Is caffeine a key to a longer life?

Was fascinated to read in World Tea News the headline: “caffeine key to a longer life.” Over my nearly 40 years in nutritional sciences, I’ve seen numerous attempts to paint caffeine as bad for your health, only to have the science prove the opposite. So was eager to read the journal article on which the headline was based.

I quickly found out that the journal article in question does not say that caffeine is what makes any difference in life span…it’s coffee itself, both caffeinated and non-caffeinated! **

Here’s the paper’s conclusion:

“Higher consumption of total coffee, caffeinated coffee, and decaffeinated coffee was associated with lower risk of total mortality.”

So to extrapolate these results to the caffeine in tea is a big leap. 

I looked for data about tea consumption and all-cause mortality from the same group and same studies and so far haven’t found anything published. Instead what the Harvard researchers have said is that drinking tea may be good for your health, but if so, they really don’t know why. Their conclusion about tea:

“So if you drink tea, keep it up, but don't take up the habit thinking it will have a dramatic impact [on longevity].” ***

… I would say instead: enjoy your tea for itself!

In my next post, I’ll discuss the second article on which the World Tea News report is based—it’s about worms and chlorogenic acid (it's not caffeine, either, but an ester of caffeic and quinic acids).

* Sam Molineaux. Good News for Tea Drinkers: Caffeine Key to Longer Life. 

July 26, 2016.

** Ming Ding, et al. Association of Coffee Consumption with Total and Cause-Specific Mortality in Three Large Prospective Cohorts. Circulation. 2015;CIRCULATIONAHA.115.017341, published online before print November 16, 2015. http://dx.doi.org/10.1161/CIRCULATIONAHA.115.017341

         ==>> NOTE: this is another in the ongoing series of papers about the Nurses' Health Study and the Health Professionals Follow-up Study run by Harvard University's School of Public Health.

*** http://www.health.harvard.edu/staying-healthy/tea-a-cup-of-good-health

Medications and green tea

You may have worried on learning from the latest World Tea News (article title: "Certain Medications, Food, Tea Could Worsen Heart Failure") that green tea is on a list published by the American Heart Association entitled “Drugs that may Cause or Exacerbate Heart Failure.”

Here’s why it’s on the list: green tea contains compounds that act like warfarin/coumadin, a “blood thinner.” People who are taking warfarin/coumadin, who then decide to start drinking green tea, may find themselves at risk for excessive bleeding because pill + green tea = too much warfarin/coumadin = inability to clot.

But of you have been drinking green tea all along, it may not be a good idea to stop or to make any sudden changes in your diet. Instead, it is critical to talk with your healthcare provider first, before making any changes, because a change in diet may cause the amount of drug you are taking to be too much or too little.

Your healthcare provider can help you with your diet, and inform you about what you should and shouldn’t eat. Be sure to tell your health care provider about any other foods and medications you take, including herbal and over-the-counter preparations—the American Heart Association Statement includes a lot of these, which have many different consequences. Your healthcare provider can make the best recommendations for your individual situation. 

Please note: as with all information on this website, this information is provided for your information only, without any warranties direct or implied, and may not be construed as medical advice or instruction. No action or inaction should be taken based solely on the contents of this website; instead, you should consult appropriate healthcare providers on any and all matters relating to your health and well-being.

Image from Morguefile.com

* Robert L. Page et al.  American Heart Association Scientific Statement: Drugs That May Cause or Exacerbate Heart Failure. Circulation. July 19, 2016, Volume 134, Issue 3.

Kokumi

Ever heard of kokumi? If not, you have certainly experienced it! Think of that full round taste that you get from some delicious piece of meat or cheese, or even onions and garlic—that’s kokumi! 

As you may have gathered from the name, kokumi is a Japanese taste concept that has proven—like umami—to be very real. The kokumi sensation is accomplished by short protein-like compounds that have a γ-glutamyl group on the end of their amino acid chain. It’s not surprising, then, that these compounds are found in foods with protein, and that they enhance the savory umami taste of proteins.

By themselves, these compounds have little if any taste. But if you add a compound that confers kokumi to a sugar solution, it will taste sweeter, and to a salt solution, it will taste saltier!

Some foods with kokumi, from http://media.eurekalert.org/multimedia_prod/pub/web/19439_web.jpg

How do kokumi compounds do this magic? 

As Kuroda and Miyamura have discovered,* these compounds increase calcium entry into taste cells (and trigeminal cells, too) by activating a calcium-sensing receptor. Normally, calcium enters these cells when their taste or trigeminal receptors are activated, leading to a taste signal. What the kokumi substances appear to do is to increase the amount of calcium that enters the cell, thus increasing the intensity of the signal, and prolonging the signal’s time of action, which means prolonged after-taste as well.

==>> And guess what…tea’s theanine, in chemistry parlance, is γ-glutamyl-L-ethylamide! 

How delicious!

*Motonaka Kuroda and Naohiro Miyamura. Mechanism of the perception of “kokumi” substances and the sensory characteristics of the “kokumi” peptide, γ-Glu-Val-Gly. Flavour, 2015, 4:11

DOI: 10.1186/2044-7248-4-11.

Here’s a graph from this paper, showing the effects of the “kokumi” peptide on a low-fat custard:

Flavor in the gut!

Been working madly on the book about our flavor system,* and enjoying a paper that discusses how our taste-sensing system interacts with the gut.** 

Believe it or not (and you should believe it—nature can be very parsimonious!) hormone-secreting cells in the gut (endocrine cells) have the same receptors for sweet, umami, bitter, and fat as does the tongue. Once you eat something with one or more of these qualities, these cells encounter what you have eaten and secrete their hormones: 

• glucagon-like peptide that enhances insulin secretion so you can handle sugars; 
• cholecystokinin, which contracts the gall bladder, releasing fat-emulsifying bile into the intestine, so you can handle fats; 
• and ghrelin, which, among many other functions, makes you feel rewarded for eating what you have just consumed and make you hungry for more. (Yes, it may help you overeat!)

* Did you take the survey about the book? — if not, please do! You can find it at:

https://apps.facebook.com/my-surveys/form/survey-for-a-project-on-tea-and-tea-pairing?from=admin_wall

** Sara Santa-Cruz Calvo & Josephine M. Egan. The endocrinology of taste receptors. Nature Reviews Endocrinology 11, 213–227 (2015) doi:10.1038/nrendo.2015.7

More about rotting fish…

Was reading about polyunsaturated fatty acids (PUFAs) and their receptors today.* Turns out that PUFAs activate TRPA1, the “cold” receptor on the trigeminal nerve in the mouth and nose. When activated, this receptor causes not only sensations of cold, but also of pain. TRPA1 also acts like a volume dial, initially enhancing the flavor of whatever activates it. However, in about a minute of continuous exposure to the PUFAs, TRPA1 becomes desensitized and ceases to be active.

Normally, the fats we eat come in the form of triglycerides, fatty acids attached to a glycerol backbone, or in the form of phospholipids, where two fatty acids are attached to a “head” structure that varies by the type of phospholipid. When the PUFAs are attached in this way they cannot activate TRPA1. But once they are free, they can. Microbes are experts at liberating PUFAs when they infest a food.

When fish spoils, it doesn’t just make the stinky amines that I discussed in my July 3rd post. Fish, especially cold water fish, have an abundance of PUFAs in their triglycerides and phospholipids. Once the microbes get going, a lot of PUFAs are released.

Neither mice nor humans enjoy the taste of these PUFAs. Flies, however, don’t seem to mind, because their TRPA1 receptors aren’t sensitive to them. 

PUFAs are another reason why rotted fish is so unpleasant…but you can get used to it…

...or add lemon—lemon activates TRPV1 and turns off TRPA1... ; )

No, this fish isn't rotten...Photo by Gregory Bourolias, unsplash.com.

* Motter AL, Ahern GP (2012) TRPA1 Is a Polyunsaturated Fatty Acid Sensor in Mammals. PLoS ONE 7(6): e38439. doi:10.1371/journal.pone.0038439.

First sleep, then a cup of tea.

Just learned from my 23andme results that I am a “deep sleeper.” What this actually means is that I have a single change in my DNA code, inherited from one of my parents*, that slows down my ability to break down adenosine.

Say what???

Adenosine is a natural chemical that accumulates in your brain as you stay awake. The more you accumulate, the sleepier you get. Eventually you can’t stay awake any more, and sleep overtakes you. Then, as you sleep, the adenosine is broken down, so you wake up. Then the cycle begins again.

The sleep that adenosine promotes is non-REM sleep—deep dreamless sleep—hence my being called a deep sleeper. Because I don’t break down adenosine as quickly as other people, I tend to have longer periods of non-REM deep sleep. 

You might also call me a napper—I work best when I have had a couple of naps in a day. My guess is that my naps, which are usually dreamless, allow me to get rid of some of my excessively accumulated adenosine, so I can be more alert.

My little granddaughter, falling asleep at her drawing...

Which brings me to tea.

Tea has two compounds, caffeine and theophylline, that bind to adenosine receptors, so adenosine can’t get to them.  That’s one way that tea wakes you up and makes you feel alert. 

These compounds will be less effective if there is a lot of adenosine around—they have a hard time competing for the receptors. But if adenosine is allowed to clear, say, by a nap, caffeine and theophylline can block the adenosine receptor more effectively, and wake you up better and for a longer time.

So if you are a deep sleeper, like me, or even if you are not: if you feel sleepy during the day, take a short nap first and then enjoy your cuppa—and you’ll feel even more refreshed!

Here’s a great website about sleep: http://www.howsleepworks.com/how_homeostasis.html.

* From my father, no doubt. He could fall asleep at will, whereas my mom had a hard time getting to sleep and staying asleep, and yet spent each day full of vim and vigor.

Odorant receptor movie

Had some fun today creating a short animation showing how an odorant activates an ion channel. 

In the animation, the odorant (red pentagon) attaches to an odorant receptor (purple). Note that the odorant receptor has 7 parts attached to each other. Each part crosses the cell membrane (grey) so part of the receptor is outside the cell, and part inside. 

Once the odorant attaches to the receptor, the last of these 7 parts changes shape, activating the 3-part G-protein (green) attached to the receptor. One part of the G-protein separates and initiates a series of reactions (green arrow) that cause an ion channel to open, and calcium and sodium ions(blue and yellow) flow into the cell. The cell can then send an electrical signal to the brain.

Let me know what you think!

What is a receptor?

With all this conversation about receptors, you may well wonder: what is a receptor?

To put it simply, a receptor is a molecule that is attached to a cell's membrane, and that can grab on to specific chemicals and send a signal to the cell that it has done so.

The way the receptor lets the cell know that a chemical has bound to it is by changing shape. The shape change leads to one of at least two types of signal: the direct movement of ions into the cell, and the indirect opening or closing of ion channels.

Some receptors are ion channels as well as receptors — when these receptors change shape, the channel opens, and ions (usually sodium and/or calcium) enter the cell. The entry of sodium or calcium causes the cell to react by changing its metabolism and/or by send a message to the next cell in line.

An example of a receptor that is also an ion channel is the epithelial sodium channel or ENaC (Na is the chemical abbreviation for sodium, called natrium in Latin). Salt-sensitive taste bud cells use ENaC to allow sodium to enter the cell and start the process of notifying neighbor cells that there is sodium present.

Some receptors are G protein–coupled receptors (GPCRs). G-proteins get their name from the fact that they use a chemical, guanine triphosphate(GTP), to start reactions inside the cell. When a G protein–coupled receptor responds to its specific chemical, its shape change activates the G-protein attached to it, causing the G-protein to start a cascade of chemical reactions inside the cell. 

Odorant receptors (ORs) are G protein-coupled receptors. When an odorant attaches to its receptor, the receptor activates its associated G-protein, which in turn initiates chemical signals inside the cell. These signals cause an ion channel to open and allow sodium and calcium to enter the cell. Once this happens, the cell can send a signal to the olfactory bulb that an odorant molecule has been attached.

You can find a good description of the process of G-protein activation by odorants — and much more about olfaction — in the 2004 press release announcing the award of the Nobel Prize to Richard Axel and Linda B. Buck (below) for their work on odorant receptors: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2004/press.html. 

Richard Axel

Linda Buck

Blueberries and raspberries together?

Blueberries and raspberries together maker a pretty picture, as you can see on my latest cover photo for the Pairteas Facebook page. But do they taste good together?

Depends on what you consider "together!"

Summer delights! -- A photo by Tiago Faifa, that I found at http://unsplash.com.

If you take both berries together in the same mouthful you won’t get much of either flavor: raspberries activate the warm/hot receptors, and blueberries activate the cool/cold, so each inhibits the other. 

Or maybe the blueberries will dominate because the cool/cold receptors are quicker to respond to a stimulus than are the warm/hot receptors.

But start with raspberries alone. Next eat a few blueberries, and feel the raspberry flavor disappear. Then wait for a few beats, or maybe a little longer. The raspberry taste will start to come back! Then of course enjoy some raspberries again, and repeat the whole experience.

Which teas make these berries happy? As you may have guessed, green teas go with blueberries—activation of the cool/cold receptors is so refreshing! And black teas are delicious with raspberries—both black tea and raspberries have the flavorful chemical raspberry ketone in them, which activates the warm/hot receptors!

Give the experiment a try and let me know what happens!

Can what’s spicy "hot" cool you down?

In this time of iced tea, it is hard to imagine that drinking something spicy “hot,” say a deliciously spicy chai, could make you feel cooler, but that may well be the case!

Drinking plain cold water can cool you down,* in part because you will tend to drink more, and therefore have more capacity to sweat; in part because cold water or even better, icy slush, seems to cool down core body temperature by mechanisms still poorly understood**; and in part through the psychological/physiological process of feeling refreshed.*

So what does drinking something spicy do? As you know, when you eat a too hot chili pepper, you start to flush and break out in a sweat. The flush may make you feel hotter, but in fact what is doing is bringing blood the body surface where it helps to lose heat, both directly and by warming up the sweat and causing evaporation—this reaction to spice is the result of activating TRPV1, the hot receptor in the mouth and throat.***

So to get the best of both worlds: enjoy an ice cold spicy chai slush—the black tea and spices activate TRPV1 while the ice refreshes and cools you down!

For delightful instructions, see: http://www.indiansimmer.com/2014/06/indian-iced-masala-chai-recipe.html, Here's what it looks like:

* Tan, P. M. S. and Lee, J. K. W. (2015), The role of fluid temperature and form on endurance performance in the heat. Scandinavian Journal of Medicine & Science in Sports, 25: 39–51. doi: 10.1111/sms.12366.

** One mechanism may be that an increase in body water content may be able to take up more of the heat your body produces, with the water serving as a heat sink.

*** Narender R. Gavva et al. The Vanilloid Receptor TRPV1 Is Tonically Activated In Vivo and Involved in Body Temperature Regulation. The Journal of Neuroscience, 28 March 2007, 27(13): 3366-3374; doi: 10.1523/JNEUROSCI.4833-06.2007.

TAARs

You have heard of the classic type of odor receptor in the nose, the type that senses the aromas of flowers and fruit and so much else. Did you know that there is a second type of odorant receptor?

These receptors are called “TAARs,” which stands for Trace Amine-Associated Receptors. They have also been called Trace Amine Receptors (TAs or TARs), though the former appellation may be more appropriate because we do not know as yet the full repertoire of molecules that bind to these receptors. 

Their existence was first described in 2001, their discovery the result of searching for genes coding for proteins with certain characteristics.* In the case of the TAARs the characteristic in question is the ability to bind to amine compounds such as dopamine and amphetamine. 

Humans have 6 functional genes for TAARs and 3 pseudogenes (= genes that have changed enough through human evolution that they no longer produce functional proteins). Of the functional gene products, one (TAAR1) exists in multiple tissues but not the olfactory tissue, and the rest (TAAR 2, 5, 6, 8s, and 9) appear to exist only in olfactory tissue. These receptors can be found on cells similar in both structure and location to regular olfactory cells, and they send their messages through the olfactory bulbs, just like regular olfactory neurons.**

What message do these TAARs send?  “STENCH!!!”

As anyone who has experienced Icelandic hákarl—fermented shark—can tell you, the process of letting fish rot creates a distinct and utterly foul smell. The chemical that imparts this stench: trimethylamine; the receptor that responds to it: TAAR5. (According to Wikipedia, Chef Anthony Bourdain described kæstan hákarl as "the single worst, most disgusting and terrible tasting thing" he has ever eaten—and he has eaten plenty of disgusting things!)

Hákarl hanging to dry in Bjarnahöfn in 2005. Photo by Chris 73 (Wikimedia Commons). 

Other compounds that bind to human TAARs: 

• phenethylamine, which lends its power to the stench of carnivore urine; this compound induces fear in rodents and serves as a warning to humans that, say, a tiger is nearby—when tigers mark their territory with urine, phenethylamine provides much of the urine’s persistent and aversive odor.
• tyramine, which occurs in certain cheeses, chocolate, and red wine, and—I might add—pu-erh; its odor has been characterized as meaty and dirty, but also as sweet and vegetal.***
• N-methylpiperidine, which, as its name implies, occurs in pepper—I believe that it gives that slightly sour unpleasant smell to old ground pepper, though I cannot be certain.

The total number of compounds to which TAARs respond is not known. One can say, however, that many of the known compounds contribute significantly to urinaceous and rotting smells.

Interestingly, some humans have genetic variants of the TAARs that lead to inability to sense some of these smells.**** Lucky them—or perhaps not—I guess it depends on the circumstances!

* Borowsky B, et al. (2001). Trace amines: identification of a family of mammalian G protein-coupled receptors. PNAS 98 (16): 8966–71. doi:10.1073/pnas.151105198; Bunzow JR, et al. (2001). Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. Mol. Pharmacol. 60 (6): 1181–8. doi:10.1124/mol.60.6.1181. 

** Stephen D Liberles. Trace amine-associated receptors: ligands, neural circuits, and behaviors. Current Opinion in Neurobiology. Volume 34, October 2015, Pages 1–7.

*** “Our results showed that among 207 kinds of tea tested, Pu’er ripe tea contains the most kinds of and the highest content of the biogenic amines, followed by Pu’er sun dried tea, and Pu’er raw tea contains the least. The method should be helpful for the quantification of biogenic amines in the tea product and the tea quality control.” Mengying Zhang et al. Determination of Eight Different Biogenic Amines in Pu'er Tea by HPLC. Focusing on Modern Food Industry (FMFI) Volume 3, 2014 doi: 10.14355/fmfi.2014.03.009.

**** Vanti WB et al. Discovery of a null mutation in a human trace amine receptor gene. Genomics. 2003 Nov; 82(5):531-6.

Electronic noses

One of the big problems with using trained panelists for tea aroma evaluations lies in the variability of the human sense of smell, both between individuals and across time for any single individual. 

A solution to this problem would be to develop an electronic nose, which would be able to detect the different chemical constituents of a mixture of volatile chemicals that make up an aroma. The ideal electronic nose would be able to detect the individual voltiles, identify them, then tell you what the resulting combo of volatiles would smell like. An example of the latter problem: two quite different chemicals—ethyl isobutyrate, which has a sweet, fruity, slightly garlicky smell, and ethyl maltol,  which is sweet with a strawberry jam aroma—when put together together give a distinct pineapple aroma.

Existing electronic noses rely on the ability of volatiles to bind to electrodes coated with specific compounds that bind different categories of volatiles. Once the volatile is bound, a current can go through the electrode, resulting in a signal that a detector can recognize. So far these “noses” are not able to perform the tasks listed above, but they can detect differences among different samples, or detect certain individual volatiles that may be indicative of the quality of a tea.

All if this by way of introduction to a paper from Italy about the comparison between volatiles in the processed leaf and ones in the cup among a sampling of Chinese teas.* Here I am going to mention one observation (among many) that I find quite fascinating, and that confirmed what I have thought might be the case for a long time, namely that oolong and white tea were more alike than you might believe when you just consider the processing of each.

The white was a Pai Mu Tan, consisting of a leaf bud and two youngest leaves (W in the graph below). The oolong was a Wuyi Shui Xian, second and third leaves from the top (O in the graph below). The other teas were greens (G), black (B), yellow (Y), and pu-erh (P).

The graphs are designed to show the patterns of volatiles in each of the teas, using a statistical technique called principal component analysis. I’ve circled in red the white and the oolong—the left panel represents the volatiles emanating from the leaf and the right panel the volatiles emanating from the infusion.

While there are obvious differences between leaf and infusion, the white and the oolong teas cluster together in each graph, suggesting that the pattern of volatiles in them is similar.

These similarities, as Torri and her colleagues suggest, are probably due to the long withering process each type of tea undergoes. This allows the leaf to produce all the injury chemicals that we find so delicious!

The typical suggestion is that white tea is ultra delicate, which it may be, but the richness of volatiles that the long withering creates makes the delicacy extremely complex. You often see white tea matched with cucumber or mint. Yes, the volatiles in white tea do activate the cold receptors, so cucumber or mint might seem to be a good match. But the compounds in cucumber and mint are so dominant you lose the wonderful complexity of the tea. 

A better suggestion? perhaps a lightly lemoned pound cake? Let me know what you think. 

* Torri, L., Rinaldi, M. and Chiavaro, E. (2014), Electronic nose evaluation of volatile emission of Chinese teas: from leaves to infusions. Int J Food Sci Technol, 49: 1315–1323. doi:10.1111/ijfs.12429.