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Semaglutide (Ozempic) - The Holy Grail Of Fat Loss?

Initially approved by the FDA back in 2017 for controlling type II diabetes in adults, semaglutide is a drug that belongs to the group of the GLP-1 (glucagon-like peptide 1) analogues. This group of substances has the ability to mimic the body's response after eating a meal, including feeling full, as well as regulating insulin response and altering gastric emptying. Before that, liraglutide, another GLP-1 analogue, had been approved by the FDA in 2010 under the brand name Saxenda.

Clinical studies involving semaglutide showed that patients on it were also losing weight, somewhere in the neighborhood of 11lbs over the course of three months. While that may not seem like much, this loss in body weight came with no dietary modifications, so take a moment and just imagine how powerful this drug can be if paired with a moderately aggressive caloric deficit.

As a matter of fact, users have reported losing 15 up to 20% of total bodyweight in that same timeframe when taken in conjunction with proper dieting and training. That's huge! If we take a 200lbs individual, we're talking about some 30lbs of weight (mostly fat, if the other variables are optimal) lost in three months.

Naturally, as this new drug hit the market under the brand names Ozempic and Wegovy, both from the Danish pharmaceutical company Novo Nordisk, we are seeing a tremendous interest in it coming from bodybuilders, fitness fanatics, soccer moms and just about anybody looking to lose weight. Ozempic is originally meant for type II diabetes control, while Wegovy was formulated more specifically for its weight loss capabilities.

Individuals taking semaglutide (or other GLP-1 analogues for that matter) can expect the following benefits:

- Once-a-week subcutaneous application;
- Loss of appetite;
- Controlled insulin levels even with higher glycemic loads;
- Easier to stay on diet;
- Especially helpful for overweight or obese individuals;
- Slower gastric emptying (feel full for longer).

We all know there's no free lunch, so you can expect as possible side effects:

- Moderate Nausea, vomiting, constipation, diarrhea and abdominal discomfort;
- Liver issues if individual is prone to it;
- Prolonged use may cause pancreas amylase levels to rise;
- Drug withdrawal has to be done slowly and gradually;
- May cause hypoglycemia since you won't feel the need to eat as often;
- Aggressive rebound, meaning if you go back to eating as you did before you'll most likely gain the weight back;

Personally, the way I see these GLP-1 drugs is as a tool to help you adhere to a better diet and lose fat, especially if you are overweight or obese. Its use should be limited to a certain period of time, paired with proper dieting and training, and discontinued as you reach a better physique, not as something that allows you to eat whatever. As such, it's very powerful and can yield amazing results.

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ESTROGEN AROMATIZATION​


Testosterone is the primary substrate used in the male body for the synthesis of estrogen (estradiol), the principal female sex hormone. Although the presence of estrogen may seem quite unusual in men, it is structurally very similar to testosterone. With a slight alteration by the enzyme aromatase, estrogen is produced in the male body. Aromatase activity occurs in various regions of the male body, including adipose, liver, gonadal, central nervous system, and skeletal muscle tissues. In the context of the average healthy male, the amount of estrogen produced is generally not very significant to one’s body disposition, and may even be beneficial in terms of cholesterol values (See Side Effects: Cardiovascular System).

However, in larger amounts it does have potential to cause many unwanted effects including water retention, female breast tissue development (gynecomastia), and body fat accumulation. For these reasons, many focus on minimizing the build-up or activity of estrogen in the body with aromatase inhibitors such as Arimidex and Cytadren, or antiestrogens such as Clomid or Nolvadex, particularly at times when gynecomastia is a worry or the athlete is attempting to increase muscle definition. We must, however, not be led into thinking that estrogen serves no benefit. It is actually a desirable hormone in many regards. Athletes have known for years that estrogenic steroids are the best mass builders, but it is only recently that we are finally coming to understand the underlying mechanisms why. It appears that reasons go beyond the simple size, weight, and strength increases that one would attribute to estrogen-related water retention, with this hormone actually having a direct effect on the process of anabolism. This is manifest through increases in glucose utilization, growth hormone secretion,and androgen receptor proliferation.
Estrogen may play a very important role in the promotion of an anabolic state by affecting glucose utilization in muscle tissue. This occurs via an altering of the level of available glucose 6-phosphate dehydrogenase, an enzyme directly tied to the use of glucose for muscle tissue growth and recuperation. More specifically, G6PD is a vital part of the pentose phosphate pathway, which is integral in determining the rate nucleic acids and lipids are to be synthesized in cells for tissue repair. During the period of regeneration after skeletal muscle damage, levels of G6PD are shown to rise dramatically, which is believed to represent a mechanism for the body to enhance recovery when needed. Surprisingly, we find that estrogen is directly tied to the level of G6PD that is to be made available to cells in this recovery window. The link between estrogen and G6PD was established in a study demonstrating levels of this dehydrogenase enzyme to rise after administration of testosterone propionate.

The investigation further showed that the aromatization of testosterone to estradiol was directly responsible for this increase, and not the androgenic action of this steroid. The non-aromatizable steroids dihydrotestosterone and fluoxymesteronewere tested alongside testosterone propionate, but failed to duplicate the effect of testosterone. Furthermore, the positive effect of testosterone propionate was blocked when the aromatase inhibitor 4- hydroxyandrostenedione (formestane) was added, while 17-beta estradiol administration alone caused a similar increase in G6PD to tesosterone propionate. The inactive estrogen isomer alpha estradiol, which is unable to bind the estrogen receptor, failed to do anything.

Further tests using testosterone propionate and the anti-androgen flutamide showed that this drug also did nothing to block the positive action of testosterone, establishing it as an effect independent of the androgen receptor.
 
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