About hordenine

Nootropics

Hordenine is a naturally-occurring atypical stimulant that is found in barley, bitter orange and cacti such as Echinopsis candicans. Sometimes it is found in weight loss or athletic performance enhancement supplements in larger amounts and sometimes it is found in fake “bitter orange extracts”, which may actually be a mixture of different synthetic phenylethylamine stimulants [1]. Is hordenine a good enhancer of coffee or a good alternative to it? Indeed, in the first place it is not very well researched. It is one of the many atypical minor phenylethylamine stimulants that is considered reasonably safe in smaller doses. In higher doses, is also sold as a supplement for weight loss or athletic performance enhancer. Are there any concerns?

Hordenine is no doubt bioactive. It is a relatively poor but selective inhibitor of monoamine oxidase B that breaks down dopamine [2] and phenylethylamine (PEA), prolonging their effect in the brain, heart and kidneys. While it does not mimic noradrenaline itself, it inhibits the removal of noradrenaline from synapses, and thus increases noradrenergic tone [2]. Therefore, it is a stimulant. Inhibiting breakdown of dopamine might reduce oxidative stress and might be useful for some neural conditions (mood disorders, Parkinson’s disease) and potentially disadvantageous in others (schizophrenia, anxiety disorders). Inhibition of noradrenaline uptake may be useful in the context of mood and attention disorders while it is reasonable to speculate that it may be dangerous in the context of hypertension and related diseases as well as anxiety disorders. The combined effect of these with other stimulants with different mechanisms may be greater than sum of their parts, and thus more potent as well as more dangerous.

It has been found that hordenine blocks synthesis of melanin, which is a molecule that protects the skin from the damaging effects of the sunlight [3]. The paper discussed that this property of hordenine might have potential pertinent to hyperpigmentation disorders. In the same time, it seems wise to consider that inhibition of normal tanning might increase the risk of skin cancer in some contexts.

An animal study has found that hordenine may be a kidney-friendly substance in mice with chemically induced diabetes. More specifically, hordenine reduced inflammation mediators IL-1beta and IL-6 as well as (in this context) harmful tissue remodeling enzyme MMP-9 [4]. Reduction of oxidative stress indicates normalization of haywire metabolism in the kidneys (ROS). While this is just one study made in animals, it is of great interest because it is not so easy to find molecules that are beneficial for kidneys (or liver).

High doses of hordenine have been investigated in the horse [5]. The responses of the horses were flehmen response (expression of intestinal discomfort, probably), defecation within 60 seconds, respiratory distress and doubling of heart rate. These responses to 2 mg/kg injection were transient and animals biological signs returned to normal within 30 minutes. When the same dose was given to animals orally, no such responses were recorded; the concentration of hordenine returned to baseline within 24 h.

Hordenine reduces the disease causing capacity of certain Pseudomonas aeruginosa or Serratia marcescens strains [6,7]. These bacteria are not so often found from healthy persons. It is unknown whether hordenine has any useful or harmful effect on the healthy persons’ beneficial bacteria that are mostly quite different from these two species.

Hordenine has weak dopamine D2 agonist properties. Consumption of beer is insufficient source of hordenine for this to become pertinent but higher doses found in food supplements with high concentrations might [8]. D2 receptor is pertinent for goal maintenance during mental tasks [9], less receptors are linked to better working memory and task switching.

While increased dopaminergic tone via MAO B inhibition might be beneficial for cognitive enhancement, substantial activation of D2 receptors might reduce cognitive performance, instead. Therefore, while it is clear that hordenine is a cardiovascular, nervous system and metabolism stimulant, nootropic properties are debatable – while it might me mildly nootroopic, the opposite may be true, instead.

 

[1] https://pubmed.ncbi.nlm.nih.gov/32497396/
[2] https://pubmed.ncbi.nlm.nih.gov/2570842/
[3] https://pubmed.ncbi.nlm.nih.gov/23768344/
[4] https://pubmed.ncbi.nlm.nih.gov/29775900/
[5] https://pubmed.ncbi.nlm.nih.gov/2269269
[6] https://pubmed.ncbi.nlm.nih.gov/29353476/
[7] https://pubmed.ncbi.nlm.nih.gov/30609368/
[8] https://pubmed.ncbi.nlm.nih.gov/31984737/
[9] https://pubmed.ncbi.nlm.nih.gov/30125286//

Alternatives to testosterone replacement

SARMs

Recently, a study has been published that considers testosterone restoration as an alternative to testosterone replacement. In aging male, the testosterone levels become lower but generally support sufficient testosterone levels. However, the low-normal levels of testosterone have been associated (causation not implied) with higher levels of mortality, about 35% all-cause mortality [2].

Human Corion Gonadotrophin (HCG) is a powerful hormone that can, in low doses, restore testosterone production but it has caused reduction of testicular volume and fertility parameters [1]. It has been to restore testosterone production of steroid abusers. In otherwise healthy men with low testosterone (<420 ng/dL-1) did not show expected increas in strength but caused significant reduction of testicular volume, gonadotrophin levels and, in a few cases, nipple tenderness. However, improved lean body mass was observed. Hence, long-term use of HGC therapy comes with significant side effects.

Antiestrogens such as clomiphene citrate (CC) counteracts effects of estrogens that give negative feedback to production of upstream sex hormones that promote production of testosterone [1]. Indeed, CC restored levels of follicles stimulating hormone FSH, luteinizing hormone LH and gonadotropin releasing hormone GnRH. While CC has consistently restored production of testosterone, effects on fertility and semen parameters have been variable, especially in older men were refractory to hormone manipulation while younger men had side effects of decreased libdo, lack of energy, decreased sports performance and worse mood.

Third group of anti-estrogenic treatment that aims to restore testosterone levels are aromate ihibitors AI such as anastrozole and letrozole. Since these drugs do not eliminate production of estrogens in men completely, these drugs are unlikely to cause osteoporosis in men. AI are more effective in raising testosterone levels than transdermal forms of testosterone such as testosterone gel [1]. The side effects of AI are minimal, mainly limited to unalarmingly modest increase of prostate specific antigen PSA (biomolecule used assess prostate pathology).

Fourth group is SARMs [3] or selective androgen receptor modulators such as ostarine, a “field leader”. Ostarine support smuscle growth and does not affect or even suppresse prostate growth, and does not significantly suppressing endogenous androgen production in clinically used doses. However, the selectivity of SARMs is not absolute, potency and selectivity appears to be a trade-off. A potent SARM such as ligandrol suppresses endogenous testosterone and also high density cholesterol – these side effects resembe side effects anabolic steroids [4]. SARMS can be expected to have cognition preserving results, some very low (cell culture) level studies with SARMS such as RAD-140 and NEP20 appear to support the theory [5,6].

Finally, some herbal medicines can improve aspects of androgen deficiency. Tribulus terrestris has been reviewed thorouhghly but with mainly positive effects in focus [7]. T. terrestris increases sex drive, appears to have properties that protect heart and blood vessels as well as nervous system from insults, has anti-inflammatory properties. Hovever, the abilities of tribulus terrestris to inreace endurance in rodents could not be replicated in controlled studies with human subjects [8,9]. Eurycoma longifolia is a herbal supplement with respectable traditional use with drawback of relatively high price, widespread distribution of fake extracts, and low bioavailability (10%) of main constituent eurycomanone (tested in rodents). Eurycoma longifolia has been reviewed comprehensively, and it has been tested in humans, mostly in association with aphrodisiac properties[10]. While E. longifolia has not been to subject of thorough exercise research, it seems to modestly improve testosterone levels, fertility parameters and libido on men with late onset hypogonadism, with additional benefits of being anti-diabetic, promoting bone strength and reducing anxiety.

[1]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650464/
[2]https://pubmed.ncbi.nlm.nih.gov/25041142/
[3]https://pubmed.ncbi.nlm.nih.gov/22459616/
[4]https://pubmed.ncbi.nlm.nih.gov/22459616/
[5]https://pubmed.ncbi.nlm.nih.gov/24177288/
[6]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959610/
[7]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503856/
[8]https://pubmed.ncbi.nlm.nih.gov/17530942/
[9]https://pubmed.ncbi.nlm.nih.gov/10861339/
[10]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274257/

„Side effects” of some pharmaceuticals are researched as medicines against COVID-19

Uncategorized

Chemicals that are designed for one particular purpose can have unexpected side effects – often adverse, sometimes useful. For example, according to anecdotal evidence one of the SARMs (that is not even scientifically tested in humans) can tint the vision green or yellow. However, it is not the side effects of SARMs this post will be about. This post is about current coronavirus COVID-19 or SARS-2 (Severe Acute Respiratory Syndrome 2), a very close relative of coronavirus that caused SARS, and somewhat less close relative to very lethal MERS (Middle East Respiratory Syndrome) and research pertaining to possible treatment.

As concerns the coronaviruses, chemical informatics has revealed that a molecule that has been designed as a SERM (selective estrogen receptor modulator) could be repurposed as a medicine against novel coronavirus [1]. Of course, a computer analysis is not comparable to the rigour of actual human study but the model seems to be legit. Some other molecules found by informatics approach include emodin that has been found as a drug candidate in an earlier study [2]. Emodin is not a SARM, though, it is principally a a molecule that is responsible for laxative and estrogenic properties of certain medicinal rhubarb species. Of note, also melatonin was a „hit” in the analyses that matched coronavirus against the drug database. No experimental data on melatonin and coronavirus was found from scientific literature, though. Nevertheless, in the melatonin is considered as a potential treatment in another white paper [3] and one of the potential mechanisms might be that melatonin does not allow the COVID-19 to kill off the hosts’ T-cells so easily [4]. It seems likely that elderberries may have the same mechanism combating the upper respiratory tract viruses [5]. The other effect of melatonin that may facilitate the favourable income include protection from reactive nitrogen species. Indeed, in addition to direct antiviral mechanisms, immune stimulation and immune stimulant drugs [6] are also considered, and the most promising one, interferon beta-1 peptide is indeed a working solution against coronavirus, and included into medical guidelines [7]. It is known that lack of interferon beta is responsible for lethal pneumonia [8], which is the key difference between serious and non-serious coronavirus infections.

MERS (Middle East Respiratory Syndrome) coronavirus was tested against several drugs. In that study, a drug against malaria, chloroquine, and a drug against parasites, nitazoxanide, also had a „side effect” against the virus that caused MERS, and these two were more than order of magnitude more selective and potent (in vitro, at least) against MERS than most of the antiviral drugs that are used in the hospitals against COVID coronavirus now [9]. Lately, chloroquine has been added to several treatment guidelines, and the United Kingdom banned the export of chloroquine [10]. A now rather uncommon drug that was formerly used to treat arthritis, indomethacin was very effective in treating both SARS and dogs’ coronavirus in dogs [11] and there is an impressive list of potential molecules that could help against coronavirus in the very earliest research phase [12].

Finally, a list of food supplements has been published that has been suggested to ameliorate respiratory tract infections caused by RNA viruses such as influenza and coronavirus in general [13]:

Substance Dose
Ferulic acid 500-1000 mg
Lipoic acid 1200-1800 mg (in place of ferulic acid)
Spirulina 15 g (or 100 mg PCB)
N-Acetylcysteine 1200–1,800 mg
Selenium 50-100 mcg
Glucosamine 3,000 mg or more
Zinc 30-50 mg
Yeast Beta-Glucan 250-500 mg
Elderberry 600–1500 mg

[1] https://www.ncbi.nlm.nih.gov/pubmed/32194980
[3] https://www.sciencedirect.com/science/article/pii/S0024320520303313
[4] https://onlinelibrary.wiley.com/doi/full/10.1046/j.1600-079X.2003.00105.x
[5] https://www.ncbi.nlm.nih.gov/pubmed/31560964
[6] https://www.ncbi.nlm.nih.gov/pubmed/32205350
[7] https://www.ncbi.nlm.nih.gov/pubmed/32164424
[8] https://www.ncbi.nlm.nih.gov/pubmed/26867177
[9] https://www.nature.com/articles/s41422-020-0282-0
[10] https://www.gov.uk/government/publications/medicines-that-cannot-be-parallel-exported-from-the-uk
[11] https://www.ncbi.nlm.nih.gov/pubmed/17302372
[12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195804/
[13] https://www.ncbi.nlm.nih.gov/pubmed/32061635

Effects of Ibutamoren on brain

Nootropics, SARMs

It seems that short-term use of ibutamoren after short-term stress reduces anxiety while long-term use during chronic stress increases anxiety.  A new paper [1] describes a mechanism wherein a ghrelin mimetic (ibutamoren mesylate) can enhance fear learning in rats in the context of chronic stress. The said mechanism showed that a ghrelin agonist did not activate HPA stress axis, whose downstream effector hormone is cortisol. Ghrelin is a stress hormone by itself. Growth hormone receptors were up-regulated during repeated stressful events, ghrelin agonist increased growth hormone levels and the fear learning of the rats grew in response to growth hormone. The mechanism was confirmed by using ghrelin antagonist that blocked the enhanced fear learning. In case of the short time frame, the opposite seems to be true, as short time stress followed by ghrelin agonist reduces stress symptoms in mice [2]. Fourth study also demonstrated that ghrelin weakens fear learning in generally unstressed rodents while chronically stressed rats had elevated levels of hunger hormone and fear learning ended up with fewer ghrelin receptors. High expression of ghrelin receptors reduces anxiety [3], while low levels have the opposite effect. Hence, it seems that long-term ibutamoren may exacerbate long-term stress, and brain ghrelin receptor down-regulation is the probable explanation. It seems likely, that transient or occasional increases in ghrelin receptor activation (such as after interval exercise [4]) may be more adaptive than chronic elevation regime.

[1] https://www.nature.com/articles/mp2013135

[2] https://www.ncbi.nlm.nih.gov/pubmed/22521145

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886665/

Get 10% off with cryptocurrency payout option

SARMs online shop

We are offering extra 10% discount when paying for SARMs and Nootropics by cryptocurrency.

Discount appears in checkout, when choosing “Bitcoin or other cryptocurrency” payment method. We are providing this as as we don’t have to pay credit card charging fees or other type of fees. At the same time we are supporting philosophy behind the cryptocurrency.

We accept Bitcoin, Ethereum, Bitcoin cash. For other cryptocurrency, please contact us.

Please see our shop for all our provided products.

SARMs bans in China and USA

SARMs, SARMs online shop

In november 2019, USA started introducing SARMs control act that would make SARMs illegal to sell or possess but it has not become a law, yet (date: 02/14/2020) [1]. While China may have banned export of SARMs in the same time, several SARMs are bidded on alibaba.com [2]. In USA, the aim of SARMs ban is to protect the consumers from unscrupulous vendors that sell SARMs as food supplements as well as buyers that unknowingly buy food supplements unknowingly. On the other hand, it will also mean that selling and buying SARMs becomes criminal, even if these substances are considered as research chemicals by both parties.

The parties that support criminalization include entertainment sports industry, pharmaceutical industry and natural products industry: U.S. Anti-Doping Agency, the American Herbal Products Association, the Consumer Healthcare Products Association, the Council for Responsible Nutrition and the United Natural Products Alliance.

Enhancetech has most of the SARMs back in stock and there shouldn’t be any problem according to our manufacturer. We might not be able to ship to US, after SARMs control act would become a law. So we suggest all US customers to order SARMs as soon as possible.

[1] https://www.congress.gov/bill/116th-congress/senate-bill/2895
[2] www.alibaba.com
[3] https://www.grassley.senate.gov/news/news-releases/grassley-whitehouse-introduce-legislation-regulate-sarms

Summary of SARMs doses used in human studies

Nootropics, SARMs

Overview of SARMs dosages used in human studies.

SARM/Nootropic and dosage used:
Ostarine 3 mg [1]
Ligandrol 1 mg [2]
YK-11 Unknown
RAD120 Unknown
Cardarine Unknown
SR9009 Unknown
SR9011 Unknown
Unifiram Unknown
PRL-5-83 5 mg [3]
Yohimbine Usually 5…30 mg [4],[5]
Hordenine Unknown but present in beer 1…6 mg [6]
PEA Unknown but see [6],[7]

[1] https://www.ncbi.nlm.nih.gov/pubmed/27138015
[2] https://www.ncbi.nlm.nih.gov/pubmed/27138015
[3] https://www.ncbi.nlm.nih.gov/pubmed/?term=PRL-8-
[4]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430403
[5] https://www.ncbi.nlm.nih.gov/pubmed/9315493
[6] https://www.ncbi.nlm.nih.gov/pubmed/30409657
[7] https://www.ncbi.nlm.nih.gov/pubmed/26481102
[8] https://www.ncbi.nlm.nih.gov/pubmed/26481102

SR9009 (Stenabolic) now available

SARMs, SARMs online shop

We have added new SARM SR9009 to our provided products.

SR9009 also known as Stenabolic is an experimental circadian rhytm modulator (RevErb-alpha agonist). In one hand, SR9009 is said to be attractive as a performance-enhancing agent, yet, in the other hand, its use has been discouraged because it is potentially harmful. The desire to discourage its use has prompted development of its screening methods. So far, SR9009 has revealed anti-inflammatory properties (suppressing activation of several pro-inflammatory cytokines including tumor necrosis factor alfa, whose downstream effect was suppression of tumor necrosis factor alpha). The anti-inflammatory effects have been shown in animal models of endometriosis, heart attack, Alzheimer’s disease and some autoimmune diseases.

Read more about SR9009 or buy SR9009 in our store.

Cholesterol, Muscle Mass and SARMs

SARMs

Excessive blood cholesterol is considered an important risk factor of cardiovascular diseases. Excessive blood cholesterol has both genetic and dietary component. It is also known that cholesterol is either LDL (low density lipoprotein) HDL, also known as “good cholesterol” and “bad cholesterol”, respectively.

The non-pharmacological strategy to improve blood cholesterol is improving diet (broadly – less junk food and more salad) and exercise, which are aimed at lowering LDL without lowering HDL[1]. The most effective foods for lowering LDL are oatmeal, kidney beans, apples, pears, bananas, berries, fish, nuts, avocados, olive oil, and, good news for body builders, whey protein. On the other hand, dairy fats (cream, butter, cheese) and trans fats (crackers and cakes, especially the cheaper ones) raise the bad cholesterol [2]. Especially in overweight subjects, calorie restriction lowers increased cholesterol [3]. For high risk patients, statins are used. From the field of herbal medicine, several lines of evidence suggest that berberine works similarly well [4],[5] with the reservation that berberine research lacks the industry-supported large studies. Cocoa is a well-researched food, and while chocolate is suspicious due to huge sugar content, cocoa supplements significantly improve the metabolic profile as well [6]. Of research chemicals, cardarine has been one of the more promising substances: while the research of the substance has been abandoned by the industry, it is used for research. While the original effects revealed very specific effect of raising good cholesterol in very low doses and lowering bad cholesterol in higher doses, later research has revealed that it counteracts especially bad, endothelium-damaging form of cholesterol called oxLDL [7].

Exercise program of older men showed that after a year or half, there were no improvements in grip strength, body mass index or bad cholesterol but there were improvements in body shape, walking speed, one leg standing and good cholesterol [8]. On the other hand, in children a rather intriguing counter-intuitive association was found: fatter children had more good cholesterol [9]. In addition, higher muscle mass may lower cardiovascular risks for boys only [10]. However, the good news is that for older folks, even two strength training sessions per week helped to lower cardiovascular risks, especially in case of higher blood pressure and elevated cardiovascular inflammation marker hsCRP[11]. Research suggests that for adults, both men and women, hand grip strength (relative to body mass) and relative fat mass (fat mass index) may be the best independent predictors of cardiovascular health [12].

SARMs are double edged swords. In one hand, SARMS seem to have good safety combined with beneficial effects on muscle and bone, they have some drawbacks similar to steroids: SARMS lower good cholesterol significantly and dose-dependently according to multiple studies [13],[14],[15],[16]. The effects of androgens on blood profile are not just negative because the triglyceride levels tend to be improved. A monkey study of a novel dermally administered SARM that demonstrated increased muscle mass without lowering good cholesterol by reducing exposure of liver to that SARM, and a SARM that atypically did not lower good cholesterol have been revealed in clinical human studies, as well [Ahv],[Ahv+1].

Time will tell whether newer SARMs will have the same benefits as those that have been investigated for a longer time (i.e. ostarine) without having the drawback of lowering the good cholesterol. The research is improtant, because the effects seem really interesting for older people especially, and the proportion of older people is increasing proportionally almost worldwide.

[1] https://www.ncbi.nlm.nih.gov/pubmed/30953636
[2]https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/cholesterol/art-20045192
[3] https://www.ncbi.nlm.nih.gov/pubmed/31252598
[4] https://www.ncbi.nlm.nih.gov/pubmed/26520899
[5] https://www.ncbi.nlm.nih.gov/pubmed/31094214
[6] https://www.ncbi.nlm.nih.gov/pubmed/31056655
[7] https://www.ncbi.nlm.nih.gov/pubmed/27573670
[8] https://www.ncbi.nlm.nih.gov/pubmed/31111014
[9] https://www.liebertpub.com/doi/full/10.1089/chi.2019.0122
[10] https://www.ncbi.nlm.nih.gov/pubmed/30813304
[11] https://www.ncbi.nlm.nih.gov/pubmed/30774600
[12] https://www.ncbi.nlm.nih.gov/pubmed/30424569
[13] https://www.ncbi.nlm.nih.gov/pubmed/28449232
[14] https://onlinelibrary.wiley.com/doi/full/10.1007/s13539-011-0034-6
[15] https://www.ncbi.nlm.nih.gov/pubmed/22459616
[16] http://www.jbc.org/content/285/22/17054.full
[17] https://www.ncbi.nlm.nih.gov/pubmed/26683992
[18] https://www.ncbi.nlm.nih.gov/pubmed/29527831

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/