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

meal.

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

promoted.

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

I’ll Wager That You Bet On Football, Or Maybe Football

Opera diva Renee Fleming (left) sang the national anthem

at the 2014 Super Bowl. Millions of dollars were

wagered on just how long it would take her to get through

the Star Spangled Banner. Pop star Kelly Clarkson (top) took

only 1:34, so the smart bettors went with a longer time for

an opera singer. The over/under was 2:25, but she came in

a solid 35 seconds under that line. Alicia Keys (bottom), on

the other hand, took almost three minutes!

It’s fall again. The NFL season just began and across the pond the English Premier League soccer season has a few games under its belt. You know what that means – lots and lots of gambling.

Between American football and football proper, literally trillions of dollars are wagered each year. And that just counts the games, not the fantasy leagues. For all the readers in the US - yes there are indeed fantasy leagues for the English Premier League.

Each sport is the top betting sport in its respective country, unless you count the massive gamble that NBC took signing a contract to show the EPL in the United States. You can bet on just about anything that concerns the games; who'll get hurt, who'll score first, even the coin toss. In 2014, betting on the Super Bowl surpassed 100 million dollars, and only 42% of that was bet on who would actually win the game!

About 4% of those people who bet on at least a semi-regular basis will go on to develop a gambling addiction, or a “pathologic gambling” problem. There have been lots of study in recent years as to why people gamble, and why only some people develop an addiction. As with most things, it comes down to which is the chicken and which is the egg.

A recent study in Thai students showed that 20% of teenagers gambled, mostly on cards, but only slightly less popular was football (soccer). Ten percent of those who gambled were considered to be addicted. Since only 4% of adults become addicted, does this mean that children are more susceptible? Maybe, but it could be other things as well.

The authors found a strong negative correlation between education and gambling. As GPA went down or the level of education stayed low, the chance of pathologic gambling went up. But which is the cart and which is the horse? Do people with poor grades or education have more chance to become problem gamblers, or does problem gambling lead to poor grades?

More betting on World Cup and other football games has led

to an increase in Chinese, Russian, and North Vietnamese

hacking syndicates that prey on gamblers. Match fixing is also

becoming a big problem as more criminal enterprises try to

make a killing on the beautiful game.

The take home lesson, beyond that Thai kids apparently have too much spending money, is that correlation does not imply causation. Just because two things occur together, it doesn’t mean that the first causes the second or that the second causes the first. One or the other might be causative, but it doesn’t follow that one must cause the other.

So why do they gamble? Is it thrill seeking, for potential monetary gain, for social reasons? There may be as many reasons for gambling as there are gamblers, but some common issues crop up in pathologic gamblers.

Two terms used in the study of gambling are “illusion of control” and “near miss.” These seem to be especially important in football and football. Illusion of control is the feeling that knowing more about the game and being up on the latest data and statistics make a tangible difference in the outcomes of wagers. It ain’t so.

A couple of recent studies give us evidence to the futility of extensive studying. A 2012 study compared the result of choosing 10 soccer games. Professional football gamblers were compared to people who knew nothing about the game and to amateurs who followed the game casually. They all succeeded at comparable rates – knowing more about the game made no difference whatsoever.

This result was supported by a 2013 study that picked the round of 16 games in the European Champions League. Again, people who were ignorant of the game bet just as successfully as the pros. Nevertheless, pathologic gamblers do seem to believe that they have more control over the outcome of wagers, and this is one of the justifications they use to continue. The more they continue to study and bet, the more likely they will develop a problem.

A recent series of experiments shows that it is more complicated than this, at least for football (or football). Gamblers of many ages and betting frequency range were queried as to whether they believed in their luck or their skill for gambling. For football, frequency of betting related more to a belief in luck than their image of themselves as “in the know.” The results were different for casino games, where a sense of skill led to more frequent betting. So football betting isn't always about thinking you have an information edge.

These are MRI scans of the brain while betting on a slot

machine. The left image is a scan of the reward center activity

in a win, but they have subtracted the activity that occurs with

a loss. On the right, the signal during a win was subtracted

from the signal in a near miss situation. There is actually more

activity in a near miss than in an actual win! No wonder

people get hooked on betting.

The “near miss” is more interesting. Having your team lose by one point, or on a fluke play (something like the Fail Mary in the Seahawks/Packers game of 2012) is excruciating – but it's also more exciting, especially for pathologic gamblers. The feeling of excitement and payoff is bigger in these games than even in games that they might win.

In the above study, rats who were trained to press a lever for food after a random press light three lights, pressed the food bar just as often when only two lights were lit – even though pressing it for a non-win (three lights was a win) induced a time penalty during which they couldn’t play again. They knew it would bring a penalty, but the near miss still had some irresistable appeal for the brain’s reward center.

It’s a dopamine thing. Dopamine is a neurotransmitter in the brain that has a lot to do with reward – things that give our brains pleasure. About ten years ago, scientists noticed that people that were started on medicine for Parkinson’s disease (a disease in which motor coordination is impaired due to the loss of dopamine producing neurons in the substantia nigra of the brain) developed gambling addictions at much higher rates than the general population.

Dopamine works in different ways for different parts of the brain. When treating the basal ganglia (BG) that controls muscle movements with dopamine (the dopamine in the BG is low in Parkinson's), you are also increasing the dopamine levels in other parts of the brain. It isn't the treatment of the tremor that causes people to gamble, it's the inadvertent actions of the dopamine on some other part of the brain that leads to gambling problems.

For example, the “near miss” releases just as much dopamine in the reward centers of the brain as does a win and correlates highly with development of gambling addiction. Does too little dopamine mean that they have to gamble more than other people in order to get the same effect, and this is exacerbated by dopamine containing medicines? Maybe. Pathologic gamblers do seem to release more dopamine in the mesolimbic area of the brain (motivation control) when gambling than do healthy control subjects.

This cartoon illustrates just how difficult it is to prove a causal

relationship between dopamine and pathologic gambling. The

different areas of the brain use different combinations of

dopamine receptors, and these can change with disease or

trauma. Each are will react differently to too much or too little

dopamine, or to changes in other neurotransmitters that affect

dopamine activity or release. But scientists are good at isolating

variables, I bet we get it sooner rather than later.

However, a 2013 study showed that the motivational area dopamine areas had more dopamine when the reward (winning the bet) was uncertain as opposed to after it was won. This leads to the idea that there is more of a thrill in uncertainty and is itself the reward. When dopamine drugs enter the brain indiscriminately, these feelings are exacerbated, and more gambling is needed to keep the reward (pleasurable feeling) going.

Unfortunately, it's much more complicated than this. There are different types of receptors for dopamine on the different types of neurons. Too much or too little dopamine can over time change the number and types of dopamine receptors found on the neurons, so dopamine activity in a healthy brain isn’t exactly the same as dopamine activity on a previously dopamine starved brain. This is exemplified by a case report in 2013 of a patient who quickly developed a strong and uncontrolled gambling problem after beginning drugs to lower the dopamine levels in his brain.

So once again, we see that just correlating dopamine levels with gambling on football (or anything else) isn’t enough to say that it causes the gambling addiction. We know dopamine is playing a role, but is it too little or too much that leads to gambling addiction? Your bet is as good as mine.

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




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