Tuesday, November 25, 2014

Tryptophan vs. The NFL Fan

A turkey dinner with all the fixins can lead to a
satisfying nap. But the meal usually takes a little
longer than this to have an effect. This fellow might
be more affected by last night’s activities than today’s
Turkey dinner at Thanksgiving brings the family together, celebrates the bountiful harvest, and puts you to sleep just as the NFL games are ready to start. Many people think that if you eat less turkey and fill up on the other goodies you can escape the post-Thanksgiving meal sleepiness. Other people look forward to eating seconds and thirds and then stretching out on the couch for a long nap, forcing Aunt Ethel to sit in the chair with the spring that surprises you every once in a while.

The culprit, or the hero, in this eat and sleep saga is said to be the tryptophan in the turkey. Other people think that it is simply how much you eat, not the turkey's tryptophan, but it isn’t quite that simple. What is tryptophan, and is it indeed responsible for the snoring that follows Thanksgiving dinner?  Some background will help.

Tryptophan is an amino acid, one of the twenty standard building blocks of proteins. However, tryptophan is the least abundant amino acid in plant and animal proteins; it accounts for only 1-1.5% of the total number of amino acids in proteins. Tryptophan’s large structure and intricate rings make it costly to produce in terms of ATP invested. In fact, it takes so much energy to make that we have stopped making tryptophan all together. Tryptophan is abundant in a number of food sources commonly available to humans, so over evolutionary time we have turned it into an essential amino acid. True, it is essential for life, but here the word “essential” means that we MUST get it from our diet, we cannot produce it ourselves.

The genetic code is how mRNA codons (3 bases sequences)
get translated into a signal to build proteins from specific amino
acids. The first base of the codon is represented by the biggest
letters (ACGU), the middle base is the middle size letters, while
the third position (wobble position) is usually where you see an
amino acid coded for by more than one codon. For instance,
serine is coded for by UCU, UCC, UCA, or UCG. But tryptophan is
only coded for by UGG. Three codons signal the protein to stop
growing, called stop codons (UAG, UAA, and UGA).
Even though it is used sparingly in proteins, tryptophan is crucial - don’t eat enough of it and you die. This is because tryptophan’s most essential functions have nothing to do with protein synthesis or structure – tryptophan is important to your brain function. The crucial neurotransmitter, serotonin, is synthesized only from tryptophan.

It takes two enzymes to turn tryptophan into serotonin (also called 5-HT).  First is tryptophan hydroxylase; hydroxylase means it splits water, here it adds an OH to tryptophan. Next, the amino acid decarboxylase removes a carboxylic acid (COOH), producing serotonin.

The feeling of general well being induced by serotonin also participates in the sleep/wake cycle. So is tryptophan – through serotonin – responsible for the post-Thanksgiving nap? Well… yes and no, it's an accomplice in a larger conspiracy.

Serotonin is used to produce the hormone melatonin, and melatonin promotes sleep, so you could say turkey dinner promotes sleep. But turkey doesn’t have that much tryptophan! Tofu has much more tryptophan than turkey, but you don’t get a post-Chinese takeout urge to sleep, so what gives?

Melatonin is made from serotonin in the pineal
gland. Sunlight stimulates the suprachiasmatic
nucleus (SCN) which inhibits the pineal from
making melatonin. As the sun goes down,
inhibition is reduced, more melatonin is made
and released from the pineal, and sleep is
The melatonin effect has to do more with how much of everything else you eat at Thanksgiving dinner, especially carbohydrates. Here is how it works – eating lots of carbohydrates causes a release of insulin into the blood (to reduced blood glucose levels). Another function of insulin is to promote the uptake of some amino acids (but not tryptophan) into muscle cells. This leaves the blood higher in tryptophan as compared to other amino acids than it would normally be.

The brain takes in amino acids through a neutral amino acid transporter, which now finds more tryptophan than other neutral amino acids, so the brain level of tryptophan goes up. More tryptophan in the brain, more serotonin – more serotonin, more melatonin. More melatonin = nap time! So if you want to avoid the post-Thanksgiving nap, eat the turkey and skip the mashed potatoes.

You didn’t know how much tryptophan controlled your daily life, did you? Well, there’s more. Tryptophan is also important in synthesizing niacin, a.k.a. vitamin B3 or nicotinic acid. Niacin is important in production of NAD/NADH for energy metabolism, for production of steroid hormones and balance of lipid forms in the blood, and as an anti-convulsant.

The tryptophan-niacin connection is made stronger by recent evidence that high dietary tryptophan can prevent epileptic seizures in mice. In this study, a whey protein called alpha-lactoalbumin (ALAC) was found to have much tryptophan, much higher levels than in most proteins. Feeding epileptic mice ALAC resulted in reduced numbers of seizures.

So even if you don’t want to sleep or think happy thoughts, you still need to eat food that contain tryptophan or niacin. And many of those foods are plants, because plants use tryptophan to control their own activities. Tryptophan is easily converted to auxins, a type of plant hormone. Auxins are responsible for several different plant behaviors, namely the falling leaves in autumn and ripe fruits all year long.

Here is an interesting attempt to get kids to read
history. During the spring, captive warriors were
killed by cutting out their hearts, then their skin was
flayed off their body, and the priests would wear them
around for 20 days. This was meant to celebrate the
god who sacrificed himself to allow a new growing
season to begin. This time period corresponds
 to when they would have had the lowest amount of
 tryptophan in their daily diet.
Having dietary choices for tryptophan is good, and plants provide our major source. However, cooking grains and corn reduces usable tryptophan and niacin levels dramatically, so poorer environments where corn is the staple food need also to have additional dietary sources of tryptophan. A deficiency of this amino acid leads to some disturbing conditions. Low tryptophan leads to low serotonin levels and agitation, insomnia, and depression. A study in the Archives of General Psychiatry stated that chronically low levels of tryptophan led to relapses of purging behaviors in bulimics.

More amazingly, studies in the 1970’s to 1990’s suggest that low tryptophan levels can lead to increases in religious fanaticism. Several studies from a single author correlate the Aztec human sacrificial ceremonies to the times of year when their diets depended more on foods that had less tryptophan. Think of all the lives that could have been saved by tofu!

Contributed by Mark E. Lasbury, MS, MSEd, PhD
As Many Exceptions As Rules

Russo, E., Scicchitano, F., Citraro, R., Aiello, R., Camastra, C., Mainardi, P., Chimirri, S., Perucca, E., Donato, G., & De Sarro, G. (2012). Protective activity of α-lactoalbumin (ALAC), a whey protein rich in tryptophan, in rodent models of epileptogenesis Neuroscience, 226, 282-288 DOI: 10.1016/j.neuroscience.2012.09.021
Bruce KR, Steiger H, Young SN, Kin NM, Israël M, & Lévesque M (2009). Impact of acute tryptophan depletion on mood and eating-related urges in bulimic and nonbulimic women. Journal of psychiatry & neuroscience : JPN, 34 (5), 376-82 PMID: 19721848

Thursday, November 20, 2014

Science Identifies The Catchiest Songs Ever – Did Your Favorite Make The List?

Humans have a deeply rooted love for music and rhythm. For reasons we’ve yet to fully understand, certain types of music bring out the warrior inside of us while other types of music are incredibly soothing. Some songs move us to tears, yet others make us angry. And humans are not alone their capacity to respond to music. There is something about these unnaturally occurring sound patterns that speaks (sings?) to all species capable of sensing the reverberations.

Music can hold great power over us. Songs can change moods, spark memories, or inspire greatness. Some of you may have seen the video of Henry, an unresponsive gentleman in a nursing home, spring back to life after hearing his favorite music. Watch this remarkable episode below as neurologist Oliver Sacks explains the phenomenon.

We are also attuned to how divergent musical tastes can be! Teens rarely like the music that their parents listen to and vice versa. David Hasselhoff has an inexplicable legion of devoted fans in Germany. Michael Bolton somehow scored multiple hits despite piercing millions of eardrums. Some only listen to country, rap, rock, or classical, yet some people have promiscuous ears that love it all. And, let’s admit it, jazz is only fun for the musicians playing it.

Germans love the music of David Hasselhof so much that they've placed an eerily realistic wax statue of The Hoff by the Brandenburg Gate.
John Mellencamp once declared that the world is “polluted” with songs. With an estimated 2-5 billion songs having been written throughout human history, it is pretty remarkable for one to gain widespread popularity. The songs that manage to stand out from the crowd are typically called “earworms” because they are so catchy that you can’t shake them out of your head no matter how hard you try. Some of these tunes dig their talons so deeply into your subconscious that it can be agonizing; for example, here’s a list of infectious songs that were actually used to torture people.

Recently, Dr. John Ashley Burgoyne, who calls himself a computational musicologist, used an online game called “Hooked on Music” as a tool to identify some of the catchiest songs humans have ever concocted. Want to know what they are?

Coming in at number 5 is the ABBA hit, “SOS”:

The fourth catchiest song is “Just Dance” by Lady Gaga:

“Eye of the Tiger” by Survivor, the theme from Rocky III, punches in at #3:

One-hit wonder Lou Bega swings in at #2 with “Mambo No.5”:

And the catchiest song ever…(fake electronic drumroll)…“Wannabe” by the Spice Girls:

It should be noted that Burgoyne’s research relied on an internet game to generate the list of catchy songs, so there is inherent bias among the participants. Other research that employed a different algorithm (or should that be “algorhythm”?) have, perhaps thankfully, revealed different results.

All the fun aside, there is a serious element to researching why catchy songs are so easily remembered. The scientists involved with these types of studies hope that their work will reveal news insights into learning and memory, which could potentially be useful in treating conditions such as Alzheimer’s disease.
Contributed by:  Bill Sullivan
Snowdon CT, & Teie D (2010). Affective responses in tamarins elicited by species-specific music. Biology letters, 6 (1), 30-2 PMID: 19726444

Tuesday, November 18, 2014

This Is Your TV On Drugs

Zyrtec used to have commercials that really bugged me.
Someone would sneeze, and everyone would stare at them
with disdainful looks. The message, take this medicine and
stop being a nuisance to polite society. That’s how drug
commercials work, any image to push you toward their drug.
If your prescription for an erectile dysfunction or diabetes drug has to come from your doctor, then why do the drug companies spend all that money on TV ads? 

Because they work! The United States is one of only two countries that allow direct to consumer advertising (DTCA) for prescription drugs. Can you guess the other? These days, there are 100 or so commercials for drugs on the TV every hour of every day.

The practice began in the States in 1985, but didn’t take off until 1997. In ’85, the FDA said it was OK to make claims and not discuss every side effect if the name of the specific drug was not mentioned in the ad. Seldane was the first success using this form of TV advertising. But the claims were so specific that when a person showed up at the doctor’s office asking about it, only one drug, Seldane, fit the description. Sales for Seldane went from a few million dollars to over 800 million dollars.   

In 1997 the FDA decided to let the commercials state the name of the drug without having to give every side effect associated with the drug. Only the major side effects had to be mentioned. And the gold rush was on. Prior to DTCA, the drug companies spent major money to push the doctors to prescribe a certain drug (and they still do), but with the TV commercials, they could actually pull a drug to success by having the patients go ask for it.

Using 2011 statistics, every dollar in DTCA advertising leads to at least four dollars in sales, which is why you’re forced to watch a couple in separate bathtubs on a hill smiling about their sex life. It just pays too well – drugs that use DTCA are prescribed 9x more often than those that are not advertised.

Some people argue that the ads are helpful – power to the people! They may bring more people to the doctor for routine screening and help the patient to see the doctor as a partner, not the boss. They encourage dialogue between the patient and the health provider, where it used to be a one way street – the doctor told you what to take and you either did or didn’t.

Abilify uses animation to sell their drug. The blue robe
represents depression. You take the drug and you don’t have
to wear the robe and it gets depressed. But the robe is always
there, looking creepy. It scares you into staying on their drug.
Some also profess that DTCA leads to a reduction in the stigma attached to certain illnesses, especially mental illness. However, this might not be so. A recent study suggests that DTCA’s for mental illness drugs actually increase the stigma associated with mental illness amongst the general population, while reducing the stigma only amongst the people that actually have mental illness. I’m not sure how helpful that actually is.

The idea that more information is better for the consumer is only true if the information they are getting is accurate and complete. This is where DTCA might have its biggest problem.

A 2014 study rated commercials based on how truthful they were. If they had no exaggerations or false claims, they were termed objectively true. Others were considered misleading, while the rest contained one or more falsehoods. Eighty-four ads for prescription drugs and 84 for over the counter (OTC) drugs were assessed.

The study found that 60% of prescription drug DTCA’s were misleading or false, and the OTC drug ads were worse, 80% contained exaggerations or falsehoods. The most common offender – erectile dysfunction drugs.

The misleading claims are not accidental; they always seem to skirt the bounds of legality. Everything is designed to promote good feelings toward the drug. For example, the study found that when Claritin was moved from prescription to OTC, the beneficial claims in the ads went up six fold.

Maybe the most obnoxious part of the ads is the list of possible side effects read at the end. Who decides what side effects have to be listed? The FDA says that the drug’s most important risks have to mentioned verbally, preferably in language the consumer can understand. Every side effect has to be easily available to the consumer. When the ads say, “Talk to your doctor,” that’s them fulfilling this obligation.

Women take Rogaine (minoxidil) for hair loss, not just men. There
is a whole industry and web community that has cropped up
about how to handle the unwanted hair growth associated with
taking the drug. Too bad that wasn’t there for the women taking
minoxidil for high blood pressure in the 1980's.
The major risks are side effects are those that represent the most severe reactions - death, physical debilitation, and cancer, NOT those that occur most often. True, possible death should be almost always be mentioned, but what about some lesser effects – some people might consider them major.

For example, a drug prescribed in the 1980’s and 90’s for high blood pressure is now marketed for something completely different. Do you think women that took minoxidil for their BP considered it major when they started growing more hair and began to take on the appearance of Kathy Bates in this season’s version of American Horror Story?

You’d think that the drug companies would hate having to use precious ad time to list side effects, but they actually like it. A 2014 study shows that when people are shown ads that don’t list side effects and ads that do, they have better feelings (trust) for the ads that list side effects.

Initially, the side effect lists have a negative effect, but with more viewings, people tend to tune out the side effects themselves. This leaves them only with the feeling of trust they have built up because the manufacturer was “honest” with them. Therefore, they trust those drugs more, but they don't really know why. But we know from above studies that the claims and statements aren’t always completely honest, so it isn't necessarily a justified feeling of trust.

Urban legend has it that the producers added a glimpse of the severed
arm in Star Wars in order to push their rating from G to PG.
But, no, they just asked for the PG rating. Come to think of it,
was there any Star Wars movie that didn’t include the severing
of an arm?
The FDA is thinking about combating this psychological effect by reducing the amount of information that has to be stated. They feel that too much side effect info might be confusing the consumer, leading they tune it out.

Interestingly, consider that the drug companies might not want to reduce the side effect information. They might continue with the long explanations even if not forced to. Did you know that Star Wars asked to have a PG rating so that it could draw a bigger audience that would assume there was more edgy content? Same concept here - they want to spend time on side effects to get the trust pay off.

BTW, the other country that allows DTCA’s for prescriptions drugs – New Zealand, of course!

Contributed by Mark E. Lasbury, MS, MSEd, PhD
As Many Exceptions As Rules

Faerber, A., & Kreling, D. (2013). Content Analysis of False and Misleading Claims in Television Advertising for Prescription and Nonprescription Drugs Journal of General Internal Medicine, 29 (1), 110-118 DOI: 10.1007/s11606-013-2604-0

Steinhart, Y., Carmon, Z., & Trope, Y. (2013). Warnings of Adverse Side Effects Can Backfire Over Time Psychological Science, 24 (9), 1842-1847 DOI: 10.1177/0956797613478948

Corrigan, P., Kosyluk, K., Konadu Fokuo, J., & Park, J. (2014). How Does Direct to Consumer Advertising Affect the Stigma of Mental Illness? Community Mental Health Journal, 50 (7), 792-799 DOI: 10.1007/s10597-014-9698-7

Friday, November 14, 2014

The Friday Five

Highlighting some of the coolest science news we’ve seen lately.

1. Paleo, Atkins, raw, juice...diets, diets, diets! Sort the fact from the fiction with this excellent article, “10 Fad Diets, Debunked”, by Esther Inglis-Arkell.

2. The new film odyssey, Interstellar, blasted into theatres recently. Director Christopher Nolan went to great lengths to try and get the science right in the movie, which included consultation with theoretical physicist Kip Thorne. The video below details how they worked together to imagine a real black hole.

Unfortunately, not all of the science in the movie is accurate

3. In this week's episode of “The Big Question”, Craig Benzine explains why your voice gets higher when you inhale helium. Interestingly, it is not the pitch that changes…

4. Here, kitty kitty…what’s the difference between a wildcat and a domesticated one? Nothing – they both hate you. Jokes aside, scientists have recently performed a genetic comparison between the two and found a number of genes that were enriched due to domestication. These genes may explain why your housecat is less shy, tamer, and more responsive to a reward. Interpreted another way, they also explain why we can't really stroll through the woods with tigers.

5. Our ongoing coverage of new species named after celebrities converged with another subject that constantly fascinates us: Ozzy Osbourne. A new species of frog was recently found in Brazil and named Dendropsophus ozzyi. The males have a bat-like mating call, which reminded the researchers of the infamous concert when Ozzy bit the head off a bat during the show.

Scientists named this new species of frog after Ozzy because it makes a bat-like noise, which reminded them of Ozzy's strange stage diet in the 1980s.

Science quote of the week:

"Science fiction has become science fact today - Hollywood is good, but Rosetta is better" –Dr. David Parker, in reference to the first time humans have landed a probe on a comet.

Contributed by:  Bill Sullivan

Follow Bill on Twitter: @wjsullivan

ORRICO, V., PELOSO, P., STURARO, M., SILVA-FILHO, H., NECKEL-OLIVEIRA, S., GORDO, M., FAIVOVICH, J., & HADDAD, C. (2014). A new “Bat-Voiced” species of Dendropsophus Fitzinger, 1843 (Anura, Hylidae) from the Amazon Basin, Brazil Zootaxa, 3881 (4) DOI: 10.11646/zootaxa.3881.4.3

  Montague, M., Li, G., Gandolfi, B., Khan, R., Aken, B., Searle, S., Minx, P., Hillier, L., Koboldt, D., Davis, B., Driscoll, C., Barr, C., Blackistone, K., Quilez, J., Lorente-Galdos, B., Marques-Bonet, T., Alkan, C., Thomas, G., Hahn, M., Menotti-Raymond, M., O'Brien, S., Wilson, R., Lyons, L., Murphy, W., & Warren, W. (2014). Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1410083111