Can Ketone Esters be Used as an Antiobesity Supplement?


Well-known member
May 24, 2021
Not all body fat is created equal in the body and, as hard it is to believe, there is actually a type of body fat that is considered beneficial and if you are trying to stay lean, you probably wish you had more of it!

The predominate type of bodyfat and the one most familiar to all of us is called White Adipose Tissue (WAT). WAT is the subcutaneous fat that many of us struggle to shed and is associated with several metabolic related disorders such as type 2 diabetes, heart disease, stroke, high blood pressure, dyslipidemia and sleep apnea. At one time WAT was thought to simply be a depository of excess energy/calories. However, with continued research, WAT has been found to be a significant endocrine organ producing many different hormones with physiological effects in the body such as: energy balance, glucose and lipid metabolism and the immune system. Strangely enough bodyfat is not lazy, it is a very active organ and impacts many functions in the body. However, having too much WAT results in a dysregulation of the hormones produced contributing to many of the disorders associated with obesity. Some (not an exhaustive list) of the hormones produced by WAT include:
  • Leptin
  • Estrogen
  • Cytokines
  • Adipsin and acylation-stimulating protein (ASP)
  • Angiotensinogen
  • Plasminogen activator inhibitor-1 (PAI-1)
  • Adiponectin
  • Resistin
  • Steroid hormones
Another form of fat found in the body is Brown Adipose Tissue (BAT). The primary function of BAT in mammals is to help the body’s core temperature from falling too low through a process of non-shivering thermogenesis when exposed to cold temperatures. The other form of thermoregulation encountered in the body in cold climates, that the majority of adults will be familiar with, is the phenomenon of shivering (infants do not have the capacity to shiver). In an evolutionary survival adaptation, babies have a larger percentage of brown fat (~5%) than adults do as their risk of hypothermia is much greater. As humans age, the amount of BAT will decrease. Typically, women will have more BAT than men and elderly adults will have less than younger adults.

BAT’s cellular composition and function is similar to muscle tissue in the way it produces energy. The body produces energy in cells via mitochondria. Mitochondria in WAT is relatively scarce and is found in a much higher concentration in BAT. Brown fat can burn triglycerides and glucose in high concentrations to produce heat energy in its attempt regulate body temperature in sufficiently cold ambient temperatures. The high presence of mitochondria and iron in BAT give it its brown color.

There is a third type of bodyfat called similar to BAT called “beige fat” (bAT) or sometimes referred to as “brite fat” (brown in white fat). Beige fat is similar to brown fat but BAT is much more metabolically active burning more than five times as much stored energy. A study (*) published in 2020 in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism concluded: “short-term cold exposure may help people with brown fat burn 15 percent more calories than those without.” “The researchers identified two groups using a PET scan -- those with and without active brown fat. They analyzed brown fat function and energy expenditure in these individuals before and after short-term cold exposure finding that the group with active brown fat not only burned significantly more calories but had a healthier fatty acid blood profile.”

Similar to the activation of brown fat, researchers discovered that beige fat is produced from WAT through a “browning process” that is predominately generated from cold exposure “typically 3°C above a person’s shivering temperature point, which is around 11°C for women and around 9°C for men.” (*) Another way WAT can be converted to beige fat is through exercise: “more recently it has been demonstrated that exercise, through a range of mechanisms, induces a phenotypic switch in adipose tissue from energy storing white adipocytes to thermogenic beige adipocytes.” (*)

The way brown fat produces heat is through a process called uncoupling that occurs during the production of energy in the mitochondria found in the BAT. Mitochondria are often referred to as the “powerhouse of the cell”. Mitochondria produce ATP which is used to power most processed in the body. No ATP, No Life! However, during uncoupling the production of ATP is essentially short circuited and instead of producing ATP, heat is generated or thermogenesis.

What makes this unique thermogenic process of heat production possible in the mitochondria of the BAT is a protein called Uncoupling protein 1 (UCP1) or thermogenin. “By this process, UCP1 uncouples respiration from ATP synthesis and therefore provokes energy dissipation in the form of heat while, also stimulating high levels of fatty acid oxidation.” (*) Obviously the part about “high levels of fatty oxidation” (a.k.a fat burning) peaks the interest of most of us wishing to shed a few extra pounds. It is also of interest to researchers how it may be possible to capitalize on and/or enhance the fat burning capabilities of BAT beyond the less than appealing teeth chattering thought of exposing one’s self to long periods of cold.

A study published in 2012 (Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet) provides us some hope of a simpler way of enhancing/maximizing the fat burning capabilities of BAT with the supplementation of a Ketone Ester (KE). The title effectively gives away the conclusion, but let’s take a closer look at the results of this research.

  • Blood D-β-hydroxybutyrate levels in the KE group were 3-5 times those reported with high-fat ketogenic diets.
  • Voluntary food intake was reduced dose dependently with the KE diet.
  • Feeding the KE diet for up to 1 mo increased the number of mitochondria and doubled the electron transport chain proteins, uncoupling protein 1, and mitochondrial biogenesis-regulating proteins in the interscapular brown adipose tissue (IBAT).
  • Plasma leptin levels of the KE group were more than 2-fold those of the Ctrl group and were associated with increased sympathetic nervous system activity to IBAT.
  • The quantitative insulin-sensitivity check index was 73% higher in the KE group.
  • The resting energy expenditure for the KE group was ~14% greater than that for the Ctrl group.
  • These results identify KE as a potential antiobesity supplement.
Digging deeper into the results of this research, it was found that that not only did the number of mitochondria (powerhouse of the cells) nearly double, but the size of the mitochondria also more than doubled in comparison to the control group. The researchers also found that although glucose levels did not change significantly between the KE diet group and the control group, insulin levels were found to be significantly lower indicating that the mice that ingested the KE had become significantly more insulin sensitive.

After the final analysis of all the collected data, the authors conclude:

"Therefore, our results of reduced voluntary food intake, increased insulin sensitivity, increased resting energy expenditure, and brown fat activity in the KE-treated group demonstrate the utility of this compound as a potential antiobesity supplement."