ThermoGum Full Write-up

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ThermoGum Write-Up

Performance gums of the past have ranged from useless to intolerable. ThermoGum represents a giant leap forward in functional gum technology, backed by science and volumes of positive user feedback. ThermoGum was created using cutting edge compounds, rapidly delivered to the bloodstream for an immediate stimulation and mood enhancing effect. With ingredients extensively backed by published research, ThermoGum can be incorporated into an effective nutrition and training program to accelerate fat loss or just to deliver a mental and physical performance boost.

Following is a presentation of the ingredients found in ThermoGum, applicable research, and reason for inclusion. The data presented demonstrates numerous beneficial effects of ThermoGum, ranging from mental and physical stimulation to an improvement in numerous oral and physiological parameters of overall health.

Ingredients
Gum Base, xylitol, raspberry ketones, caffeine anhydrous, cinnamon oil, geranium extract, black pepper extract, isomalt, calcium stearate, natural and artificial flavors, gum arabic, sucralose, carnauba wax.

Geranium Extract

Originally intended for use as a nasal decongestant by the pharmaceutical industry, this compound has recently gained favorable attention for its potential mood elevating and fat burning properties through modulation of norepinephrine signaling. In the early 1970’s, geranium extract (methylhexanamine) was implicated in a patent for reversing gum hypertrophy due to its sympathomimetic and local vasoconstriction properties (1).

Norepinephrine Signaling

What is Norepinephrine (NE), and why do we care? Let’s start with a basic overview. NE is a catecholamine that functions both as a hormone and a neurotransmitter. Molecularly, it’s very similar to epinephrine, aside from a methyl group attached to it’s nitrogen as opposed to a hydrogen atom.

Along with epinephrine, it binds to adrenergic receptors to deliver blood to skeletal muscles and help to break down energy stores. Upon stimulation through the proper channels, the adrenal medulla typically secretes epinephrine:norepinephrine at approximately an 80:20 ratio. This ratio is reversed in the sympathetic nerves to favor NE. Since it functions as a “stress” hormone, it takes on the role of preparing the body for action peripherally, and in the brain NE’s neurotransmitter function causes an increase in arousal and alertness.

Both NE and epinephrine increase the amount of free fatty acids (FFA’s) in the bloodstream, which makes pre exercise a great time for ThermoGum, as the body will be able to burn off the newly liberated FFA’s during the workout.

Geranium Extract not only causes a release of NE into the synaptic cleft, but it also acts as a Norepinephrine Reuptake Inhibitor (2). When NE is released, your body decides when to halt its actions by use of the Norepinephrine Transporter (NET), which carts the NE back to the vesicles for later use. With an NRI, you can block the action of the NET so the effects of released NE last longer. So Geranium Extract gives you a double shot, more NE release, and less NE removal.

Some benefits of NRI’s:
A general and subjective alteration in consciousness
Increased alertness, awareness, and wakefulness
Enhanced attention, focus, and concentration
Increased desire, drive, and motivation
Improved cognition, memory, and learning
Antidepressant benefits and mood elevation
Aphrodisiac effects
cAMP Modulation
Cyclic Adenosine Monophosphate (cAMP) is an intracellular molecule known as a second messenger. It is synthesized from ATP and functions as a relay mechanism to incorporate molecules into cells that can’t get in on their own (epinephrine, norepinephrine, glucagon, and more).
Oral Health
Geraninum Extract has been implicated in reduction of oral inflammation and gum hypertrophy in a patent titled Process for the treatment of hypertrophied gums (2). Combined with other oral-friendly ingredients in ThermoGum, this is not only a stimulant gum but it also serves a dual function as an oral health supplement.
Energy and Mood Elevation
Since being delivered to the market in Ergopharm’s AMP (and the torchbearing E-pharm’s Clearshot Concentrate), geranium extract has become well recognized as a potent mood elevator, with an augmented effect over traditional stimulants such as caffeine and ephedrine. Its inclusion in ThermoGum allows for an immediate delivery and rapid pronounced onset, yet it lasts for many hours even after the cessation of chewing.
Nasal Decongestant

Eli Lilly conducted research on geranamine extract as a nasal decongestant, and although never brought to the market it was deemed effective for this purpose. The original formula was intended as a nasal inhalant; however the gum delivery offers similar olfactory stimulation that an oral dose of geranamine extract would not, and preliminary anecdotal feedback tends to support this theory.

Benefits of Geranamine Extract

Norepinephrine Reuptake Inhibitor
Norepinephrine Releasing Agent
cAMP Modulator
Treatment for Hypertrophied Gums
Oral Anti-inflammatory
Mood Elevator
Nasal Decongestant


Raspberry Ketones

Structurally similar to capsaicin and synephrine, Raspberry Ketones (RK’s) display a lipolytic effect through the activation of the transient receptor potential vanilloid type 1 (TRPV1) protein located throughout the central and peripheral nervous system in the body. In addition RK’s may cause an increase in skin elasticity (which means the skin will take on a more youthful structure, not turn you into a floppy lipped basset hound) through activation of sensory neurons and elevation of dermal IGF-1, which is also active in gum tissue (3).

TRPV1 modulation has been a hot area of research lately, implicating numerous benefits throughout the body, such as…

Pain and Anxiety

Researchers from Current Pharmaceutical Design reported that activation of TRPV1 receptors in the brain can potentially alleviate symptoms of pain and anxiety (4).

Depression

A team out of Brown University found that TRPV1 activation may be an effective angle at treating depression through interneuron formulation, stating “TRPV1 channel activation is necessary and sufficient to trigger long-term synaptic depression (LTD)” (5).

Body Comp Effects

Through modulation of norepinephrine and hormone sensitive lipase, RK’s appear to be a powerhouse for encouraging fat loss and prevention of fat gain. When mice were fed a high fat diet, RK’s prevented visceral and liver fat accumulation as well as reversing the gain in previously obese mice (6). Recently liver fat has been implicated in metabolic disturbances to an even greater degree than the previous villain, visceral fat, so this is a benefit of great magnitude for overall health (7).

In another study, after 120 days of a TRPV1 agonist researchers concluded adipogenisis and obesity were prevented by activation of TRPV1 channels (8).

Benefits of Raspberry Ketones and TRPV1 activation

Increases lipolysis through Norepinephrine
Enhances activity of Hormone Sensitive Lipase (HSL)
Anti-obesity properties


Caffeine

Caffeine has numerous psychological and physiological benefits, coupled with a rapid onset and applicable duration of action (half life of about 5 hours); this compound makes a great addition to ThermoGum (9). Research has shown caffeine ingestion to stimulate alertness, increase lipolysis (breakdown of fatty acids into the blood stream), increase time to exhaustion in exercise, and more. Caffeine exerts the majority of its effects by blockade of adenosine A1 and A2A receptors, the latter of which causes modulation of dopamine transmission (10). For an excellent in depth review of caffeine, see Chemically Correct: Caffeine by Andrew Novick.
Bioavailability and Pharmacokinetics
The bioavailability of caffeine from chewing gum is about 75%, based on the dosage used in ThermoGum. While it is generally accepted that the oral bioavailability of caffeine nears 100%, this is largely dose dependant, with low to moderate doses not reaching this level of oral efficiency. Although the bioavailability is slightly lower than an oral dose, obtaining caffeine through gum alters pharmacokinetics favorably by reducing the time of onset. The Tmax (time to max concentration in blood) for caffeine absorbed through chewing gum ranges between 44 – 80 min, as compared to a similar oral dose which postpones the Tmax to 84 – 120 min, or close to double the time on average to reach peak blood concentration.
Keep in mind the Tmax refers to peak blood levels, and the stimulatory effects of caffeine are realized much earlier than this, and with gum delivery it is almost instantaneous. Researchers from a study published in the International Journal of Pharmacology concluded “…there may be an earlier onset of pharmacological effects of caffeine delivered as the gum formulation, which is advantageous in situations where the rapid reversal of alertness and performance deficits resulting from sleep loss is desirable” (11). It should be noted that individual response to caffeine has been shown to vary greatly, over an 8-fold range in individual variation of steady state plasma levels which partly explains the subjective variability in dose-response with different subjects (12). But the really good news…the bioavailability of caffeine in ThermoGum is likely much higher than that of previous gum studies (and could theoretically reach close to 100% with a more rapid onset), due to the inclusion of black pepper extract in the formula which inhibits an enzyme responsible for caffeine metabolism (13,14).
A recent study in the journal Human Psychopharmacology looked at caffeinated chewing gum on various parameters of mental performance in 118 adult subjects. One group received inert gum (placebo), and the other group received gum containing 40mg caffeine (the dose provided in ThermoGum). The group receiving the caffeinated gum noticed elevation of mood and better performance on sustained attention tasks. The researchers concluded that the caffeinated gum group improved the speed of encoding of new information, and that “chewing caffeinated gum has been shown to improve performance efficiency and mood by its alerting and energizing effects” (15).
A final note on pharmacokinetics while we’ve got our learning caps on, if you’ve ever wondered how dosages from rat studies equate to humans, it appears that 10mg/kg in rat models will deliver a similar effects to 3.5mg/kg in humans (9).
Performance, Thermogenesis and Lipolysis
In a 2008 placebo controlled study, researchers tested caffeine on high intensity time trail cycling. They found that when the subjects were given caffeine, they rode significantly longer than they did in the trials without caffeine. Aside from improved performance, they also noted that the subjects did so with no increase in heart rate compared to control (16).
Studies have also shown caffeine to increase strength and muscular endurance in upper and lower body exercises (39,41), decrease rate of perceived exertion and prolong fatigue during weight training (40,42), cause ergogenic effects by heightening CNS activity during exercise (43), and increase speed and power output in running events from 60 seconds up to 2 hours in duration (44).

Aside from directly affecting performance, it’s possible that ThermoGum could actually aid in building muscle by causing reduced nutrient uptake at the fat cell. Subjects in a recent study were given caffeine with a post workout beverage containing carbohydrates, and researchers noticed increased rate of glycogen synthesis compared to carbohydrates alone (17). Theoretically, this is due to caffeine causing whole body insulin resistance but due to the effect of exercise on GLUT4 translocation at the muscle cell, nutrients were basically given a direct route to the myocyte. Caffeine basically blocked the fat cell from stealing any nutrients, and even though muscle cell insulin resistance has been shown to be increased with caffeine consumption, the effect of exercise caused a shift in the right direction.
Caffeine has been shown to increase thermogenesis to 6% above baseline at a dose of only 50mg, whereas Green Tea Extract and L-Tyrosine did not increase thermogenesis whatsoever (18).
Similar to geranamine, caffeine stimulates lipolysis through cAMP and Norepinephrine. For a better understanding of that process, review the section on geranium extract. Caffeine also has the unique ability to stimulate AMPK, which can lead to accelerated fat loss through an increase of fatty acid fuel usage in the skeletal muscle, and insulin independent glucose transport (19).
Benefits of Caffeine
Increased Mental Alertness
Increased Thermogenesis
Increased Exercise Performance
Increased Lipolysis

Black Pepper Extract (piperine)

Extracted from black pepper, piperine is the alkaloid responsible for pepper’s spicy, biting flavor. Initially investigated for its ability to inhibit certain liver enzymes responsible for drug metabolism, piperine has recently been the subject of research looking at various fields of health enhancement and positive modulation of multiple physiological systems, as discussed below.

Mood Elevation, Cognitive Enhancement, Anti-Depression
Researchers out of Thailand noted in a recent study, “…that piperine at all dosage range used in this study possessed anti-depression like activity and cognitive enhancing effect at all treatment durations. Therefore, piperine may be served as the potential functional food to improve brain function.” (20). Although this particular study involved rats, it still may very well be applicable to humans. In a University Study out of China, researchers looked at the MAO inhibition properties of piperine and found an anti-depressant effect due to serotonin modulation (21).
Another related study covered the IC50 values (the concentration of a drug that is required for 50% inhibition in vitro, as defined by the FDA) of piperine’s function as an MAOa and MAOb inhibitor at 20.9 microM and 7.0 microM respectively. Called a “promising pharmacotherapeutic candidate as an antidepressant agent”, the researchers determined this was due at least in part to its MAO inhibition properties (22).
The Institute of Neuroinformatics in Dalian, China, looked at piperine’s action in mice exposed to Chronic Mild Stress (CMS). They found that after two weeks of administration, piperine “reversed the CMS-induced changes in sucrose consumption, plasma corticosterone level and open field activity”, which basically means they stopped guzzling sugar and feeling sorry for themselves and started becoming more active. Piperine was also found to be neuroprotective by reversing the effect on the brain of elevated corticosterone by up-regulation of the progenitor cell proliferation of hippocampus (23).

TRPV1 Modulation
Previously discussed in the Raspberry Ketone section, piperine is another favorable modulator of the TRPV1 protein. Since research started looking at TRPV1, capsaicin has been the predominant compound used for modulation due to its predictable efficacy for desired outcomes. A study published in the British Journal of Pharmacology was the first to implicate piperine as a TRPV1 modulator, stating “our data suggest that the effects of piperine at human TRPV1 are similar to those of capsaicin except for its propensity to induce greater receptor desensitization and, rather remarkably, exhibit a greater efficacy than capsaicin itself.” (24). Shortly after this study was published, a review of piperine in Trends in Pharmacological Sciences stated, “This finding raises the intriguing possibility that piperine can be used as a chemical template for the design of improved TRPV1 agonists.” (25).
Anti-Inflammatory, Anti-Arthritic, Blood Pressure Reduction

A 2009 study out of Seoul, Korea looked at the effect of piperine on various markers of pain and biochemical inflammation in arthritic models, with exciting results. They demonstrated that piperine “significantly reduced the inflammatory area in the ankle joints”, and concluded that “piperine has anti-inflammatory, antinociceptive, and antiarthritic effects in an arthritis animal model.” (26). For those unfamiliar with the term, antinociceptive basically refers to a pain reduction effect.

Previously, researchers from the Molecular Immunogenetics Laboratory in India set out to find how piperine exhibits its anti-inflammatory effects, finding that it blocks TNF-alpha induced expression of certain cell adhesion molecules (27). TNF-alpha regulation is a crucial factor in whole body inflammation and overall health, when levels get out of range (high or low), numerous problems arise.

Research published in the Journal of Cardiovascular Pharmacology found that piperine exhibits a blood pressure lowering effect possibly through blockage of calcium channels with effects similar to the prescription hypertension drug verapamil (28). Stimulants such as caffeine are known to have a blood pressure elevating effect in some users, so the addition of piperine to ThermoGum could balance out this undesirable effect.
 
Immunostimulation, Chemoprotection, Gum Health, Antioxidant

In a recent study out of India, researchers looked at the chemoprotective ability of piperine (combined with curcumin) in oral cancers. They developed oral cancer in hamsters through a known carcinogen, then gave another group the piperine/curcumin combination and noted a complete prevention of oral carcinoma (29). The researchers determined this was probably due to the antilipidperoxidative and antioxidant potential of the piperine/curcumin. The fact that curcumin was included in this study cannot be ignored (as it is not in ThermoGum), but piperine was almost certainly a contributing factor to the positive outcome, and therefore the research is worth noting.

Another study out of India looked at the chemoprotective capabilities of piperine alone, along with its antioxidant and immunostimulatory properties (30). The researchers induced immunocompromisation in murine splenocytes with cadmium, which induces apoptosis (suicide, basically) at 6 hours onwards in treated cells. Piperine was able to completely abolish the toxic effect of the cadmium, and the researchers concluded, “The findings strongly indicate the anti-oxidative, anti-apoptotic and chemo-protective ability of piperine in blastogenesis, cytokine release and restoration of splenic cell population and is suggestive of its therapeutic usefulness in immuno-compromised situations”.

Liver Enzyme Inhibition (CYP34A), P Glycoprotein Inhibition, Increased Absorption of ThermoGum Ingredients
Last but certainly not least, a brief discussion of the gastrointestinal and liver enzyme modification effects of piperine. A review paper titled “Black pepper and its pungent principle-piperine: a review of diverse physiological effects (31)”, detailed many numerous benefits of the compound including (bullets paraphrased from review):
Protection against oxidative damage by inhibiting or quenching free radicals and reactive oxygen species
Inhibitory influence on enzymatic drug biotransforming reactions in the liver
Strongly inhibits hepatic and intestinal aryl hydrocarbon hydroxylase and UDP-glucuronyl transferase
Documented to enhance the bioavailability of a number of therapeutic drugs as well as phytochemicals
Bioavailibility enhancing property partly attributed to increased absorption as a result of its effect on the ultrastructure of intestinal brush border
Non-genotoxic and has been found to possess anti-mutagenic and anti-tumor influences
Researchers out of Germany were actually the first to clinically demonstrate piperine’s drug metabolism effects in a study titled ”Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4” (32). Their summary concluded, “…we showed that piperine inhibits both the drug transporter P-glycoprotein and the major drug-metabolizing enzyme CYP3A4. Because both proteins are expressed in enterocytes and hepatocytes and contribute to a major extent to first-pass elimination of many drugs, our data indicate that dietary piperine could affect plasma concentrations of P-glycoprotein and CYP3A4 substrates in humans, in particular if these drugs are administered orally”.
P-glycoprotein or PGPs, can be thought of as first-pass eliminators, meaning they can block absorption of certain compounds in the gut, acting as goalies for the later actions by enzymes in the liver. Piperine blocks PGPs as well as key liver enzymes, leading to elevated concentrations of active ingested compounds in the bloodstream, i.e., many other ingredients in ThermoGum.
Benefits of Black Pepper Extract:
Anti-inflammatory
Gum Health
Blood Pressure Reducer
Mood Elevator
Cognitive Enhancer
TRPV1 modulator
CYP34A Liver Enzyme Inhibitor
Immunostimulatory
Antioxidant
Chemoprotector
Increases absorption of other ThermoGum compounds
Anti-depressant (serotonin modulation)
MAO Inhibitor
Anti-arthritic
P-Glycoprotein inhibitor

Xylitol

Xylitol provides an important dual-function in ThermoGum, acting as a sweetener and an oral health promoting agent. This was chosen over other sweetener options to further enhance ThermoGum’s potent effect on oral health.
Caries Prevention, Dental Plaque Reduction
Caries is another term for tooth decay or dental cavities. In a head to head study with sorbitol, xylitol lozenges outperformed its counterpart in modification of dental plaque and subsequent reduction of plaque acidogenicity (33). In another comparison study, researchers looked at the differences in effect from dental sealants vs. xylitol in the outcome of caries prevention (34). Taken from the study “Regular use of xylitol chewing gum during 2 or 3 school years was compared with application of occlusal sealants in a randomized study”, and the researchers went on to conclude, “After 5 years, no statistically significant differences between the sealant and xylitol groups were found”.
Reduction/Inhibition of Oral Bacteria
A one year follow up study conducted on females in Korea showed that in the group using xylitol, the colonies of the oral bacteria S. mutans steadily decreased, bacterial adhearance became weak, and the size of the colonies reduced in comparison to the control group (35). The researchers concluded “These findings indicate that regular chewing of xylitol gum over a long period may lead to decreased gtfB expression, which can negatively affect the synthesis of extracellular polysaccharides by S. mutans, which could reduce the size and growth of S. mutans colonies and change their morphology as a result”. S. mutans is a common bacteria in human oral cavities, and has been shown to cause tooth decay (35,36).
In an effort to assess the concentrations of xylitol required for inhibition of various oral bacteria, a study conducted at Indiana University tested different preparations of xylitol in chewing gum. They found that of S. mutans, S. salivarius, and S. sanguis, “All three strains were inhibited significantly at xylitol concentrations of 12.5% and higher; however, only S. mutans was inhibited significantly at a xylitol concentration of 1.56%” (37).
Finally, a study out of a Korean University found that xylitol inhibits inflammatory cytokine expression responsible for a decline in oral health (38). They found xylitol inhibited growth of P. gingivalis bacteria, concluding that, “xylitol may have good clinical effect not only for caries but also for periodontitis by its inhibitory effect on the LPS-induced inflammatory cytokine expression”.

Benefits of Xylitol
Caries Prevention
Dental Plaque reduction
Reduction/inhibition of oral bacteria
Peridontitis prevention/reversal
Tooth decay prevention on par with dental sealants
Oral Anti-inflammatory


Review of ThermoGum Benefits
Norepinephrine modulation (releasing and reuptake inhibition)
Cyclic Adenosine Monophosphate (cAMP) Modulation
Increased thermogenesis
Anti-obesogenic
Increased lipolysis
Enhances activity of Hormone Sensitive Lipase (HSL)
TRPV-1 modulation
Elevates mood
Increases mental alertness
Increases exercise performance
Encourages healthy blood pressure
Antioxidant
Anti-inflammatory
Encourages gum health
Promotes Reduction in dental plaque
Promotes reversal/prevention of peridontitis, cavities and tooth decay
Potential nasal decongestant
Inhibition of CYP34A liver enzyme and P-Glycoprotein
Serotonin modulation
Immunostimulation
Chemoprotection
Anti-arthritic


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Great write-up, dsade!
 
strategicmove said:
Great write-up, dsade!
Click to expand...
ThermoGum would like to thank Marc McDougal for his ungodly effort and organizational abilities. Without his assistance, you would not have seen this for another 6 weeks.

Marc's discovery of the oral health benefits of the ingredients has led to a whole new direction of product development that we are pursuing.

I would urge all of you to sign up for his excellent Fitport newsletter (link elsewhere in this forum).
 
dsade said:
ThermoGum would like to thank Marc McDougal for his ungodly effort and organizational abilities. Without his assistance, you would not have seen this for another 6 weeks.

Marc's discovery of the oral health benefits of the ingredients has led to a whole new direction of product development that we are pursuing.

I would urge all of you to sign up for his excellent Fitport newsletter (link elsewhere in this forum).
Click to expand...

1) We are certainly indebted to him. Fitport newsletter subscription should be doable.

2) I have read so much feedback about ThermoGum that I can taste it somehow in my mouth, even without having tried it! :biglaugh: My ThermoGum order should reach me before end-October (USA -> Europe). Then I can pacify my taste buds.

3) This full ThermoGum write-up is certainly an all-time record holder in terms of the most detailed chewing-gum description ever! A damn good one at that!
 
The UK distributor will have stock by Thursday of next week as well...in case you can't wait! :)

I agree...the implications of the writeup are FAR reaching as far as alternate product lines. Strange how research in one directions branches into unforeseen territory.
 
This write-up should be a sticky.
 
strategicmove said:
I should have seen that coming!
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I always close my eyes when I am about to... errr, wait, nevermind. :blink:

I am going through this gum too fast. I am enjoying 6.75mg of ephedrine every 2 hours, and 1 piece every four. At this rate, my goals will be met quickly!
 
Iron Lungz said:
I always close my eyes when I am about to... errr, wait, nevermind. :blink:

I am going through this gum too fast. I am enjoying 6.75mg of ephedrine every 2 hours, and 1 piece every four. At this rate, my goals will be met quickly!
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Your first comment...then your second using the exact words "too fast" make me think there's something Freudian going on here.
 
dsade said:
Your first comment...then your second using the exact words "too fast" make me think there's something Freudian going on here.
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Well, maybe there is, but maybe nothing is happening too fast... slow down and jump quickly.

I cannot wait until the other flavors come out.
;)
 
dsade said:
Your first comment...then your second using the exact words "too fast" make me think there's something Freudian going on here.
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What's on a man's mind?
 
Fantastic write-up, Matt. I can't wait to try this out. :)
 
dsade said:
Obviously your punctuation indicates more enthusiasm.

/enthusiasms....
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What?!?!?!?!?!?!?!?!

:D

After 12 hours of documenting patient assessments at work, my grammar skills and focal concentration begin to fade a bit. :hypnotized:

The write-up is very impressive, Matt!! <---:flowers1:
 
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