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Clean and Natural

Four simple ingredients

What's in it?

iCalm is the first product that acts on 8 key cellular pathways involved in anxiety. Our ingredients were carefully picked and studied to find the most synergistic combination and ratios of all natural ingredients. We are also sure to use doses well above what has been shown to be clinically effective to ensure anyone that consumes the product will have noticeable relief.


Pillars of iCalm effectiveness:


1

Reduce hyperactive neurons

2

Decrease stress hormones

3

Stop inflammation in its tracks

4

Improve mood and focus



If you’re like us, a true health nut that really likes understanding HOW different supplements work in your body, then keep reading below for a deeper dive into the scientific explanations as to what anxiety is at the molecular level and how iCalm can extinguish even the most severe anxieties and keep them at bay for extended periods of time.

The science behind how iCalm works.


Our mood is dictated by various neurotransmitter systems. Different areas of your brain communicate through electrical messages that are conducted through neuron cell bodies. The tiny gap between the end of one neuron and beginning of another is a space called a synapse. It is here where neurotransmitters, the tiny chemical messengers that transmit signals between neurons, are released from the first neuron and bind receptors on the following neuron. There are many kinds of neurotransmitters, each having both distinct and overlapping functions with other types of neurotransmitters.

Everyone has heard of serotonin and dopamine, which are responsible for long-term senses of well-being and short-term pleasure, respectively. There’s also norepinephrine and noradrenaline, which are excitatory neurotransmitters. Whether you’re overwhelmed, anxious, or living through a full-blown panic attack, these two are dramatically elevated, thus leading to the classical symptoms of anxiety. We sought to create an all-natural drink that you can down in one gulp to instantly shift your brain chemistry away from stress and anxiety and towards an uplifting, focused, zenful state.
Ingredient 1

GABA

Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. Its primary function is to counteract the action of excitatory neurotransmitters. When released in the synapse between neurons, GABA binds to GABA receptors. This acts as a “brake” on neuron circuits to slow down excessive neuronal firing. In fact, it’s been shown that those with both anxiety and depression are often deficient in GABA1. Many prescription anxiety medications target these same GABAA receptors, but users often report rapid tolerance build up, side effects, and worst of all withdrawal symptoms including severe panic and anxiety. Thus, when starting our search for natural alternatives, we knew that GABA simply had to be in iCalm, as supplementing with GABA helps send messages to the brain, heart, and lungs to slow down.
Ingredient 2

Taurine

Taurine is an amino acid that occurs naturally in the body across numerous organs with a wide array of functions. In fact, it is one of the most abundant amino acids in the human body and is also found in animal meats, fish, and eggs. In the context of anxiety, Taurine has been proven to calm anxiety through numerous mechanisms. First, Taurine binds glycine receptors, which are like GABAA receptors in that they slow down neuron firing2,3. In addition, Taurine increases the expression and activity of glutamic acid decarboxylase (GAD) enzymes4. GAD enzymes are responsible for converting glutamate, an excitatory neurotransmitter, into GABA. So not only does Taurine increase inhibitory signaling via glycine receptors, but it also increases natural GABA production. As if this wasn’t good enough, this powerhouse molecule also blocks NMDA receptors5, which prevents the excitatory neurotransmitter glutamate from ramping you up. Thus, Taurine is not only promoting inhibitory brain signaling, but also blocking excitatory brain signaling!

While balancing excitatory and inhibitory signaling is critical for anxiety, inflammation has also been linked to anxiety6. Luckily, Taurine has even been demonstrated to quell inflammation through a conversion into Taurine chloramine in response to inflammation7. This metabolite stops the production of interleukin-6 and -8, which are pro-inflammatory cytokines produced by white blood cells to promote inflammation8. This inflammation-anxiety link works both ways, as high stress has also been shown to initiate inflammation9. In today’s world of processed foods and pollutants, minimizing inflammation can not only be an uphill battle, but also a critical component in reducing stress. Given the wide array of calming mechanisms exerted by Taurine, it comes as no surprise that Taurine deficiencies are very common in not only anxiety, but epilepsy, and depression as well. Whether its intranasal administration of Taurine to mice10 or long term taurine supplementation in aging humans11, Taurine has been definitively proven to enhance not only GABA, but overall inhibitory signaling to reduce overexcitation.
Ingredient 3

L-theanine

L theanine is an amino acid analog of the amino acids L-glutamate and L-glutamine. It is primarily found in green and black tea leaves. Similar to taurine, L-theanine also blocks NMDA receptors and boosts natural GABA production. However, L-theanine has also been shown to elevate serotonin and dopamine levels. Not only does theanine lower anxiety, but also improves your overall mood so you’re calm AND happy! In addition to this, human trials have shown that L-theanine supplementation also decreases cortisol production12. Cortisol is the body’s primary stress hormone released during stressful situations, with chronically elevated cortisol being a hallmark of anxiety13,14. Increases the expression of glutamate receptor subunit zeta 1 (GluN1). To keep it simple, this is a subunit that NMDA receptors are comprised of. The less GluN1, the more likely hyperactivity and anxiety is to occur15,16. In short, L-theanine promotes the formation of NMDA receptor types that promote more stable neuron firing, which synergizes greatly with the NMDA blockage caused by both L-theanine and Taurine. Putting these all together, it makes sense why L theanine has been shown to increase focus and attention for those with anxiety by promoting alpha frequency brain waves17. These waves are critical for focus and attention by silencing excessive intrusive thoughts so you can focus clearly on the task at hand!
Ingredient 4

Lemon Balm Extract

When neurotransmitters are released, they are eventually degraded by enzymes to turn off their signaling. We wanted to design iCalm in a way that you wouldn’t need to drink a bottle per hour to maintain your zen state. How could this be accomplished? By preventing the degradation of the GABA not only ingested directly from the product itself, but also the GABA that the Taurine and L-theanine signaled your own body to create! When looking for natural ingredients that blocked the GABA degrading enzyme GABA transaminase, we identified numerous possible candidates. We decided to use whole plant extracts of Melissa officinalis (Lemon Balm), as not only is it known to inhibit GABA degradation18, but also has multiple human trials indicating it is effective in relieving anxiety and other stress-related symptoms19,20. Keep in mind these trials were using just Lemon Balm alone, imagine the degree of calming effects iCalm achieves when combining it with so many synergistic natural compounds! We also decided to use Lemon Balm because it has been shown to promote acetylcholine signaling in the brain, which is responsible for memory and learning. This is achieved by inhibiting the acetylcholinesterase enzyme, which is responsible for degrading acetylcholine21. This means on top of the calming effect, Lemon Balm can keep your brain sharp so you can power through any task in a calm, focused fashion. In addition, Lemon Balm has been shown to reduce inflammation and acts as a potent antioxidant by elevating key antioxidant cellular machinery22,23. These mechanisms made Lemon Balm stand out as the clear winner for the ingredient that would sustain iCalm’s effects, and further testing confirmed this.

Our extensive testing results.


Through extensive testing, we have developed a proprietary blend of these ingredients to balance several converging anti-anxiety cellular mechanisms, including:

  • GABAA receptor activation
  • Promoting GABA synthesis
  • Inhibition GABA breakdown
  • Glycine receptor activation
  • NMDA receptor inhibition
  • Inhibiting Cortisol production
  • Reducing pro-inflammatory cytokine production
  • Antioxidant production

    So rather than flooding your brain with excessive signaling for one signaling pathway (which could lead to drowsiness or other side effects), iCalm spreads out its therapeutic actions across numerous pathways and implicated in anxiety; resulting in rapid relief of both the mental and physical effects of anxiety, while also ensuring its therapeutic effect to persist for extended periods of time. It’s worth mentioning that our goal here was to leave you calm and cool as a cucumber, and NOT drowsy or sleepy. Thus, we made it a point to not use any overly sedating ingredients such as melatonin.


REFERENCES CITED
1. Nuss, P.J.N.d. & treatment. Anxiety disorders and GABA neurotransmission: a disturbance of modulation. 11, 165 (2015).
2. Jan, D.D.S., David‐Watine, B., Korn, H. & Bregestovski, P.J.T.J.o.P. Activation of human α1 and α2 homomeric glycine receptors by taurine and GABA. 535, 741-755 (2001).
3. Mori, M., Gähwiler, B.H. & Gerber,U.J.T.J.o.p. β‐Alanine and taurine as endogenous agonists at glycine receptors in rat hippocampus in vitro. 539, 191-200 (2002).
4. El Idrissi, A. & L'Amoreaux, W.J.N. Selective resistance of taurine-fed mice to isoniazide-potentiated seizures: in vivo functional test for the activity of glutamic acid decarboxylase. 156, 693-699 (2008).
5. Chan, C.Y. et al. Direct interaction of taurine with the NMDA glutamate receptor subtype via multiple mechanisms. in Taurine 8 45-52 (Springer, 2013).
6. Liu, Y.-Z., Wang, Y.-X. & Jiang, C.-L.J.F.i.h.n. Inflammation: the common pathway of stress-related diseases. 11, 316 (2017).
7. Kim, C. & Cha, Y.-N.J.A.A. Taurine chloramine produced from taurine under inflammation provides anti-inflammatory and cytoprotective effects. 46, 89-100 (2014).
8. Kontny, E. et al. The mechanism of taurine chloramine inhibition of cytokine (interleukin‐6, interleukin‐8) production by rheumatoid arthritis fibroblast‐like synoviocytes. 43, 2169-2177 (2000).
9. Salim, S., Chugh, G., Asghar, M.J.A.i.p.c. & biology, s. Inflammation in anxiety. 88, 1-25 (2012).
10. Jung, J.H., Kim, S.-J.J.B. & therapeutics. Anxiolytic action of taurine via intranasal administration in mice. 27, 450 (2019).
11. El Idrissi, A. et al. Functional implication of taurine in aging. in Taurine 7 199-206 (Springer, 2009).
12. White, D.J. et al. Anti-stress, behavioural and magnetoencephalography effects of an l-theanine-based nutrient drink: A randomised, double-blind, placebo-controlled, crossover trial. 8, 53 (2016).
13. Vreeburg, S.A. et al. Salivary cortisol levels in persons with and without different anxiety disorders. 72, 340-347 (2010).
14. Lenze, E.J. et al. Elevated cortisol in older adults with generalized anxiety disorder is reduced by treatment: a placebo-controlled evaluation of escitalopram. 19, 482-490 (2011).
15. Kim, S., Jo, K., Hong, K.-B., Han, S.H. & Suh, H.J.J.P.b. GABA and l-theanine mixture decreases sleep latency and improves NREM sleep. 57, 64-72 (2019).
16. Barkus, C., Dawson, L., Sharp, T., Bannerman, D.J.G., Brain & Behavior. GluN1 hypomorph mice exhibit wide‐ranging behavioral alterations. 11, 342-351 (2012).
17. Nobre, A.C., Rao, A. & Owen, G.N.J.A.P.j.o.c.n. L-theanine, a natural constituent in tea, and its effect on mental state. 17(2008).
18. Awad, R. et al. Bioassay‐guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity. 23, 1075-1081 (2009).
19. Cases, J. et al. trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances. 4, 211-218 (2011).
20. Scholey, A. et al.Anti-stress effects of lemon balm-containing foods. 6, 4805-4821 (2014).
21. Obulesu, M. & Rao, D.M.J.J.o.n.i.r.p.Effect of plant extracts on Alzheimer’s disease: An insight into therapeutic avenues. 2, 056-061 (2011).
22. Ribeiro, M., Bernardo-Gil, M. & Esquıvel, M.J.T.J.o.S.F. Melissa officinalis, L.: study of antioxidant activity in supercritical residues. 21, 51-60 (2001).
23. Zeraatpishe, A. et al. Effects of Melissa officinalis L. on oxidative status and DNA damage in subjects exposed to long-term low-dose ionizing radiation. 27, 205-212 (2011).
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