In 2013, Evolutionary Muse rocked the industry by releasing the first product designed to cause white adipocytes to convert into BRITE adipocytes. Aptly named BRITE, these adipocytes are named for being BROWN IN WHITE cells—white adipocytes which behave like brown adipocytes. Brown adipocytes are metabolically active cells which, unlike white adipocytes, use their fat stores to generate body heat. Long thought to be non-existent or very rare in humans, brown adipocytes were discovered to be quite active, though through evolution, environmental mastery (i.e., comfortable living via climate control), and more than adequate dietary satisfaction (leading to its own hormonal milieu), brown fat activation became almost dormant. This brown fat:white fat reduction has instead led to massive insulin resistance, leptin chaos, and major obesity.
With years more painstaking research, Evolutionary Muse has once again taken huge leaps forward, finally perfecting a formula that is easily encapsulated in a powdered version, while delivering a powerhouse formula that triggers a huge shift in damaging white fat towards metabolically hyperactive BRITE fat.
Difference between WAT and BAT Brown Adipose Tissue (BAT) is abundant in small mammals like rodents, as well as newborn humans, and is thought to offer an evolutionary protection against cold temperatures to increase survival rate. BAT works quite differently, if not opposite, to White Adipose Tissue (WAT). BAT is dense in mitochondria and considered a highly thermogenic fat cell, responsible for creating heat through a process called “non-shivering thermogenesis”. This process burns calories through a futile cycle of shuttling protons to the mitochondria to generate heat. WAT, however, is what we all think of when we hear the term “body fat”. It stores calories so they can be used later during periods of hunger or famine, and secretes various adipokines. This is a crucial part of our physiology, and we would not exist today without it. But these WAT cells can become dysfunctional (for genetic reasons, poor diet, lack of exercise, etc.) and get too good at storing fat.
It was previously thought that adult humans have an inconsequential amount of BAT. In recent years, however, it has been determined that we have more than originally thought. We have also learned that we don’t need a large volume of these cells to have a significant impact.
Even more recently, we have discovered another player in the adipocyte story—Brown-In-White cells, or “BRITE”. At a microscopic level, these cells display a color between brown and white, and behave in a similar thermogenic fashion to BAT cells. They are also known as beige, inducible, recruitable-brown, and brown adipocyte-like cells, but we will refer to them as beige/brite moving forward.
The research on brite cells is still in early stages, but we now know enough about how they are formed and the metabolic advantage they are capable of providing that we can target them as a viable and important angle in weight management and metabolic optimization. UCP1 expressing adipocytes are lower in obese and older subjects. While we don’t know yet if reduced thermogenic activity is a cause or consequence of obesity, we do know that an increase in BAT and/or brite cells improves glucose tolerance and insulin sensitivity.
Two distinct pathways exist towards increasing brite cells in adult humans, (1) triggering precursor cells into becoming brite cells, and (2) turning mature WAT cells into brite cells. We want to target these pathways directly so that we can increase the ratio of brite cells to WAT cells, allowing your body to constantly burn more calories.
Let’s dive into some of the known methods of brite cell creation and activation.
Irisin and PGC-1alpha Exercise causes increased expression in muscle of PPARg coactivator 1-alpha (PGC-1a), which downstream results in a hormone/myokine called irisin. This irisin contributes to a browning of WAT cells. So not only does exercise burn calories directly, but also secondarily through triggering the browning process with irisin. Fortunately, this is an exploitable angle independent of exercise by triggering the PPARg cascade.
Cold Therapy, B3 adrenergic activators Cold exposure triggers macrophages in BAT to produce catecholamines like norepinephrine (NE). NE agonizes b-adrenergic receptors on fat cells. Cold also activates beige cell development and function. The effect can be mimicked with b3 adrenergic activators, which also trigger PGC-1a and brite cell development. It can also be mimicked with TRPM, or cold-sensor activators.
PRDM16, BMP-7 Prdm16 is a transcriptional cofactor, substantially enriched in human BAT compared to adjacent WAT. It acts by binding to and modulating other factors like C/EBPb, PPARy, PPARa, and the aforementioned PGC-1a. Knocking out Prdm16 negates the thermogenic effect of brown cells, and increases WAT. Considered a key driver of brown fat cell fate, this cofactor is quite important. Bone Morphogenetic Protein-7 (BMP-7) increases expression of Prdm16 in precursor cells, and is essential for brown fat development. BMP-7 is fortunately something we can target with supplementation.
Adenylyl Cyclase (AC) and Alpha-1 adrenergic activation AC is an enzyme that catalyzes the conversion of ATP to cyclic AMP. We mentioned beta-adrenergic receptor agonism, but it turns out this is greatly enhanced with simultaneous AC upregulation and alpha-1 activation. So targeting AC, alpha-1, and beta-adrenergic agonism together causes enhanced brite cell creation.
UCP1 BAT mitochondria respond to something called UCP1 (uncoupling protein 1) to burn fat and generate heat, while brite cells seem to express lower levels of UCP1. However, brite cells potentially burn fat independently of UCP1 signaling, and furthermore, with the proper triggers, brite fat can actually turn on high levels of UCP1. Multiple ingredients in the BRITE formula will encourage WAT cells to upregulate UCP1 levels.
Some of you may be familiar with a somewhat popular drug in the bodybuilding community years ago called DNP (which actually has roots in the 1930s as a weight loss drug). DNP was meant to mimic activated UCP1, which drastically elevated thermogenesis. While extremely effective, unregulated uncoupling can (and did) cause hyperthermia and death. Fortunately, we now have effective ways of targeting UCP1 safely.
Ingredients and Function
Butcher’s Broom Extract Butcher’s Broom is an herb, also known as Ruscus aculeatus. It gets its name from the practice of butchers using it for its supposed antibacterial properties to clean their cutting boards. It has been used in traditional medicine for its vasoconstrictive and anti-inflammatory actions (reducing swelling, preventing hemorrhoids, etc).
The plant contains a variety of saponins, which have been shown to activate alpha-1 adrenergic receptors and stimulate the release of norepinephrine. It also has a protective effect on capillaries, strengthens blood vessels, and helps maintain healthy circulation (1).
As discussed previously, this alpha-1 activation is important and has been shown to shift preadipocytes to beige cells as opposed to white adipose tissue (2). As well, recent research shows that when hibernating animals’ thermosensitive merchanisms detect ambient and body temperatures falling under threshhold, the SNS releases norepinephrine to activate BAT in order to maintain viable body temperatures.
Andrographolides SREBPs are major transcription factors involved in adipogenic differentiation from precursor cells, as well as factors in fat storage. Andrographolides downregulate the expression of SREBPs and target genes in BAT, decreasing fat storage and encouraging differentiation to brite cells. Andrographolides also target the activation of the TRPV4 and TRPV1 receptors. Finally, andrographolides trigger an increase in Wnt/b-catenin signaling, contributing to the WAT browning process (14–17).
Safflower Leaf Extract By enhancing angiogenesis through the VEGF signaling pathway, SLE promotes differentiation from precursor cells away from the WAT pathway.
Several studies have looked at the effect of SLE on rodents given obesogenic diets, with a long list of benefits elucidated. By promoting the browning of subcutaneous WAT and activating the IRS1/AKT/GSK3b pathway, the SLE groups saw reduced body fat mass, inflammation, fasting blood glucose, and total cholesterol and triglycerides, with an increase in insulin sensitivity (18–20).
Another study, in addition to reaffirming the above findings, also showed an interesting benefit in gut function by increasing short chain fatty acid production and improving gut microbiota (21).
Gypenosides Gypenosides are saponins found in the Jiaogulan plant. This ingredient targets both WAT and BAT. We get WAT browning, and an increase in fat oxidation genes in both WAT and BAT. Obesogenic diet mice treated with gypenosides had a significantly reduced bodyweight vs. control, with lower cholesterol and insulin resistance. Interestingly, similar to Safflower Leaf Extract, research also shows improved gut microbiota with gypenosides supplementation (22).
Menthol Aside from b3 adrenergic receptor activation, the other most important way to start the browning process of WAT browning, as previously discussed, is through cold exposure. By exposing the body to cold temperatures long term, it activates the TRPM8 receptor, which triggers browning in order to more effectively use WAT to create body warmth (23).
TRPM8 activation also enhances the thermogenic function of brown adipocytes through UCP1 and the b-adrenergic pathway.
Menthol mimics long-term cold exposure by activating the TRPM8 channel, and has been shown to induce WAT browning, as well as an upregulation in BAT thermogenesis. This has been shown to increase core temperature, reduce body fat and improve glucose metabolism (24–26).
Piperonal Piperonal is an active constituent of piper nigrum seeds and also found in vanilla. It has been called a “potent antiobesity agent”, and is another ingredient in the formula that brings the one-two punch of inhibiting preadipocyte differentiation and upregulating thermogenic genes in WAT (27).
In rodents fed obesogenic diets, piperonal did everything you could hope for. It attenuated body fat gain, adipocyte size, glucose and insulin elevation. It stimulated AMPK and elevated circulating adiponectin (28,29).
Black Pepper Extract TRPV1 is a capsaicin and vanilloid receptor in the body that is responsible for detection and regulation of body temperature and pain. More recently this receptor has been identified as a major player in obesity and body fat regulation. Stimulation of TRPV1 has been shown to upregulate BAT and increase fat oxidation and energy expenditure. TRPA1 is a similar receptor that functions to recognize cold and pain.
Piperine, as well as several other compounds in black pepper have been shown to be TRPV1 and TRPA1 agonists, with an even greater efficacy than capsaicin (30,31).
Trans-Cinnamaldehyde Trans-Cinnamaldehyde is a pungent compound from cinnamon or dried cassia bark. TC has been shown to increase UCP1 in both WAT and BAT, inducing browning of WAT cells. It also activates the cold receptor TRPA1. Back to those rodents fed obesogenic diets, TC inhibited hypertrophy of adipose cells, decreased body fat (including visceral fat), decreased voluntary food intake, and improved insulin sensitivity (42,43).
Wasabi Leaf Extract From the Japanese Wasabi plant, this leaf extract targets body fat loss in a few different ways. One of the most important ways to cause a browning of WAT is through the b3 adrenergic system. WLE has been shown to upregulate expression of the b3 adrenergic receptors in BAT (44).
In multiple studies looking at mice and rats fed an obesogenic diet, groups given WLE showed significantly less body fat. Fat storage markers were suppressed (SREBP-1c, PPARy, C/EBPa), and thermogenic/fat burning markers were enhanced (PPARa, adiponectin, AMPK). Adipose cell hypertrophy was inhibited, and fatty acid oxidation was enhanced (45,46).
Sesamol Sesamol is a phenol derivative of sesame oil with antioxidant and anti-inflammatory properties. This is another ingredient in the formula with the aforementioned two-pronged attack. It downregulates adipogenic differentiation factors (C/EBPa, PPARy, SREBP-1), and decreases fat accumulating enzymes like fatty acid synthase (FAS), while upregulating fat oxidizing enzymes like HSL, LPL and AMPK. In mice on an obesogenic diet, it decreased fat mass and adipocyte size in both WAT and BAT by increasing UCP1 and PCG1a (53–55).
Strawberry Fruit Extract A new and surprising set of studies recently done on Strawbnerry Fruit yielded potent results in the area of BRITE formation. A methanol extract proved incredibly potent in triggering BRITE formation in adipocytes, arrest of development of preadipocytes into mature fat cells, AMPk activation in mature adipocytes as well as SIRT1/PGC1a/and UCP1. The extract also showed potent triggering of mitochondrial biogenesis in adipocytes, probably the biggest indicator of browning as the actual site of heat generation.
Raspberry Fruit Extract Recent discoveries in AMP kinase, that potent pathway activated during demanding exercise which facilititate fat burning and metabolic adaptation, yielded some interesting observations – notable a subtype of AMPk that was adipocyte specific. If you are beyond a certain level of understanding, you will already have your interest piqued. You see, AMPk activation (the dreaded cardio catabolism), in conventional understanding, prevents mTOR activation, which normally short circuits protein synthesis. This newly discovered subtype of the AMPk receptor, as mentioned, is adipoctye specific – meaning we can hit this HARD, and shrink those fat cells rapidly, without deleterious effects on muscle grown. The specialized Raspberry Fruit extract we have used is insanely potent not only triggering previously mentioned pathways (UCP1, nonshivering thermogenesis, etc) but preferentially activates this new AMPk-alpha1 subtype. We are able to combine this in a way that will minimize that “do I want to build muscle or burn fat” conundrum, and allow for best of both worlds results.
Mulberry Leaf Extract One of the superstars of this new version of BRITE Capsules is the Mulberry Leaf Extract. In addition to hitting some of the above pathways, the unique polyphenols and other compounds not only contribute to ideal Leptin signaling, massive BRITE cell activation/uncoupling, but manipulate our gut microbiota to push towards a lean phenotype. In our guts there dwell different subtype of bacteria that act as master controllers of things like glucose metabolism, inflammatory state, etc. These two subtypes (among others: see Gut Health) are called Bacteriodetes and Firmicutes. When the Firmicutes dominate then “cute” is not what we wind up. These bacteria cause metabolic dysfunction and obesity. By enhancing the Bacteroidetes domination, our bodies reduce inflammation, normalize glucose metabolism, reduce metabolic disorder, and re-express that lean phenotype we all crave.
Other ingredients: When I released the previous version of the BRITE capsules, it was an attempt to duplicate the incredible potency of the BRITE liquid, in a much simpler form. At the time, I had yet to delve into the labyrinth that was “absorption”, and so much of the previous formula was not ideal. Since then, as you know, I have done a tremendous amount of work here.
While each formula requires a different approach to absorption, the two angles we are hitting are :p-GP inhibition and Physical contact enhancement with enterocytes.
Borneol – Borneol is a very potent p-Glycoprotein efflux pump inhibitor. While “distracting” the p-GP pump, the ingredients of BRITE are able to enter the body unhindered by this physiochemical saboteur.
Chitosan – Chitosan forms a very thin “film” that sticks to the walls of the intestine, pressing the active ingredients tightly against the enterocytes and pushing them physically into the bloodstream.
Conclusion As you can see, we have exhaustively targeted all of the known pathways of creating and activating BRITE cells in the body through either recruiting precursor cells or converting mature white cells. Regular supplementation should encourage fat loss and mimicking of a lean phenotype acutely, and even more so when taken chronically—as BRITE cells don’t immediately revert back to white adipose upon cessation of the product. BRITE is a long-term solution to an ongoing, serious problem plaguing modern society.
The Epitome of Fat Loss
Epitome is a brand new, cutting-edge development in fat loss. It works in ways we've only previously been able to fantasize about. Epitome helps control appetite and accelerates fat burning by manipulation of the leptin pathway. By increasing leptin sensitivity and keeping leptin levels within normal range, the brain and body self-adjust to drive your physique where it should be: Lean. Leptin signals will tell your body that it's not hungry while at the same time telling your brain to burn that fat!
With the addition of Gypenosides we boost AMPk signals, literally causing the body to react as if you are smack dab in the middle of a heavy demanding workout, causing additional acceleration of fat loss. Epitome is exactly what it promises — the epitome of fat loss.
Epitome Fat Loss Amplifier 120 Capsules
Serving size: 2 caps
Birch Bark Extract 20:1
Orthosiphon Staminus Ethanol leaf Extract 20:1
Gynostemma Pentaphyllum 98%
Stem Bromelain (800,000 U/g)
Betulinic Acid/Ascorbic Acid Crystalline Complex
Magnolia Officianalis (60% Magnolol)
semen cassiae 20:1 Hydroalcoholic
We have moved to a MUCH upgraded formula, while trying to keep the price close to the same. Upgrades are:
Betulinic Acid - The herbal extract will be blended with a Betulinic Acid / Ascorbic Acid cocrystal, which increases solubility and absorption over 20 fold. In addition, the
Chitosan forms a mucoadhesive which will increase time in contact with the intestinal wall, also increasing absorption.
Gypenosides are comparable to Queen Bee Acid as an AMPk activator, but at a much lower cost, offsetting the very expensive BA.
Stem Bromelain inhibits an enzyme called PDE3B. PDE3B is activated by insulin, and contributes to the blunting of lipolysis through elevated insulin levels. This means Epitome, in addition to all of the potent effects, will also not be affected as bad by food intake/elevated insulin.
*Magnolol - potent Magnolia compound which suppresses Cortisol induced visceral fat accumulation (belly fat), inhibits aromatase, as well as inhibiting PTP-1b (same as BA)
*Semen Cassiae - is an ingredient that boosts lipolytic function. Working with the rest of the formula, SC acclerates release of fatty acids from fat cells to be burned, as well as boosting fat burning pathways.