SARMs for Fat Loss: New Evidence

Although SARMs are traditionally researched for their ability to increase lean body mass, there has always been interest in how SARMs can influence body fat specifically. Fortunately, recent research sheds new light on how SARMs can modify fat cell metabolism and alter levels of fat-storing hormones in the body. This new evidence suggests further research and development of SARMs to help manage body weight while supporting mass and strength.

Carrying excess body fat impacts quality of life and decreases life expectancy. In many individuals, being overweight is a chronic condition that cannot be solved with lifestyle changes alone. Being overweight promotes insulin resistance, type 2 diabetes, and it is associated with many related chronic diseases. Altering your lifestyle can obviously lead to weight loss in the early stages of weight management strategies, yet unfortunately most people relapse and regain those unwanted pounds.

Treatment strategies for maintaining an ideal weight requires evidence-based therapeutic options. Lifestyle modifications are always recommended, but any strategy designed for treatment and management of excess body fat are rarely successful long term because of lack of willpower to maintain a low-calorie diet. The limited benefits of currently available FDA-approved drugs, and the unwanted side-effects they cause have contributed to less than stellar results.

Androgens & Fat Burning

It is widely believed that testosterone helps fat burning. There is abundant research showing that testosterone can suppress fat gain, prevent the creation of new fat cells, and inhibit fat uptake. Crucially, high levels of bioavailable testosterone are associated with reduced fat mass in men. Testosterone replacement in men with metabolic syndrome leads to decreased body weight, reduced waist circumference, and less visceral fat mass. Moreover, low levels of testosterone and sex hormone-binding globulin (SHBG) can predict accumulation of abdominal fat and onset of obesity.

Androgens & Fat Burning

Another underappreciated aspect of androgens and body fat is that men who decrease body fat via low calorie diets can inadvertently decrease their total testosterone levels and free testosterone levels, thus making it more difficult to keep the weight off.

Men affected by androgen resistance due inactivation of the Androgen Receptor at the genetic level also have more visceral fat (ie. belly fat). Although this is a relatively uncommon genetic mutation, this is nevertheless an important indicator of how androgens help to prevent the “spare tire” around the belly. Other insights into androgens and body fat come from studies in which men with prostate cancer are given anti-androgens (ie. androgen-deprivation therapy) to slow the growth of tumors. In this context, 

Another androgen, dehydroepiandrosterone (DHEA) has been shown to reduce body fat in humans, increase glycerol release from fat cells, and stimulate the breakdown of triglycerides which leads to less fat mass. In addition, DHEA increases resting metabolic rate (RMR), which makes it easier to lose unwanted mass without increasing energy expenditure (ie. exercising more often or longer). All of these results suggest that in some men, DHEA supplementation can decrease body fat.

Unfortunately, DHEA can also reduce “good cholesterol” levels which in the long-term can paradoxically lead to body fat rebound. DHEA also has side effects (distinct from the well-known testosterone side effects) including fatigue, insomnia, and congestion.

Key points:

  • Long-term testosterone replacement therapy improves body composition, but only in men with pre-existing testosterone deficiency.
  • Unfortunately, long-term testosterone replacement therapy and DHEA treatment both have many undesirable side effects.

SARMs & Body Fat Metabolism

Since androgens have shown beneficial effects with regards to body fat metabolism, it was only a matter of time before researchers refocused their efforts on examining whether SARMs could similarly benefit body composition.

Enobosarm/Ostarine/MK-2866 is an AR activator which has shown positive effects in humans. It has undergone preclinical studies and toxicological testing in Phase I, II, and III clinical trials and it has demonstrated anabolic effects in humans. It has been shown to stimulate the growth of lean muscle with limited side effect compared to anabolic steroids. Multiple studies have shown that body-produced androgens regulate lipolysis (ie. fat burning) and hormonal activity of white adipose tissue (ie. visceral fat). Ostarine has undergone the most extensive clinical safety trials thus far, so it is emerging as one of the best candidates for further exploration of how SARMs can affect body fat metabolism.

SARMs & Body Fat Metabolism

Up until recently, there was no data about the effects of Ostarine on fat tissue specifically. Therefore, researchers decided to investigate the effect of Ostarine on the intensity of lipolysis (ie. fat burning ) and lipogenesis (ie. fat storage) and on the secretion of fat tissue-regulating hormones from isolated fat cells in vitro. They also wanted to test the effect of Ostarine on the levels of two key circulating hormones important for body weight management: leptin and adiponectin.

Leptin is a hormone produced and secreted by fat cells in a tight relationship with overall body fat mass. Leptin tells the brain about the status of energy stores in the body. However, this relationship is slightly more complicated than originally thought because people who are overweight have high leptin are resistant to the effects of leptin and feel hungry regardless of its secretion. Although the mechanism of action of leptin in regulation of AR remains a mystery, recent work demonstrates that Ostarine reduces the secretion of leptin from fat cells. This is crucial because high levels of leptin in the blood can cause suppression of the hypothalamus-pituitary-gonadal (HPG) axis leading to lower body-produced testosterone, so it’s beneficial that Ostarine lowers leptin levels.

Leptin is highly involved in a process called lipolysis, which is how the body extracts energy from fat by “burning” it. Intriguingly, Ostarine has been shown to increase lipolysis. This phenomenal discovery led researchers to investigate how else Ostarine might affect different measures on body composition changes.

Ostarine has also been shown to increase the levels of AR in fat cells. This is crucial for weight loss since AR works to increase metabolism in fat cells.

In other preclinical research, S4 Andarine has been shown to reduce body fat, although this study was conducted in female rats.

It is essential to point out that not all SARMs have the same effect on body fat metabolism. For instance, Ligandrol LGD-4033 has been shown to increase lean body mass in a dose dependent way, yet it does not decrease fat mass specifically. Thus, future clinical research geared towards managing body weight in the context of maintaining muscle mass may not utilize 

Key points:

  • There is new evidence that some SARMs, including Ostarine MK-2866 and S4 Andarine, can promote lipolysis (ie. fat burning) and alter fat-storing hormone profiles in beneficial ways.
  • Not all SARMs affect body fat metabolism the same way. LGD-4033 has not been shown to reduce body fat like other SARMs.
SARMs for Fat Loss Conclusion

SARMs for Fat Loss: Conclusion

Recent evidence supports further development of various SARMs, including Ostarine MK-2866 and S4 Andarine, in clinical trials studying sustainable body fat loss in long-term studies. Given that most dietary interventions for weight management are unsuccessful long-term due to unsustainable changes in caloric intake, it is essential that future research evaluates alternate mechanisms for promoting body fat loss and maintaining ideal bodyweight in fit, healthy men.

Fat Loss, Research, SARMs

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