That Cool Mint Feeling

That Cool Mint Feeling

When I was in elementary school the teachers would hand out peppermints before we would take our tests.  They told us that peppermint was a brain stimulant, that it would help us think and concentrate.  As a child, I took hold of the idea that mint somehow simply makes you smarter, yet now I am also concerned with having pleasant smelling breath when interacting with others, and as a result I consume a fair deal of mint, be it gum, Altoids, etc.  It is therefore impossible not to notice the peculiar sensation one gets when drinking cold water after eating mint; as though the water is far colder than it actually is.  I had never thought to question why this phenomenon occurs until this project put me on the lookout for interesting questions such as this. 

My first response was identical to that of any person with a question these days: Google it.  I was unsure how to phrase this question, so I began “How does mint..” and Google filled in “make water colder”.  The second hit lead me to a site called “Mental Floss” that provided a brief overview of the process that I was looking for; the page was titled with the simple question: “Why does mint make your mouth feel cold?”  The page explained that the sensation is due to a specific protein channel in sensory cells called the Transient receptor potential cation channel subfamily M member 8, or TRPM8.  The page described that this protein is an ion channel, regulating the movement of ions across the membrane of the cell.  In order to gain a better understanding of this protein, I dissected its name.  Transient is defined as brief, temporary, or non-enduring.  I can gather from this that the protein channel in question does not remain open for very long after receiving the stimulus that activates it.  The page then goes on to explain that this channel opens in the presence of cold temperature, allowing Na⁺ and Ca²⁺ ions into the cell and sending the sensory message to the brain.  Interestingly, it seems that menthol, an organic compound in peppermint and various mint oils, also activates this protein channel, leading to the “cold” sensation we feel when tasting mint.  The page explains that the stimulus of something cold (i.e. cold water) on these already sensitized sensory cells will cause the neurons to fire again, causing the brain to be assailed with input from both the menthol and the cold temperature.  This “double dose” of sensory information is what causes the extra cold sensation.

As interesting as this page was, it was not cited and raised a good deal of questions.  How is it that menthol activates a cold sensitive receptor? How do receptors respond to a change in temperature?  I retraced my steps to my Google query and searched for something more detailed and legitimate.  I eventually stumbled upon a blog style article from a website called “The Science Creative Quarterly” in which all the information was nicely cited.  This article (thankfully) agreed nicely with the un-cited information from the last page and presented a good deal of new information.  Apparently, two separate groups of scientists identified the cold/menthol receptor and it therefore is named CMR1 in addition to TRPM8.  This is the receptor that monitors temperature, and is therefore found all over the body.  Upon reading this, I thought immediately of pain relief products, icy-hot for example, that induce a cold sensation after application.  Sure enough, another Google search revealed that the main ingredient of icy-hot is menthol, whose organic structure is shown in Figure 1.

Figure 1.  The organic chemical structure of Menthol.

Disappointingly, by the end of this article, I still had not learned anything about the actual process that occurs when menthol acts on the receptors and activates the ion channels.  I required a more in-depth analysis of the actions of these cold receptors.  I therefore logged into the University of Illinois’ library website and searched “menthol receptors” in the online journal database.  I immediately found a nature publication from 2002 titled “Identification of a cold receptor reveals a general role for TRP channels in thermosensation”.  This article focused on the molecular and cellular mechanisms involved in how the body senses cold and how it responds to such a stimulus.  They found that the receptors responded in a manner indicating that the menthol response is dose dependent.  The results suggest that more than one menthol molecule is required for receptor activation.  This was discovered by measuring the response current from the sensory cells while altering the concentration of menthol.  As the menthol concentration increased, the current showed a sigmoidal shaped increase, as seen in figure 2. 

Figure 2.  Normalized current vs. Concentration of Menthol

It was also observed that the current decreases in the sensory cells as the temperature is raised.  The authors interpreted this data to mean that “increasing the temperature of the perfusate (from room temperature to 30^o C) completely antagonized currents evoked by 100 mM menthol”.  This, along with the data from Figure 2, led the authors to believe that there is a common molecular site of action for the menthol. 

Finally I was getting somewhere.  One question on my mind, however, was how do we know that the same sensory cells are being stimulated by both cold and menthol? Couldn’t there easily be two different sensory cells reacting to the two stimuli at the same time?  Thankfully, the authors of this article also addressed that question.  They performed an experiment in which they lowered the temperature of the perfusate from around 35^o C to about 5^o C and observed the current activity in the sensory cells.  This decrease in temperature showed an increase in current activity, indicating that these sensory cells do indeed respond to both the cold and menthol.  Cold seems to have an effect on the conformation of the receptors, allowing ions through the channel and eliciting the sensory response in the brain.  Heat was shown to antagonize the currents caused by menthol; this is likely a result of the increased temperature changing the conformation of the agonist or the active site in a way that does not allow for the exchange of ions across the cell membrane.  

Crystal Structure of a TRP ion channel

As helpful as this article was, it still did not answer my question of how the actual menthol molecule interacts with the TRP channel.  At this point I was feeling slightly exasperated, and attempted to broaden my search in hope of discovering any information on temperature affected ion channels.  Unfortunately, this endeavor proved fruitless, as I found nothing applicable to menthol from these search results.  It was with what must have been luck that I eventually stumbled across a helpful article after a desperate Google scholar search.  The article was entitled “Ligand Stoichiometry of the cold and menthol activated channel TRPM8”.  With a title this applicable, I’m honestly unsure how I missed this article before. 

The objective of this article was to investigate ligand stoichiometry of TRPM8 by creating tandem tetrameric TRPM8 contructs.  This was done using a cloning technique in which wild type and mutant TRPM8 coding sequences were linked together.  This is a way of characterizing the behavior of what is naturally a tetramer (TRPM8); now the researchers could alter subunits between mutant and wild type to gain a better understanding of the molecular mechanisms in this process. Using this technique, the researchers discovered some very interesting things.  The results of the experiments with mutating the various subunits of the tetramer indicate that “up to four menthol molecules can independently bind to a single TRPM8 channel, and that each bound menthol causes a similar energetic stabilization of the open channel.”  These results are in accordance with the conclusions of the McKemy article, which demonstrated the sigmoidal curve as menthol concentration increased (Figure 2). 

TRP ion channel in the cell membrane.

Another of their more significant results is that they found: “menthol shifts the voltage dependence of channel activation to more negative values by slowing channel deactivation”.  This is very significant to my question because it supports a claim made by the first web page I visited which stated that menthol acts on the receptors, leaving them sensitized for when the second stimulus is applied (i.e. cold water) resulting in the enhanced sensation.  This mechanism of binding is very clearly different from the mechanism of cold affecting the TRP channels.  This is why the sensation is increased when both stimuli are applied, yet is not affected after addition stimulation from the same stimuli (i.e. eating another mint).  I finally have a solid understanding of how this particular phenomenon occurs, and continue to discover that this is a very common cellular action, as menthol is present in a great deal of products.  It would be interesting to discover how many companies advertising menthol based products actually know how it functions.

Works Cited

Soniak, Matt. "Why does mint make your mouth feel cold?" Mental_floss. N.p., 19 Apr. 2010. Web. 13 Mar. 2012. <http://www.mentalfloss.com/blogs/archives/52885>.

Ting, Lillian. "Dude, You got some gum?" The Science Creative Quarterly. N.p., 17 Oct. 2011. Web. 13 Mar. 2012. <http://www.scq.ubc.ca/dude-you-got-some-gum/>. 

David D. McKemy, Wemer M. Neuhausser, and David Julius. 2002. Identification of a cold receptor reveals a general role for TRP channels in Thermosensation.  Nature 416: 52-61.

Annelies Janssens and Thomas Voets. 2011.  Ligand Stoichiometry of the cold and menthol activated channel TRPM8.  The Journal of Physiology 589: 4827-4835.

DMT: A Neurotransmitter for the Human Soul?

We as human beings are unique in the sense that we live in two realms, the physical and the spiritual. We can go about our typical day with relative ease, interacting with others, fulfilling obligations and caring for our physical bodies. Yet there’s so much more to our species that isn’t quite as obvious or apparent. We meditate, we pray to gods and most importantly, we dream. And then there are individuals who have claimed that with the help of psychedelic assistance they can experience moments of complete and total spiritual and metaphysical clarity, and claim to have transcended beyond the scope of our physical world to an entire new state of being or consciousness. Traditionally when one thinks of hallucinogens drugs such as LSD or ‘Magic Mushrooms’ come to mind, but the truth is that there’s something else out there. Something naturally present in most living matter that has the ability to rip through all ties of the physical world and connecting us to a higher, almost mystical consciousness- it’s called DMT.   In this post I will be discussing the nature of this mysterious molecule, including its structure, origins and hypothesized purposes

            DMT, or N,N-dimethyltryptamine is a small non-polar molecule of relatively simple origins that can cause profoundly powerful effects on human consciousness. The compound itself is only three mechanistic steps away from its humble derivative, the natural amino acid tryptophan. Biosynthesis of DMT begins first with the decarboxylation of L-tryptophan by an aromatic amino acid decarboxylase, which produces tryptamine. A methyl group is then transferred from cofactor S-adenosyl-methionine (SAM) to tryptamine via a nucleophilic attack that is catalyzed by the enzyme indoethylamine-N-methyltransferase (INMT). The resulting intermediate product (N-methyltryptamine) is then again transmethylated by INMT using a methyl group taken from another molecule of SAM. Decarboxylation and two transmethylation reactions of tryptophan thus produces this incredibly powerful and potent drug that has been revered by many cultures as the mother of all hallucinogens.

                       An overview of the basic mechanism of DMT's biosynthesis from L-tryptophan

                                    

      What many don’t realize, however, is that DMT is present in all of us. There is a significant amount of it found in plants such as the acacia genus, or mimosa shrub, and trace amounts have been found in mammals. It’s not surprising, seeing as its derivative tryptophan is so common, but its presence in our bodies has sparked tremendous interest from biologists and psychologists to mathematicians and physicists. In 1965, German researchers H. Gross and F. Franzen first claimed that they had discovered the presence of endogenous DMT in mammalian blood and urine, though their findings were widely disputed. Then in 2005 a more modern study was done using liquid chromatography-tandem mss spectrometry, a much more selective, sensitive and generally supported method for detecting DMT. In this study scientist found evidence of endogenous DMT present in Human, Rat and Rabbit tissue. While DMT’s presence and method of biosynthesis is mostly clear and confirmed, its purpose for existence is not. Though there is much research that needs to be done on this, the fact remains that DMT exists in our bodies along with all the necessary catalysts, cofactors and starting materials needed to synthesize it, but why?

From a physiological standpoint it has been suggested that DMT might function as a neurotransmitter, as it is very similar to the established neurotransmitter serotonin.

                       

          Structures of serotonin (top) and n,n-dimethyltryptamine (bottom)

 Still others believe that this powerful chemical is released during meditation and is in fact the substance responsible for eliciting natural mystical phenomena in people. But then there is the popular, yet still unproved, hypothesis that this molecule is released in our brains during dreams or near-death experiences. This could possibly explain the intense imagery that individuals experience on a nightly basis during dreams, or that survivors of near-death experiences describe.

In his novel, DMT: The Spirit Molecule, Dr. Rick Strassman hypothesized that DMT is synthesized in the pineal gland of our brain. The pineal is a gland that is often otherwise referred to as our “third eye” and carries a great deal of spiritual importance to many cultures. It was mentioned by Strassman that this gland becomes visible around the 49^th day of fetal development, which is the same time the gender of a fetus can be determined, and, according to the Tibetan Book of the Dead, is the time it takes for the soul of one recently dead to “reincarnate.”

This gland may be responsible for the production of DMT as well as melatonin (a derivative of serotonin).

Shown above is the structure of melatonin. In mammals both melatonin and serotonin are produced from the essential amino acids tryptophan. Melatonin is four enzymatic steps away from tryptophan, with serotonin being the product of the second step.

If this gland does in fact secrete DMT while we sleep and cause us to dream, then what is the purpose of this secretion? What could be the evolutionary purpose of having a part of the brain that facilitates these otherworldly, mystical experiences? No one knows for certain why we dream, and why our excursions into such chaotic and mystical dreamscapes are so important. Could it be that the regular release of such a powerful hallucinogen gives us a nightly glimpse into an entirely different level of consciousness?

In 1990 Dr. Strassman began a five year study of the effects of N,N-dimethyltryptamine, the first government-sanctioned look into DMT in over 20 years. Strassman’s approach focused on administering DMT to patients then measuring as many variables as possible. To begin, sixty volunteers were gathered in a hospital in New Mexico, blindfolded, and given varying doses of the drug. The subjects selected for this study reported varying levels of past experience with psychedelic substances, and were given varying levels of doses accordingly.  Patients’ vitals were closely monitored throughout the experiment, and they were then interviewed after the effects had worn off.

Physically most symptoms of the drug were similar from patient to patient and included rapid heartbeat, dilated pupils and an overall obvious disconnection with the real world for a period of 5-15 minutes. The accounts given by the individuals during drug administration, however, are where results varied. Those given smaller doses of DMT report experiences similar to those brought on by other more mild psychedelic drugs. However, those given large doses of the drug describe their experience as being completely overwhelming. Patients describe the rapid appearance of incredible geometric patterns or landscapes. Though specific experiences vary from individual to individual, common themes throughout these “trips” include a ‘warm golden glow’ emanating from the chest, a complete loss of time awareness, and the feeling of ascending into a ‘different world’ that is both new and completely overpowering, full of colorful patterns and strange lights, yet somehow strangely familiar. It is also interesting to note that many of the patients describe becoming aware of unfamiliar individuals or civilizations around them. Many patients given higher doses would completely dissociate from reality for a span of a few minutes, and upon return be shocked that they were only out for such a short time. Overall the consensus amongst some of the more ‘poetic’ patients was that the drug made one “Lose one’s sense of being, one’s sense of time, sense of purpose and all separation with everything between oneself and surrounding world. Under the effects of DMT the lines between any and everything disappear, and what we are left with is the essence of a soul.”

Over the course of the five year study, Dr. Strassman administered over 400 doses of N,N-dimethyltryptamine to his 60 volunteers. In the end he discontinued the study without proving or disproving his theories that DMT played a role in dream creation. He stopped studies primarily for moral reasons, as he simply could not explain what was happening to these people or why. He notes in his book that he felt as if he were ‘pushing people off a cliff, without knowing what was happening to them, or why it was happening’ and that he could indeed be tinkering with something that could simply be spiritual.

Many of the views on DMT are skeptical at best, but the fact remains that this mysterious compound exists in plants, in us and in most, if not all, of our mammalian relatives. If it serves no function then why, from an evolutionary standpoint, have we retained this drug that induces all kinds of out-of-mind experiences in our bodies through millions of years of divergent evolution? Currently we really have no idea what its real purpose may be, but there are so many interesting possibilities and questions that DMT’s mere presence and potential raises. Could this be a link that ties us, and all life around us, to something that lies beyond what we know of the physical world? We as humans have the ability to live a physical and spiritual existence. We have a body and perhaps a soul. Could this simple drug be the link capable of tying these two together? Could this be the door to our future evolution? Or is this just a simple neurotransmitter whose existence has been taken entirely out of context? We may never truly know.

REFERENCES

• Strassman, Rick. "DMT: The Spirit Molecule." Rick Strassman MD. Web. 30 Apr. 2012. <http://www.rickstrassman.com//index.php?option=com_content&view=article&id=59&Itemid=74>.
• Fontanilla, Dominique. "The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator -- Fontanilla Et Al. 323 (5916): 934 -- Science Signaling." Science/AAAS. 2009. Web. 30 Apr. 2012. <http://stke.sciencemag.org/cgi/content/abstract/sci;323/5916/934>.
• Hanna, Jon. "Erowid DMT Vaults : DMT and the Pineal: Fact or Fiction? by Jon Hanna." Erowid. 29 June 2010. Web. 30 Apr. 2012. <http://www.erowid.org/chemicals/dmt/dmt_article2.shtml>.
• DMT: The Spirit Molecule. Dir. Mitch Schultz. Perf. Rick Strassman and Joe Rogan. Spectral Alchemy, Synthetic Pictures, 2010. DVD.
• Meyer, Peter. "Apparent Communication with Discarnate Entities Induced by Dimethyltryptamine (DMT)." Erowid. 23 Aug. 2010. Web. 30 Apr. 2012. <http://www.erowid.org/chemicals/dmt/dmt_writings2.shtml>.

Pain is Beauty

As I was eating ice cream, I realized that when the frozen deliciousness touched directly on my teeth I experienced pain. I thought to myself, “Why are some people’s teeth sensitive while other peoples are not? Why does the temperature of the foods and drinks people consume make their teeth more or less sensitive? Are there any solutions to tooth temperature sensitivity?” As a person who suffers from tooth sensitivity to frozen foods and drinks, the questions mentioned previously are ones I have asked myself several times. However, I am not alone in my pain; millions of people suffer from sensitive teeth.

Before I embarked on my search to discover what causes tooth sensitivity, I decided learning a little more about the tooth itself would be essential. I started with the anatomy of the tooth and found that it is fairly complex(see Figure below). The outer layer is a hard structure called enamel. Enamel is actually the hardest structure in vertebrates.  The next layer is softer and thinner and is called dentin.  The dentin covers the inside of the tooth which is also known as the pulp of the tooth. Tooth sensitivity arises when dentin is exposed to the environment of the mouth (Chemistry Provides Solution to Plug Pores in Teeth, 2007).
Naturally, the next question I wondered was how dentin actually becomes exposed to the oral environment.  After investigation, I learned that there are several ways dentin can become exposed. Examples of ways dentin can become exposed are brushing too hard, gum disease, gum recession, grinding of teeth, cracked teeth, age, whitening treatments, and acidic foods. Dentin can become exposed when the gum lines recede and the roots of the tooth, which are only covered with dentin and not enamel, are exposed to the environment.

What are some ways the gum line can recede? Receding of the gum line can be caused by everyday practices such as brushing too hard or using a toothbrush that does not have soft bristles (Medicine, 2007).  Dentin is made up of small tubules that can transmit fluids to the pulp of the tooth. The pulp contains soft tissue and several nerves so when liquid reaches the pulp the nerves become excited leading to pain.  Extremely cold or hot foods traveling to the nerves can stimulate more severe pain due to not only liquid touching the nerves but the difference in temperature compared to body temperature.  Aside from surgery, gums will not recover or grow back over the exposed dentin.

  

This diagram shows the anatomy of an adult human tooth. The diagram shows how the enamel, dentin, and pulp are oriented

If the dentin layer was responsible for all the pain myself and others were experiencing, I realized that knowing the structure of dentin would be essential to understanding possibilities for preventing and treating sensitive teeth. Dentin is a highly studied structure and is formed through a complex mineralization process involving sodium and calcium. Ninety percent of dentin is composed of fibrous collagen and the other ten percent is composed of other proteins. During tooth development, dentin is formed into a primary matrix at a very fast rate.  The matrix gives a framework for mineralization. It is thought that an active transportation system exists between the matrix and the tubules because injured teeth have higher dentinal fluid calcium and higher sodium concentrations than intact teeth. After the primary dentin layer is formed, ostdontoblasts (cells in the pulp of the tooth that produce dentin) continue to form a secondary dentin layer around the primary dentin layer. The secondary layer of dentin is formed much more slowly than the primary layer of dentin and  eventually causes the pulp chamber to decrease in size. The majority of dentin is primary dentin. The secondary layer of dentin is much less structured than the primary layer of dentin.  The tubules of dentin form a matrix around the pulp, or inside, of the tooth. In the case of trauma and some dental work, a tertiary layer of dentin forms. This tertiary dentin can repair damaged dentin and is very irregular in shape and size (Dentin formation and mineralization, 2003).

At this point in my research, I began to wonder if I would be doomed with living with sensitive teeth for the rest of my life. As I continued to search, I found that prevention, treatments, and recently even a CURE for sensitive teeth are possible. The key to prevention is to prevent gums from receding. Prevention can include practicing good oral hygiene and not brushing too hard. If good oral hygiene is not practiced, the bacteria that live and thrive in the mouth can cause diseases such as gingivitis and periodontal disease. Gingivitis and periodontal disease can eventually lead to gum recession. Brushing too hard one time will not cause sensitive teeth, however, after years of hard brushing, the cells on the gum line are worn away and gum recession occurs.

 If prevention of sensitive teeth is not successful, there are treatments available. Some toothpastes such as Sensodyne work to alleviate tooth sensitivity by temporarily plugging the tubules and depolarizing nerves using potassium nitrate compounds. However, this can cover up more serious dental health issues. There are also special toothbrushes on the market that are sensitive to pressure that have an alert when one is brushing too hard. For years, fluoride has been used and recommended by dentists and is even added to our water to improve bone and tooth health.

Fluoride is used by the cells that make teeth and tooth enamel. Topical fluoride has also been a common treatment to make teeth harder. Topical fluoride can be administered  in the form of pastes, rinses, and gels. Fluoride uses a re-mineralization effect to help harden teeth and prevent scratches and enamel wear from occurring and can also make teeth much more resistant to acid.  Fluoride makes the crystals that are already present in enamel stronger to prevent acid and other substances from wearing off the enamel. Fluoride does not rebuild the crystals or the tooth enamel (Roveri, Foresti, Lelli, & Lesci, 2009). While fluoride is a good treatment option, it cannot replace the original structure of the tooth.

The most promising solution for sensitive teeth I have found has the capability of not only relieving pain but also of rebuilding the enamel of teeth.  Now, scientists have created a solution called Novamin. Novamin is proving to be a breakthrough in treating tooth sensitivity. Novamin is a tasteless powdery substance that can be added to toothpaste to reduce tooth sensitivity and pain. Novamin forms a thin layer over the teeth. Pain is reduced because Novamin can form plugs for the tiny holes thereby blocking fluid from reaching the nerves. Novamin is made up of the natural minerals that are already found in human saliva. However, by adding Novamin to toothpaste, the concentration of the minerals is greatly increased. The ingredients in Novamin are calcium, phosphorus, silica, and sodium. These minerals do not do much for tooth repair in their natural forms.  However, in the rare ionic form these minerals are able to renew and regenerate teeth.  Each Novamin particle contains the ionic forms of these minerals so when the Novamin particle reacts with water, whether it is saliva or drinking water, the minerals are released. The mineral ions combine with hydroxyapatite crystals which will plug the open tubules and help to reform the tooth. When the tubules have been plugged, liquid cannot travel down them and reach the pulp to excite the nerves to cause pain(see Figure below).  Hydroxyapatite crystals also prevent the decay of teeth by reforming enamel once it has been worn or scratched away.  Novamin can also be added to fluoride toothpastes to provide the same benefits as increasing fluoride levels by four hundred percent; however, with the Novamin added, there is not the risk of high levels of fluoride causing toxicity. Novamin can also protect against cavities by making the teeth stronger (Chemistry Provides Solution to Plug Pores in Teeth, 2007).

This Jmol image is what the molecular structure of hydroxyapatite crystals looks like.

There was a clinical study performed to determine the effectiveness of Novamin. One group of people with sensitive teeth was given Novamin and another group of people with sensitive teeth was given a placebo. The study was double-blind. This means that not only did the subjects not know what tooth treatment they were receiving, the researchers performing the experiment did not know either while the study was taking place. The testing was repeated five times and each time included two treatments. The results showed that Novamin caused a significant reduction (p<.001) in tooth sensitivity. The test group receiving Novamin and the test group receiving the placebo showed no differences at the beginning of the trial. At each time point the group receiving Novamin showed improvement in having reduced tooth sensitivity.

Hydroxyapatite crystals(see Figure for structure) have many useful biochemical properties such as bio-compatibility, bio-activity, and can form bonds directly with the tooth or bone. Once a layer of hydroxyapatite crystals have been applied to the teeth, improvement can be seen on a scanning electron microscope within hours. During a study it was observed that there was a significant difference between brushing with fluoride and brushing with hydroxyapatite crystals. It was discovered that when teeth were brushed after using fluoride, most of the fluoride molecules were brushed away. However, brushing after using hydroxyapatite crystals did not brush the crystals away suggesting that bonds were made with the existing tooth fairly quickly. Fluoride makes teeth stronger by changing physical and chemical  enamel surface modifications while hydroxyapatite crystals actually showed re-mineralization (Roveri, Foresti, Lelli, & Lesci, 2009).

This picture shows the enamel of a tooth after Novamin has been applied. The picture shows how the open tubules in the enamel have been closed to prevent liquid from reaching the pulp.

  

 

This diagram shows the chemical structure of hydroxyapatite crystals.

The desire to have healthy, white teeth that last longer has been greatly improved by the use of hydroxyapatite or substances such as Novamin that contain hydroxyapatite crystals. Users of whitenings solutions or pastes no longer have to experience pain after undergoing a whitening treatment. Other options that have obtained patents include a silicate that that is made from mixing an aqueous solution of phosphoric acid, sodium silicate, and calcium phosphate. It is thought that hydroxyapatite crystallization will occur on the surface of the tooth when two different calcium phosphates such as tricalcium phosphate, calcium hydrogen phosphate, calcium dehydrogen phosphate, octacalcium phosphate or calcium pyrophosphate combine.  Aside from relieving sensitive teeth and the pain associate with them, there is now a way to repair enamel, a component of the tooth that was once thought to be irreplaceable. The future holds many prospects for hydroxyapatite crystals. Aside from the re-mineralization benefits, some scientists add them to toothpastes to deliver antimicrobial ions like silver and zinc which have been shown to deliver strong anti-plaque action (Roveri, Foresti, Lelli, & Lesci, 2009).  It is no longer necessary for people to suffer from sensitive teeth. There are many ways to prevent, treat, and cure the dilemma of sensitive teeth. The solution can be as simple as brushing your teeth if you’re using the correct pastes.

Works Cited

Chemistry Provides Solution to Plug Pores in Teeth. (2007, June 1). Retrieved March 2, 2012, from Science Daily: http://www.sciencedaily.com/videos/2007/0609-soothing_sensitive_teeth.htm

Dentin formation and mineralization. (2003). Retrieved March 1, 2012, from Matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs) in mature human odontoblasts and pulp tissue: http://herkules.oulu.fi/isbn9514270789/html/x280.html

Medicine, C. U. (2007). Illustrations: How a Tooth Decays. Retrieved February 27, 2012, from Colgate Oral and Dental Health Resource Center: http://www.colgate.com/app/CP/US/EN/OC/Information/Articles/Oral-and-Dental-Health-Basics/Common-Concerns/Cavities-Tooth-Decay/article/Illustrations-How-A-Tooth-Decays.cvsp

Roveri, N., Foresti, E., Lelli, M., & Lesci, I. G. (2009). Recent Advancements in Preventing Teeth Health Hazard: The Daily Use of Hydroxyapatite Instead of Fluoride. Advancements in Preventing Teeth Health Hazard , 197-215.

Sensitive Teeth. (2012). Retrieved March 1, 2012, from Medicine.Net: http://www.medicinenet.com/script/main/art.asp?articlekey=43132

What You Should Do About Sensitive Teeth. (2010). Retrieved March 3, 2012, from SaveYourSmile: http://www.saveyoursmile.com/healtharticles/sensitiveteeth.html

It taste good, but is it good for you? The dangerous chemical in crystal light packages: Aspartame

While growing up, my mother was never a big fan of juice. She kept only water in the house for everyone to drink. Although, she didn’t allow us to use sweeteners, my mother always added them to her water for flavor. She used a range of different brands, but within the past three years, she has mostly used crystal lite. Due to the excessive amount of water sweeteners that she consumed, over the past two years my mother has been in and out of the doctor very often due to constant migraines. She informed the doctors what her normal diet consisted of and after running numerous test, the doctors told her that she must stop using the sweeteners due to toxic chemicals they produced. The doctors informed my mother that there was Aspartame in the water sweeteners that cause damage to the brain, which had a popular side affect of headaches. The doctors did not go into detail about how this happened, so I took it upon myself to research and find out. Due to my prior knowledge of biology and chemistry, it was not hard to grasp the concept of why this chemical is so dangerous. While explaining it to my mother on the other hand, she did not understand quite much. This led me to understand why many doctors don’t go into great detail with their patients.

Aspartame is a well-known natural sweetener that is used in many different products. For example, equal, cereal, breath mints, carbonated soft drinks, fat free yogurt, and a plethora of other common food products. It is commonly used as a substitute for sugar and artificial sweeteners. It has been found in over 6,000 products throughout the world. The primary source of consumption of Aspartame in the US is through dietary soft drinks, like diet coke and diet sprite. Aspartame is made of aspartate, glutamate, phenylalanine, and methanol

When inside the body these can turn into aspartic acid, and glutamic acid. Since 1974 the compound, Aspartame, has been a huge controversy product since being used as a known ingredient due to the side affects that it has on its consumers.

Aspartame

The primary use for Aspartame is as an artificial sweetener in place of sugar. For example; crystal lite, and MIO. It is believed that Aspartame is not as fattening as sugar, and is therefore widely used in dietary foods and drinks. Exotoxins like Aspartame actually have a reverse effect of the body by increasing a person’s appetite, while weight loss foods are supposed to do the exact opposite. According to many researchers, experiments have been done proving that Aspartame actually causes weight gain. Due to the adverse effects of Aspartame, the FDA has revoked manufacturers rights to publish any products containing Aspartame as a weight reduction food, although it can still be labeled under dietary content.

According to an article I found written by Dr. Mercola, there are many acute as well as chronic illness caused by high ingestion of Aspartame. These symptoms that arrive consist of:

Acute Symptoms	Chronis Effects
Anxiety attacks	Brain tumors
Memory loss	Multiple sclerosis
Loss of taste	Epilepsy
Difficulties breathing	Parkinson’s disease
Hearing loss	Alzheimer’s
Blurry vision	Mental retardation
Insomnia	Lymphoma
Fatigue	Birth defects
Depression	Diabetes
Rashes
Weight gain
Seizures
Dizziness
Headaches

These illnesses are more sever in children, pregnant women, and senior citizens due to their weak immune systems. Children have underdeveloped and immature immune systems, allowing the slightest amount of Aspartame to cause damage. Senior citizens on the other hand, have immune systems, which are constantly disintegrating, making their bodies very acceptable to illnesses. Aspartame is very dangers to pregnant women, not necessarily on the woman but the baby she is carrying.

The way aspartame causes damage to the body is due to the production of aspartate glutamate and phenylalanine. During digestion of aspartame, it releases aspartate and glutamate. Glutamate is found in high protein food such as meat. Aspartate and glutamate are excitatory amino acids and neurotransmitters that facilitate the transfer of information between neurons. Excitatory amino acids are amino acids that are essential to the body. They are normal brain chemicals and are freely able to cross the brain barrier. Due to this, the brain cannot detect an excess amount of aspartate or glutamate
The brain barrier is only able to protect and exclude harmful chemicals from entering the brain. When a large amount of neurotransmitters enter the brain, it builds up and eventually reaches a toxic level. When in extremely high conditions, Aspartame generates methanol. After a while, the build up begins to act as a poison and results in the death of nerve cells and neurons located throughout the brain. These enzymes (aspartate and glutamate) do so by exciting the nerve cells until they die. Over twenty five percent of the nerve cells can be killed before any symptoms of illness arise. Below is a diagram of how the blood-brain barrier works in which necessary compounds are able to pass this barrier freely, while others are blocked, and certain ones can pass utilizing ATP. Excitatory compounds such as Aspartate and glutamate are compounds, which do not need assistance of transport molecules to pass the brain barrier.

Aspartame is made up of Phenylalanine, which when ingested can causes a huge influx in the brain and blood system. An increase of phenylalanine in the brain causes a reduction of serotonin. This in turn causes emotional disorders. Along with emotional disorders, serotonin affects decision making by inhibiting impulse behavior, and when the serotonin levels decrease a person will be more likely to act off impulse, for example: hypo activity, hyperactivity and depression. It also causes a decrease in one's appetite. A decrease of serotonin leads to constant hunger and increased food consumption. An excess build up of phenylalanine can also cause schizophrenia and seizures. Phenylalanine also breaks down into toxin called aspartylphenylaline diketopiperazine, which cause brain tumors and damaging in blood cholesterol levels throughout the body.

Cholesterol

Methanol is another harmful component of Aspartame; it acts as a deadly poison. Methanol is formed by hydrolysis when Aspartame is exposed to high acidic environments. Hydrolysis is the transformation of the methyl ester and water to methanol and the carboxylic acid. When aspartame is ingested, methanol is released into the small intestine. Once methanol is in the small intestine it breaks down into toxic formic acid and formaldehyde. Formic acid is the main primary component of methanol poisoning a deadly neurotoxins. It concentrates in the brain, kidneys, and spinal fluid. Formaldehyde interferes with the DNA replication process by binding to DNA and causing it to break. Once Formaldehyde is attached to DNA it is extremely hard to remove causes it to remain in the body.

and at sufficiently high concentration is

“Aspartame is, by far, the most dangerous substance on the market that is added to foods,” said Dr. Mercola. While doing research, I have came across many statements such as this one, addressing the dangers and side effects caused by the consumption of Aspartame. Aspartame is a topic constantly discussed by doctors and food nutritionists around the world. Although there are so many dangers caused by the ingestion of aspartame, the FDA still approves it to be in foods. Many doctors are completely against the productions of food containing aspartame due to the thousands of research and experiments, which has clinically proven the dangers, caused by this compound. The FDA fails to document the dangers and illnesses directly caused by Aspartame. "Out of 90 independently-funded studies, 83 of them found one or more 
problems caused by aspartame, but out of the 74 studies funded by the aspartame, every single one of them claimed that no problems were found?” – Joseph Watson. Many researchers believe that the FDA and Aspartame companies are covering up their findings and still allowing this dangerous chemical to be present in foods despite its harmful characteristics. There have been many attempts by numerous health nutritionists and doctors to ban the use of Aspartame in foods, but the FDA continues to allow it.

Aspartame is far more dangerous when ingested by young children as opposed to adults. Adults have the enzymes to detoxify the excitatory amino acids (aspartate and glutamate) when they enter the brain. Children on the other hand do not have the ability to do so, due to their immature protective enzymes. Pregnant women have the ability to expose their unborn child to high glutamate levels by consuming foods with Aspartame. Studies show that an infants brain is four times more sensitive to effects caused by excitotoxins than in an adult brains. It is apparent that people will eat foods with Aspartame due to the fact that it is a component of thousands of foods, but it is very important for pregnant women to monitor the amount of Aspartame they consume.

Blood Brain Barrier

http://www.answers.com/topic/blood-brain-barrier

H.J. Roberts, MD.  Aspartame (NutraSweet): Is it Safe? Philadelphia: Charles Press, 1989.

Martini, Betty. Two New studies on Aspartame and Dietary Drinks. Mission Possible International, Duluth Ga, 2005.

http://www.wnho.net/new_aspartame_studies.htm

Mercola, MD. Aspartame is, by far the most Dangerous Substance on the Market that is Added to Foods, 20011

http://articles.mercola.com/sites/articles/archive/2011/11/06/aspartame-most-dangerous-substance-added-to-food.aspx

Russell L Blaylock.  Excitotoxins: The Taste that Kills.  Health Press, Santa Fe, NM, 1995, p. 35-39.

Watson Paul. Government says Aspartame is good for you.

http://prisonplanet.com/articles/april2006/050406goodforyou.htm

Blood Brain Barrier

http://www.answers.com/topic/blood-brain-barrier

Alcohol a Cause for Cancer??

Asian Glow, a Sign of  Intoxication or a Cause for Cancer?

When I was browsing facebook one day, I received a notification from my friend Jeff. He had linked something to my profile. The title of the article read “The Body Odd – ‘Asian flush’ red flag for risk of cancer.” Being of Asian descent and a person who suffers from “asian glow” when consuming alcohol, I was intrigued by this article but initially thought it was a hoax that my friends wanted me to believe. The article posted on msnbc.com stated that people who are deficient in a specific gene linked to a liver enzyme are ten times more likely to develop esophageal cancer compared to a person who can metabolize alcohol properly. The “Asian Glow” is caused by an inability to metabolize alcohol completely due to a deficiency in a gene for alcohol dehydrogenase 2(ALDH2) enzyme. This deficiency leads to alcohol being broken down partially to acetaldehyde which is a known carcinogen as opposed to the harmless acetate end product. Finishing the article, I was still skeptical so I looked up alcohol metabolism on Wikipedia to enhance my general understanding.

Alcohol when consumed is broken down in the body using two enzymes, alcohol dehydrogenase and acetaldehyde dehydrogenase to form acetate, a nontoxic compound. Alcohol dehydrogenase oxidizes ethanol: CH₃CH₂OH + NAD⁺ → CH₃CHO + NADH + H⁺ in order to produce acetaldehyde within the body. Acetaldehyde dehydrogenase catalyzes the reaction of CH₃CHO + NAD⁺ + CoA → acetyl-CoA + NADH + H⁺.

Thereafter, I read the article “The Alcohol Flushing Response: An Unrecognized Risk Factorfor Esophageal Cancer from Alcohol Consumption” written by Philip J. Brooks et al in 2009 which was referenced as the main article studying the effects of alcohol. The abstract described how individuals with ALDH2 deficiency suffered from an increase in acetaldehyde, which damages DNA by altering deoxyguanosine through various methods such as adding methyl groups, substituting sidechains, and reducing carbonyl groups. Such changes leads to symptoms such as nausea, tachycardia, and facial flushing which many refer to as “Asian flush” or “Asian glow”

 Data from the study provided information on the genetic alteration between wild and mutant phenotypes of alcohol dehydrogenase. ALDH2 codes for the protein that breaks down alcohol, but mutations at position 487 from glutamine(Gly) to lysine(Lys) leads to a partially functional protein. Proteins that are Glu/Glu homozygotes retain full protein activity, while Glu/Lys heterozygotes have partial function and Lys/Lys homozygotes lose all function. Glu/Lys heterozygotes develop a tolerance to acetaldehyde, leading to a higher risk of developing cancer with an odds ratio ranging from 3.7-18.1. This higher risk is due to the gradual resistance to acetaldehyde effects on the body such as flushing and increased heart rate while the carcinogenic effects remain.  

Figure 1

The data from Figure 1 details the odds ratio of esophageal cancer at different alcohol consumption levels per week. Low intake constituted 1-8.9 units, moderate 9-17.9 units, and high was greater than 18 units. Each unit is equivalent to 22 g of ethanol. The odds ratio increases accordingly from about 8 to 40 to almost 80, showing that cancer risks increase drastically with alcohol consumption rates. On the other hand though, the journal article did not explain what the odds ratio equivocated to in relation to cancer development besides a general correlation.

The presence of acetaldehyde led to DNA damage in white blood cells and concentrations of acetaldehyde being 10-20 times higher in saliva than blood, which correlated to esophageal cancer risks being raised. After reading the article, I felt dissatisfied with the incomplete data and results which were unclear.  I began wondering how exactly acetaldehyde creates such damaging effects on the body.

Through a Pubmed search, I found an article describing the effects of acetaldehyde produced from drinking called “Formation of Acetaldehyde-derived DNA adductsdue to alcohol exposure” by Hsu-Sheng Yu et al. The article explained how acetaldehyde affects deoxyadenonsine and deoxycytidine but has a higher specificity for deoxyguanosine. The major adduct that forms from deoxyguanosine covalently bonding with acetaldehyde is N²-ethylidene-2′-deoxyguanosine (N²-ethylidene-dG), which was measured by detecting N²-ethyl-2′-deoxyguanosine (N²-ethyl-dG) following reduction of N²-ethylidene-dG by sodium cyanoborohydride (Figure 2).

Figure 2

The increase in DNA adducts lead to a higher frequency of DNA-protein or DNA-DNA cross-linking, inhibiting processes such as replication, transcription, and recombination. Also tumor suppressors can be inactivated along with proto-oncogenes activation in the presence of DNA adducts. Additionally, chronic alcohol consumption induces the expression of CYP2E1, which creates reactive oxygen species such as superoxide (O₂⁻), hydrogen peroxide (H₂O₂), and hydroxyl radicals (OH). These oxygen species react negatively by causing oxidative damage to proteins, nucleic acids, and lipids. 

Reading about the problems that ALDH2 deficiency creates led me to googling the acetaldehyde and I found a website describing “How Hangovers Work” on howstuffworks.com. The webpage described that acetaldehyde is targeted by glutathione, a cysteine rich substance, and acetaldehyde dehydrogenase to form acetate. This got me thinking that maybe an additive or enzyme could be given through a food supplement or a drug to someone who is deficient in acetaldehyde dehydrogenase in order to facilitate the breakdown of acetaldehyde.

Following my idea, I began searching for journal articles related to acetaldehyde and its toxicity. I went to Pubmed.com to search for articles and initially returned one called “Eliminating carcinogenic acetaldehyde by cysteine from saliva during smoking” written by Ville J. Salaspuro et al. L-cysteine reacts covalently with acetaldehyde in saliva to form stable 2-methylthiazolidine-4-carboxylic acid (Figure 3). The method used to collect the data required participants to take a tablet of cysteine then smoke a cigarette. Saliva samples were taken from each participant before smoking, then at 5 minute intervals after smoking the cigarette.

The results of the experiment show that smoking raised acetaldehyde levels to 91-352µmol/L in saliva and that 5mg was cysteine significantly lowered acetaldehyde levels. This article proved to me that acetaldehyde can be oxidized to a non-toxic form using cysteine, however I wanted to find a way to remove acetaldehyde in the bloodstream and in the digestive system.

Continued searching for articles on Pubmed about using cysteine as a possible solution to reduce acetaldehyde concentrations resulted in an article written by Klas Linderborg called “Reducing carcinogenic acetaldehyde in the achlorhydricstomach with cysteine.” The study examined concentrations of cysteine and acetaldehyde in the stomach following ingestion of select concentrations of cyteine and ethanol. L-cysteine was formed into granules in order to prevent rapid dissolving and administered through capsules. Samples were taken from participants using a nasogastric tube and measured using high pressure liquid chromatography to measure cysteine concentrations and perchloric acid to measure non-bonded acetaldehyde. Results showed that cysteine greatly decreased the amount of acetaldehyde in the stomach by 2.6 times compared to the placebos that were administered as a control (Figure 4). The use of slow release cysteine was successful with the capsulated granules, and was present in the stomach after 40 minutes following ingestion.

Figure 4

From the results of the last two articles regarding cysteine to reduce the concentrations of acetaldehyde, I believe that the negative cancer inducing effects alcohol has on the people who are ALDH2 deficient can be treated by using cysteine to covalently bond with acetaldehyde. Although, the solution is not a cure to eliminating all the acetaldehyde in the body when consuming ethanol, cysteine is still an option in at least lowering the concentrations of acetaldehyde that can damage DNA and possibly cause cancer.
For many, a pill is not an ideal source to increase cysteine in a body system, there are other natural ways to increase the intake of cysteine. According to wikipedia, foods that contain natural cysteine include most high protein foods such as eggs, pork, chicken, turkey, milk, yogurt, whey protein. Cysteine is even found in broccoli, onions, brussels sprouts, red peppers, and granola. However, the amount of cysteine in each food varies and could alter the effects of cysteine reacting with acetaldehyde. 

Extensive research of this topic has shown me that people who have a deficient ALDH2 gene suffer from an inefficient acetaldehyde dehydrogenase enzyme. Thus, DNA adducts form along with reactive oxygen species, causing damage to DNA and other cellular molecules. However, cysteine was found to be a suitable metabolite to reduce the amount of acetaldehyde in saliva and the stomach. Slow releasing cysteine was found to be fully active within the stomach for up to 40 minutes reacting with acetaldehyde following ingestion, showing that cysteine can be an effective treatment to reduce cancer inducing acetaldehyde. 

Work Cited

1. Mapes, Diane. "'Asian Flush' a red flag for risk of cancer." MSNBC.com Dec. 28 2011. Web Jan. 8 2012. 

2. Brooks, Phillip, et al. "The Alcohol Flushing Response: An Unrecognized risk Factor for Esophageal Cancer from Alcohol Consumption.” PLoS Medicine. Mar. 24 2009. Web. Feb 16 2012.

3. Yu, Hsu-Sheng, et al. “Formation of acetaldehyde-derived DNA Adducts due to alcohol Exposure.” Sciencedirect.com. Aug. 31 2010. Web. Mar. 2 2012.

4. Perry, Lance. “How Hangovers Work.” HowStuffWorks.com. Web. Feb 21 2012.

5. Salaspuro, Ville J, et al. “Elimination Carcinogenic Acetaldehyde By Cysteine From Saliva During Smoking.” Jan. 24 2006. Web. Mar. 2 2012.

6. Linderborg, Klas, et al. “Reducing Carcinogenic Acetaldehyde Exposure in the achlorhydric Stomach with Cysteine.” Dec. 8 2010. Web. Mar. 2 2012. 

Useful Links
Alcohol Dehydrogenase http://en.wikipedia.org/wiki/Alcohol_dehydrogenase
Cysteine Sources http://en.wikipedia.org/wiki/Cysteine