Carnitine Fumarate (CF)
L-Carnitine is an amino acid with a primary function of carrying fatty acids into the mitochondria so they can be oxidized. It also favorably manipulates the Acyl COA/Acetyl COA ratio in favor of fat burning, and plays a key role in energy metabolsm (18).
Fumarate is a component of the Krebs cycle and plays a key role in generating energy.
The Carnitine & Fumarate combination, as CF, will help re-supply depleted carnitine to support optimal fat oxidation while also positively modulating osteoblast function at a rate about 10-fold greater than regular L-Carnitine, which has a significant impact on whole body metabolism and energy expenditure (also previously discussed in the AI section) (19,20). If you’ve read the EvoMuse BMP write-up, you’ll know how big of a deal this osteoblast angle really is.
In rats fed a fattening diet for 16 weeks, to the point of giving them metabolic syndrome, they developed central obesity, dyslipidemia, hypertension, impaired glucose tolerance, hyperinsulinemia, and NAFLD. The rats that were given Carnitine experienced an attenuation of ALL of these issues (21). Another rat study demonstrated that Carnitine was able to counteract obesity induced muscle fiber transition, and restore a muscle oxidative metabolic phenotype (22).
Momordin 35%
Momordin is a bioactive glycoside extracted from the bitter melon fruit grown throughout Asia, Africa & The Caribbean.
This is the third ingredient in the formula to target PPAR-d, in addition to GM and AI.
As a refresher, increased expression of this nuclear receptor has been shown to increase fatty acid oxidation in skeletal muscle by shifting the body's metabolic preference away from carbohydrate in favor of lipids (23). Momordin has been shown to upregulate human PPAR-d expression in vitro (24).
A study done in 2011 showed Bitter Melon Juice (containing momordin) was able to have a two-pronged attack on fat metabolism by inhibiting its storage as well as increasing rate of lipolysis in human fat cells (25).
In mice fed a high fat diet, the group receiving Bitter Melon bioactives lost weight, improved glucose metabolism and raised insulin sensitivity by increasing GLUT-4 density in skeletal muscle cells (26). It can also potentially slow gastric emptying, which improves glucose metabolism and insulin signaling (27).
Mangiferin
Mangiferin is known as a xanthanoid, and it is found in mangoes as well as a few other places in nature. It represents the 2nd DCP ingredient to target PPAR-a, along with GM.
As a refresher on PPARa, its activation is directly involved with all three stages of fat burning, and is one of the most important players in lipid metabolism. It is triggered naturally during calorie deprivation and in severe carbohydrate restriction to aid in the production of ketones. Mangiferin has been shown in several studies to effectively upregulate PPAR-a (28–30).
Unlike PPAR-a, PPAR-g is responsible for increasing storage of fat in the fat cell. Mangiferin has been shown to reduce its activity thereby reducing fat storage (31).
As discussed previously in the RE section, Mangiferin also targets DGAT. As a refresher, diglyceride acetyltransferase (DGAT) is the enzyme responsible for the third and final step in producing a triglyceride from glycerol and fatty acids. Downregulate DGAT, which Mangiferin has been shown to do, and you reduce fat accumulation and increase leptin sensitivity significantly (28).
Remember CPT1 from the AI section? Mangiferin hits this angle as well, causing an upregulation of CPT1, encouraging increased fat burning. It also cranks up Lipoprotein Lipase (LPL), another necessary enzyme in the fat burning process (28).
Mangiferin has been shown to improve glucose utilization by increasing GLUT4 density on the muscle cell, while activating AMPK (31,32). Along these lines, it has also been shown to reduce the cognitive decline associated with the downstream effects of diabetes by reducing Advanced Glycation End Products, oxidative stress, and inflammation (33).
A brand new human study on Mangiferin showed some excellent results. Subjects were overweight with hyperlipidemia. After 12 weeks of either Mangiferin or placebo supplementation, the Mangiferin group had decreased triglycerides, improved insulin sensitivity, increased HDL, increased ketones, and increased LPL. Mangiferin also promoted an increased oxidation of FFA’s (34).
Lastly, Mangiferin has been shown to prevent the differentiation of adipocytes, steering satellite cells away from becoming fat cells (35).
The one side effect that comes hand in hand with Mangiferin supplementation is carnitine depletion. Thanks to the CM in this formula, this will not be an issue.
Quick Overview of FTO
The “Fat mass and obesity-associated protein” is an enzyme encoded by the FTO gene, which does a pretty good job of describing itself in the name. Subjects with a gene variant overexpressing FTO show higher levels of insulin and insulin resistance.
FTO predisposes individuals to fat gain and obesity, whereas FTO-negative subjects are resistant to obesity due to enhanced energy expenditure, and reduced conversion of carbohydrates to fat (de-novo lipogenesis).
Fat cells deficient in FTO exhibit 4x higher expression of UCP1 in the mitochondria, and this FTO deficiency leads to a “browning” of white adipocytes (see EvoMuse BRITE for more on why that’s awesome, which is our product directly targeting this browning effect through multiple angles) (41–43).
The next two ingredients in DCP, among other things, target FTO.
Quercetin-Theobromine cocrystals
Quercetin is one of the most studied flavonoids, and has tons of extremely impressive research backing its benefits. Problem is, most of that research is either in vitro, or, in animals with dissimilar digestion/absorption framework.
The reason for the lack of good human in vivo data, is that the efficacy of this nutrient is extremely limited in humans due to low bioavailability, caused by low aqueous solubility and minimal absorption in the gut. The human liver also does a number on it through some pretty unfavorable conjugation.
One study in particular looked at human ingestion of a huge oral dose of quercetin (4g), and found no measurable increase in plasma or urine quercetin concentrations…yikes. What the researchers did find, however, was that about 53% of the quercetin dose was recovered in subject’s feces, suggesting extensive degradation by microorganisms in the gut (44).
Now comes the cool part.
Cocrystals are multi-component molecular crystals that dramatically improve bioavailability of certain nutrients (flavonoids in particular). By turning quercetin into a cocrystal with theobromine, the pharmacokinetic properties become vastly superior, and this process yields a quercetin which is able to completely overcome the problem of water insolubility and bioavailability (45).
This means we can finally reap all of the awesome benefits of quercetin.
For our purposes in the DCP formula, these benefits relate to multiple, potent angles to augment fat loss.
First things first, quercetin has a very high binding affinity to the aforementioned FTO gene. This means it will basically put FTO in a headlock and prevent it from carrying out its diabolical plan to keep you from losing fat. Through FTO inhibition, quercetin will favorably tip the lipolysis/adipogenesis ratio, encouraging fat loss while reducing fat storage (46,47).
Then it hits that same idea through a different pathway, just to be sure. Specifically, it does so by increasing the expression of ATGL and HSL, while downregulating FAS, LPL, and aP2 (48). Simply put, it cranks up fat burning enzymes while suppressing fat storing enzymes.
Quercetin also targets the AMPK pathway. Here’s what you need to know about AMPK in 10 seconds:
AMPK is an enzyme that regulates energy balance. When activated, it triggers fat oxidation (liver and skeletal muscle), puts the brakes on fat storage, encourages ketone production, tells the muscles to take up glucose, and as a few other cool things. Some of the benefits of exercise can be tied back to simple AMPK activation.