Weight loss: causes and options


The current pharmaceutical options such as lorcaserin have clearly not been an adequate solution to problem of obesity. Extreme measures such as surgery, mitochondrial decouplers, tapeworm ingestion and illegal stimulants are not discussed.

While weight gain may be caused by medical conditions that alter water balance, commonly the weight gain is understood as accumulation of fatty tissue. Fatty tissue is caused by excess energy intake and deficit of energy expenditure (production of work, production of heat and bypass). In a biological system, such as a human, the energy intake is regulated first by availability, then by appetite and finally, by bioavailability of energy sourches such as fat, sugar, alcohol and protein. Assuming that food as an energy source is available, the energy intake is mainly regulated by appetite unless there is an overt mechanism that causes loss of energy sources, such as digestion disorders.

At the fundamental, biochemical level, there are certain biomolecules that increase or decrease appetite. Originating from the gut, Ghrelin is the primary hormone that creates sense of hunger [1] while, also originating from the gut, anorectic hormone peptide YY3-36 (PYY), cholecystokinine (CCK) and glucagon-like peptide-1 (GLP-1) reduce the appetite in response to energy intake and reduce reward to food intake in the responsible brain parts. Bile acids have an important role: these stimulate PYY and GLP-1 as well as modulate gut microbiota, which participates in appetite regulation in the one hand and energy accumulation efficiency in the other hand [2].

Fatty tissue, by default, “should” inhibit food intake by signalling via leptin and insulin that no more energy is necessary. However, due to cultural pecularities of food overconsumption in certain geographical regions especially, metabolic syndrome may be acquired. Metabolic syndrome is characterized by resistance to insulin (and probably leptin), and it is a risk factor for cardiovascular diseases and type 2 diabetes [3]. Insulin and/or leptin resistance destroys appetite control. Hence, obese people may feel hungry, probably against both their better judgement and superfluous energy reserves.

Food has hedonic reward, taste influences food intake. Food industries and art of culinary have been competing to produce as tasty foods as possible for generations. Children like sugar, for example. Considering these preferences, it is probably no wonder that corn flakes, former healthy food, has become sweeter and sweeter during course of the history [4]. In the same time, in some areas with well-entrenched healthier cuisine, such as Japan, do not experience obesity epidemic to an extent comparable to, for example, USA or Saudi Arabia. Technically, it is not even an addiction [5], and sugar preference is used in animal studies of a marker of normal enjoyment [6] despite having some traits that are sought to identify addictive substances such as dopamine and endorphin release in pleasure center of the brain [7]. While classifications may be of great academic interest, the desire to consume sweets may be comparable to desire to addictive substances and this clearly identifies it as an practical problem. It must be solved lest the situation be determined by rather hard-wired appetite and competition of capitalist food industry[8]. However, tastes can be acquired – for example when a child becomes accustomed to healthy food, that child develops a a preference for healthy food (reviewed in [1]). Taken that into account, the aquired taste of obesity-causing food is the major interventable culprit of obesity behind “junk food” eating cultures that can be identified from the world obesity maps readily available with the help of online search engines. Indeed, genetics plays a part, about 20% according to a huge population based genome-wide population study [9]. It is known that the americans of japanese origin have above-average rates of diabetes in USA [10]. Japan has experienced infiltration of western-like foods such as instant noodles to everyday diet of the japanese, and now the prevalence of type II diabetes or glucose resistance in Japan is 13.5% [11]. However, in Japan people tend to walk instead of driving, eat different foods and do not accept obesity as ‘normal’, and rate of their obesity is much lower than everywhere else in the world. Hence, the nutritional solution is exercise combined with diet of Japan 1975 (it was the maximally healthy one according to analysis) [12]. While the debate about the superiority of low-fat or low-carb diet is continuing in mainstream media, in the scientific literature the debater is more or less over. Low-carb diet and Mediterranean diet are clearly superior to low-fat approach [13], far superior.

Pharmaceutical solutions are at best secondary, unclear at worst. Surgery is the last resort. There are certain other add-on interventions provided by cosmetic industry but these, too, are supplementary. The primary interventions are exercise and diet. The supremacy of (A) traditional Japanese diet, (B) low-carb diet (see also ketogenic diet) and (C) traditional Mediterranean diet are established and most likely, must be part of the solution.

[1] https://pubmed.ncbi.nlm.nih.gov/28229538/
[2] https://pubmed.ncbi.nlm.nih.gov/28356427/
[3] https://pubmed.ncbi.nlm.nih.gov/24582089/
[4] https://www.diabetes.co.uk/blog/2015/03/sugar-in-cereal-who-are-the-worst-offenders/
[5] https://pubmed.ncbi.nlm.nih.gov/27372453/
[6] https://rndb.clps.brown.edu/task/sucrose-preference-test/
[7] https://pubmed.ncbi.nlm.nih.gov/20648910/
[8] https://pubmed.ncbi.nlm.nih.gov/23719144/
[9] https://pubmed.ncbi.nlm.nih.gov/25673413/

Alternatives to testosterone replacement


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.


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/

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-
[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


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
[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


“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

The Proposed SARMs Control Act


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.