Excessive free radicals foster a state of oxidative stress in the body, frequently leading to chronic, low-grade inflammation, which is associated with numerous adverse effects on both short and long-term cellular health and well-being. For instance, oxidative stress and inflammation are known to damage mitochondrial components and cell structures as well as contribute to the development of insulin resistance, dyslipidemia, hypertension, cognitive decline, and liver damage.

Recognizing the need for natural alternatives to support an increasingly unhealthy world population, researchers discovered a ground-breaking synergistic combination three nutraceuticals, Butyrate, Vitamin A, and Beta-Caryophyllene, that improves antioxidant capacity and decreases inflammatory processes generated by free radicals and oxidative stress.

Gut health has been at the forefront of consumer demand as researchers continue to uncover the myriad ways the gut microbiome impacts health, performance, and well-being. Butyrate is a short-chain fatty acid (SCFA) naturally produced in the gut via fermentation of dietary fiber. It plays a critical role regarding intestinal homeostasis and energy metabolism.

With anti-inflammatory properties, butyrate improves intestinal barrier function and mucosal immunity, improving nutrient absorption while combating “leaky gut.” Furthermore, a growing body of evidence has highlighted the impact of butyrate on the gut-brain axis, gut-liver axis, and the gut-skin axis.

Carotenoids are fat-soluble pigments found in various foods that exert multiple beneficial functions in human health. Primarily, carotenoids offer antioxidant benefits, but they may convey beneficial effects on eye health, skin health, cognitive function and cardiovascular health.

For example, carotenoids may reduce the influence of inflammation on brain function by interacting with inflammatory signaling cascades. Β-carotene, the most studied carotenoid, is a precursor to vitamin A, and has been suggested to modulate cerebral plasticity. Lutein and zeaxanthin are the only carotenoids found in the human eyes and are responsible for filtering high-energy wavelengths of blue light, resulting in reduced oxidative stress in the retina. Because they interact synergistically with other antioxidants; carotenoid blends (like the one included in Caraflame) are more effective than single compounds.

Beta-Caryophyllene (BCP) is an important resin found in significant amounts in the essential oils of many different plants and foods, including oregano and cinnamon, that has traditionally been used for its anti-inflammatory and analgesic properties. In addition to its high anti-inflammatory capacity, BCP also offers unique cell-signaling properties that help to mitigate potentially hazardous cell replication.

In addition, beta-caryophyllene has been shown to act as a fully functional agonist of the CB2 receptor. CB2 receptors are involved in the modulation of inflammatory response not only at the immune system level, but also in the brain. BCP has also been demonstrated to interact with and up-regulate members of the PPARs family. More specifically, it can activate PPARα, supporting healthy lipid metabolism. Finally, PPARγ was demonstrated to be involved in BCP-dependent neuroprotection, vascular inflammation amelioration, anxiolytic, joint support effects.

After extensive testing, the prolific scientists behind CARAFLAME documented a unique synergy between Butyrate, Carotenoids, and Beta-Caryophyllene, especially in regards to benefits in muscle and liver cell tests. In particular, Caraflame demonstrated significant reductions in NF-kB phosphorylation (NF-kB is a key signaling protein involved in inflammation).

So, how do these nutraceuticals work together?

Pay attention, because it’s about to get heavy…

Cells contain a variety of receptors, which are turned “on” or “off” depending on the substances that bind to them, and thereby promote a distinct biological response. A crucial family of receptors in the body are peroxisome proliferator-activated receptors (PPARs) that function as transcription factors regulating the expression of genes, mainly affecting inflammatory processes.

Beta-caryophyllene acts as an agonist on two of these peroxisomes (PPAR-ɑ, and PPAR-ɣ). When activated, PPAR-ɑ controls nuclear factor-kappa beta (NF-kB), which is the main protein associated with inflammatory cytokines. Another function of PPAR alpha is to act as a transcription factor in mitochondrial biogenesis.

However, in the cell nucleus, PPAR-ɑ is always associated with another receptor of the same nature (homodimer) or a receptor of a different nature (heterodimer) to trigger the peroxisome proliferator response element (PPRE). When activated together, PPRE increases its activity in controlling NF-kB by curbing the biochemical cascade associated with inflammation.

Since beta-caryophyllene can act as an agonist for both PPAR-ɑ, and PPAR-ɣ, it plays an intriguing role in the mechanisms of homodimers, but not in heterodimers.

Among the carotenoids including in Caraflame is retinyl palmitate, which converts into a specific retinoic acid called 9-cis retinoic acid (9-cis RA), that, unlike other retinoic acids, acts as an on a receptor called retinoic X receptor (RXR) which heterodimerizes with both PPAR-ɑ, and PPAR-ɣ.

Essentially, it’s akin to using two different keys on two different deadbolts for the same door. This offers numerous benefits to inflamed tissues.

Last, but not least, butyrate, in addition to activating PPAR-ɣ, is converted into 9-cis RA in the epithelium (the outer layer of your skin), acting as a precursor of this retinoic acid, which can act simultaneously on heterodimer receptors. Furthermore, butyrate acts as a modulator of inflammatory cytokines, and interacts with specific receptors that modulate immunoinflammatory processes in the liver, controlling both the release of pro-inflammatory and anti-inflammatory cytokines (thereby supporting liver health).