Posted by: R. Douglas Fields | November 26, 2015

The Taste of Thanksgiving

5176608082I took a sip of sugary Coke and was struck by a hideous intense blast of aluminum. I rushed to the sink and spit out the tainted drink. Poison! What’s wrong with this Coke! I took another tentative sip. I was slammed again by the overwhelming metallic taste. I spat out the poison by rapid reflex. This can of Coke must have been contaminated during manufacturing! Or, had the likes of the Tylenol Killer switched to soft drinks? Then I remembered. . . the taste of Thanksgiving and mountain climbing!

An hour earlier I had taken a pill to help me combat the effects of high altitude in preparation for climbing Cotopaxi, a 19,347 foot active volcano in Ecuador. The pill works by resetting the pH (acidity) in the blood to offset the effects of panting at high altitude in the body’s struggle to extract oxygen from the thin atmosphere. At high altitude, a mountain climber pants breathlessly as if running a marathon, but the effort only collects enough oxygen molecules to fuel muscles sufficiently to lug one leg a step forward. Then the climber pants some more–three quick breaths– and heaves the other leaden leg one step forward. It is pure misery–and ecstasy!

The problem with this is that when we exhale, we release carbon dioxide from our blood stream, but all that huffing and puffing in high altitude eliminates too much CO2 from the body. This drops the acidity in the blood sharply (making it alkaline), because CO2 dissolves into solution to make carbonic acid. The proper amount of carbonic acid in the blood is crucial to keep the acidity in our blood at the level needed for hemoglobin in our red blood cells to extract oxygen. Part of the acclimatization process that mountain climbers undergo by taking days or weeks to slowly ascend a mountain to avoid getting altitude sickness involves changes in the body’s chemistry to restore normal levels of acidity in the blood. (Stick with me here–this will soon come back to Thanksgiving dinner!)

Within minutes of our blood becoming alkaline, our kidneys respond by increasing excretion of bicarbonate in urine until this offsets the low CO2 levels in our blood. (Bicarbonate is the same stuff used as an over-the-counter antacid to treat indigestion. Dumping the body’s natural antacid restores acidity in the blood stream to normal levels.) There are many other bodily responses in acclimatization to high altitude, but this one is vital, and it is quite obvious and annoying as climbers find themselves suffering frequent and urgent exits from the warmth of a down sleeping bag to let their kidneys do their work overtime throughout the freezing cold night.

Acetazolamide (the trade name is Diamox), is a carbonic anhydrase inhibitor. Inhibiting carbonic anhydrase in the kidney stimulates excretion of bicarbonate in the urine. By taking the pill before climbing, a mountaineer can jump start the process of acclimatization and help prevent high-altitude illness. This is important because high altitude illness can be far more serious than a pounding headache–it can be deadly. One of the effects of low oxygen is to make blood capillaries in the brain leaky. As fluid oozes out of capillaries the brain swells inside the bony skull, causing brain damage and death.

That’s when I suddenly remembered that one of the side effects of acetazolamide is to disrupt the sense of taste in a very specific way. Our sense of taste comes from five main categories, sweet, salty, bitter, sour, and umami; each of which is the result of a specific set of taste receptors in our tongue that respond selective to one of these tastes. Umami is the taste that we associate with savory flavor, but sour is the body’s pH meter–it is a sensor for acid. In a paper published in the journal Science in 2009, researchers reported that they had identified a class of taste-receptor cells in the tongue that respond to carbon dioxide (carbonic acid). This is the gas that gives sodas, beer, champagne, and other carbonated beverages their distinct tang. The molecular sensor in these taste cells was found to be an enzyme called carbonic anhydrase-4, and here’s the punchline–acetazolamide (Diamox) quashes that enzyme in these taste buds, as a side effect of its action on the kidneys. So as I enjoyed my salty salami sandwich for lunch, I had no idea that the Diamox I had taken earlier had temporarily killed my ability to taste the acid of CO2, until I took a sip of Coke and found the flavor horribly wrong and off-putting. All the other taste receptors in my tongue were working just fine, but not the ones that savor the fizz of carbonated drinks.

More amazing to me than this fascinating bit of neuroscience in taste reception was that it did not matter a whit that I understood completely–down to the chemical equations involved–that there was absolutely nothing wrong with my Coke. It was utterly impossible for me to drink it. So powerful is our sense of taste, it overrides our conscious reasoning and force of will in controlling our eating behavior. (The same is true for the sense of smell. Can you eat anything with the smell of vomit in the air?) These are deeply embedded life-saving neurocircuits that protect us from poisoning.

So as we savor the distinct and wonderful flavors of Thanksgiving dinner, the sweet potatoes, the salty gravy, umami of turkey breast, the tartness of cranberries, the sweetness and spice of apple pie, the bitter bite of beer, and the tang of sparkling wine; give a moment to reflect on the festival of amazing sensory reception going on in our nervous system.

Keep in mind too that everyone has different likes and dislikes when it comes to flavor, and that is in part because things do not always taste the same to everyone. The bitter taste of Brussel sprouts on a child’s tongue may have taste buds screaming, “Poison!” in shock from the strong bitter flavor, while the parent’s taste buds might not even detect the bitterness. An analysis of my personal genome, for example, revealed that I have a gene variant that reduces my ability to detect bitter flavor. This explains why I love a hoppy IPA, but my wife can’t stand the taste of a sip of beer. Children and adults have a different sense of taste because the human tongue and taste buds do not develop into the adult form until about 11-12 years of age. This makes sense because the nutritional needs of rapidly growing children are different from those of adults. A child’s sweet tooth fuels the active young body. Taste buds last only about 8-12 days and they are renewed constantly. As we age, our ability to replace taste buds declines and our sense of taste becomes less acute. Females tend to have greater taste sensitivity than males because they have more and larger fungiform papillae (the bumps on the tongue where taste buds reside). This sex-specific difference may relate to differences in behavioral roles of males and females throughout the course of evolution, where women needed to gather high-quality foods, detect potential toxins, and prepare food in their maternal role of caring for their offspring.

Differences in taste reception have important consequences. Eating disorders are associated with differences in taste reception. Many diseases alter the sense of taste, and conversely, changes in taste perception can be diagnostic of certain diseases. The bacterium that causes stomach ulcers, H. pylori, results in a poor ability to distinguish between bitter and acid tastes, for example. Interestingly, the same receptor that senses bitterness, T2Rs, is also found in our airway. It turns out that these bitter sensing cells in our sinus can detect a bitter molecule, acetyl-homoserine lactone, which is secreted by gram-negative bacteria, including the very nasty Pseudomonas. Upon sensing the bitter secretions of bacteria in our nasal cavities, these taste receptors stimulate cells in our nasal cavity to sweep away and kill the bacteria. Research is underway to determine if people with chronic sinus infection may lack the gene for T2R bitterness detection.

The last example shows that taste receptors are hardly limited only to the surface of our tongue. People have long realized that the sense of smell and taste are closely linked, but only in the last few years have researchers discovered that we also have taste receptors in our gut! Yes, even after we have swallowed and started digesting our meal, our brain is still sensing the content of what we have consumed through taste receptors in our gut. Presumably this unconscious monitoring can give us pleasure of a satisfying meal or alarm as what we have eaten “turns on us.” Taste is a vital protective system that is essential for our health and survival, and these remote sensors have powerful effects in the brain that alter mood and control behavior through neurotransmitter systems that include serotonin, norepinephrine, ATP, acetylcholine, and GABA.
However, if you were taught in school that the tongue is divided up into different territories to detect the different tastes in different spots, that bit of “science” has been debunked. Amazing that this myth persisted so long, given that anyone could easily taste the truth simply by touching the tip of the tongue to salt and finding that the flavor briny and not sweet. Happy Thanksgiving!


Chandrashekar et al., (2009) The Taste of Carbonation, Science 326, : 443-445.

Fields, R. D. (2009) Outside Magazine, September, 2009,

Fields, R. D. (2008) Into thin air: Mountain climbing kills brain cells. Scientific American, April 3, 2008

O’Connor, A. (2008) The Claim: Tongue is mapped into four areas of taste. The New York Times, November 10, 2008.

Photo credit: Tongue taste map: “Taste buds” by Messer Woland – own work created in Inkscape. Licensed under CC BY-SA 3.0 via Commons –

Turkey dinner: Steve A. Johnson



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