutamoren moderately decreased glucose tolerance in the long term, which reduces its potential utility for diabetic (as indicated by elevated glucose levels and glucose intolerance) and pre-diabetic (as indicated by elevated glycosylated hemoglobin levels in blood) humans. The effects of ibutamoren may be dependent on age and duration of administration. The negative effects may be more prominent in the elderly, as it was associated with congestive heart failure and elevated blood pressure in a study of elderly patients with hip fracture [4]. While there were some improvements in the gait speed and prevention of falling, the study was terminated early due to this side effect.

[1] https://www.ncbi.nlm.nih.gov/pubmed/11282052
[2] https://www.ncbi.nlm.nih.gov/pubmed/15525587
[3] https://academic.oup.com/jcem/article/83/2/362/2865156
[4] https://www.ncbi.nlm.nih.gov/pubmed/21067829

SARMs overview 2018 – 2019

SARMs

There were 135 PubMed-indexed Studies about SARMs (steroid androgen receptor modulators) at the end of January 2019.

SARMs were a hot topic in American Society of Bone and Mineral Research conference held in Quebec, Canada. The established technologies for improvement of bone function are high dose vitamin D, bisphosphonate drugs and somewhat more novel combination therapy of monoclonal antibodies that attack osteoclasts (cells that normally remodel the bone but cause osteoporosis if their proportion is out of balance) and recombinant parathyroid hormone that supports osteoblasts (bone-building cells) if used intermittently [1]. However, the SARMs were the most interesting from the novelty perspective.

A really interesting study published in 2019 discusses a SARM found from the nature (wild bitter gourd extract) and compared the SARM with testosterone in castrated mice (to unmask the effects of treatment from endogenous male steroid hormones). While testosterone increased the mass of both muscles and male accessory glands (prostate and seminal vesicles), the bitter gourd extract increased grip strenth and acrobatic/balance performance measured with as measured by the typical rotarod test [2]. Boosting mitochondria and their oxidative capacity as well as negating castration-induced muscle decline was proposed as mechanism of action.

A review paper was also published in 2019. It is somewhat a non-news that no SARMs are available as prescription drugs. In summary, the research has found that these molecules seem to have few if any drug interactions and the clinical studies suggest potential future applications for pathological muscle loss, benign prostate hyperplasia (BPH), hypogonadism and breast cancer [3] as well as, possibly, Duchenne muscular dystrophy (a disease which causes progressive weakness of muscles that is eventually lethal due to withering of breathing muscles). In contrast to uses related to disease, the use of SARMs as performance-enhancing agents was briefly discussed, as these drugs have anabolic effects with less side effects (without excluding potential for abuse), that make SARMs interesting for bodybuilding community.

In addition to regular additions to the set of studies dedicated to development of methods of doping detection, a few other studies were published in 2018: development of transdermal system of administration of SARM LY305 [4] – it improved the speed of muscle and bone repair without overt adverse effects in laboratory rodents, and was well-tolerated in human volunteers. Another study discovered that SARM S42 inhibited proliferation of prostate cancer cell line PC-3 [5]. Third study, expectedly, found that YK11 supported the function and proliferation of bone-building osteoblast cells of mice [6], and another study weighed in additional evidence by showing the anti-osteoporosis effects for the currently perhaps the best-known SARM ostarine [7].

Animal studies (especially optimistic ones for the sake of caution) must be taken with a grain of salt, though. A study found that LGD-4033 (that may also be known as ligandrol) metabolizes moderately differently in humans and horses, which adds a layer of complexity to interpretation of animal studies in general as well as doping detection in different species specifically [8].

While the aim of this text was to summarize the studies published in 2019 and 2018, a few studies of interest were published in 2017 deserve mentioning. We will cover this in future posts.

[1] https://www.ncbi.nlm.nih.gov/pubmed/30590370
[2] https://www.ncbi.nlm.nih.gov/pubmed/30600821
[3] https://www.ncbi.nlm.nih.gov/pubmed/30503797
[4] https://www.ncbi.nlm.nih.gov/pubmed/29527831
[5] https://www.ncbi.nlm.nih.gov/pubmed/29444261
[6] https://www.ncbi.nlm.nih.gov/pubmed/29491216
[7] https://www.ncbi.nlm.nih.gov/pubmed/29785666
[8] https://www.ncbi.nlm.nih.gov/pubmed/29334634

What to to against low testosterone – Replacement, SERMs, SARMs or something else?

SARMs

There’s a new review paper on an interesting topic, titled “Novel Therapy for Male Hypogonadism” from Miami University. We are let known that the last author of the paper [1] was the lead investigator of a drug trial in the past (Natesto, a formulation of testosterone for hypogonadism). The researchers are from Miami. Whether its tropical climate and beautiful beaches play a role on choice of the topic, remains unknown.

Word ‘hypogonadism’ comes from Ancient Greek – hypo meaning sub-; gonad meening seed seed). Hypogonadism is a clinical entity diagnosed with repeated measurement of low testosterone. Clinically, age-related hypogonadism is a type of sexual development delay in boys. Late-onset of hypogonadism can resemble some aspects of old age that are not liked very much by older men.

The paper discusses the recent papers on the clinical meaning of hypogonadism: one of the key issues is that older men with the hypogonadism complaints do not have low testosterone and vice versa.

Several treatment options are available. In addition to physical activity and lifestyle modification that is very important for late-onset hypogonadism, testosterone replacement treatment is the approved treatment while several experimental treatment options have been used as off-label treatments or in scientific studies.

Testosterone replacement is effective against hypogonadism symptoms, but is likely to adversely affect endogenous testosterone production and fertility parameters.

Selective estrogen receptor modulators (SERMs) have different estrogenic and antiestrogenic activity. SERMs such as tamoxifen and clomiphene improve serum lipids and bone density but tend to increase the incidence of venous thrombembolia. A SERM, Clomiphene citrate works by reducing negative feedback from estradiol to hypothalamus that is at the top of cascade leading to testosterone production. Clomiphene is quite widely used by doctors despite indication being off-label. Clomiphene raises rather than suppresses endogenous testosterone, and spares fertility, and the cost to the patient is lower.

Aromatase inhibitors such as anastrozole and exemestane work by reducing conversion of testosterone to estradiol. Estradiol in low doses has beneficial effects but increased levels of estradiol cause undesirable effects other than negative feedback to hypothalamus as well that can be summarized as feminization. While clomiphene is better at increasing testosterone concentration, aromatase inhibitor anastrozole was better at increasing testosterone : estradiol ratio.

Human chorionic gonadotropin (HCG) can raise endogenous testosterone production but also FSH is necessary for preservation of fertility. HCG has been used to treat azoospermia caused by steroid abuse. It may be combined with testosterone replacement to preserve the intratesticular levels of endogenous testosterone and and normal semen parameters.

Anabolic steroids such as nandrolone have also been revisited, lately, and considered as possibilities alternative to testosterone replacement because anabolic steroids have desirable effect of muscle selectivity

Finally, SARMs are considered as a novel option for testosterone replacement treatment. The selectivity of SARMs is more desirable than that of anabolic steroids, largely lacking androgenic activity in prostate or sebaceous glands, therefore making these compounds interesting for future pharmacy. However, as is often the case with novel substances – more research is needed before more widespread application may take place.

Source:
https://www.ncbi.nlm.nih.gov/pubmed/29886559

One may only wonder, which of the above would be the first to be considered as an alternative to testosterone replacement treatment first.

Using cryptocurrency to buy SARMs

SARMs online shop

Enhancetech accepts cryptocurrency payments. We support Bitcoin (BTC), Ethereum (ETH) and Bitcoin Cash (BCH).

Cryptocurrencies are getting more popular and many of our customers would like to use cryptocurrencies to pay for their orders. We are accepting main cryptocurrencies like Bitcoin, Ethereum and Bitcoin Cash. If needed we can accept also other common currencies like Litecoin, just let us know.

By using cryptocurrency to pay, we still need you to accept our sale terms. Please remember all our products, including SARMs, are for research use only.

 

 

New review for Unifiram

Nootropics

We have updated overview article of Unifiram. 

Unifiram (CAS# 272786-64-8) is a substance that was reported in year 2000 to have similar properties to piracetam but more potent in a mouse passive avoidance test. However, unifiram has shown pro-cognitive effects for mice by preventing amnesia induced by scopolamine (muscarinic antagonist), mecamylamine (nicotinic antagonist), baclofen (GABA-B agonist), clonidine (alpha-2 agonist), NBQX (AMPA antagonist) in passive avoidance test. Read more about Unifiram.

Unifiram is also available in our shop.